Abstracts for the 7th European Congrfess on Menopause, 3 - 7 June 2006, Istanbul, Turkey

Maturitas 54S (2006) S1–S112

Abstracts

7th European Congress on Menopause, 3–7 June 2006, Istanbul, Turkey

Sunday, 4 June 2006 08:30–09:00 KL01—Keynote Lecture Gender differences in mortality and morbidity: epidemiological aspects Vera Regitz-Zagrosek Center for Cardiovascular Research (CCR), Gender in Medicine, Cardiovascular Disease in Women, Charit´e, Berlin, Germany In all societies where the yearly income per inhabitant exceeds about US$ 3000 women live longer than men, in the mean about 6 years. The reasons for these differences are yet unknown. Distribution of major diseases could play a role as well as social factors. Major diseases with prominent sexual dimorphisms include cardiovascular diseases, malignant diseases, metabolic diseases such as diabetes, nephropathies, rheumatic inflammatory and neurological diseases as well as others. The detection of a disease in the population depends on the applied diagnostic procedures and on the awareness among patients and physicians about the disease. For example, cardiovascular diseases are under-diagnosed in women in western societies since they are less suspected to occur. Symptoms in women somehow differ from those of men and the symptoms of men are accepted as classical leading to a under-recognition in women. Frequently used diagnostic procedures such as exercise ECG have a lower 0378-5122/$ – see front matter doi:10.1016/j.maturitas.2006.03.001

sensitivity in women compared with men and techniques that are suitable for diagnosis in women such as imaging procedures are underused. Interestingly some cardiac events and interventions such as myocardial infarctions and bypass surgery have a higher mortality in younger women than in older ones. In contrast heart failure has a better outcome in women compared with men. Life-threatening arrhythmia occur mainly in men but some specific forms are more frequent in women. Metabolic diseases diagnosis heavily depends on the test used. Diagnosis of pre-diabetes by fasting glucose or oral glucose tolerance tests will include different percentages of women and men. Interaction between metabolic and cardiovascular diseases is more prominent in women than in men. The underlined pathophysiology is yet unclear. Gender differences are found in almost all major internal diseases. Nephropathies have a more severe course in men and inflammatory diseases are more severe in women. Interaction of gender and aging is disease-specific and hormonal and environmental factors affect women and men differently. Sunday, 4 June 2006 09:00–09:30 KL02—Keynote Lecture Gender differences in mortality and morbidity: biological aspects Speaker to be determined Abstract not available at the time of printing.

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Sunday, 4 June 2006 10:30–12:30 OF01—Open Forum: Hormonal interventions updated The HRT story so far John WW Studd UK Abstract not available at the time of printing. Sunday, 4 June 2006 10:30–12:30 S01—Symposium: Urogenital issues S01.1 Sexual dysfunction in men Speaker to be determined Abstract not available at the time of printing. S01.2 Sexual dysfunction in women Christine Bodmer-Hindermann Department of Obstetrics & Gynecology, University of Bern, Switzerland Sexuality is a highly complicated process, which is exposed to different influences. Biological, psychological as well as social factors are responsible for a good sexual life. In this lecture, we are focussing on the local urogenital aspects playing a role in sexuality such as arousal disorders, vaginism, dyspareunia and orgasmic disorders. These aspects are part of phase II (arousal phase) and III (orgasmic phase) of the old concept published by Singer Kaplan. In addition, the new pathway of the sex response cycle has to be taken into account, as it has been reviewed by an international multidisciplinary group more recently. Physiology and pathophysiology of the above mentioned phases are discussed. However, we are looking not only at the organic but also at the psycho-social (including the interpersonal) factors, which can lead to a sexual dysfunction. Lastly, we are considering the different possibilities of treatments and forms of consultations. Finally, the most important fact for the patient is the guarantee of an integral view used by the therapeutic approach.

S01.3 Urge incontinence Ralph Peeker Sahlgrenska University Hospital, Urology Department, Gothenbyrg, Sweden Bladder overactivity imposes problems of varying degree in some 15% of the population above 40 years of age. A substantial proportion (25–35%) of patients with overactive bladder (OAB) also suffer from incontinence (OAB wet). The diagnostic strategy is founded upon a thorough history, careful physical examination, micturition protocols, urinalysis and pad test. In selected cases postvoid residual urine measurement, full-scale urodynamic assessment and endoscopy are also valuable diagnostic tools. Once an adequate diagnosis has been established, and significant concomitant pathology of the lower urinary tract has been ruled out, the therapist may present several treatment options to the patient, including behavioural treatment, pharmacological intervention, electrical stimulation including neuromodulation, and surgical reconstruction. This presentation will give an in-depth explanation of the benefits of various diagnostic strategies. It will cover available pharmacological agents for the treatment of urgency and urgency incontinence. There will also be a presentation of various kinds of functional electrical stimulation strategies, including sacral neuromodulation with percutaneous nerve evaluation or two-stage implant technique. Finally, different strategies of major reconstructive surgery for the correction of urgency incontinence will be presented, including continent and non-continent diversionary procedures. S01.4 Stress Incontinence Dudley Robinson Department of Urogynaecology, King’s College Hospital, London, UK The female genital and lower urinary tract share a common embryological origin, arising from the urogenital sinus. Both are sensitive to the effects of female sex steroid hormones. Oestrogen is known to have an important role in the function of the lower urinary tract throughout adult life with oestrogen and progesterone receptors demonstrated in the vagina, urethra, bladder and pelvic floor musculature. This is supported

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by the fact that oestrogen deficiency occurring following the menopause is known to cause atrophic changes within the urogenital tract and is associated with urinary symptoms such as frequency, urgency, nocturia, incontinence and recurrent infection. These may also co-exist with symptoms of vaginal atrophy such as dyspareunia, itching, burning and dryness. Oestrogen therapy alone has been shown to have little effect in the management of urodynamic stress incontinence and some evidence suggests that it may have a deleterious effect on urinary symptoms. When considering the irritive symptoms of urinary urgency, frequency and urge incontinence oestrogen therapy may be of benefit although this may simply represent reversal of urogenital atrophy rather than a direct effect on the lower urinary tract.. However, more recently evidence from large epidemiological studies investigating the long term effects of hormone replacement would appear to contradict some of the studies specifically investigating incontinence. Neither menopausal symptoms nor urinary incontinence are life-threatening conditions although both have a significant effect on quality of life. The current evidence from all trials suggests that oestrogen replacement therapy may have a minor role in lower urinary tract dysfunction and that the vaginal delivery route may be preferable to the oral. Sunday, 4 June 2006 10:30–12:30 S02—Symposium: Diabetes S02.1 Epidemiology Renato Pasquali Italy Abstract not available at the time of printing. S02.2 Do sex hormones influence features of the metabolic syndrome in middle-aged women? Yasameen Shakir (Sweden), G Samsioe, P Nyberg, J Lidfeldt, C Nerbrand, CD Agardh Abstract not available at the time of printing.

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S02.3 Hormone and insulin sensitizers Lily Stojanovska School of Biomedical Sciences, Victoria University, Melbourne, Australia Diabetes mellitus type 2 (DT2) is a chronic disorder characterised by hyperglycemia resulting from insulin resistance, an insulin secretory defect, and/or an increase in hepatic glucose production. DT2 and oestrogen deficiency at the time of menopause, are associated with stiff large arteries, which play an important role in the pathogenesis of cardiovascular disease (CVD) and subsequent morbidity and mortality in women. Good glycemic control and the subsequent amelioration of hyperinsulinemia and hyperglycemia can delay the onset of vascular complications. The thiazolidinediones (TZD), rosiglitazone (ROS) and pioglitazone (PIO) are insulin-sensitising agents widely used to treat postmenopausal women with DT2, either as a monotherapy or in combination therapy with sulfonylureas, metformin, insulin or hormone therapy. Thiazolidinediones significantly decrease fasting glucose, insulin and glycated haemoglobin in diabetic patients, and delay the progression of insulin resistance/impaired glucose tolerance into DT2 through early treatment. TZDs, however, also have a number of anti-atherogenic effects independent of their influences on glucose and insulin metabolism. Pioglitazone improves blood lipid profiles by converting small, dense LDL particles into larger, less atherogenic lipoprotein particles, while rosiglitazone, on the other hand, in combination with HRT has shown to improve endothelial function, increase large artery compliance, and lower blood pressure in postmenopausal women with DT2. The disease preventative actions of TZDs may be the result of their agonistic effects on peroxisome proliferator-activated receptors (PPARs), ligandactivated transcription factors that regulate the expression of numerous genes and affect glycaemic control, lipid metabolism, vascular tone and inflammation. Therefore, ROS and PIO are effective treatments to improve glycaemic control and reduce the risk of CVD in postmenopausal women with DMT2, with stronger evidence that PIO is associated with greater beneficial effects on lipids than ROS.

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S02.4 Nutrition and diets Ulrich Keller Division of Endocrinology, Diabetes and Clinical Nutrition, University Hospital, Basel, Switzerland The prevalence of diabetes is rising worldwide, not only in industrialized countries, but also in formerly developing countries, where a western lifestyle has become more and more common. The incidence of diabetes type 1 is also increasing although to a lesser degree than diabetes type 2. Dietary risk factors for the development of diabetes Risk factors for diabetes type 1 (only validated in epidemiological studies): Omission of cow’s milk during 6 months after birth has been shown to lower diabetes risk [1]. Vitamin D deficiency in Finnish studies has been reported to increase risk [2]. Consumption of fish oil has been suggested to lower diabetes risk [3]. However, none of these factors have been proven to affect the risk of type 1 diabetes in intervention studies. A randomized controlled intervention trial with the antioxidant nicotinamide demonstrated no effect on insulin requirements [4]. References [1] [2] [3] [4]

Virtanen et al., Diabetes 2000;49:912. Hypp¨onen et al., Lancet 2001;358:1500–3. Stene et al., Am J Clin Nutr 2003;78:1128–34. Endit Study, Gale et al., Lancet 2004;363:925–31.

Risk factors for diabetes type 2: Protective factors are: • • • • • •

Voluntary weight loss in overweight subjects Dietary fibre Low glycaemic index foods Nuts Coffee Alcohol

Promotive factors are: • Excess adiposity, especially visceral type • Saturated fatty acids/low intake of polyunsaturated fatty acids • Trans fatty acids

These risk factors have been demonstrated independently of each other in large epidemiological studies. Evidence for the importance of lifestyle changes and of certain drugs has been provided by controlled intervention trials. In particular, the effect of lifestyle changes in diminishing diabetes risk was impressively shown in the Finnish and in the US Diabetes Prevention Programs. These studies randomized subjects with increased diabetes risk (impaired glucose tolerance) to either lifestyle intervention, or to no intervention (observation only). In the Finnish study, the following lifestyle goals were set: 1 Weight reduction, >5%. 2 Fat consumption, <30% of total energy; saturated fats, <10% of total energy. 3 Dietary fibre, ≥15 g/1000 kcal per day. 4 Physical activity, > 4 h moderate intensity The surprising result was that during the approx. 5 years follow-up 58% of the new cases of type 2 diabetes were avoided by lifestyle intervention. When the number of individual goals reached were analysed separately, the protective effect of each goal reached was cumulative. When all four goals described above were reached the excess risk for diabetes was completely abolished! Weight loss can be achieved long-term in weight loss programs, which should include three components: (1) Nutritional education and nutritional changes; (2) behavioural changes; (3) increased physical activity. All these three components act synergistically in a weight loss programme in order to achieve longterm success. Dietary changes should aim for slowly progressive, modest weight loss, by improving dietary habits, e.g., learning to eat in a more structured and unstressed way to eat foods with relatively low caloric density. Recently, low carbohydrate diets have become popular to induce weight loss in obesity; however, the long tern success (>12 months) was not better than with conventional diets. In addition all diets, which require extreme changes of eating habits may increase the risk of eating disorders, which already have a prevalence of about 20% in obese subjects (“binge eating disorder”). A weight loss of 10 kg leads to a significant decrease of glycaemia in newly discovered type 2 diabetics and

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in an improvement of cardiovascular risk factors: • • • •

15% decrease of LDL-C 30% decrease of serum triglycerides 8% increase in HDL-C Decrease of syst. blood pressure by 6 mmHg, and of diast. BP by 4 mmHg • 15% decrease of HbA1c in subjects with type 2 diabetes These changes result in a calculated cumulative reduction of CV mortality by 25%! Nutritional therapy in diabetic subjects Nutritional therapy is essential in all patients with diabetes mellitus. Diabetes type 2 is treated by weight reduction, by decreasing the consumption of energy dense foods and particularly by avoiding consumption of large amounts of carbohydrate-containing foods or drinks with a high glycaemic index. In addition, a change towards a “healthy diet” with frequent consumption of vegetables or fruits and with low amounts of saturated fats exert additional benefits on cardiovascular health. The more severe the diabetes, the more it is important to intensify nutritional therapy. If insulin therapy is necessary, a major goal of nutritional treatment is to separate carbohydrates into several (three to five) meals per day, and to adapt the amount of insulin injected (units) to the quantity of carbohydrates (g) to be ingested. The amount of carbohydrates in a meal is the single most important factor, which determines postprandial glycaemia. Other nutritional factors such as glycaemic index, proteins or fats in the diet are additional factors, which modify the effects of carbohydrates per se. This means that the patient has to be trained to weigh or to estimate the quantity of carbohydrates in ordinary foods he or she likes to eat. Secondary nutritional goals are depending on the individual patient, if dyslipidaemia or hypertension are present, additional goals are stated. Lowering of saturated fat intake to lower LDL-C, limitation of rapid carbohydrates and alcohol to lower serum triglycerides, or reduction of salt intake and increase in fibre intake in the presence of elevated blood pressure are additional effective measures in conjunction with drug therapy.

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Sunday, 4 June 2006 12:30–14:00 LS01—Lunch Satellite Symposim Tibolone STEAR: effects on the endometrium Sponsored by Organaon NV LS01.1 Tissue selective effects of tibolone; mechanism of action on the endometrium Jean-Michel Foidart Department of Obstetrics and Gynecology, University of Liege, Liege, Belgium Clinically, a protective effect of tibolone on the endometrium has been reported in many studies in postmenopausal women. A number of preclinical findings contribute to the understanding of this observation. Results of in vitro studies in cell lines, ex vivo studies in human tissue and in vivo studies in animals show that two different processes are involved in the mechanism of action of tibolone on the endometrium: (1) regulation of the sulfatase/sulfotransferase pathway; (2) local formation of the progestogenic
4 tibolone metabolite.In vitro, sulfotransferase enzymes have been demonstrated to be present in endometrial tissue and the activity is stimulated by tibolone,
4 tibolone and 3␤OH-tibolone. As a consequence, free estrogenic metabolites, 3␣-OH and 3␤-OH tibolone, are converted into sulfated metabolites. Tibolone also inhibits the enzyme sulfatase, preventing the local formation of active estrogens from estrone sulfates and the sulfated 3␣-OH tibolone. These mechanisms combined lead to high levels of sulfated tibolone and sulfated estrogen metabolites, which are inactive at the receptor level and thus reduce the estrogenicity of the tibolone metabolites on the endometrium. In addition, in vitro data have shown that tibolone and
4 -tibolone induce progestogen-sensitive parameters in endometrial cell lines. In endometrial tissue, these progestagenic effects presumably counteract potential stimulation by any remaining estrogenic activity. Measurements of tissue levels of tibolone metabolites would provide further evidence for these mechanisms.In conclusion, the lack of estrogenic effects of tibolone on the endometrium is explained by a shift in the sulfotransferase/sulfatase system towards sulfation and an increase in local progestagenic activity.

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LS01.2 Clinical effects of tibolone on the endometrium Speaker to be confirmed Abstract not available at the time of printing. LS01.2 Tibolone and endometrial safety: results from THEBES Alec Ferenczy USA Abstract not available at the time of printing. Sunday, 4 June 2006 12:30–14:00 LS02—Lunch Satellite Symposim Sponsored by Novo Nordisk FemCare Abstract not available at the time of printing. Sunday, 4 June 2006 14:15–16:15 AS01—Afternoon Symposium: Climacteric medicine across the continents AS01.1 Thailand as an Asian paradigm in climacteric medicine Khunying Kobchitt Limpaphayom President, Thai Menopause Society In the past decade, the science of climacteric medicine has increasingly acquired medical and public attention since global population becomes aging. The dependent ratio seems to be increasing in every part of the world not only in the developed countries. Aging health is considered to be a crucial issue that will certainly influence future social and economic development. Asia is the continent that inhabited by more than half of the world population of which the changes in demography will have a huge impact on global health issue. Up until now, Thailand population has been increasing up to 63 millions, half of which is female. Approximately 6 millions of women are over the age of 45 which is the climacteric period. In 1996, the Ministry of Public Health, Thailand conducted a nationwide health survey in 8300 women aged between 40 and 60 years. The results reveal that less than 20% of interviewees reported significant hot flashes compared with 80% of

prevalence in some European countries. The top five complaints were backache, headache, dizziness, joint pain, and forgetfulness of which the hot flashes rank the tenth. The prevalence of osteoporosis, when used the WHO criteria of −2.5 S.D. below the young adult mean, was lower than the report from England and Wales. The incidence of hip fracture in Thai female is much lower than the Caucasian but higher than black women and comparable with her neighborhood in Asia. Generally, genetic and environmental factors are considered to play key role in determining health status. It has been demonstrated that Asian and Caucasian have different Vitamin D receptor genes and estrogen receptor polymorphism which determine calcium metabolism and as a consequence, the risk of osteoporosis. This may partly explain the higher incidence of osteoporosis in Caucasian even though the latter intakes more dairy products. Environmental factors are the essential component involving the prevalence of osteoporosis and incidence of fractures. The difference in lifestyle, culture, living environment and family bonding may be the essential condition in prevention of fall as a consequence, decreasing the risk of fractures. As a matter of fact, women in different parts of the world experience menopausal symptoms in different manifestation, frequency, and severity. In addition to biological variation, women’s perception and attitude towards menopausal transition may influence the symptom occurrence and interpretation of its severity. Nutritional factor has been claimed to be an important component determining the prevalence of the symptoms owing to the fact that Asian diet is semivegetarian, which contains higher element of phytoestrogen. It is perceptible that Asian women have lower prevalence and incidence of vasomotor symptoms, osteoporosis and fractures, not mentioning of the lower incidence of cardiovascular diseases and cancer. It is interesting to look at local remedy that may explain the lower occurrence of these ailments. The difference in bio-cultural and psychosocial condition may play significant role in prevention of those catastrophic events and the severity of symptoms during the transition.

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AS01.2 Sexual dysfunction in postmenopausal women: when to treat/when to refer Philip Sarrel Yale University, USA Menopause health care frequently involves assessment of sexual dysfunctions. Because these problems may be caused by several factors, the primary role of the health care provider for these patients is to offer understanding and accurate diagnosis. Listening to the patient and clarifying her concerns can define the nature and extent of the problem and determine her motivation for treatment. Physical examination and laboratory testing may provide additional information for developing a treatment plan. Sexual problems in postmenopausal women are often amenable to fairly simple interventions that are (or can and should be) within the competence of primary care providers. Relevant and reassuring reading materials can help reduce anxiety. Some menopause-related dysfunctions are helped by hormonal interventions with estrogens alone or in combination with androgens. Specific suggestions drawn from sex counseling principles can be offered and are often helpful. Initial assessment may indicate the patient is a candidate for referral to a sex therapist or psychotherapist and not for primary care provider interventions. Arranging referral to a specialist in sexual health is also an option for primary care providers who do not have the time, feel uncomfortable with, or feel unprepared to deal with sexual dysfunctions. When primary care provider education, counseling and medical treatments prove inadequate for resolving patient sexual dysfunction, referral is also indicated. In such circumstances, making a proper, effective referral is a provider responsibility. This presentation provides a perspective on the appropriateness of interventions (treatments) which the primary care provider can carry out and offers guidelines for making appropriate referrals for women experiencing postmenopausal sexual dysfunction. AS01.3 Routes of delivery Barry G Wren Sydney Menopause Centre, Australia Achieving successful patient compliance for hormonal therapy requires physicians to not only understand the pharmacology and pharmacokinetics of the

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hormones they are prescribing but they must be flexible in deciding on the route of administration of those hormones. Not all women respond to the same hormonal therapy in the same way. Some develop adverse reactions to one delivery system or one type of hormone, other women choose or request a “natural” therapy rather than a “synthetic” commercial regimen, while for medical reasons, other women should be administered their hormonal regimen by a route designed to provide an advantage not available by a regular delivery system. Most hormonal regimens are composed of an oestrogen with a progestogen added. When administered orally, about 90% of the oestrogen passes directly to the liver where it exerts a positive influence on the production of proteins (pro-coagulant factors, SHBG) and on hepatic cell cholesterol receptors. Therefore women who are at risk of thrombosis should be advised to avoid using oral oestrogen therapy and instead use another portal for delivery (trans-dermal, sub-dermal, transnasal or trans-buccal) whereas women who have high cholesterol levels may gain an advantage by using the oral route to increase the hepatic production of cholesterol receptors. Because most progestogens are “synthetic”, derived by manipulating the molecule of C-19 or C-21 steroids, there are occasional adverse reactions which some women find unacceptable. In an attempt to overcome these problems there has been a vogue to use a “natural” progesterone with or without oestrogen. Unfortunately natural progesterone is rapidly metabolised when administered by the oral (gastric) route while insufficient is absorbed through the skin to be clinically effective when applied as a cream. For this reason the administration of progesterone using the trans-buccal route (troches) has been employed as an alternative and this portal of entry has resulted in levels sufficient to inhibit endometrial growth among those women desirous of using “natural” (bio-identical) progesterone with a “natural” oestrogen. Other innovative routes of administration of hormonal therapy include intra-nasal, vaginal and intrauterine delivery systems. Each of these routes of delivery has some advantages for some women and it is important that the medical profession be aware of the various systems so that an appropriate regimen can be initiated to treat the many and varied requirements of individuals without compromising the aims

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of the hormonal treatment. Patches, sprays, creams and lozenges (troches) are all being developed to improve the delivery of appropriate hormones to postmenopausal women and it is important that physicians have knowledge of the various systems and their advantages as well as their drawbacks before prescribing a regimen. Particular attention will be given in the presentation to the trans-nasal, trans-buccal (troche) and intrauterine routes of administration of HRT. AS01.4 Special Session: Climacteric Medicine Across the Continents The Postion of EMAS Sven O. Skouby Dep. Ob/Gyn, Frederiksberg Hospital, University of Copenhagen and University of Southern Denmark The European Agency for the Evaluation of Medicinal Products (EMEA) has through statements on the appropriate use of postmenopausal hormone therapy (HT) December 2003 pointed to the favourable benefit/risk balance in the treatment of climacteric symptoms that adversely affect quality of life. The EMEA emphasised, however, that the minimum, effective dose and the shortest duration should be used because of new evidence on risk associated with HRT published within the last years. The background data were those published from the Heart and Estrogen/progestin Replacement Study (HERS) in postmenopausal women with CHD, the Women’s Health Initiative (WHI) study (combined and estrogen only arms) and the Million Women Study (MWS). Subsequently, a re-analysis of the original data of the WHI (combined arm) and the results from the estrogen only arm of the WHI study have informed about reduced risk of breast cancer and a possible preventive effect on CHD in young postmenopausal women. The Executive Committee of the European Menopause and Andropause Society (EMAS) has therefore considered available information in it’s 2005 Position Paper and EMAS has recently updated the 2005 recommendations as a consequence of further new and reassuring information from the estrogen only arm of the WHI study and from the Nurses Health Study on cardiovascular disease (http://emas.obgyn.net/). These data are

together with the overall information from early postmenopausal women supportive for a rehabilitation of HT based upon individualized management of each candidate. The challenge for EMAS during this 7th Congress is therefore to deliver high quality science and avoid recycling of previously presented and maybe misleading research. EMAS considers that the clinicians’ main goal is to provide safe and effective relief of climacteric complaints, and advice on all aspects of climacteric medicine. In most cases benefits will outweigh any of the risks pertaining to those years where HT exposure is clinically needed. Sunday, 4 June 2006 14:15–16:15 AS02—Afternoon Symposium Organised by Austrian Menopause Society AS02.1 Preventive oncology for post-menopausal patients Johannes Huber Austria Abstract not available at the time of printing. AS02.2 The new demographic development in the European countries: problems and prospctives for tomorrow Wolfgang Clementi Austria Abstract not available at the time of printing. Sunday, 4 June 2006 14:15–16:15 AS02.3 Atherosklerosis and their prevention by phytohormones Markus Metka Austria Abstract not available at the time of printing. AS03—Afternoon symposium: Women’s e-health Organised by JW van der Slikke (The Netherlands) Abstract not available at the time of printing.

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Sunday, 4 June 2006 14:15–16:15 FC01—Free Communication Session: Hormone therapy FC01.1 No negative effect of testosterone addition on mammographic density during estrogen/progestogen treatment Marie Hofling1 , E Lundstrom1 , G Svane2 , E Azavedo2 , B von Scholulz1 1 Karolinska University Hospital, Department of Womens Health, Stockholm, Sweden; 2 Karolinska University Hospital, Department of Radiology, Stockholm, Sweden Objective: To study the effect of testosterone addition on mammographic density during estrogen/progestogen treatment. Methods: A 6 months prospective, randomized, double-blind, placebo controlled study. Postmenopausal women were given continous combined estradiol 2 mg/norethisterone acetate 1 mg and were equally randomized to receive additional treatment with a testosterone (300 ␮m/day) or placebo patch. Mammograms were performed at baseline and after 6 months. The effects on mammographic density was quantified by visual classification scales and also by a computer assisted technique, digitized mammography. Digitized assessment showed a strong correlation with the visual classification scales. Mammographic density was correlated with serum levels of hormones, growth factors and binding proteins. Results: At baseline, digitized mammographic density was negatively correlated to levels of total testosterone (rs −0.27; p = 0.01) and free testosterone (rs −0.35; p < 0.1), and positively correlated to levels of SHBG (rs 0.24; p = 0.02). After treatment, mammographic density was increased, but there was no significant difference in mammographic density between the two groups. Conclusion: The androgen status of untreated postmenopausal women is associated with mammographic density. This study showed no negative effect on mammographic density of testosterone addition. The current

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discussion on breast safety during HT has stimulated the interest in alternative treatments. Increased mammographic density is associated with an increased risk of breast cancer and should be regarded an un adverse event during hormone treatment (HT). FC01.2 The relation of hormone replacement therapy and soy foods with mammographic density: a longitudinal investigation in the multiethnic cohort Gertraud Maskarinec, I Pagano, G Lurie, L Kolonel University of Hawaii, Honolulu, USA Mammographic densities reflect the cumulative exposure to breast cancer risk factors. Given the concerns that hormone replacement therapy (HRT) or soy foods may affect breast cancer risk, this report explored their association with mammographic density change over time. The study population consisted of 607 breast cancer cases and 667 frequency matched controls with 1956 and 1619 mammographic readings, respectively. Mammograms performed over more than 20 years and before a breast cancer diagnosis were assessed for densities using a computer-assisted method. HRT use for each year, HRT type, and life-time soy intake were obtained by questionnaire. Using multilevel modeling to allow for repeated measurements, we estimated the effect of HRT and soy intake on initial status and longitudinal change while adjusting for confounders. Percent densities decreased approximately 5.6% per 10 years. Combined HRT use (3.3% per 10 years, p < 0.01) and, to a lesser degree, estrogen only therapy (1.6% per 10 years, p = 0.03) were related to a significant delay in the decline of densities. Early life soy intake was weakly related to lower percent densities at initial status (−8.6%, p = 0.07), while soy consumption during adulthood predicted significantly higher densities (8.9%, p = 0.04). The rate of change was not significantly affected by soy intake. This longitudinal investigation confirms the long-term risk associated with combined HRT use on breast cancer and also suggests a small adverse effect of estrogen only therapy on breast density. In comparison, the relation of soy intake with mammographic densities was relatively weak.

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FC01.3 Hormone therapy re-initiation and first-time initiation by type, dose and route, after the Women’s Health Initiative Katherine Newton1,2 , D Buist1,2 , U Yu1 , C Hartsfiels3 , S Andrade4 , F Wei5 , M Connelly6 , KA Chan7,8 1 Group Health Cooperative, Center For Health Studies, Seattle, USA; 2 University of Washington, School of Public Health and Community Medicine, Seattle, USA; 3 Kaiser Permanente, Denver, USA; Meyers Primary Care Institute, Worcester, USA; 4 HealthPartners Research Foundation, Minneapolis, USA; 5 Department of Ambulatory Care and Prevention, Harvard Pilgrim Health Care, USA; 6 Harvard Medical School and Menopause Consultation Service and Harvard Vanguard Medical Associates, Boston, USA; 7 Channing Laboratory, Brigham & Women’s Hospital and Harvard Medical School, Boston, USA; 8 HMO Research Network’s Center for Education and Research on Therapeutics, Boston, USA Objective: Describe re-initiation and first-time initiation of hormone therapy (HT: estrogen with/without progestin) and factors associated with re-initiation and first-time initiation, after publication of the WHI results in July 2002. Methods: Observational cohort study (1999–2003), of women 40–79 years from five US health plans. Participants were using HT in July 2002 and subsequently discontinued (n = 20,205), or had not used HT (n = 90,261) as of July 2002. We used automated pharmacy dispensings and encounter data to identify HT type, route and dose, and to identify women with diabetes, cardiovascular disease, hyperlipidemia, and fracture. We used multivariable Poisson regression, adjusted for study site, month, and sample characteristics, to calculate relative risks (RR) and 95% confidence limits (95% CI). Results: 15.8% (3203/20,205) of women who discontinued HT re-initiated; 78.1% (2500/3203) reinitiators resumed the same type and dose. Reinitiation was higher among women using unopposed estrogen (23.8%), versus estrogen with progestin (11.3%) (adjusted RR = 2.94, 95% CI 2.82–3.05). Lower re-initiation rates were associated with diabetes (RR = 0.68, 95% CI = 0.63–0.74), cardiovascular disease (RR = 0.88, 95% CI 0.84–0.92), and hyperlipidemia (RR = 0.83, 95% CI 0.79–0.87). Only 2.3%

(2072/90,261) of never-users became first-time initiators during follow up 8/2002–12/2003. The first-time initiation rate was highest among women aged 50–54 versus younger and older women, and higher among women with cardiovascular disease (RR 1.18, 95% CI 1.12–1.22) or hyperlipidemia (RR 1.24, 95% CI 1.20–1.29). Conclusions: Following the WHI a small proportion of women who discontinued HT later re-initiated. Women with cardiovascular disease, diabetes and hyperlipidemia were less likely to re-initiate. Among never users, few initiated HT. FC01.4 Hormone replacement therapy and cognitive performance Evangelia Papavasiliou, S Sunram-Lea Lancaster University, UK Objectives: The aim of this study was to assess the effects of HRT on cognitive performance and to explore whether participants’ age and educational level might have generated the negative clinical findings reported by the WHIMS. Methods: Forty healthy postmenopausal women (private clinic patients; last natural menstrual period <3 years), screened with a family, medical and gynaecological history and matched for age and education, freely consented to enter the study and were allocated to two groups depending on whether they were currently on HRT or not (i.e. HRT versus non-HRT). Women in the HRT condition had an average duration of treatment >1 year without interruption since menopause. Cognitive performance was assessed using tests of verbal declarative memory, attention/concentration and problem solving. Results: No statistically significant differences between groups were observed for attention/concentration and problem solving ability. However, the HRT group performed significantly better on the immediate and delayed recall components of the memory tests. Discussion: The results of this study support previous reports suggesting that HRT use is associated with improved verbal declarative memory in healthy postmenopausal women. Consequently, the negative results published by the WHIMS could be attributed to subjects’ age and educational level that might have

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confounded the effects of HRT on cognitive performance. FC01.5 Prescribing of Tibolone in primary care: comparison between 2000 and 2005 Sarah Gray1 , H Lambert2 , L Nutt2 , E Roberts2 1 Central Cornwall PCT, UK; 2 Peninsula Medical School, UK Objective: Following publications of the Million Women Study (MWS) and Women’s Health Initiative (WHI) hormone therapy use fell. It’s effectiveness for symptom relief and prevention of osteoporosis was not questioned but the risk profile was emphasised. Women and their doctors sought alternatives that were perceived to be safer. One of these alternatives was Tibolone, a synthetic steroid. Use of Tibolone within a stable practice population has been audited at the 5year interval that spanned these publications. Method: All women in a primary care population of 13,300 who were prescribed Tibolone over a 6month period in 2005 were identified from prescribing records. Both computerised and paper versions of their lifelong health record were searched to identify all hormone therapy regimes, noting changes of regime and duration of use. A parallel search was performed for the same 6 month period in 2000. Results: Thirty five women were prescribed Tibolone in 2005 compared with 24 in 2000. Seven as opposed to three had had a hysterectomy. Average age of user was 58 in 2005 with 56 cycles having been prescribed. This compared to 56 with 25 cycles in 2000. 3.5 (v2.3) changes of regime had occurred prior to initial Tibolone prescription with an average of 65 (v54) cycles of conventional hormone therapy. Discussion: Within this population, Tibolone users have increased in number and duration. It appears to be an individual choice often following years of conventional regimes. attributable risk becomes difficult to isolate and endometrial data in particular are thrown into doubt.

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FC01.6 Endometrial safety after 5 years of continuous combined transdermal estrogen and intrauterine levonorgestrel delivery for postmenopausal hormone substitution Dirk Wildemeersch1 , K Pylyser2 , N De Wever2 , W Tjalma3 1 Contrel Research, Technology Park Zwijnaarde, Ghent, Belgium; 2 Department of Histopathology, St. Augustinus Hospital, Veurne, Belgium; 3 Department of Obstetrics and Gynecology, University of Antwerp, Belgium Objective: To investigate endometrial histology after long-term use of continuous transdermal estrogen substitution combined with intrauterine release of levonorgestrel (Femilis LNG-IUS) in postmenopausal women. Design: A 5-year non-comparative prospective clinical trial. Subjects: One hundred and two postmenopausal women, who used two consecutive LNG-IUSs, were selected from a group of 182 women with the aim to study the long-term effects on the endometrium. The mean duration of use of the regimen was 70 months (range 25–98). The mean age of the women was 57 years (range 47–71). The majority of women received percutaneous 17 beta-estradiol, 1.5 mg daily, or an equivalent dose by patch or orally, on a continuous basis. Main outcome measure: Endometrial histology after a period of approximately 5 years of use. Results: The dominant endometrial histologic picture was that of profound endometrial suppression with glandular atrophy and stroma decidualization (Kurman classification 5b). No cases of endometrial hyperplasia were found. Conclusion: The results demonstrate that the LNGIUS effectively opposes the estrogenic effect on the endometrium resulting in strong suppression during the entire period of EST. Due to its high efficacy and absence of systemic effects on organ tissues (e.g., breasts), target delivery in the uterine cavity could be a preferred route to administer a progestagen in women using EST.

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FC01.7 Hormonal profile in adolescent patients with anorexia nervosa Stefanos Zervoudis1 , G Iatrakis1 , I Virtej2 , P Tsikouras3 , G Galazios3 1 Lito Maternity Hospital Athens, TEI University of Athens, Greece; 2 Parhon Hospital, C. Davila University of Bucarest, Romania Background: Adolescents who have an eating disorder, particularly anorexia nervosa, could report a delay of menarche or cease to menstruate after a few months of “normal” or irregular cycles. The purpose of this work was to study the menstruation pattern and the hormonal profile of adolescent patients with anorexia nervosa behaviour before and after eating alterations. Material and method: The hormonal profile, the onset of menstruation and the body mass index of five adolescent patients (mean age 13.7) with anorexia nervosa were studied in a 38 months period. Body mass index was below 19 in all patients. A patient reported a negative progestogen stimulation test 2 months before the inclusion in the study. Results: Mean levels of oestradiol were lower than 70 pmol/L in repeated measures of 6–8 months intervals. Gonadotropins were below normal values in a total of two measures for each patient. The treatment of these girls consisted of an increase of caloric intake and psychological support. Recovery rate of eating behaviour was observed in four patients and in these girls onset of menstruation was reported 1–3 months after obtaining a normal or almost normal body mass index (18.8–20.5) “irrespectively” of hormonal values. Taking into account that the date of menstruation could not predicted in advance, oestradiol levels were measured 3 and 4 months before (two patients) or 10 days to 2 months after (three patients) the actual “first” menstruation and the range of values was 130–170 pmol/L. The present study suggests that the onset of menstruation in anorexia nervosa is observed after obtaining a normal body mass index a few weeks earlier, and probably recent normalization of hormonal profile.

FC01.8 Measurement of steroid hormone levels, in menopause and andropause: techniques and pitfalls Wolfgang Ziemann VP Export, Kiel-Wellsee, Germany Most of the current steroid hormone determinations are done from serum samples even if results in the low or very low concentration range are expected like in elderly patients. This is a real challenge for any diagnostic laboratory. The problems even increase taking into consideration the episodic secretion pattern of steroid hormones. It is known since the 80th that steroid secretion shows a significant episodic pattern in serum as well as in saliva. Nevertheless still today most of the determinations are done from just one serum sample. Moreover the measurement of serum concentrations in the low concentration range technically is rather difficult as it recently has been shown in the recent scientific literature. In general serum measurements only can give the total steroid hormone concentration whereas saliva testing results in the measurement of the free active hormone fraction. Therefore salivary testing is a reliable alternative provided multiple sampling is done. We are recommending to collect five or six samples within 2 or 3 h and the successive measurement of one mixed sample. The analytical sensitivity of current commercial saliva testkits do allow a reliable and reproducible measurement even in the very low concentration range (below 1 pg/ml). These results in fact do represent the free hormone concentration; this is the active hormone fraction. Therefore saliva hormone measurements also might be a good and convenient alternative for the follow-up of HRT in males and in females. Blood contamination of saliva samples can be excluded by visual inspection. The stability of saliva samples is superior to serum samples. Absorption of the analyte might be a problem, which can be overcome by selecting proper plastic material for the sampling device. Influence of hormone containing food is similar in serum and in saliva samples. Meanwhile simple commercial ELISA kits are available for the reliable quantification of free steroid hormones in saliva even in the very low concentration range.

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Sunday, 4 June 2006 14:15–16:15 FC02—Free Communication Session: Cancer FC02.1 Aromatase expression in endometrial polyps during menopause Hugo Maia Jr.1 , J Casoy1 , T Correia2 , LA Freitas3 , C Athayde1 , EM Coutinho1 1 CEPARH, Salvador, Bahia, Brazil; 2 Escola Bahiana de Medicina, Salvador, Bahia, Brazil; 3 Fiocruz, Salvador, Bahia, Brazil Objective: To study aromatase expression in endometrial polyps in menopausal patients and correlate its presence with both proliferation rates and Cox-2 expression. Patient and methods: Thirty five patients with endometrial polyps and no history of hormone use in the previous 6 months were retrospectively included in this study. The polyps were removed by hysteroscopy using the Versapoint electrode. Aromatase p450, Cox-2 and ki-67 expression were measured by immunohistochemistry. Results: Aromatase p450 expression was detected in the glandular epithelium of 25/35 cases (71%) of endometrial polyps during menopause. Mean ki-67positive values were 12% in the glandular epithelium of aromatase-positive polyps and 4% in aromatasenegative polyps. This difference was statistically significant (p < 0.01). Cox-2 expression, on the other hand, was detected by immunohistochemistry in the glands of both aromatase-positive and aromatase-negative polyps, and the differences in mean scores between the two groups was not statistically significant. Conclusions: The presence of aromatase p450 expression in endometrial polyps is associated with higher rates of ki-67-positive cells, thus suggesting that local estrogen production from androgen precursors may play a role in polyp growth. No association between Cox-2 and aromatase expression was found in this study sample.

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FC02.2 Pippele and direct hysteroscopic biopsy in evaluation of the endometrium in postmenopause Iuliana Ceausu, H Rahimian, A Ciulcu, D Hudita ‘Carol Davila’ University of Medicine and Pharmacy, ‘Dr. I. Cantacuzino’ Department of Obstetrics and Gynecology, Bucharest, Romania Objective: The aim of this study was to compare the efficacy of blind endometrial biopsy by Pipelle with that of histeroscopic biopsy with biopsy forceps under direct view. Material and methods: The study included 23 postmenopausal women in the gynecology department of the Dr. I. Cantacuzino Hospital selected for endometrial biopsy because of irregular bleedings in menopause or for endometrial thickness 4–6 mm. All women were between 45 and 62 years, at least after 1 year without any menstrual bleedings and without hormonal therapy. Results: All women undergo biopsy with Pipelle and in 12 cases the results indicated endometrial hyperplasia, nine with atrophy, one polyp and one case with insufficient tissue sample. The hysteroscopy was performed after 4 weeks from the first biopsy, and enabled a selective biopsy of the areas of visualized endometrium. The results were 14 hyperplasia, four polyps and five atrophic endometrium. The rate of confirmation rate for polyps by Pipelle was one to four, the rest of three polyps were initially considered atrophy (two cases) or hyperplasia without atypia (one cases). Also, three cases of initially considered atrophy were discovered with simple hyperplasia without athypia, and in three cases of simple hyperplasia it was discovered a complex hyperplasia without athypia. The conformity rate calculated by analysis between blind and under direct visual control biopsy for hyperplasic endometrium was 84.61%. Conclusion: Histeroscopic biopsy under visual control is necessary at least for the patients with any hyperplasic changes at the blind biopsy.

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FC02.3 Mammographic density and the menopause transition: a longitudinal study Janet R Guthrie1 , R Milne1 , NF Boyd2 , L Dennerstein1 , HG Burger3 , JL Hooper1 1 The University of Melbourne, Parkville, Vic., Australia; 2 Ontario Cancer Institute, Toronto, Ont., Canada; 3 Prince Henry’s Institute of Medical Research, Clayton, Vic., Australia Background: After adjusting for age and other established risk factors, mammographic density, is a strong and independent risk factor for breast cancer. Objective: To investigate variables associated with mammographic density during the menopausal transition. Methods: Mammograms obtained from a population-based cohort of 252 Australian-born women (mean age 56, range 45–67 years), participants in a longitudinal study which included annual interviews, blood and physical measurements. Eight hundred and sixty nine original films of the right cranio-caudal views were digitised. Total area of the breast and the area of dense tissue appearing on the mammogram were measured. Data analysed using time-series regression models. Results: Median number of scans per woman was 4. Multivariate analysis found that, in women who had never used hormone therapy, increasing age (p < 0.5) and BMI (p < 0.05), having had children (p < 0.05), higher than average age (p < 0.05), higher than average BMI (p < 0.5) and higher than average free testosterone levels (p < 0.05) were associated with increased amounts of non-dense breast tissue. Increasing age (p < 0.05) and BMI (p < 0.05), and higher than average BMI (p < 0.5) were associated with decreased percentage of mammographically dense tissue (PMD) and explained 21% of variance. There was a tendency for higher than average free testosterone levels (p < 0.07) and having had children (p = 0.07) to be associated with lower PMD. Conclusion: In this longitudinal observation study of middle-aged women the changes in age, BMI and higher than average free testosterone levels through the menopausal transition that are associated with nondense breast tissue have small but statistically significant effects on explaining variation in PMD tissue.

FC02.4 Short-term oral contraceptive use and the risk of epithelial ovarian cancer JB Greer, F Modugno, GO Allen, Roberta B Ness University of Pittsburgh, Department of Epidemiology, PA, USA Background: Oral contraceptive (OC) use has been consistently linked to a reduction in ovarian cancer in a dose-dependent fashion. Whether short-term OC use is protective remains controversial. Methods: In 1994–1998 in the Delaware Valley of Pennsylvania, the authors examined the association between short-term OC use and ovarian cancer in a population-based case-control study comparing 608 incident epithelial ovarian cancer cases with 926 community controls. Results: Using unconditional logistic regression and adjusting for known confounders, we found a significant reduction in ovarian cancer risk for women who had used OCs for <6 months (odds ratio = 0.73, 95% confidence interval: 0.54, 0.99).This protective effect was observed in only that group who had used OCs for <6 months and stopped because of side effects (odds ratio = 0.59, 95% confidence interval: 0.40, 0.87 for side effects and odds ratio = 0.91, 95% confidence interval: 0.60, 1.37 for non-side effects).Women who used OCs for >6 months were at a reduced risk independent of their reason for stopping. Results were similar when stratifying by parity and hormone therapy use. Conclusions: OC use for as little as 6 months provides significant protection against ovarian cancer risk, protection that appears limited to those women who stop using OCs because of side effects. Mediating factors may reflect endogenous hormone levels, OC metabolism, or OC bioactivity. FC02.5 Anthropometry and the risk of epithelial ovarian cancer JB Greet, F Modugno, Roberta B Ness, GO Allen University of Pittsburgh, Department of Epidemiology, USA Background: We investigated the association between anthropometric factors and ovarian cancer risk using data from 762 cases and 1348 controls participating in a population-based case-control study in the Delaware Valley from 1994 to 1998. Because fac-

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tors such as oral contraceptive (OC), hormone therapy (HT) and parity may affect weight and hormone levels, we examined associations in women with and without these characteristics. Methods: Unconditional logistic regression was used to calculate odds ratios and 95% confidence intervals while controlling for age, race, parity, family history of ovarian cancer, tubal ligation and OC use. Results: Compared to controls, cases were taller and heavier in recent years and at age 18. Results did not differ by OC or HT use. However, anthropometric associations differed significantly based on parity, as increasing anthropometric measures were associated with increased ovarian cancer risk among nulliparous women only. Adjusted OR for recent BMI quartile 4 compared to quartile 1 for nulliparous women was 2.53 (95% CI: 1.39, 4.61) compared to 0.96 (95% CI: 0.70, 1.31) for parous women. Additionally, adult weight gain was significant only for nulliparous women. Adjusted OR for weight change quartile 4 compared to quartile 1 for nulliparous women was 3.73 (95% CI: 1.88, 7.42) versus 1.09 (95% CI: 0.78, 1.51) for parous women. Conclusions: Body mass index and weight in women’s adult lifetime may be positively associated with ovarian cancer risk. Observations were most apparent for nulliparous women, possibly reflecting an interaction between local inflammation caused by incessant ovulation and increased estrogen exposure on ovarian epithelium. FC02.6 Tibolone and endometrial safety: results from THEBES, a randomized 2-year studycomparing tibolone with CEE/MPA Alec Ferenczy1 , D Archer2 , J Rymer3 , SO Skouby4 , W Den Hollander5 , F Helmond6 1 McGill University and SMBD-Jewish General Hospital, Montreal, Que., Canada; 2 CONRAD Clinical Reasearch Center, Norfolk, VA, USA; 3 Department of Women’s Health, St Thomas’ Hospital, London, UK; 4 Department of Obstetrics & Gynecology, Frederiksberg Hospital, Copenhagen, Denmark; 5 NV Organon, Oss, The Netherlands; 6 Organon International, Roseland, NJ, USA Background and objectives: THEBES was a 2year, prospective, multicountry, multisite, randomized, double-blind, controlled clinical trial to determine

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theendometrial response to oral tibolone (1.25 and 2.5 mg/day) versus continuous, combined, daily oral CEE plus MPA (0.625 mg + 2.5 mg/day). Methods: Endometrial lining was assessed at baseline and after 1 and 2 years by transvaginal ultrasound and suction biopsy curettage. Vaginal bleedingpatterns were self-recorded in a bleeding episode log. Results: Three thousand two hundred and forty healthy postmenopausal women, mean age 54, were randomized in a 1:1:2 ratio (tibolone 1.25; tibolone 2.5; CEE/MPA). Mean baseline, doublewall endometrial thickness was 3.1 mm for the combined tibolone group and 3.0 mm for the CEE/MPA group and 3.6 and 3.4 mm after 2 years treatment. Endometrial histology during 2 years of observation in both tibolone andCEE/MPA intent-to-treat groups is presented in Table 1. During the entiretreatment period, 75% of the women in the tibolone group experienced no bleedingor spotting compared to 45% of the women treated with CEE/MPA. Conclusion: This study provides evidence that the endometrial morphology profilein postmenopausal women is similar with tibolone and CEE/MPA. Sunday, 4 June 2006 14:15–16:15 FC03—Free Communication Session: Symptomatology I FC03.1 Uterine bleeding and breast pain in postmenopausal women on Tibolone 2.5 mg or continuous therapy with 1 mg Estradiol and 0.5 mg Norethisterone Henk Franke1 , M Hammar2 , P Van De Weijer3 , E Nijland4 1 Medisch Spectrum Twente, The Netherlands; 2 Link¨ oping University, Sweden; 3 Gelre Ziekenhuizen, The Netherlands; 4 NV Organon, Netherlands Background/objectives: The TOTAL study was a 48 week randomized, double blind controlled trial to compare the vaginal bleeding pattern and tolerability in postmenopausal women treated with tibolone 2.5 mg or continuous combined E2/NETA 1.0/0.5 mg/day. Methods: Vaginal spotting and bleeding patterns were recorded at daily diary cards as well as the frequency of hot flushes. Breast pain was collected by adverse event forms.

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Results: Five hundred and seventy two postmenopausal women were included in the trial, mean age 55 years. In all four 3 monthly periods mean bleeding/spotting rate in the tibolone group was lower than in the E2/NETA group: 18.3%, 18.3%, 11.4% and 10.0% in the tibolone group and 33.1%, 25.1%, 19.9% and 13.8% for periods I to IV in the E2/NETA group. In periods I and III these differences were statistically significant (p < 0.01 and p < 0.05, respectively).Vaginal hemorrhage reported as an adverse event was lower in the tibolone group (3.5%) versus the E2/NETA group (5.6%). The relief of vasomotor symptoms was similar for both treatment arms and showed a significant improvement when compared to baseline. The frequency of breast pain and tenderness was significantly lower in the tibolone group compared to the E2/NETA group (p < 0.001). A significant increase from baseline in mammographic density in the E2/NETA group was seen (p < 0.034) whereas for the tibolone group no statistically significant increase was observed. Conclusion: Tibolone 2.5 mg improves vasomotor symptoms as effectively as E2/NETA but has a better tolerability profile because of less irregular vaginal bleeding and less breast pain. FC03.2 Results from the Estonian postmenopausal hormone therapy (EPHT) trial Piret Veerus1,5,7 , S-L Hovi2,5 , K Fischer3 , M Rahu1,7 , H Karro4 , M Hakama5 , R Tuimala6 , F Kirss4 , S Vorobjov1 , T Sevon2 , E Hemminki2 1 National Institute for Health Development (TAI), Estonia; 2 National Research and Development Centre for Welfare and Health (STAKES), Finland; 3 Department of Public Health, University of Tartu, Estonia; 4 Women’s Clinic, University of Tartu, Estonia; 5 Tampere School of Public Health, University of Tampere, Finland; 6 Women’s Clinic, University of Tampere, Finland; 7 Estonian Center of Excellence in Behavioral and Health Sciences, Tallinn-Tartu, Estonia Objectives: The trial aimed to study the effects of hormone therapy (HT) on health, health care costs, and health-related quality of life. Methods: One thousand eight hundred and twenty three postmenopausal women aged 50–65 years were recruited from 1999 to 2001 and randomised to a blind group of HT versus placebo and to a non-blind

group of open-label HT versus non-treatment. Participants received 0.625 mg of conjugated oestrogens plus 2.5 mg of medroxyprogesterone acetate daily or placebo or no treatment until May 2004. Women were followed by annual clinical follow-ups, annual surveys, and annual linkages to the Estonian Health Insurance Fund database, Estonian Cancer Registry, and Estonian Mortality Database. Results: During the follow-up period from 2 to 5 years, the hazard ratio for coronary heart disease was 1.12 (95% CI: 0.90–1.40), for cerebrovascular disease 1.28 (0.75–2.58), for total cancer 1.39 (0.75–2.58), and for bone fractures 0.62 (0.43–0.91). Outpatient health care costs and drug expenses were higher in the HT arms. The mean EQ-5D scores at the end of the second trial year were 72.9 (70.5–75.3) in the blind HT arm, 71.6 (70.5–72.7) in the placebo arm, 71.9 (69.8–74.0) in the non-blind HT arm, and 71.4 (69.5–73.1) in the control arm. Conclusions: The results of the EPHT trial show a reduction in bone fractures. The risk of coronary heart disease, cerebrovascular disease, and cancer increased, but the differences were not statistically significant. HT increased expenses on health care, but had no effect on quality of life measured by EuroQoL scores. FC03.3 Menopausal status and satisfaction with life in Polish women Maria Kaczmarek Adam Mickiewicz University, Department of Anthropology, Poznan, Poland Climacteric transition from reproductive to nonreproductive stage of life has been viewed as a period of profound physical and psychosocial changes that effect woman’s satisfaction with life. This paper is aimed to judge the statement that woman’s life satisfaction depends on her menopausal status. From data base, gathered in Poland in 2000–2004, in cross-sectional, population-based study, healthy women were chosen: 2785 of premenopausal status (mean age 36.59 years), 419 at perimenopause (mean age 44.78 years) and 1258 of postmenopausal status (mean age 56.97 years). Satisfaction with life and its domains was evaluated using Polish version of Life Satisfaction Index developed and validated by Campbell (1976). Climacteric complains were assessed using MRS. Findings revealed significant difference in global life satisfaction among women

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of different menopausal status (F = 3.81; p < 0.05). Premenopausal women were likely to enjoy a higher level of satisfaction as compared to women after menopause. This picture changed when marital status and education were included into multivariate ANCOVA models with age controlled. Married/partnered women were likely to enjoy a higher level of well-being and fare better than their non-partnered peers on many life outcome variables irrespective their menopausal status and severity of menopausal symptoms (as given by MSR). Multiple correspondence analysis was run to evaluate satisfaction with particular life domains. Its findings revealed that the choice of most satisfactory life was related to marital status and education of women rather than to their menopausal status. FC03.4 Determinants of midlife satisfaction: a gender specific approach Maria Kaczmarek Adam Mickiewicz University, Department of Anthropology, Poznan, Poland This paper provides an evaluation of factors predictive for subjective well-being in middle-aged Poles. One thousand seven hundred and seventy six men and 1258 women, aged 40–65 years, were polled in cross-sectional, population-based inquiry, using Polish version of Life Satisfaction Index (Campbell, 1976). The findings confirmed that the effects of some predictors, which were bivariately associated with life satisfaction, had disappeared in multivariate models that included other variables (e.g. menop/androp symptoms). ANCOVA models revealed that gender, marital status and education were main predictive factors for variation in global midlife satisfaction, when age and BMI were controlled. The three main predictive factors of midlife well-being explained 29% of variation in global life satisfaction. Marital status appeared most powerful determinant of life satisfaction among men and education among women. Satisfaction with particular life domains: marriage, family, health, friends, work, housing, leisure time, standard of living, acquired education, income, life in Poland, were presented in multiway tables and the Chi-square test was used to test their interdependence. Thereafter, the association among qualitative data was estimated using Euclidean distances obtained from the model of Multiple Correspondence Analysis (MCA). The general

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picture for midlife Polish people drawn from the study indicated men enjoyed a higher level of subjective wellbeing than do women, a moderate level of global life satisfaction and the lowest level of satisfaction with social life (income, living standard and life in Poland) in both men and women, and different life domains declared as most satisfactory for men and women. FC03.5 Black cohosh versus tibolone in menopausal symptoms relief in Chinese women W Bai1 , Hans-Heinrich Henneicke-von Zepelin2 , S Zheng1 , J Liu3 , L Geng4 , L Hu5 , S Wang6 , E Liske2 1 The First Hospital of Peking University, Department of Gynecology, Beijing, China; 2 Schaper & Bruemmer GmbH & Co. KG, Medical Department, SalzgitterRingelheim, Germany; 3 The General Hospital of PLA, Department of Gynecology, Beijing, China; 4 The Third Hospital of Peking University, Department of Gynecology, Beijing, China; 5 West China Second Hospital of Sichuan University, Department of Gynecology, Chengdu, China; 6 Jiangsu Province People’s Hospital, Department of Gynecology, Nanjing, China We compared the benefit-risk-balance of the isopropanolic Cimicifuga racemosa extract (iCR, Remifemin® ) with tibolone in menopausal symptoms treatment. The randomized, double-blind, controlled 3-month study in five centres of three cities in China enrolled 244 menopausal patients aged 40–60 years and with a Kupperman Menopause index (KMI) ≥15. The participants were assigned to either iCR corresponding to 40 mg crude drug/day (n = 122) or tibolone 2.5 mg/day (n = 122) orally. The primary endpoint was the combination of the Mann–Whitney values (MWV) of the KMI and the frequency of adverse events (benefit-risk balance) at end of treatment. Remarkable and clinical relevant reduction in KMI was seen at 4 and 12 weeks, similar in both treatment groups showing statistical significant non-inferiority of iCR to tibolone. The KMI-responder rate was similar in both groups. The safety evaluation showed for both groups a good safety and tolerability profile, however, there is a significant lower incidence of all adverse events (p < 0.01) in favor of the herbal treatment. No serious adverse event was observed in the iCR-group. The benefitrisk balance for iCR was significantly (p = 0.01) superior to tibolone (MWV = 0.56; 95%-confidence interval [0.51–0.62]). The efficacy of iCR (Remifemin® ) is

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as good as tibolone for the treatment of climacteric complaints, whereby Remifemin® is clearly superior regarding the safety profile. Remifemin® is an excellent option for treatment of climacteric complaints which has now been verified in Chinese women. FC03.6 One year treatment with isopropanolic black cohosh extract (iCR) V Briese1 , U Stammwitz2 , Hans-Heinrich Henneickevon Zepelin2 1 Universitaets-Frauenklinik am Klinikum S¨ udstadt, Rostock, Germany; 2 Schaper & Bruemmer GmbH & Co. KG, Salzgitter, Germany The efficacy of the isopropanolic Cimicifuga racemosa extract (iCR) in alleviating climacteric symptoms has been shown by numerous randomised controlled trials. In general, the treatment lasted up to 6 months revealing no safety concerns. In daily medical practice, mean cumulative iCR treatment duration is 1.5 years. Such a time period is secured by preclinical toxicological data. In a prospective non-interventional study we explored routine efficacy and safety for a 12-month iCR treatment using either the fixed combination of St. John’s Wortand iCR (Remifemin® plus) or iCR alone (Remifemin® ).Climacteric symptoms were assessed by using the Menopause Rating Scale I (MRS) at month 0, 3, 6 and 12. Adverse events were unveiled by open inquiry followed by assessment for adverse drug reactions. of 736 patients, 337 received iCR alone. Mean age and duration of complaints were 53 years and 32.6 months, respectively. iCR alone is primarily used for relief in vasomotor symptoms, whereas the combination is applied in patients with additional psychical climacteric symptoms. for both preparations there was a sharp and significant decline in climacteric symptoms as detected by MRS within the first 3 months of treatment. A further slight decrease in MRS was observed after 6 months which was stable up to 12 months. Frequency of adverse drug reactions was 0.1% (gastro-intestinal complaints). Our clinical data support the treatment of menopausal symptoms with iCR alone or in combination with St. John’s Wort for 12 months.

FC03.7 Compliance issue after the WHI study—What’s the difference Damir Franic Outpatient Cinic for Obstetrics & Gynecology, Rogaska Slatina, Slovenia Objectives: To find out the factors influencing women’s decision for starting HRT, to stop HRT, as well as to evaluate the influence of educational intervention on the hormone replacement therapy (HRT) continuation rate in Slovenia after the publication of WHI results. Methods: Sixteen Slovenian gynecologists from primary, secondary and tertiary levels, enrolled 125 early postmenopausal women in a 24-month prospective, randomized, controlled, multicentric study. The study group women (n = 62) attended educational lectures; the control group women (n = 63) did not. Data were collected by two types of questionnaire: before starting HRT, at follow up visits at 3, 6, 12 and 24 month. The educational lectures were balanced, based on “deductive” and “holistic” approach toward menopausal problems and HRT. The aim was to put the women into decision-making process, so they should decide whether to use or not to use HRT. The continuation rate was measured on the basis of women’s self-reports. The results were analyzed according to the “intentionto-treat” principle. For comparision of groups, Chisquare, t-test and Mann–Whitney tests were used. The Kaplan–Meier test and Cox proportional hazard model was used for the final (survival) analysis. Results: A gynecologist’s suggestion, climacteric symptoms and quality of life were the prevailing reasons for starting HRT. The prevailing factors affecting continuation of HRT were: no or irregular previous OC use (hazard ratio 2.25), no educational lectures (hazard ratio 1.85 climacteric disorders as the reason for start HRT (hazard ratio 1.97), QoL as the reasons for start HRT (hazard ratio 0.51) and friends recommendation (hazard ratio 1.83). In the women who discontinued HRT within the first 3 months, the fear of endometrial cancer, breast cancer, and bleeding problems were statistically more significant than other factors (p = 0.013). In the women who stopped HRT use within 6–12 months, the fear of breast and endometrial cancers increased substantially (p = 0.001), and in the women who stopped within

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13–24 months the fear of breast cancer and negative impact of the media were much more important than other factors (p = 0.001). Conclusions: Previous OC use and educational lectures on menopausal problems and HRT significantly improve the HRT continuation rate. The main reason for discontinuing HRT is fear of breast cancer, intensified by media. Monday, 5 June 2006 08:30–09:00 KL03—Keynote Lecture Is there a need for selective prevention strategies? Pierre Ducimetiere France Abstract not available at the time of printing. Monday, 5 June 2006 09:00–09:30 KL04—Keynote Lecture Gender specific differences in the aging processes Karen Schenk Gustafsson Sweden Abstract not available at the time of printing. Monday, 5 June 2006 10:30–12:30 S03—Symposium: Cardiovascular disease S03.1 Diagnostic aspects Karen Schenk Gustafsson Sweden Abstract not available at the time of printing. S03.2 Postmenopausal hormone therapy: is there a need for selective management in the venous area? Pierre-Yves Scarabin Inserm, Cardiovascular Epidemiology Unit, Paris, France Despite evidence that oral estrogen activates blood coagulation in postmenopausal women, hormone therapy (HT) has long been believed to have little effect on the risk of venous thromboembolism (VTE). Recent data, including both observational studies and randomised trials, consistently showed an increased VTE

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risk among postmenopausal women using HT. The VTE risk is substantially higher within the first year of treatment, but past users have similar risk as nonusers. Most studies of HT focused on oral estrogens, but the Estrogen and ThromboEmbolism Risk (ESTHER) study has shown that transdermal estrogens had little or no effect on VTE risk. However, in the ESTHER Study, transdermal estrogen combined with 19-norpregnane derivatives was associated with an increased VTE risk, whereas, transdermal estrogen alone or combined with either progesterone or pregnane derivatives appeared safe with respect to thrombotic risk. Oral estrogens increase the VTE risk associated with overweight or obesity, and factor V Leiden, but recent data suggest that transdermal estrogen does not confer additional risk on women at high risk for VTE. Biological evidence lends support to the difference between routes of estrogen administration. Randomised trials have shown that oral estrogen increased plasma levels of markers for in-vivo thrombin activation (prothrombin fragment 1 + 2) and lowered both antithrombin activity and protein S plasma level, whereas transdermal estrogen had little or no effect on coagulation and fibrinolysis. Activated protein C (APC) resistance has emerged as a risk factor for venous thrombosis. An acquired APC resistance has been found in users of oral estrogen, but two randomised trials recently showed that these results did not apply to users of transdermal estrogen. In conclusion, there is clear evidence that oral estrogen increases the VTE risk among postmenopausal women, but recent data suggests that transdermal estrogen alone or combined with either progesterone or pregnane derivatives is safer. Current data have limited ability to investigate the wide variety of hormone regimens available, especially the route of estrogen administration and the impact of progestogens. Efforts to avoid oral estrogen among postmenopausal women at high risk for VTE are advisable. S03.3 Is there a need for selective management in arterial disease? Tomi S Mikkola Helsinki University Central Hospital, Department of Obstetrics and Gynecology, Helsinki, Finland Coronary heart disease (CHD) is the major cause of morbidity and mortality for both men and women. The

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fact that CHD risk of women rises sharply after premature ovarian failure, or surgical or natural menopause indicates that estrogen deficiency is a key modulator of atherosclerosis progression. Furthermore, a compelling body of experimental data provides a biological basis for beneficial estrogen-mediated vascular effects. These findings led to the belief that postmenopausal hormone therapy (HT) could/would be cardioprotective, as shown by numerous observational studies. However, in the past years that belief has come to be questioned by many health care professionals mostly based to the results from the large randomized clinical trials. This controversy is in part due to neglecting the differences in the vascular biology between recently menopausal and older women. Therefore, the “window of therapeutic opportunity” to reduce CHD risk by HT is most likely only in women entering menopause and not in older women well beyond menopausal transition. Thus, results from the recent randomized clinical trials on CHD are not fully applicable to typical healthy menopausal women starting modern HT to control climacteric symptoms. Although randomized clinical trials of older postmenopausal women have not supported the observational and experimental data indicating a cardiovascular benefit of HT, the crucial question is whether HT for the treatment of climacteric symptoms provides cardiovascular benefits that offset its risks. Monday, 5 June 2006 10:30–12:30 S03.4 Is there a need for new programmes in the treatment of cardiovascular diseases? Tabassome Simon France Abstract not available at the time of printing. Monday, 5 June 2006 10:30–12:30 S04—Symposium: Immune dependant diseases S04.1 Sex steroids and the immune system Farook Al-Azzawi UK Abstract not available at the time of printing.

S04.2 Thyroid Levent M Senturk Istanbul University Cerrahpasa School of Medicine, Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology, Istanbul, Turkey An increasing prevalence of high levels of thyroid stimulating hormone (TSH) with age—particularly in postmenopausal women was known. Overt hypothyroidism can develop over time. Little is known about the effect of hormone replacement therapy (HRT) on thyroid function in postmenopausal women since there are few data available in the current literature about changes in thyroid hormone profiles after HRT. Aging is characterized with altered thyroid hormone metabolism. The feedback control system maintains the concentrations of total and free T3 and T4. The production and the clearance rates of the thyroid hormones are decreased in a parallel fashion. The tissue responsiveness to thyroid hormones is reduced with age. The clinical correlation of age related alterations in thyroid metabolism is the clinical features of hypothyroidism in elderly euthyroids. The incidence of primary hypothyroidism increases with age, especially in postmenopausal women. Elevated TSH level is the evidence for this change. Our group has confirmed that about 2.4% of postmenopausal women have clinical thyroid disease, whereas, subclinical thyroid disease to be about 23.2%. Among the group with subclinical thyroid disease, 73.8% were hypothyroid and 26.2% were hyperthyroid. Furthermore, the incidences of multinodular and nodular hyperplasia were 22% and 17%, Hashimoto’s thyroiditis 17.7% and Grave’s disease 1.8%, respectively. Even thyroid carcinoma was diagnosed in 0.3% of cases. It has been estimated that 4.4% of the population over age of 60 has primary thyroid failure. Moreover, surgical menopause patients are a unique subgroup of patients who experience physiological alterations during perimenopause occurring suddenly. There is only one trial addressing thyroid functions after surgical menopause in which the response of TSH to TRH following oophorectomy was significantly less than before. It has been concluded that this significant decrease in the thyrotropin response to TRH observed in surgical postmenopausal women might be explained by lower endogenous estradiol levels.

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Because of its hepatic first-pass effect, oral estrogen therapy, the most commonly used modality of estrogen replacement therapy, causes an increase in the circulating levels of thyroxine-binding globulin (TBG), thereby increasing the bound fraction and decreasing the free (bioactive) fraction of circulating T4. As a consequence, oral estrogen therapy may increase the T4 requirements in women being treated for primary hypothyroidism. The prior studies with conjugated estrogen in doses ranging from 0.625 to 2.5 mg/day, found no change in serum TSH concentrations. There are reports stating that oral route with estrogen and progestogen produced moderate increases in T4 and TBG levels. Our group, again, has found out that any kind of HRT is beneficial for thyroid functions, especially for the estrogen containing regimens and even, in part, for tibolone. To conclude, thyroid disease is frequently seen in the climacteric period and the symptoms of thyroid disease can be similar to postmenopausal complaints and are clinically difficult to differentiate. Therefore, serum TSH and freeT4 concentrations should be measured and thyroid USG and other additional tests should be performed, in case. S04.3 Connective tissue disease Jean-Charles Piette France Abstract not available at the time of printing. S04.4 Eye diseases Omur Taskin Turkey Abstract not available at the time of printing. Monday, 5 June 2006 10:30–12:30 S05—Symposium: Dental and dermatology S05.1 Dental health Guzun Dilsen Turkey Abstract not available at the time of printing.

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S05.2 Alopecia and hirsutisme Johannes Huber University of Vienna Hospital, Department of Obstetrics & Gynecology, Vienna, Austria The aetiology for hairlose and hirsutisme is great difficult. From the point of endocrinology, hypoandrogenemia, hypoestrogenemia and thyroid disorders are the most common causes for this dermatological problem. In many patients, the endocrinological disturbances is limited on the hair follicles, therefore a topical treatment with anti-androgens or estrogens seems to be justified. The same is the case for hirsutisme, which is also limited to special areas of the body in the most cases. New strategies for the treatment of hirsutism applied topically are presented and discussed. S05.3 Skin ageing in women – the menopause and HRT Mark P Brincat Department of Obstetrics and Gynaecology St. Luke’s Hospital, G’Mangia, Malta Skin aging is a natural phenomenon that can be accelerated or delayed by a number of variable factors. A number of factors have been identified namely chronological, genetic, lifestyle habits such as smoking, solar damage. Other factors are endocrine notably in women, a lack of sex steroids in postmenopausal women. Other endocrine factors also affect the skin such as a tendency to hirsutes and acne in hyperandrogenic women. Following the menopause a lack of estrogen affects a number of structures in the skin. Studies have shown effects to the epidermis to the dermis. Capillary peripheral vascular control are affected and the most characteristic symptom of the menopause (25%) is the hot flush. Dermal skin collagen content declines rapidly after the menopause and this has been demonstrated as does skin thickness. Several studies have shown that it is possible to reverse most of these changes with approprate oestrogen use. Studies have also shown that not only is skin collagen and skin thickness affected by the menopause but also affects the biomechanics of the skin namely elasticity is also affected by hypoestrogenism and improved with oestrogen replacement. These changes in dermal connective tissues provide the paradigm for changes in connective tissues in vari-

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ous parts of the body that is affected by oestrogen loss following the menopause and their benefit following oestrogen therapy. S05.4 Vulvar diseases S Sinan Ozalp Osmangazi University, Faculty of Medicine, Department of Obstetrics & Gynecology, Eskisehir, Turkey Vulva is affected by reduced levels of estrogens in menopause and vulvar changes begin to take place. Symptoms of atrophy include itchiness, tenderness, a burning sensation, painful intercourse and sometimes painful urination. Vulvar pruritus and irritation are more common complaints during menopause. In menopause the vulvovaginal area becomes pale, thin, and dry, which may be the reason of pruritus and vulvar irritation. However, vulvar complaints should not be accepted as the signs of normal menopausal atrophy and proper evaluation must be done to rule out specific diseases. Acute vaginal infections may cause these vulvar symptoms, so the vagina must be evaluated for the presence of any infection. Complete evaluation involves speculum examination of the vagina and cultures for sexually transmitted diseases should be done when needed. Among chronic vulvar disorders, lichen sclerosis and squamous cell hyperplasia are the most common and generally long term treatment is required. Lichen sclerosis is atrophic skin disease and etiology is unknown but may have association with autoimmune disorders. Signs and symptoms include itching, irritation, white, thinned, and wrinkled skin, fissures or tears. It may be asymptomatic in some patients. Pathologic examination shows thinning of squamous epithelium. Over time, the introitus becomes narrowed and appears fibrotic. This may cause coital difficulty. Treatment of lichen sclerosis is local application of 2% testosterone. Squamous cell hyperplasia is a white lesion with the thickening of the squamous epithelium and may result as a reaction to chronic pruritus of different etiologies. Local use of fluorinated steroids, clobetasol and hydrocortisone can be effective. The combination of squamous cell hyperplasia and lichen sclerosis can be found in the same woman. Surgical intervention can be the choice for squamous cell hyperplasia and lichen sclerosis when medical treatment is ineffective or vulvar epithelial changes are severe. But even after surgical

treatment, recurrence rate is very high. Lichen sclerosis and squamous cell hyperplasia have malignant potential, which must be kept in mind the follow up of these women. Vulvar intraepithelial neoplasia has the malignant potential and has various appearances such as white, gray or red. The diagnosis is done by taking multiple biopsies. Most patients have pruritus but some have no symptoms. Treatment is wide local excision or ablative treatment such as laser ablation. Before any ablative treatment, biopsy is imperative to determine that the lesion does not contain invasive cancer. The cause of vulvodynia with vulvar burning or rawness is unknown. Subsets of vulvodynia, vulvar vestibulitis may cause entrance dyspareunia. In dyaesthetic vulvadynia there is chronic vulvar burning, irritation, stinging and rawness. Vulvar cancer is mostly diagnosed in the postmenopausal period. Every new lesion seen in the menopausal period should be biopsied to rule out cancer. Conclusion: In the menopausal period complaints should never be assumed to reflect normal menopausal atrophy and thorough vulvar examination and biopsy of any lesion are prerequisites to treatment. The physician and the patient must know that satisfactory treatment may take long time and patience is required. Monday, 5 June 2006 12:30–14:00 LS03—Lunch Symposium Sponsored by Schering AG Abstract not available at the time of printing. Monday, 5 June 2006 12:30–14:00 LS04—Lunch Symposium Sponsored by Wyeth Pharmaceuticals Abstract not available at the time of printing.

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Monday, 5 June 2006 14:15–16:15 AS04—Afternoon Symposium: HRT and CVD revisited AS04.1 New approach for non-invasive assessment of artery wall ageing: long-term estrogen replacement preserves the artery morphology against aging effects? Tord Naessen1 , KA Rodriguez-Macias1 , L Lind2,3 1 Uppsala University Hospital, Departments of Women’s and Children’s Health, Section for Obstetrics and Gynecology, Uppsala, Sweden; 2 Uppsala University Hospital, Department of Medical Science/Internal Medicine, Uppsala, Sweden; 3 Astra Zeneca R&D, M¨olndal, Sweden Objective: (1) A new approach for non-invasive assessment of carotid artery wall using high-frequency ultrasound was evaluated with regard to image the presence of cardiovascular disease (CVD). (2) Effects on artery wall of estrogens therapy were evaluated in a group of long-term estrogen users using the proposed method. Design: (1) One hundred consecutive 70-year-old participants in a large health study were included. (2) Group comparisons of long-term estrogen users (mean duration 20 years), age matched non-users and 20 healthy women of fertile age (mean age 39 years). Group differences analyzed with parametric, nonparametric tests or matched-pair analysis, as appropriate. Spearman rank correlation test for associations. Analysis of receiver operative curve (ROC). Results: (1) Separate estimates of artery intima and media thicknesses and calculation of the intima/media thickness ratio differed significantly (p < 0.001) between subjects with or without a diagnosis of CVD, in 100 70-year-old subjects. The method had a high sensitivity for detecting presence of CVD, and was far superior to conventional assessment of carotid intima-media thickness (IMT) using a 7.5 MHz probe. (2) Long-term estrogen therapy (ET) (mean duration 20 years) seemed to preserve a thin intima layer and a low intima/media thickness ratio, at values similar and not significantly different from those in premenopausal women. In age-matched control subjects (mean age 68 years) carotid intima layer was thicker and I/M ratio higher (both p < 0.001).

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Conclusion: (1) Separate estimates of artery intima and media layers appear to be far superior to conventional IMT assessment to image age-related changes in the carotid artery and to identify subjects with a diagnosis of CVD. (2) Preservation of artery morphology, including a thin intima layer and low intima/media thickness ratio, might be partially responsible for the beneficial cardiovascular effects of long-term estrogen therapy when it is initiated at the time of menopause. AS04.2 HRT and CVD: are there valid biomarkers? Antonio Cano University of Valencia, Spain Cardiovascular disease is a generic denomination including coronary heart disease (CHD), cerebrovascular disease, and venous thromboembolic disease (VTED). Atherosclerosis has emerged as the main determinant of the arterial forms of the disease. The attention to the action of hormones, consequently, has concentrated on their role on atherogenesis or on the complication of the so-called unstable atherosclerotic plaques. Interestingly, the work on the effects of hormones on atherogenesis has focused on their ability to modulate risk factors. Changes in the lipid profile as well as in the oxidative status of lipoproteins have confirmed a protective effect of hormones in atherogenesis. However, the notion that atherosclerosis is an inflammatory process has set in motion the concept of biomarker as complementary of that of risk factor. The subject has gained interest as a result of data suggesting that hormones might be protective against atherogenesis but harmful whether atherosclerosis, particularly unstable plaques, is constituted. Only a few of the several biomarkers described, however, have been confirmed to be of clinical value in female CVD. Among them, C-reactive protein (CRP) seems to provide the strongest risk predictive potential. CRP is an acutephase reactant synthesized by the liver that is expressed in the atherosclerotic lesion as well. Other markers independently associated with increased cardiovascular risk in women include homocysteine, interleukin-6 (IL-6), and lipoprotein (a) [Lp(a)]. The interest on IL6 derives from its role in the generation of the hepatic acute-phase response that makes it a crucial factor in the increase of CRP, fibrinogen, platelet number and activity, and blood viscosity. An alternative perspective

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has investigated the role of mediators in the digestion process of the extracellular components of the fibrous cover giving stability to plaques. Several studies have explored the modulation of these markers by distinct hormone combinations. Despite some data raising concern on a role of some biomarkers favoring plaque rupture, it is still uncertain whether interventions modifying their circulating levels have a clear-cut clinical influence in susceptibility to the disease. AS04.3 HRT and endothelial function Mar´ıa Natalia Cruz Sweden Abstract not available at the time of printing. AS04.4 Hormone therapy and risk of myocardial infarction: a national cohort study Ellen Løkkegaard, Ø Lidegaard, C Agger, AH Andreasen, RK Jacobsen, T Jørgensen Background: The randomised Women Health Initiative Study (WHI) tested an unopposed estrogen and continuous combined estrogen/progestagen Hormone Therapies (HT). The aim of the present analyses was to assess the association between HT and risk of myocardial infarction (MI), with focus on the influence of age, duration, regimen, type of progestagen, dose of estrogen and route of administration. Methods: We followed a National Cohort of 693,710 women aged 51–69 from 1995 to 2001 free from previous ischemic heart disease or cancer. Based on central prescription registry daily updated information on HT was available. From the National Registry of Patients 4671 incident MI cases (ICD I21–22) were identified. National registers provided information on potential confounders. By Poisson regression analyses rate ratios (RR) with various definitions of HT exposure were estimated. Results: We found RR of MI of 1.25 (1.02–1.52) for women aged 51–54 on HT compared to never users, corresponding RR for 55–59, 60–64, 65–69 years old were 0.90 (0.77–1.06), 1.02 (0.89–1.18) and 0.87 (0.75–1.01) in multiple analyses. For younger women there was increasing risk with increasing duration of HT that could not be demonstrated for older age groups. In all age groups the highest increased risk of MI was found with continuous HT whereas no

increased risk was found with cyclic combined therapy. No association with type of progestagen or no consistent influence of estrogen dose was found. There was tendency of lower risk with transdermal than oral unopposed estrogen therapy (p = 0.05). Conclusion: In a national cohort study we found that HT regimen and potentially route of application influence risk of MI. Monday, 5 June 2006 14:15–16:15 AS05—Afternoon Symposium: Effects and clinical application of prgestogens Organised by European Progestin Club AS05.1 Classification and pharmacology of progestogens Ren´e Druckmann France Progestogenic compounds are classified according to their different compounds. The various progestogens exert different partial effects at varying compositions and intensities. Besides the natural progestogen, progesterone, there are different classes of progestogens, such as retroprogesterone (i.e. dydrogesterone), progesterone derivates (i.e. medrogestone) 17␣-hydroxyprogesterone derivates (i.e. chlormadinone acetate, cyproterone, megestrol acetate), 19-norprogesterone derivates (i.e. nomegestrol, promegestone, trimegestone, nesterone), 19nortestoterone derivates (i.e. norethisterone, lynestrevol, levonorgestel, desogestrel, gestodene, norgestimate, dienogest) and spironolactone derivates (i.e. drospirenone). Some of the newer progestogens have particular characteristics, for example, the antimineralocorticoid effect of drospirenone and the more pronounced antiandrogenic activity of dienogest. Trimegestone is highly progestational; Nesterone, which may only be applied parenterally, is strongly progestogenic and antigonadotropic. Due to their various partial low, medium and high biological activities, each progestogen has a particular profile of action that may be exploited chemically. Familiarity with the spectrum of biological effect of the different progestogens is important in selecting the

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profile that is best suited to the particular condition of the patient seeking treatment. Same of the synthetic progestogens are prodrugs, which need to be metabolized to become active compounds. Besides the progestogenic effect, which is in common for all progestogens, there is a wide range of biological effects, which are different for the various progestogens and have to be taken into account, when medical treatment is considered. AS05.2 Progestogens and insulin-like growth factor-I Carlo Campagnoli, C Abb`a, S Ambroggio, C Peris Unit of Endocrinological Gynecology, Ospedale Ginecologico Sant’Anna, Azienda Ospedaliera OIRM-S. Anna, Corso Spezia 60, 10126 Torino, Italia Insulin-like growth factor I (IGF-I) is a polypeptide endowed with potent mitogenic and antiapoptotic effects. Circulating IGF-I is mainly produced by the liver under GH stimulation and is influenced by nutrition and insulin. IGF-I bioavailability is regulated by interactions with specific binding proteins (IGFBPs). Available data suggest that different kinds of HRT have different effect on the IGF-I system, depending on route of administration, estrogen dose, basal IGF-I values and type of progestogens. Estrogen administration reduces circulating IGF-I mainly through a hepatocellular effect. The decrease is sharper when oral estrogen is used (first pass hepatic effect) and in women with higher basal IGF-I levels. The progestogens endowed with androgenic effects – the 19-nortestosterone derivatives and, to a lesser extent, medroxyprogesterone acetate (MPA) – tend to reverse the IGF-I decrease induced by estrogens. In contrast, progestogens devoid of androgen-like hepatocellular and metabolic actions (e.g. dydrogesterone) do not interfere with the IGF-I decrease induced by estrogens. Moreover, androgenic progestogens oppose the two to three-fold increase in IGFBP-1 level induced by oral estrogens. The levels of circulating IGF-I could be relevant from a clinical point of view: for instance, they are related to breast cancer risk in most studies. The differential effects on IGF-I could be one of the reasons of the different impact of the various progestogens on breast cancer risk.

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AS05.3 Long-term effects of progestins on bone Jos HH Thijssen Endocrinological Laboratory, University Medical Centre Utrecht, The Netherlands Although the fracture rate at advancing age is the most important clinically relevant parameter to judge effects of preventive measures, very little data from prospective studies are available concerning the effects of hormone therapy in women on fracture rates ad high age. Many more clinical research studies have used changes in Bone Mineral Density (BMD) as surrogate endpoint. Clearly, BMD is a risk indicator for fractures but from epidemiological studies there are good arguments that the chance of falling is more important for fractures than BMD as such. Effects of progestins on bone have been studied in different ways: 1 by in vitro experiments using cell lines; 2 by observations during experimental studies in animals; 3 by observations in patients during prospective controlled trials. From in vitro studies some evidence has been obtained for a beneficial effect of progestins on bone, mediated by progesterone receptor expression in osteoblasts and perhaps also by reducing the influence of glucocorticoids via the glucocorticoid receptor. Studies with progestins using chicken and rat bones provide evidence for modulation of bone remodeling, resulting in protection against bone loss. However, results of clinical studies are more important in judging the effects of progestins on bone remodeling processes in humans. Prospective studies have been conducted following the use of progestincontaining oral contraceptives, alone or in combination with oestrogens; long-term contraception by injection of depot preparations; so-called “add-back” hormonal therapy that is used to reverse the adverse effects of gonadotropin releasing hormone agonists on bone; and after different regimens of hormone replacement therapy in postmenopausal women. From the available data there are no indications that the various progestins, used in clinical practice, have either a bone-protective or an oestrogen antagonistic activity. Thus, progestins do not add or subtract much from the protective action of oestrogens on bone.

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AS05.4 Progestogens and endometriosis K-W Schweppe Department of Obstetrics & Gynecology, Frauenklinik Ammerland, Westerstede and Academic Teaching Hospital University of G¨ottingen, Germany Oral progestins without estrogen component have been described to be effective in the treatment of endometriosis. A number of different substances have been tried, which are on one-side derivatives of the natural progesterone or on the other side derivatives of C-19-nortestosterone. They are different in respect to their profile and potency of action on hypothalamicpituitary axis, metabolic processes, breast tissue and genital organs. Their common characteristic is the secretory transformation of estrogen primed uterine endometrium for which different dosages are necessary because of their different biological activities. The mode of action on the target tissue – the endometriotic implant – is still a matter of debate. Earlier studies postulated activities via steroid receptor mechanism as known from the uterine mucosa. Recent studies raised some doubts on this hypothesis. Endometriotic foci contain progesterone receptors in a very low concentration or they are even absent (Kauppila et al., 1986) and enzyme systems differ widely in eutopic and ectopic endometrial tissue (Vierikko et al., 1985). In addition, new data about the molecular biology of endometriotic implants demonstrated a progesteron blockage due to low or missing progesterone receptors and the impossibility to activate the 17-betahydroxysteroid dehydrogenase type 2, which is defect in ectopic endometrium. As a consequence there is a low inactivation and a high biosynthesis of estradiol in endometriotic lesion compared with eutopic endometrium (Attar et al., 2006). A new mechanism of controlling the growth of endometriosis by progesteron and progestogens has shown by Horie et al. (2005). TNF-alpha and estradiol induced via nuclear factor (NF)-kappaB the proliferation of endometriotic stroma cells whereas progestogens reduce the TNFalpha induced NF-kappaB activation. Since during the last 30 years new effective substances are introduced for medical therapy of endometriosis, there has been little scientific interest in progestins in the recent years. Vercellini et al. (1997) found in a literature review 4 randomised con-

trolled trials with very limited number of patients only. Progestins today have their place in the symptomatic management of pain and other symptoms caused by endometriosis, when long-term medication is indicated, or when repeated courses of treatment are acceptable. A new aspect is the intra-uterine administration of progestogens, which can be an effective treatment of symptomatic endometriosis. For example, a 3-year follow-up study found a pain free continuation rate or 56% for the levonorgestrel intrauterine device (Lockhat et al., 2005). AS05.5 Polymorphisms in progesterone Johannes Huber Department of Obstetrics and Gynecology, Division of Gynecologic Endocrinology and Reproductive Medicine, Vienna, Austria The progesterone receptor (PR) mediates the physiological effects of progesterone. It exists in two isoformes, PR-A and PR-B. PR-A opposes estrogen or progesterone induced cell proliferation, whereas PRB contributes to estrogen or progesterone immediated cell proliferation. A polymorphism (POS 331 G → A) within the promoter of the progesterone receptor gene increases the expression of the PR-B isoformes and is associated with endometrial cancer and breast cancer. This increased risk has been documented in a prospectively studied cohort within the Nurse Health Study (De Vivo et al., 2002.) Another study could not demonstrate an association between this polymorphism and breast cancer, nevertheless the higher proliferation rate induced with progesterone in carriers of this polymorphism is well documented. This should be acknowledged when patients are suffering from hypermenorrhea or mastalgie without any therapeutic effect of progesterone, or where progesterone makes the situation in the breast and on the endometrium worser. Progesterone is metabolized in different progesterone derivates; they have specific effects on the breast and in other extragenital tissues and depend from the genetic situation of the given metabolizing enzymes. This should be discussed and investigated in infiltrales furtheron.

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AS05.6 Progestogens in benign and malignant breast disease Adolf E Schindler Institute for Medical Research and Education, Essen, Germany

nant breast disease in pre- and postmenopausal women will be presented.

Basically, progestogens are able both to stimulate or inhibit the cell cycle of benign and malignant glandular breast cells. Independent of that, estrogens are the most important determinants of breast cell proliferation. The main sources of estrogen activities in preand postmenopausal women are: (1) the circulating serum estradiol and estrone (free and sulfates) levels and (2) the continuous in situ synthesis of estrogens from androgen precursors through sulfatase, aromatase and 17-␤-hydroxysteroid dehydrogenase type 1 and type 2 activities. In addition, this can be further modified by differences in estrogen metabolism at the tissue level (2-OH-, 4-OH-, 16-OH-estrogens), cellular levels of estrogen-, progesterone- and androgen-receptors as well as the stage of the individual cell cycle. The main estrogen antagonistic effects of progestogens are primarily their ability to decrease ovarian estradiol production through their antigonadotropic effects, to stimulate 17-␤-hydroxysteroid dehydrogenase type 2 activity (metabolizing estradiol to the biologically less active estrone) and to downregulate estrogen receptors. For the incidence of breast disease there is a tendency to decrease with lower doses of estradiol and a higher dose of progestogen. Some synthetic progestogens with androgenic properties may act as estrogen agonists in some women. Furthermore, the effect on 17-␤-hydroxysteroiddehydrogenase activity are quite different from one progestogen to the other. For instance, medroxyprogesterone acetate, norethisterone and norgestrel have been shown to preferentially stimulate 17-␤-hydroxysteroid dehydrogenase type 1, metabolizing estrone to estradiol, where as this is not the case, for example, with progesterone. In addition, the action of progestogen on glandular breast cells may be influenced by the different, partial biological effects of the various progestogen (such as estrogenic, antiestrogenic, androgenic, antiandrogenic and glucocorticoid like actions). In the normal breast gland final differentiation and maturation are achieved by the first full-term pregnancy in young age. Various clinical studies with progestogens in benign and malig-

Organised by the British Menopause Society

Monday, 5 June 2006 14:15–16:15 AS06—Healthy ageing in women AS06.1 The future of menopause training Nick Panay Consultant Gynaecologist, West London Menopause & PMS Centre, Queen Charlotte’s & Chelsea and Chelsea & Westminster Hospitals, United Kingdom Until recently training in the menopause for gynaecologists and other health professionals was largely unregulated. For gynaecologists, it usually required an interested individual to take some time out from their general training, usually 2 years, to perform research supervised by a menopause specialist. General practitioners and specialist nurses would have to attend specialist clinics and meetings to acquire the necessary expertise. Not surprisingly, in the absence of a formal syllabus and training programme, the skill levels achieved by “menopause specialists” varied considerably. This had repercussions on the standard of: • Menopause patient care • Training of juniors and other health professionals • Research into the specialty. Recognising this deficiency in training, the British Menopause Society (BMS) set out to formalize the training of gynaecologists and primary care physicians. Gynaecologists can now undertake a special skills training module in the menopause administered through the BMS and Royal College of Obstetricians and Gynaecologists (RCOG). This and other modules were developed for RCOG trainees working in the British Isles who had completed their core training. However, this training is also suitable for Consultants, Staff Grade and Associate Specialists as part of their continuing professional development. General Practioners and Family Planning doctors can perform their training through the Faculty of Family Planning and Reproductive Healthcare. This leads to the issuing of a menopause certificate by the faculty on successful

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completion. The training for specialist nurses is still in development. Both courses are performed under the supervision of a recognized preceptor who should be a member of the BMS. It is hoped that the introduction of these training programmes with formal syllabi and accredited supervisors has improved the future of menopause patient care, training and research. AS06.2 Future management of osteoporosis David H Barlow Executive Dean of Medicine, Professor of Reproductive Medicine, University of Glasgow, Scotland, UK The management of osteoporosis has been a subject of considerable interest in the UK in recent years. It is now recognised that the consequences of osteoporosis, particularly hip and vertebral fractures, are a huge burden on health services and on society but the optimal approach to people with osteoporosis is a subject of controversy. We know that through the use of therapy it is possible to maintain bone mineral density (BMD), at least for the duration of the therapy. What is questioned is the end result of the therapies in terms of fracture prevention. Those who have to weigh up health priorities ask what impact the therapies have on fractures and at what cost so that they can weigh this against other competing claims for resources. Others argue that it must be good to maintain BMD so that individuals can avoid osteoporosis without necessarily considering the level of individual’s risk of fracture. These two philosophies are hard to bridge but in real-life medicine these issues have to be faced by professionals and their patients and clinical decisions are being made. National guidance in the UK NHS, by bringing in consideration of cost effectiveness in fracture prevention is tending to move funding decisions towards demonstrable prevention of fractures rather than maintenance of BMD. AS06.3 Individualisation of HRT—What does it really mean? John Studd Professor of Gynaecology, Lister Hospital, Department of Obstetrics & Gynecology, London, UK The WHI study worked on the assumption that one dose would fit all asymptomatic postmenopausal women. The investigators therefore, used the wrong

dose, of the wrong hormones on the wrong patients and came up with the wrong conclusion. Different combinations of different hormones are necessary for different symptoms and different age groups. HRT may be commenced in the peri-menopausal phase, the early postmenopause, the late postmenopause or after hysterectomy and bilateral salpingo-oophorectomy and premature menopause. These all require different treatments. Similarly different indications such as vaso motor symptoms, sexual problems, depression or the treatment/prevention of osteoporosis all need different combinations of oestradiol and possibly progestogen and testosterone according to the specific requirements of the patient. These will be discussed. AS06.4 Menopause and the quality of life Mary Ann Lumsden Professor of Gynaecology and Medical Education, University of Glasgow, Scotland, UK The assumption is frequently made that the relief of Menopausal Symptoms will be associated with an improvement in Quality of Life (QoL). This seems a logical conclusion if, for example, there are vasomotor symptoms leading to embarrassment and loss of sleep or uro-genital atrophy resulting in dyspareunia; their relief should be associated with improved QoL. However, it is not that simple since there are many aspects to QoL and also many means of assessing it. QoL is a personal view that cannot be estimated by another person. It is influenced by both health and nonhealth related factors such as family or work. These factors are also closely linked with the response of a person to unpleasant symptoms and need to be taken into account when assessing the affect of those symptoms on QoL. Generic instruments are available that have been used in other areas of gynaecology. This test the totality of an individual’s well being and investigate the influence of many factors including physical, social and mental functioning. More specific assessment questionnaires, such as the Green Menopause Questionnaire or the Kupperman index, are available, but these are usually most suitable for assessing the symptoms themselves and changes resulting from treatment rather than addressing the question of the effect on QoL itself.

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One of the publications resulting from WHI suggested that HRT did not improve QoL. This is likely to be because many women with severe symptoms were not considered suitable for randomisation and also, the aim of WHI was not to investigate this as a primary endpoint. However, good QoL data concerning menopausal women and the treatment of their symptoms is lacking making the findings less easy to refute. It is vital, therefore, that appropriate means of assessing QoL are developed for use in future studies in this group of women, including evaluation of symptoms and the factors that might influence a woman’s response to them, which thus impact on her quality of life. A stronger message must be sent out that Menopausal Symptoms and their relief should be an important part of policies concerning Women’s Health. AS06.5 The future direction of HRT trials Malcolm Whitehead UK Abstract not available at the time of printing. AS06.6 Cardiovascular disease and premature ovarian failure John C Stevenson National Heart & Lung Institute, Imperial College London, Royal Brompton Hospital, London, UK Loss of ovarian function results in adverse changes in a number of risk factors for cardiovascular disease, and in particular, coronary heart disease (CHD). These changes include increases in LDL cholesterol and triglycerides, decreases in HDL cholesterol, increases in pancreatic insulin secretion, increases in abdominal fat distribution, and decreases in vascular endothelial function. The menopause itself results in an increase in cardiovascular disease incidence, which is superimposed on aging, and it has long been known that premature menopause results in premature CHD. There are no large studies of the cardiovascular effects of hormone replacement therapy (HRT) in women with premature menopause. However, findings from the Women’s Health Initiative (WHI) have shown a more beneficial effect of HRT on CHD in those women who were younger or closer to the menopause than in older women. Indeed, the latest findings have demonstrated a significant reduction in certain CHD

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outcomes in women aged 50–59 years given estrogenalone HRT, with no such benefit seen in women of older ages. It has therefore been proposed that HRT will benefit the cardiovascular system in younger postmenopausal women because they usually have less atheroma development, and hence less diseased arteries, than older women. This has given rise to the concept of a “window of opportunity” existing in the early fifties age group for HRT to confer cardiovascular benefit. Obviously, women with premature menopause are even younger in age and therefore more likely to benefit from HRT. However, this concept is now perpetuating the myth that diseased arteries cannot respond to estrogen, yet available evidence has shown quite clearly that women with CHD are capable of responding beneficially to HRT. A likely reason that the older women in the WHI failed to show a beneficial response was that the doses of estrogen used were inappropriately high for their ages. There is no doubt that relatively healthy arteries should respond better than diseased arteries to any intervention, and it seems very likely that HRT should help prevent the increased CHD risk seen in women with premature menopause. In such women HRT should in any case be regarded as obligatory, at least until the age of normal menopause. AS06.7 New developments in menopause management David Sturdee Solihull Hospital, Women’s Health Unit, Solihull, UK The interpretations of the various large studies that have been reported over the last few years and the statements from regulatory authorities have resulted in some changes in clinical management but also in the need for even more discussion and education of both patients and their doctors. There is a greater emphasis and awareness of the holistic approach to menopause management and consideration of life-style and health related matters in general for the adult woman, not solely around the menopause. In addition new data particularly on lower dose regimens of oestrogen and progestogen combinations have meant that menopausal women can now be started on lower doses of hormone therapy (HT) than in previous years and especially compared to the large studies. Intrauterine delivery of progestogen is the logical route of administration and the levonorgestrel-releasing device Mirena® is now

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licensed in many countries for use as the progestogen component of continuous combined HT regimens, producing low systemic levels of progestogen, which may minimise the impact on breast tissue. Current ongoing studies of certain selective serotonin reuptake inhibitors are trying to identify suitable non-hormonal treatments for hot flushes. These will be especially helpful for the many women who are experiencing distressing flushes but are unable to take oestrogen. Monday, 5 June 2006 14:15–16:15 AS07—Afternoon Symposium Organised by Pantarhei Bioscience Abstract not available at the time of printing. Monday, 5 June 2006 14:15–16:15 FC04—Free Communication Session: Cardiovascular disease I FC04.1 The effect of various menopausal hormone therapies on markers of inflammation, coagulation, fibrinolysis, lipids and lipoproteins in healthy postmenopausal women Branka Zegura1 , B Guzic-Salobir2 , M Sebestjen2 , I Keber2 1 Maribor University Hospital, Department of Gynaecology and Obstetrics, Maribor, Slovenia; 2 Clinical Centre Ljubljana, Department of Angiology, Ljubljana, Slovenia Androgenic progestins such as NETA may influence the effect of E2 therapy. We compared the influence of oral E2, with and without NETA, and transdermal E2 on markers of coagulation, fibrinolysis, inflammation and on lipids and lipoproteins in healthy postmenopausal women. 112 women were randomized to receive treatment with either oral E2, with or without NETA, transdermal E2, or placebo. Of the fibrinolytic parameters, oral E2 (p < 0.05) and E2 with NETA (p < 0.01) shortened euglobulin clot lysis time. Oral E2 decreased plasminogen activator inhibitor (PAI-1) activity (p < 0.05). Oral E2 with NETA reduced PAI-1 antigen levels (p < 0.01) and increased D-dimer antigen levels (p < 01). Of the coagulation parameters,

both routes of E2 therapy decreased fibrinogen levels (p = 02 for oral and p = 0, 007 for transdermal E2), while E2 with NETA showed no effect. Oral E2 (p = 0.04) and E2 with NETA (p < 0.01) increased CRP. Transdermal E2 showed no influence on CRP. The addition of NETA influenced the change in CRP, as the increase in CRP was more pronounced after E2 without NETA (p = 05). Of the lipids and lipoproteins, oral E2 decreased LDL-C (p < 0.01), Lp(a) (p < 0.05) and increased HDL-C (p < 0.05). Transdermal E2 decreased triglycerides (p < 0.02) and increased HDL-C (p < 0.03). Oral E2 with NETA decreased total cholesterol (p < 0.01) and HDL-C (p < 05). Oral E2, with or without NETA, produced no net activation of coagulation but improved fibrinolysis. Both modes of oral MHT have a greater impact on markers of inflammation, coagulation, fibrinolysis, lipids and lipoproteins than transdermal E2. NETA attenuates some E2 effects. FC04.2 No increase in CRP during intranasal compared to oral hormone therapy Majoie Hemelaar1,2,3 , P Kenemans1,2,3 , 3,4 5 C Schalkwijk , D Braat , M van der Mooren1,2,3 1 VU University Medical Center, Department of Obstetrics & Gynaecology, Amsterdam, The Netherlands; 2 Project ‘Ageing Women’; 3 Institute for Cardiovascular Research, Vrije Universiteit (ICaR-VU), The Netherlands; 4 VU University Medical Center, Department of Clinical Chemistry, The Netherlands; 5 Radboud University Nijmegen Medical Centre, Nijmegen, Department of Obstetrics & Gynaecology, The Netherlands Objectives: To compare the effects of intranasal and oral administration of 17beta-oestradiol (E2) and norethisterone (acetate) [NET(A)] on C-reactive protein (CRP) and other markers of inflammation in healthy postmenopausal women. Methods: Ninety healthy postmenopausal women (age 56.6 ± 4.7 years) participated in this 1-year trial. After computerised block randomisation they daily received, in a double-blind fashion, intranasal E2/NET 175 (g/275 ␮g (n = 47) or oral E2/NETA 1 mg/0.5 mg (n = 43). Concentrations of high sensitivity CRP and adhesion molecules were measured at baseline and after 12, 24 and 52 weeks of treatment.

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Results: CRP levels were increased (p = 0.1) in the oral, but not in the intranasal group. The increase in the oral group was highest in week 12 (64.9%), and was larger (p < 0.01) compared to the non-significant increase (8.6%) found in the intranasal group. Both groups showed decreases (p < 0.1) in soluble vascular cell adhesion molecule (sVCAM), intercellular adhesion molecule (sICAM) and sE-selectin. The decreases were larger (p < 0.01) in the oral than in the intranasal group. Conclusions: Intranasal E2/NET therapy did not significantly increase CRP levels, in contrast to the oral E2/NETA treatment. Intranasal and oral therapy both lowered plasma concentrations of adhesion molecules, however, more so in the oral group. FC04.3 Abstract No.: 203 Presentation Preference: free communication— oral or poster presentation Keyword: 03—Cardiovascular Less effect of intranasal than oral hormone therapy on APC resistance Majoie Hemelaar1,2,3 , J Rosing4 , C Thomassen4 , D Braat5 , M van der Mooren1,2,3 1 VU University Medical Center, Department of Obstetrics & Gynaecology, Amsterdam, The Netherlands; 2 Project ‘Ageing Women’; 3 Institute for Cardiovascular Research-Vrije Universiteit (ICaR-VU), The Netherlands; 4 Cardiovascular Research Institute Maastricht University, Maastricht, The Netherlands; 5 Radboud University Nijmegen Medical Centre, Nijmegen, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands Objective: To compare the effects of intranasal and oral administration of 17beta-oestradiol (E2) and norethisterone (acetate) [NET(A)] in healthy postmenopausal women on activated protein C resistance (APCr) and other haemostatic parameters associated with venous thrombosis. Methods: In this two-centre, randomised, doubleblind, 1-year trial 90 postmenopausal women (age 56.6 ± 4.7 years) daily received either an intranasal spray with E2/NET 175 ␮g/275 ␮g (n = 47), or oral E2/NETA 1 mg/0.5 mg (n = 43). Normalised APC sensitivity ratios (nAPCsr) were determined with a thrombin generation-based APC resistance test.

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Results: Both groups showed a significant increase in nAPCsr. After 1 year, the increase in nAPCsr was smaller (p < 0.1) in the intranasal (+11%) than in the oral group (+53%). Both groups showed a significant decrease in protein C (−11% and −12%) and antithrombin, the latter decrease being less (p < 0.01) in the intranasal (−6%) than the oral (−11%) group, whereas free protein S was only lowered (−2%) in the intranasal group. Only non-significant changes were seen in Factor VIII. Prothrombin was equally decreased in both groups (both −5%). Increases were seen in prothrombin fragment 1 + 2 in the oral group only (+19%), and in D-dimer in both groups. For D-dimer the increase was higher in the oral (+51%) than the intranasal (+16%) group in week 12. Conclusion: Compared to oral E2/NETA therapy, intranasal E2/NET had less effect on nAPCsr and several other parameters associated with venous thrombosis. This observation suggests a lower venous thrombosis risk for intranasal E2/NET compared to oral therapy. FC04.4 Osteoarthritis as cardiovascular risk factor in postmenopausal women Artem Popov, N Izmozherova Department of Internal Medicine No. 2, Ekaterinburg, Russian Federation Aim: To assess frequency of cardiovascular diseases and severity of menopausal symptoms in postmenopausal women suffering from osteoarthritis (OA). Methods: The first group of 117 postmenopausal women with OA (“cases”) and the 2nd group of 117 women (‘controls’) without OA were examined. Frequencies of arterial hypertension (AH) and coronary heart disease (CHD), levels of serum lipids were registered. Results: Cases had significantly higher body-mass index, lower high density lipoproteins and higher triglycerides levels than controls. OA also increased odds of AH (OR = 2.18; 95% CI 1.24–3.84) and CHD (OR = 2.47; 95% CI 1.08–5.69). Menopausal symptoms were much more severe in OA patients (median 40 points) against 26 points in controls (p < 0.001). Conclusion: OA and cardiovascular diseases are frequently co-morbid in postmenopausal women. Severe course of menopause pain and limitations of physical activity in postmenopausal women with OA should be

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taken into consideration when CHD and AH management program is being designed. FC04.5 The elements of metabolic syndrome in postreproductive period Milka Drezgic, L Marina, S Vujovic, M Stojanovic, M Ivovic, Z Penezic Institute of Endocrinology, Department for Reproductive Endocrinology, Belgrade, Serbia & Montenegro The elements of the metabolic syndrome: insulin resistance, body mass index (BMI) and waist circumference are risk factors for developing cardiovascular diseases. The objective of this study was to compare the insulin resistance through homeostasis model assessment of insulin sensitivity (HOMA index) and anthropometric characteristics such as BMI and waist circumference in women in early menopause with women in physiological menopause. We evaluated 100 women prior to the hormone replacement therapy. They were divided in two groups. 1st group: 67 women, mean age 49.52 ± 4.06 years, mean BMI 25.32 ± 4.17 kg/m2 , with laboratory proven menopausal levels of FSH and LH. 2nd group: 33 women, mean age 34.39 ± 7.78 years, mean BMI 23.01 ± 3.25 kg/m2 , with laboratory proven premature ovarian failure. Statistical analysis was performed with Mann–Whitney’s U-test. Mean age of entering physiological menopause in the 1st group was 45.98 ± 3.44 years and 28.21 ± 7.03 years in the 2nd group. In the 1st group, the average period from the occurrence of menopause to the period when they were tested was 3.53 ± 2.78 years and in the 2nd group 6.18 ± 5.95 years. Mean HOMA index in the 1st group was 3.10 ± 2.52 versus 1.40 ± 0.54 in the 2nd group. Mean waist circumference was 81.16 ± 14.13 cm in the 1st group versus 67.76 ± 11.73 cm in the 2nd group. For every tested parameter the difference between the groups was highly significant, p < 0.01. According to our study women in physiological menopause have much higher HOMA index then women in early menopause. The possible explanation lies in the age difference between the two groups.

FC04.6 Bioflavonoid-rich botanicals reduce blood serum atherogenicity in perimenopausal women Vera Korennaya1,5 , V Myasoedova2 , N Nikitina4 , I Sobenin3 , A Orekhov1 1 Institute for Atherosclerosis Research, Moscow, Russian Federation; 2 Institute of General Pathology and Pathophysiology, Moscow, Russian Federation; 3 Instituteof Experimental Cardiology, Moscow, Russian Federation; 4 Instituteof Physical and Chemical Medicine, Moscow, Russian Federation; 5 Russian Medical Academy of Postgraduate Education, Moscow, Russian Federation Aim: To develop a combination of bioflavonoid-rich botanicals, for blood serum atherogenicity reduction, and therefore primary atherosclerosis prevention, in perimenopausal women. Methods: The content of polyphenols, procyanidis, genistein, daidzein, rezveratrol, flavone in studied plants was estimated chromatographically. Blood serum was obtained from apparently healthy perimenopausal women before and 2, 4 and 6 h after single oral administration of phytoestrogen-rich natural substances in doses of 50–1000 mg. Blood serum atherogenicity that is defined as the ability of the serum to induce intracellular cholesterol accumulation in a primary cell culture of human blood-derived monocytesmacrophages, was measured. Results: Dried extract from grape seeds, fermented grape stems, hop cones and green tea leaves have shown the reduction of serum atherogenicity on average by 68.2%, 36.4%, 48.5%, 85.6%, respectively. The antiatherogenic effects of plant compounds correlated positively with the content of polyphenols (r = 0.957, p < 0.01), procyanidis (r = 0.971, p < 0.01) and the sum of phytoestrogens (genistein, daidzein, rezveratrol, flavone) (r = 0.764, p < 0.01). Conclusion: Based on the results of this and previous studies, we have developed bioflavonoid-rich natural combination representing all major groups of bioflavonoids (phytoestrogens) for atherosclerosis prevention in perimenopausal women, containing dried grape seeds extract, fermented grape stems, hop cones, green tea leaves, garlic powder and vitamins. The recommended dosage and regiment covers daily needs of those compounds and adequate reduction of blood serum atherogenicity, that is inhibits intra-

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cellular cholesterol accumulation—the initial step of atherosclerosis development. Further studies of the influence of this natural combination on intima-media thickness and menopause symptoms are on their way. Monday, 5 June 2006 14:15–16:15 FC05—Free Communication Session: Symptomatology II FC05.1 The efficacy of HRT in treating oestrogen deficiency symptoms in women taking concomitant tamoxifen in the UK HRT trial Jo Marsden1 , D Lawrence2 , R A’Hern2 , K Briggs2 , J Bliss2 , on behalf of the HRT Trial Management Group 1 Kings Breast Care Unit, Kings College Hospital NHS Trust, London, UK; 2 The Institute of Cancer Research Clinical Trials and Statistics Unit, Surrey, UK Introduction: In the UK trial of HRT in symptomatic women with early stage breast cancer, participants were randomised to receive HRT or information about non-hormonal prescription/complementary HRT alternatives for 2 years. We tested the observation of the IBIS-I tamoxifen chemoprevention trial investigators that HRT is not efficacious in the presence of tamoxifen. Methods: Participating women completed validated, self-assessment questionnaires documenting the frequency, severity and impact of vasomotor symptoms and vaginal dryness. Analyses are limited to women taking tamoxifen at baseline and questionnaire response 6 months after randomisation. Results: At baseline, 132 women were taking tamoxifen; 67 were allocated to receive HRT and 65 were not. HRT significantly reduced the frequency of hot flushes and night sweats (p = 0.01, p = 0.03, respectively) and their impact being perceived as problematic (p = 0.003, p = 0.04), causing distress (p = 0.006, p = 0.04) and interfering with daily life (p = 0.007, p = 0.30). There was no significant difference in vaginal dryness by allocated treatment group over 6 months but the number of responders was small (20 patients). Conclusion: HRT confers considerable symptomatic benefit in the presence of tamoxifen. Further research should continue to identify sub-groups of symptomatic breast cancer survivors who could ben-

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efit from HRT without incurring an increased risk of recurrence. FC05.2 Resveratrol: an estrogen agonist? Christine Jablonski1 , C Rodrigue2 , A Gompel1 1 APHP, Hˆ opital Hˆotel Dieu, Unit´e de Gyn´ecologie, Paris, France; 2 INSERM U673, Hˆopital Saint-Antoine, Paris, France Phytoestrogens are widely used by women since the drastic decrease in hormone therapy due to recent concerns. Resveratrol (3,4 ,5-trihydroxy-trans-stilbene), a common phytoalexin, is the most extensively studied stilbene. In the occidental world, grapes are the main source of resveratrol (RES) which is found in the leaves and skin. It is different from the other phytoestrogens in that it has an equal affinity for both estradiol receptors. Various biological and clinical effects of RES are already well-known. RES exhibits antiinflammatory, neuroprotective, antiviral, cardioprotective and chemopreventive properties. Besides chemopreventive effects, resveratrol appears to exhibit therapeutic effects against cancer. A literature search revealed that there was no previous report of estrogenisation following red grapes intake. We report an original clinical observation strongly indicative for estrogenic effects on breasts of a post-menopausal woman following a large ingestion of grapes. A 57year-old post-menopausal woman who had stopped her Hormonal Replacement Therapy (HRT) some 7 months earlier developed severe mastalgia. Mammography/ultrasonography showed typical fibrocystic disease. The only putative source of estrogen that could explain this transient mastopathy was a large ingestion of grape during a 2-week holiday. After stopping grape consumption, her clinical symptoms disappeared within 2/3 weeks. Nine months later, mammography/ultrasonography found a single cyst and the breast density has decreased. The literature mainly reports in vitro data showing that resveratrol acts as a mixed estrogen agonist/antagonist in breast cells. This is the first known report of a possible estrogen effect of resveratrol in vivo.

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FC05.3 Use of sertralin and tianeptin in treatment of depressive disorders in women with surgical menopause Svetlana Yureneva, G Kamenetskaya, V Babayan Research Center of Obstetrics and Gynecology, Russian Academy of Medical Sciences, Moscow, Russian Federation Objectives: To study efficacy of antidepressive effect of sertralin and tianeptin in treatment of depressive disorders in women with surgical menopause. Methods: Clinical, psychopathological, pharmacological. Results: We studied 103 patients with depressive disorders using IDS-10 criteria, Hamilton’s Depression scale 17. Clinical and psychopathological study allowed to reveal chronic affective disorders of emotional sphere in 49.5% (F34), episodes of depression in 46.6% (F32), recurrent depressive disorders in 3.9% (F33). Mean age was 45.5 1.3 years, duration of disorders was 2.9 1.4 years. Sertralin was used in the dose of 50 mg/day, tianeptin 37.5 mg/day. Two main groups were registered depending on the regimen of use of antidepressive means and estrogen replacement therapy (ERT). Dynamics of psychopathological symptoms was assessed with HDRS17. In the group of patients (n = 45) who received ERT prior to psychopharmacotherapy, sertralin was used by 23, tianeptin by 22 patients. Analysis of the results of efficacy according to HDRS didn’t reveal any reliable difference between sertralin and tyaneptin. Differences in some HDRS parameters were found: azitation indexes were higher in tianeptin group, somatic anxiety, insomnia, pcychic anxiety, ipochondria and self-estimation parameters were higher in sertralin group. The number of responders in this group made up 74%. In the group of the 2nd variant of therapy regimen (II) indication of antidepressants was done on the background of ERT (period from 3 to 6 months) in case of the signs of depressive disorders (n = 58). Sertralin was taken by 23, tianeptin was taken by 25 patients. There were differences in some HDRS17 parameters: sense of guilty, ‘slow down’ state, excitement, psychic and somatic anxiety, general somatic symptoms, selfestimation were higher in the sertralin group. By the end of the study the percent of respondents in the 2nd group made up 75.8%. Side effects were transitory,

were evaluated as light ones and were reduced with the reduction of the dosage. In the process of study we used the criterion of minimum sufficiency. Conclusions: (1) The study allows to consider it proved to use modern antidepressants in the abovementioned conditions. (2) No reliable differences were found between the efficacy of certralin and tianeptin in both groups of patients with depressive disorders, in surgical menopause. (3) The choice of the drug may be done taking into account individual clinical characteristics of the patient’s status. The obtained data do not permit to prefer sertralin or tianeptin in the group of selective inhibitors of serotonin re-uptake drugs. FC05.4 Efficacy of low dose continuous HRT combined regimen upon vasomotor symptoms in postmenopausal women Daniel Tutunaru, DF Lebit Elias Emergency Hospital, Bucharest, Romania Aim: To assess the efficacy of 1 year continuous administration of 0.5 mg 17 ␤-estradiol combined with 2.5 mg dydrogesterone upon vasomotor menopausal symptoms. Methods: One year, prospective, open label study. Inclusion criteria: women age over 47 years, at least 1 year after last menstrual period, with menopausal symptoms (hot flushes, night sweat, mood swings, sleeping problems, etc.), whose FSH and E2 were within menopausal range, with endometrial biopsy showing no malignant or premalignant changes. Exclusion criteria: pap smear class III or more, mamographic signs of malignancy, severe liver disfunction, noncontrolled arterial hypertension and diabetes. Clinical and paraclinical essessment was done by TVUS for endometrial thickness, endometrial biopsy, mammography, pap smear, clinical exam at screening visit and by TVUS for endometrial thickness every each 3 months, beside vital signs assessment, bleeding patterns and QOL evaluation (hot flushes, night sweats, irritability, nervousness, bone and joint pains, vaginal dryness, mood swings, sexual life, breast pain, sleep disturbances, headache, etc.). Results: From 120 patients, 117 patients matched the inclusion criteria and 105 ended the study. There was a substantial improvement of the menopausal symptoms in 87 patients, 16 showed a slight improvement and two had no modification.

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Conclusion: Low dose continuous HRT combined regimen with 17 ␤-estradiol/dydrogesterone in postmenopausal women proved to be very effective in removing negative menopausal symptoms and in improving quality of life. FC05.5 Propensity of gynaecologists towards osteoporosis management and treatment Serge Rozenberg, D Murillo, R Gevers, J Vandromme Department of Obstetrics and Gynaecology, Free Universities of Brussels (VUB-ULB) CHU Saint-Pierre, Brussels, Belgium Background: Regulation authorities have recently advised against the use of hormone replacement therapy (HRT) as a first choice treatment for postmenopausal osteoporosis, modifying the past consensus. Aim: Analyse the sensibility to and prescription attitude for osteoporosis. Setting: Survey. Population: Belgian gynaecologists. Methods: Case construction: two cases to assess whether gynaecologists are prone to detect osteoporosis, and six others to evaluate their prescription attitude for osteoporosis. Results: About 80% of the physicians would prescribe a bone density measurement (BMD) to a 66 year non-HRT user. About 60% prescribed calcium and Vitamin D when the BMD was normal, 90% would prescribe it when the BMD showed osteopenia or osteoporosis (p < 0.001). Few prescribed HRT (<25%). Few advised SERMS for normal BMD, 19–47% prescribed it in osteopenia or osteoporosis (p < 0.001). Few considered a biphosphonate in normal BMD, or osteopenia in the absence of risk factors, 25% considered it in osteopenia in the presence of risk factors, and 80% in osteoporosis (p < 0.001). Conclusion: Most gynaecologists are aware of the osteoporosis problem. They often screen non HRT users and in the event of osteoporosis, they initiate a specific treatment, not HRT, but generally a combination of calcium, Vitamin D and biphosphonates.

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FC05.6 Vaginal estrogen preparations: an assessment of prescribing trends over a 2-year period Nuttan Tanna, J Pitkin NW London Hospitals NHS Trust, The Northwick Park Menopause Clinical & Research Unit, London, United Kingdom Introduction: Based on randomized controlled trial data, the current evidence base for systemic HRT suggests that risks outweigh benefits with long term usage. This may be particularly applicable to older postmenopausal women, with other co-morbidities. Many women use estrogen therapy for localized symptom relief, but duration of safe use has not been well studied. Licensed indications advocate 3–6 months use. Objectives: An audit encompassing a local district general hospital with nine primary care organizations providing care for a population of 2,304,379 people was designed to assess whether doctors within primary care were prescribing local estrogen preparations and trends in prescribing. Methods: Prescribing data over a 2-year period (August 2003–July 2005) was used for this analysis. Results: Overall total local estrogen prescribing remained consistent, averaging at 3954 (range 3297–4376) cycles per month. Trends of prescribing analysis exhibited an upward trend for a vaginal tablet formulation (Vagifem Rx) as compared to other local estrogen products on the UK market. for these prescribing trends were level or gradually falling. Discussion: Prescribing of systemic HRT is reported as declining in the literature. Reasons include doctor prescribing and patient preferences. Interestingly, this audit showed that local estrogen prescribing remained fairly consistent over the 2 years studied. Conclusions: This audit identifies a need for further research to demonstrate safety with long term use of local estrogen therapy, considering it may be used for up to 2 years by postmenopausal women.

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Tuesday, 6 June 2006 08:30–09:00 KL05—Keynote Lecture Genetic and environmental determinants in breast cancer Joseph HH Thijssen The Netherlands Abstract not available at the time of printing. Tuesday, 6 June 2006 09:00–09:30

proteomics huge efforts are being made, and initial benefits have reached clinical practice. International and interdisciplinary collaboration are key for advancing cancer research and consequently improving the quality and the length of the lives of cancer patients. Tuesday, 6 June 2006 10:30–12:30 S06—Symposium: Improving quality of life after breast cancer

Novel management of early breast cancer Fatima Cardoso Jules Bordet Institute & TRANSBIG, Brussels, Belgium

S06.1 Climacteric symptoms Margaret Rees Reader in Reproductive Medicine, University of Oxford, UK

Management of early breast cancer has evolved remarkably in this last decade. Sustained efforts in widespread screening and education, early detection, new diagnostic techniques, and crucial therapeutic developments, particularly in the area of new drugs, have led to a slow but steady decline in breast cancer mortality since the 1990s, despite its ever increasing incidence. Individualization of treatment, also known as treatment tailoring, has become the main focus of breast cancer research. Large clinical trials and meta-analyses have been our best tools to proven the benefit of adjuvant systemic therapy in terms of both disease free and overall survival of breast cancer patients. However, they only provide the average benefit in the patient population, which needs to be extrapolated to each individual. This inevitably leads to over or under-treatment of some of the patients. Additionally, the costs of the new biological or targeted agents, the paradigm of which is trastuzumab (Herceptin® ), are unfortunately too high and a judicious use is mandatory. An accurate definition of who needs adjuvant treatment and of the most efficacious therapy for each patient is indispensable, and therefore new and powerful prognostic and predictive tools are urgently needed. Translational research based on the fundamental principles of “bench-to-bedside” and “bedside-tobench” has taken the leading role in the discovery and validation of these new tools. From expression of individual markers to high technology of genomics and

Breast cancer survivors are usually advised to avoid systemic estrogens because of the concerns that this will adversely affect prognosis. The use of standard medical alternatives as well as alternative and complementary therapies is discussed [2]. Medical alternatives Progestogens such as norethisterone 5 mg/day or megestrol acetate 40 mg/day can be effective in controlling vasomotor symptoms. Of concern doses, which achieve vasomotor symptom control increase risk of venous thromboembolism [3]. Short-term studies show that selective serotonin-reuptake inhibitors such as venlafaxine, fluoxetine and paroxetine are effective in treating hot flushes and increase the range of options. However, there are concerns about safety and addiction and their efficacy has been questioned in longer studies [1]. Limited evidence also shows that gabapentin is effective. Clonidine is of limited value and effectiveness and propranolol is ineffective. A variety of vaginal lubricants and bioadhesive moisturisers are available and may help with dysparuenia. Low dose vaginal estrogens may also be used. Alternative and complementary therapies There is little scientific evidence that complementary and alternative therapies can help menopausal symptoms or provide the same benefits as conventional therapies. Yet many women use them, believing them to be safer and “more natural”. The choice of treatments is confusing and, unlike conventional medicines, not much is known about their active ingredients, safety or side effects or how they may interact with other

KL06—Keynote Lecture

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therapies. They can interfere with warfarin, antidepressants and anti-epilpetics with potentially fatal consequences. Some herbal preparations may contain oestrogenic compounds and thus there is concern about their use by breast cancer survivors. There is also concern about contaminants such as mercury, arsenic lead and pesticides. References [1] Suvanto-Luukkonen E, Koivunen R, Sundstrom H, et al. Citalopram and fluoxetine in the treatment of postmenopausal symptoms: a prospective, randomized, 9-month, placebo-controlled, doubleblind study. Menopause 2005;12:18–26. [2] Rees M, Mander T. Managing the menopause without oestrogen. RSM Press; 2004. [3] Vasilakis C, Jick H, del Mar Melero-Montes M. Risk of idiopathic venous thromboembolism in users of progestagens alone. Lancet 1999;6(354):1610–1. S06.2 Psychological support in breast cancer Fabienne Liebens, M Aimont, B Carly, A Pastijn, M Degueldre Breast Unit, Department of Obstetrics & Gynecology, CHU Saint-Pierre, Brussels, Belgium The diagnosis of breast cancer (BC) induces a variety of mood disorders and psychosocial distress in patients and their families. A growing body of research data indicates that recovery from BC is improved if the patient receives emotional support during and after the initial stages of diagnosis and treatment. The benefits of psychological care extend beyond BC patients themselves. Spouses, who must offer both emotional and practical support while dealing with their own feelings, children, parents, and friends involved in caretaking can also benefit from psychological interventions. Since 1991 our Breast Unit team has been staffed with a specialised psychologist. We will present the results of this integrated approach to BC care, based on a cohort of 925 women who have been operated on and followed in our institution. This large cohort study is unique in that we used structured interviews and standardised diagnostic criteria to assess emotional distress. Furthermore, all the interviews were conducted by the same psychologist. Depression and anxiety were assessed

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using Hospital Anxiety and Depression Scale (HADS). The main results of this study indicate that in some women with early breast cancer, depression and anxiety in the year after diagnosis reach a level that is twice that of the general female population. The risk factors for depression and anxiety are related to the patient rather than to the disease or its treatment. Social support can also play a key role in a woman’s coping strategy, as demonstrated by the extended psychological followup of BC patients in our unit. The benefits of such an integrated psychological care for patients, partners, children, and even health professionals in the medical team will also be discussed, together with problems encountered when implementing this approach within the Belgian health care structure. S06.3 Sexuality after breast cancer Rossella E Nappi, F Albani, F Polatti Research Center for Reproductive Medicine, Department of Obstetrics & Gynecology, IRCCS Policlinico S Matteo, University of Pavia, Italy Virtually every illness has an impact on sexual activity and behavior because of the diagnosis, of sideeffects related to disease, surgery and pharmacological interventions, and of the consequences on self-image and esteem, mood and relational issues. Personal education and experiences, coping strategies and life cycle stage, as well as partner’s and social support, play a major role in helping women to overcome the distress. Breast cancer diagnosis and treatment strongly affect sexual function, identity and relationship. Indeed, the breasts are one of the most predominate features of a woman and stand out as a symbol of womanliness, livelihood and eroticism. On the other hand, stage of cancer, type of breast surgery, lymphedema, hair loss, iatrogenic premature menopause and age influence intimacy and body image contributing to different amount of sexual dysfunction. Apart psycho-relational issues, the consequences of surgical and therapeutical approaches deeply interfere with the integrity of the biological substrate (mainly neuroendocrine circuitries and neurovascular/neuromuscular pathways) of the sexual response. A high percentage of women experiences difficulties in arousal, reduced lubrication and dyspareunia, especially if treated with chemotherapy following breast surgery, and may develop low satisfaction and poor libido. Tactile impaired or unpleas-

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ant sensations may be the result of breast mutilation and/or reconstruction, while altered genital sensitivity may arise from the loss of trophism of vulvo-genital tissues. A good physical and emotional relationship with the partner represents the most important factor to preserve self-esteem and intimacy after primary treatment. Sexual support is mandatory in oncologic services to improve the quality of life of breast cancer patients and survivors. S06.4 Improving quality of life after breast cancer: other diseases Serge Rozenberg, C Antoine, S Fuller, B Carly, A Pastijn, F Liebens Department of Obstetrics and Gynaecology, Free Universities of Brussels (VUB-ULB, CHU Saint-Pierre, Brussels, Belgium Follow-up of breast cancer patients generally aims at optimal treatment of their disease and prevention of recurrences. Logically, most oncologists are focused on the breast disease. Nevertheless, as a consequence of improved early diagnosis and treatment of breast cancer, breast cancer survivors live longer today. These patients may suffer also from other conditions. Actually, because of shared risk factors of breast cancer, they may also be at increased risk of some other diseases. Furthermore, some of the used treatments such (as SERMS, Aromatase inhibitors, GnRH agonists) may also induce an increased risk of pathologies. This presentation analyses the relationship between breast cancer and other cancers, cardiovascular diseases and osteoporosis as well as the effect of breast cancer treatments. Method: a systematic review was conducted using the following key words “breast neoplasm and prevention and either osteoporosis or cardiovascular disease, or endometrium cancer or ovarian cancer or colon cancer, or thrombosis” with limitation to “Metaanalyses, randomised trials, clinical trials and review articles”. Extrapolation of possible prevention strategies towards these diseases, with inclusion of a cost analysis will be attempted.

Tuesday, 6 June 2006 10:30–12:30 S07—Symposium: Hormones and breast cancer S07.1 Estrogen: genomic and nongenomic effects Michele De Bortoli Institute for Cancer Research & Treatment and Center for Complex Systems in Molecular Biology & Medicine, University of Torino, Italy Estrogen exert profound effects on many tissues by controlling several processes. At the cellular level, estrogen control the expression of many genes (genomic effect) and also induce transitory changes in ion transport and protein phosphorylation (“nongenomic” effects). The genomic pathway is reasonably well understood. Estrogen bind to ER␣ and ER␤ receptors, which are ligand-dependent transcription factors that bind to target genes either directly or undirectly and activate or repress transcription. Conversely, rapid and transient nongenomic responses may depend on the putative interaction of estrogen with several proteins, included membrane-bound ERs, the endoplasmic reticulum seven-helix GPR30 receptor, ER-X or others. Changes in ion concentration, as well as phosphorylation of proteins such as the MAPK, are likely to evoke transcriptional effects, as well. A different approach can be used to understand the effects of estrogen in a global manner. We can analyze the whole genomic regulation and derive information on the possible signalling pathways involved using a bottom-up approach. Treatment of breast cancer cell lines with estrogen and antiestrogen was followed up kinetically by DNA microarray analysis and changes in the level of expression of several hundreds of genes recorded. Next, bioinformatic analysis of regulatory sequences upstream of target genes is performed, unraveling the presence of putative EREs, other known transcription factor binding sites or unidentified sequences in groups of coregulated genes. The data obtained constitute a system in which the complexity of estrogenic response can be appreciated and several hints to possible alternative signalling pathways can be deduced.

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S07.2 Progestins, androgens in HRT and breast cancer risk Anne Gompel APHP, Hotel-Dieu de Paris and Universit´e Paris V, France Within countries, progestins used in Hormone replacement therapy (HRT) vary widely. In the USA, medroxyprogesterone acetate (MPA) is the foremost used, whereas in northern Europe, norethisterone acetate (NETA) is predominant as well as norsteroids in the UK. In France, progesterone is used in 20% of the women. The properties of these progestins vary according to their structures. In addition to their progestin activities, the norsteroids are androgenic and estrogenic whereas pregnanes have no estrogenic potencies. MPA is particular by its androgenic and glucocorticoid potencies. Progesterone (P) is a relatively pure progestin. It is rapidly metabolised which is not the case for the synthetic progestins. The breast impact of these compounds may thus depend on their structures and metabolism. The relative risk reported with these compounds during HRT varies from a RR of breast cancer between 2 and 4 with NETA to 1.3 with MPA and no increase so far reported with P in France. Biology cannot provide a simple view to explain these different risks. In particular, the knowledge of progestin interactions with non classical steroid receptors is lacking. Androgen receptors are frequently expressed in hormone dependent breast cancer. In pre-clinical studies, androgens have antiproliferative effects on breast cells. Epidemiological studies correlate the androgen levels in post-menopausal women with an increased risk in breast cancer. Given the importance of aromatase in breast cancer, it is might be discuss a role for the aromatisable androgens in breast cancer promotion. The current knowledge will be discussed. S07.3 Estrogens and breast cancer: new pharmacological approaches Pascal Pujol Centre Hospitalier Universitaire de Montpellier, INSERM 540, France Estrogen is a key player in the etiology and progression of breast cancer. In last decades, the use of hormonal therapies aiming to blockade estrogen pathway has

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been used successfully both in the adjuvant setting and for prevention purpose. Classical pharmacological approaches that target the estrogen pathway include: (i) selective estrogen receptor modulators (SERM) that possess both estrogen antagonist and agonist activities depending upon the tissues (tamoxifen, raloxifene, toremifene, arzoxifene, lasoxifene); (ii) estrogen deprivation such as oophorectomy and LHRH agonists in premenopause or aromatase inhibitors (AI) in post menopause; (iii) pure estrogen antagonists (fulvestrant, ZK-703 and 253). New pharmacological approaches also included : estrogen receptor (ER) beta selective ligand (since most of known SERMs act as pure antagonists) and estrone sulfatase inhibitors that blocked estrogen formation from sulfoconjugates. In the adjuvant setting of postmenopausal breast cancer, AI of third generation (anastrozole, letrozole, exemestane) have been shown to be more effective than tamoxifen in large-scale randomized trials. This benefice of AI compared to SERMs may be in part explained by the blockade of non-genomic effect of estrogens. Moreover, the crosstalk between ER and growth factor receptor is thought to be a cause of endocrine resistance. Since the HER-2 related signaling cascade reduces the antagonist effect of tamoxifen, AI or combined tamoxifen plus tyrosine kinase inhibitor (gefitinib) or antibody (trastuzumab) may counteract this resistance in HER-2 overexpressing/ER+ tumors, and deserved to be analysed in future clinical studies. For prevention purpose, new SERMs have been developped, with the goal of reducing toxicity and improving efficacy. Preliminary results preclinical and clinical studies with raloxifene are promissing. AI also shown a high potential preventive efficacy, as shown by the reduction of contralateral breast cancer in the adjuvant trials. Breast cancer prevention studies using AI in high-risk women are ongoing. S07.4 Clinical implications Ole-Erik Iversen Haukeland University Hospital, Bergen, Norway The breast issue related to HRT is probably the main concern of both women seeking advice and the prescribing physicians. Among the most frequently raised questions in the clinical setting are the following:

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To what extent is the risk increased? Do progestins modify risk estimates? Is morbidity in HRT-users different? Is mortality of breast cancer affected? Can it be given to breast cancer patients? The available evidence consists mainly of at least 70–80 observational studies. More recently, some information from randomized controlled trials have become available and the results are mainly in line with those from the observational studies, although the target populations were of considerably higher age (mean 63–67 years) than the typical woman starting HRT. It is important to emphasize that for short-term treatment (<3–5 years), overall and breast cancer risk is of limited importance in the risk-benefit equation. In sum, the relative risk of breast cancer associated with more than 5 years of use is estimated to be approximately 1.35. The risk for every year of use is comparable to that of postponing the menopause for 1 year. The increased risk is not measurable 5 years or more after cessation of treatment. Several studies have been reported after the extensive collaborative review, published in 1997. More focus has recently been on risk modulation of the added progestagen. Many of the studies published after 1997 report a higher risk estimate for HRT compared to ERT, but the picture is not quite consistent. Neither is it consistent whether there is a difference if progestagens are given continuously combined or sequencially. Further, another unresolved issue is whether the drugs used in Europe (mainly E2/NETA) confers a higher risk than the preparation mostly used in the USA (CEE/MPA). Most studies on the distribution of prognostic factors in breast cancer in HRT-users have so far shown favourable results regarding tumor size, stage and grade, while that was not the finding in the WHI-study. Similarly, it seems to be a fairly consistent observation that mortality and survival of breast cancer is better among previous HRT-users. The MWS-study on the other hand, tended in the opposite direction. Previous breast cancer has been considered to be an absolute contra-indication for HRT, although this has never been scientifically proven in clinical trials. A recent Norwegian Health Technology Assessment (HTA) concludes that there is not scientific evidence either to recommend or warn against use of HRT in women previously treated for breast cancer. Prelimi-

nary data from two randomized clinical trials on this particular issue are also conflicting, and more mature data are awaited from these studies. In the overall equation regarding HRT and cancer, the consistent reduction of colorectal cancer incidence and mortality from it should also be brought into the overall consideration. Tuesday, 6 June 2006 10:30–12:30 S08—Symposium: Hormones and other neoplastic S08.1 An overview of systemic menopausal hormone therapy (HT) and risk of ovarian cancer Eva Glud Department of Gynaecology and Obstetrics, Hillerød Sygehus, Denmark Introduction: Over the past two decades hormone therapy (HT) has been used increasingly in developed countries by menopausal women to alleviate menopausal symptoms, and to prevent diseases. Despite accumulating evidence of serious health risks associated to use of HT, it is still used to alleviate menopausal symptoms in many healthy women. HT is associated with an increased risk of breast and endometrial cancer. Because cancer of the ovaries shares some risk factors with these cancers, it has been suggested that HT could also increase the risk of ovarian cancer, probably by promoting proliferation and malignant transformation of ovarian epithelial cells. Results: The association between HT and risk of ovarian cancer has been elucidated through an abundant number of observational as well as randomized controlled trials. Earlier observational studies on the risk of ovarian cancer and HT were equivocal, but observational studies and randomized trials (The WHI study) published in recent years, shows results of an increased risk of ovarian cancer. An updated review of the results will be presented, with specific emphasis on the risk relating to different hormone dose, types or regimens. Conclusion: Results from recent studies indicate that HT is associated with a significant risk of ovarian cancer. However data regarding risk related to different hormone regimens require judicious analysis and interpretation. Because ovarian cancer is the most lethal of the gynaecologic cancers, an increased risk could have important implications.

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S08.2 Prevention and treatment of prostate cancer with phytoestrogens? Wolfgang Wuttke Clinical and Experimental Endocrinology, University of Göttingen/Germany The Cimicifuga racemosa extract BNO 1055 (CR) inhibits proliferation of human prostate cancer-derived LNCaP cells. Therefore we tested the capability of this extract to inhibit formation and/or proliferation of tumors induced by subcutaneous (s.c.) inoculation of LNCaP cells in immunodeficient nu/nu mice. After inoculation of 1 mio cells 12 of 18 animals developed solid tumors while tumor development was seen in only 5 of 18 CR-treated animals of which the size at termination of the experiments 10 weeks after inoculation was significantly smaller than in the control animals. Upon histological inspection the amount of tumor tissue in the control animals was significantly larger than in the CR-treated animals while in the latter connective tissue was predominant. It is concluded that compounds in CR inhibit tumor development, proliferation and dignity of the tumors following s.c. inoculation of LNCaP cells. Hence, the CR extract may prove to be efficient in preventing and treatment of prostate cancer. S08.3 The endometrium David Sturdee Solihull Hospital, Women’s Health Unit, Solihull, UK Inappropriate use of hormone replacement therapy (HRT) may increase the risk of endometrial cancer. Unopposed oestrogen is associated with the development of endometrial hyperplasia and if continued of endometrial cancer. The addition of progestogen for at least 12 days in each cycle will prevent hyperplasia in the short term but with use over 5 years there will still be an increased risk of endometrial disease. Long cycle therapy with a progestogen course every 3 months or more will reduce the frequency of bleeding, which will be popular, but protection of the endometrium is less certain. The addition of continuous progestogen to oestrogen has the merit of correcting endometrial hyperplasia without atypia to normal and in the long-term will keep the endometrium atrophic. There is no increase in the

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risk of endometrial cancer with such continuous combined regimens and probably even a reduced risk. The progestogen in HRT is only required for endometrial protection, so it is logical to give the hormone direct to the endometrial cavity. The Mirena® intrauterine system that releases levonorgestrel has been available for many years as a contraceptive and treatment for menorrhagia, and recently also for the progestogen component of combined HRT regimens. For women who have had complete removal of a stage 1 endometrial cancer, there is no evidence that subsequent HRT will increase the risk of further disease. S08.4 Hormone replacement therapy and colorectal cancer Carlo La Vecchia Istituto di Ricerche Farmacologiche “Mario Negri”, Milano and Istituto di Statistica Medica e Biometria, Universit`a degli Studi di Milano, Milano, Italy At least nine cohort studies reported information on HRT and colorectal cancer risk, including a total of over 2500 cases. A significant inverse association was found in two cohort investigations, including the largest one focusing on fatal colon cancers. Of 14 casecontrol studies for a total of over 6000 cases, five reported 20–40% risk reductions among ever users of HRT. Two additional investigations showed moderate, non-significant inverse associations. With reference to randomized clinical trials, in the Women’s Health Initiative (WHI) study, after 7 years follow-up, 45 cases of colorectal cancer were observed in the combined HRT group versus 67 in the placebo one, corresponding to a RR of 0.63. A combined re-analysis of the WHI with the Heart and Estrogen Progestin Replacement study (HERS) data included 56 cases in the combined HRT treatment and 83 cases in the placebo group (pooled RR = 0.64, 95% CI 0.45–0.92). The issue of any impact of HRT on colorectal cancer mortality does not appear promising. In fact, at the 7-year follow-up of the WHI, 43 invasive colorectal cancer cases were observed in the combined HRT group versus 72 in the placebo one (RR = 0.56, 95% CI 0.38 to 0.81). However, cancers diagnosed in the HRT group were more advanced and had a greater number of positive lymphonodes. Furthermore, the estrogen only arm of the WHI in hysterectomized women did not show any difference at the

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8-year follow-up between treated women (n = 61) and control ones (n = 68). Tuesday, 6 June 2006 12:30–14:00 LS05—Lunch Satellite Symposium Sponsored by Procter & Gamble Abstract not available at the time of printing. Tuesday, 6 June 2006 14:15–16:15 LS06—Lunch Satellite Symposium Sponsored by Merck Theramex Abstract not available at the time of printing. Tuesday, 6 June 2006 14:15–16:15 AS08—Afternoon Symposium: Sexuality after Menopause Organised by Esme Nijland, Organon NV AS08.1 Sexual well being after 50: results from the European SWB survey 2006 Rik van Lunsen The Netherlands Abstract not available at the time of printing. AS08.2 The role of hormones on female sexuality Rosella E Nappi Research Center for Reproductive Medicine, Department of Obstetrics & Gynecology, IRCCS Policlinico S. Matteo, University of Pavia, Italy There are a large number of biological, psychological and socio-relational factors related to women’s sexual health. These factors can negatively affect the entire sexual response cycle inducing significant changes in sexual desire, arousal, orgasm and satisfaction. Sexsteroids, particularly low estradiol levels, are extremely relevant for sexual awareness and vaginal receptivity in naturally menopausal women. In surgically menopausal women, a significant lack of androgens

can also negatively impact libido and sexual responsiveness. Estrogen modulates genital blood flow, peripheral nerve function, vaginal tissue structural integrity, and therefore, the process of lubrication. Within the central nervous system, estradiol plays a permissive role on sexual receptivity by acting on its own receptor and by increasing progesterone receptor expression. Testosterone also contributes to the initiation of sexual activity, permission and receptivity for sexual behavior, both directly and through its aromatization to estradiol. At the genital level, androgens directly modulate vaginal and clitoral physiology by facilitating smooth muscle relaxation, especially in the proximal vagina, producing distinct physiological responses to those brought about by estradiol. Finally, progesterone may indirectly influence sexual receptivity by modulating mood and cognition. Hormonal therapy (HT) including estro-androgenic preparations and tibolone has been successfully used to alleviate sexual symptoms, with noticeable results on drive, enjoyment, lubrication, ability to reach orgasm and initiation of sex. Since HT may not be the complete answer for women experiencing sexual difficulties and reduced sexual desire post-menopause, an accurate assessment and individualized management of sexual symptoms are essential in obtaining meaningful and long-lasting results. AS08.3 Tibolone versus transdermal continuous combined estrogen + progestagen in the treatment Female Sexual Dysfunction in naturally menopausal women: results from the LISA trial Susan R Davis, EA Nijland, SW Weijmar Background/objectives: The LISA study was a 24 week randomized, double blind, double dummy controlled trial to compare the efficacy on sexual function and vaginal bleeding pattern of tibolone 2.5 mg versus continuous combined transdermal E2/NETA (50 ␮g/140 ␮g) in naturally postmenopausal women with sexual dysfunction (decreased sexual desire, sexual interest or sexual arousal).

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Methods: To be included, women needed to have sexuality related personal distress assessed by the Female Sexual Distress Scale (FSDS) with a score ≥15. Overall sexual function was assessed with the self reported FSFI (Female Sexual Function Index) at baseline, week 12 and week 24. The vaginal bleeding pattern was recorded on daily diary cards. Results: 403 women with identified FSD (Female Sexual Dysfunction) were included, mean age 56. After (blinded) exclusion of the subjects with major protocol violations (35 subjects equally divided over the two study arms mostly due to serious non-compliance with the trial medication and/or failing to fulfull inand exclusion criteria) the statistical analyses showed a significantly higher increase on the total score of the FSFI in favour of the tibolone group when compared to the transdermal E2/NETA group (p = 0.025). Bleeding rates were significantly lower in tibolone group (12%) versus the E2/NETA group (50%) p < 0.001. Conclusion: In naturally postmenopausal women with sexual dysfunction tibolone improves sexual function over and above its documented ability to relieve climacteric symptoms when compared to continuous combined transdermal E2/NETA. In addition, this trial confirms the excellent bleeding profile of tibolone, which may lead to a better tolerability. Tuesday, 6 June 2006 14:15–16:15 AS09—Afternoon Symposium: Imaging techniques Organised by JW van der Slikke (The Netherlands) Abstract not available at the time of printing. Tuesday, 6 June 2006 14:15–16:15 AS10—Afternoon Symposium: Cancer Organised by Alessandra Graziottin (Italy) Abstract not available at the time of printing.

n (%)

Rate per 1000 Hazard ratio (95% Placebo woman confidence (N = 1103) (years) interval)

20 (1.8) 17 (0.8)

3.2

1.3

Raloxifene (N = 2185)

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Tuesday, 6 June 2006 14:15–16:15 FC06—Free Communication Session: Breast cancer FC06.1 Effect of Raloxifene on invasive breast cancer incidence in postmenopausal women in Europe Joaquin Calaf-Alsina1 , S Martino2 , JL Mershon3 , D Disch3 , F Marin4 , SA Dowsett3 , AR Genazzani5 1 Hospital De La Santa Creu I Sant Pau, Barcelona, Spain; 2 Angeles Clinic & Research Institute, Santa Monica, CA, USA; 3 Eli Lilly and Company, Indianapolis, IN, USA; 4 Eli Lilly and Company, Alcobendos, Spain; 5 University of Pisa, Pisa, Italy Purpose of study: Raloxifene is indicated for osteoporosis prevention and treatment in postmenopausal women (PMW) and being studied for invasive breast cancer (BC) risk reduction. The Continuing Outcomes Relevant to Evista (CORE) trial was a double-blind, placebo-controlled, 4-year follow-up to the 4-year Multiple Outcomes of Raloxifene Evaluation (MORE) trial. BC was the primary endpoint in CORE, and secondary endpoint in MORE. In the 7705 PMW from 25 countries participating in MORE only or MORE/CORE, raloxifene was associated with a 66% reduction in invasive BC incidence versus placebo. The aim of the present analysis was to assess raloxifene’s effect on invasive BC incidence in PMW with osteoporosis in Europe who participated in MORE and CORE (80 sites). Methods: Women randomized to raloxifene 60 or 120 mg/d in MORE were assigned raloxifene 60 mg/d in CORE; those randomized to placebo in MORE were assigned placebo in CORE. Time to first invasive BC was analyzed using Cox proportional hazards models. Results: Of the 3288 PMW from Europe participating in MORE, 1982 also chose to participate in CORE (placebo, 628; raloxifene, 1354). Results by treatment group for all invasive and ER-positive invasive BC cases are shown in the table: Placebo (N = 1103)

0.41 (0.21–0.77) 16 (1.5) 9 (0.4) 2.6 Invasive ER+ BC

Raloxifene (N = 2185)

All invasive BC

0.7

0.27 (0.12–0.61)

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Conclusion: With up to 8 years of follow up, raloxifene was associated with a 59% reduction in the incidence of invasive BC, and a 73% reduction in the incidence of invasive ER-positive BC in PMW with osteoporosis in Europe. These findings are similar to those for USA/Canada. FC06.2 Cromosomal changes causing breast cancer begin during adolescence: a review of the evidence Barry G Wren Sydney Menopause Centre, Australia Breast cell hyperplasia, sometimes progressing to atypia, CIS and microinvasion is a cellular disorder which begins in adolescence and pre-menopausal women. Conversion of a normal breast cell to malignancy follows a series of genetic mutations in immature stem cells which sequentially induce autonomous activation of cytoplasmic growth factors, suppression of tumour inhibitor/repair activity, voiding the apoptotic system and enhancement of telomere repair function. Invasion involves further genetic mutations in adjacent cells causing over-expression of angiogenic growth factor, inactivation of thrombospondin-1 or angiostatin and corruption of the immunoglobulins (cadherins and integrins). The process of converting a normal breast cell to cancer involves millions of mitoses, spontaneous mutations which corrupt promoters and inhibitors and take many years to achieve, From autopsy studies it is known that adolescent and young menstruating women develop hyperplasia, atypical hyperplasia and even cancer in-situ as their ductal/lobular breast cells change from immature basal (stem) cells into the mature cells capable of lactating. Although up to 50% of women have experienced several chromosomal changes by the time they reach the menopause, only a small number accumulate alterations causing invasive cancer. Undiagnosed invasive cancer is found in 1–2% of women prior to the menopause and this disease doubles every decade after the menopause. Not all corrupted cells advance to invasive malignancy because the complex defence system within breast cells and the extracellular matrix maintains the integrity of the cell in relation to its neighbour.

FC06.3 Prognosis value of PR isoforms disruption in breast cancer PA Mote1 , Anne Gompel2,3 , A Lavaur2 , D Hugol3 , CL Clarke1 1 Westmead Institute of Cancer Research, University of Sydney at Westmead Millennium Institute, Westmead Hospital, Westmead, Australia; 2 INSERM U673, AP-HP, Service de Gyn´ecologie, Paris, France; 3 Laboratoire d’Anatomie-pathologique-Hˆopital Hˆotel-Dieu, Paris, France Progesterone, while essential for normal growth and function in the human breast, is also associated with risk of breast cancer. The two progesterone receptors, PRA and PRB, are suggested to have differential functions, and although they are co-expressed at equivalent levels in normal breast, their disruption often occurs early in breast carcinogenesis, resulting in frequent predominance of one isoform. The consequences of PRA:B dysregulation on disease outcome or response to treatment are unknown, neither is it clear whether PR isoform predominance is influenced by hormonal or reproductive factors, or alters during tumor growth. The relative levels of PRA:B proteins were determined by dual immunofluorescent histochemistry in archival breast tumors (n = 138) and correlated with clinical and reproductive history and disease outcome. PRA:B expression was not modified by endogenous hormonal or reproductive history, although exogenous hormone use favored expression of PRB. Predominant expression of PRA, but not PRB, was associated with high tumor grade, indicating that isoform predominance was intrinsic to the tumor. Tumors with disrupted PRA:B expression had a significantly poorer outcome, as women with lymph node positive tumors overexpressing PRB were more susceptible to relapse and had significantly shorter disease-free survival times after chemotherapy.

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FC06.4 Influence of hormone replacement therapy on prognostic factors for breast cancer: a systematic review after the Women’s health initiative trial C Antoine, F Liebens, B Carly, A Pastijn, Serge Rozenberg Department of Obstetrics and Gynaecology, Free Universities of Brussels (VUB-ULB) CHU Saint-Pierre, Brussels, Belgium Introduction: Increased breast cancer risk has been observed in the WHI study evaluating (0.625 mg CEE + 2.5 mg MPA) versus placebo, but not using CEE only. On the other hand, many observational studies reported lower mortality in HRT users than in non users. This has been attributed, to earlier diagnosis and to better prognosis. Nevertheless, more advanced disease was reported, by the WHI in CEE + MPA users. Objectives: To review systematically whether the data of the WHI are in contradiction with observational data. Material and methods: We selected 25 studies, for which we evaluated the methodology, the characteristics of the populations, risk and prognostic factors. Results: The WHI study, showed a worsening of breast cancer prognosis, and is in contradiction with most observational studies. This difference may be attributed to the fact that the WHI refers only to one HRT regimen and was studied in older women. On the other hand, most observational studies are retrospective and not well matched. Their methodology and selection criteria varied and the sample sizes were small. No differences in the distributions of histology, grade or steroid receptors were observed in the WHI trial, while this was the case in some observational studies. Other parameters (S Phase, protein Neu, Bcl-2 gene, protein p53 and E-Cadherin, Cathepsin D) were not reported in the WHI trial. Conclusion: In view of these data, the current clinical message to patients should be changed: one can no longer declare that breast cancers developed using HRT are of better prognosis.

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FC06.5 Treatment of menopausal symptoms after breast cancer: a systematic review C Antoine, S Neusy, F Liebens, B Carly, A Pastijn, Serge Rozenberg Department of Obstetrics and Gynaecology, Free Universities of Brussels (VUB-ULB) CHU Saint-Pierre, Brussels, Belgium Introduction: Many breast cancer survivors (BCS) will live through menopause and suffer from it even more so than other women. The seek of an effective and safe strategy to alleviate their climacteric symptoms has become essential. This systematic review analyses the safety of medications commonly used to alleviate menopausal symptoms in BCS. Material and methods: We selected 22 studies focusing on safety of drugs in BCS and evaluated the methodology, the characteristics of the populations, potential sources of bias and the consequences of treatment on disease evolution. Results and discussion: About half of the studies are retrospective. Only a restricted number of patients were actually using HRT in most of these trials rendering most of these studies underpowered. Heterogeneity in methodology, selection criteria, type of HRT and tamoxifen use characterise these trials. Most observational studies and the Stockholm Trial concluded that HRT had no negative influence on breast cancer prognosis in opposition to the HABITS’ results, which reported increased breast cancer events using HRT. Very few data are actually available about the absence of harm of the other molecules used to alleviate menopausal symptoms in BCS. They lack considerably power to detect any differences in breast cancer recurrence or mortality. Conclusions: We have currently no reassuring data about the effects of drugs commonly used to alleviate climacteric symptoms in BCS. When prescribing drugs, physicians should inform patients about the absence of safety data, and a safety registration data base should be created.

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FC06.6 Effects of hormonal treatments on PR isoforms expression and on two PR target genes (ERa; and bcl-2) in breast cancer cell lines A Courtin2 , C Buet2 , N Roullet2 , P Forgez2 , Anne Gompel1,2 1 APHP , Hotel-Dieu de Paris and Universit´ e Paris V, France; 2 INSERM U673 Hopital Saint Antoine. France The risk of breast cancer is the major concern with HRT. The risk might vary according to the progestin (natural or synthetic). The action of steroids depends on the ratio of their receptors. The ratio of progesterone receptor isoforms (PR-A and PR-B) is 1 in normal human breast epithelial cells whereas this ratio is disrupted in some cases of human breast cancer. To know if E2 and some progestins (progesterone, Org2058, MPA, NETA, tibolone) could modulate PR isoforms levels and two PR target genes (bcl-2 and ERa;), we studied their pharmacological profile in T-47D, MCF-7 and BT-474 breast cancer cell lines. In MCF-7 and BT 474 cells, E2 restored the PRA/B ratio to 1. The magnitude of the Ps effects on PR isoforms levels varied according to their pharmacological characteristics but also to the studied cell line. E2 decreased ERa; level whereas the pure Ps did not alter it in T-47D and BT-474. Ps with some estrogenic effects and combined treatments (E2+Ps) decreased ERa; to various extents according to the cell line. Tibolone was the most potent inhibitor. The hormonal bcl-2 regulation was similar to our previous results. Nevertheless, bcl-2 inhibition by Ps was weaker in cells with a strong ERa; expression. Conclusions: Ps act on PR isoforms level according to their structure and to the phenotype of the target cell. E2 increased both isoforms but preferentially PRA. Bcl-2 inhibition by progestins was less important in ERa; enriched cells. Progesterone combined with E2 was a mild progestin.

FC06.7 Do lower doses of estrogen have a less effect on breast tissue? Cemal Tamer Erel, LM Sent¨urk, MH Yilmaz, G Esen, ¨ Gelen, S Kaleli, H Seyisoglu, E Oral, S Sahmay, O E Ert¨ungealp Istanbul University Cerrahpasa School of Medicine, Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology, Istanbul, Turkey Objective: We have aimed to test the hypothesis that lower doses of estrogen in certain types of HRT regimens may have a less effect on mammographic density increase. Materials and methods: In this retrospective study, we included 24 women receiving 1 mg 17␤-estradiol plus NETA and 17 women 2 mg 17␤-estradiol plus NETA. We confirmed that all the women included into the study were in menopausal state by taking their history, performing clinical examination and detecting serum E2 and FSH levels. Two senior radiologists, independently, compared their initial (before starting HRT) and the last (still on HRT) mammographies and classified them according to the BIRADS system. One-way ANOVA was used for statistical analysis. Results: The average age was found to be significantly higher in women receiving 2 mg 17␤-estradiol plus NETA. Serum E2 and FSH levels and BMI scores were comparable. Duration of HRT use was significantly longer in women using 2 mg 17␤-estradiol plus NETA. Mammographic density increase between the initial and last mammograms was not significant in both groups of women using different doses of estrogen. However, women using 2 mg 17␤-estradiol plus NETA had less dense breast parenchyma (p = 0.033). In addition, the number of women who had their BIRADS scores increased was not different between two groups (one woman (4.2%) in the 1 mg 17␤-estradiol plus NETA group, and five women (29.4%) in the 2 mg 17␤-estradiol plus NETA group) (p > 0.05). In a woman who had been using 1 mg 17␤-estradiol plus NETA for the last 4 years and had her BIRADS score increased, breast cancer was diagnosed. Conclusions: This retrospective study has shown that different doses of estrogen in certain types of HRT did not have an important effect on mammographic density increase. That is to say, lower doses of estro-

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gen do not necessarily mean a less density increase in the breast parenchyma. Table 1 Characteristics of women in the two groups are summarized

Age (years) BMI (kg/m2 ) Duration of HRT E2 (pg/mL) FSH (IU/mL) Initial BI-RADS Last BI-RADS Density increase n (%)

1 mg 17␤E + NETA (n = 24)

2 mg 17␤E + NETA (n = 17)

52.50 ± 3.41 27.31 ± 4.15 46.75 ± 27.06 31.00 ± 11.91 55.04 ± 25.83 2.29 ± 0.75 2.29 ± 0.75 1 (4.2%)

56.12 ± 5.36 27.87 ± 5.89 71.29 ± 43.42 27.18 ± 8.08 62.00 ± 23.53 1.82 ± 0.53 2.12 ± 0.70 5 (29.4%)

Tuesday, 6 June 2006 14:15–16:15 FC07—Free Communication Session: Cardiovascular disease II FC07.1 Effects of intranasal versus oral hormone therapy on asymmetric dimethylarginine in healthy postmenopausal women: a randomised study Marieke O Verhoeven1 , M Hemelaar1 , T Teerlink2 , P Kenemans1 , MJ van der Mooren1 1 VU University Medical Center, Department of Obstetrics and Gynaecology, Amsterdam, The Netherlands; 2 VU University Medical Center, Department of Clinical Chemistry, Amsterdam, The Netherlands Objectives: To compare the effect on asymmetric dimethylarginine (ADMA), an inhibitor of nitric oxide synthase and independent risk factor for coronary heart disease, between intranasal and oral 17b-oestradiol (E2) combined with norethisterone (acetate) (NET(A)) administration in postmenopausal women. Methods: In two centres, a randomised, doubleblind, comparative study was conducted in which 90 healthy postmenopausal women (age 56.6 ± 4.7 years) received daily continuous combined intranasal E2/NET 175 ␮g/275 ␮g (n = 47) or oral E2/NETA 1 mg/0.5 mg (n = 43) for 1 year. At baseline, week 12 and 52, plasma concentrations of ADMA, arginine and symmetric dimethylarginine (SDMA) were measured by high-performance liquid chromatography.

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Results: Oral E2/NETA reduced ADMA concentrations (−7.4%; 95% confidence interval (CI) −10.4 to −4.4%), while intranasal E2/NET had no effect (−0.8%; 95% CI −3.7 to 2.1%) after 52 weeks. In both groups, arginine was transiently decreased compared to baseline at week 12 (intranasal: −6.1%; 95% CI −9.1 to −3.0%; oral: −6.5%; 95% CI −10.9 to −2.1%). Only oral E2/NETA reduced SDMA concentrations. Conclusions: Oral administration of E2/NETA reduced ADMA and SDMA concentrations, whereas intranasal administration did not. Both treatments transiently reduced arginine. The decrease in ADMA by oral oestrogens could be a key phenomenon in the modulation of nitric oxide synthesis by postmenopausal hormone therapy. FC07.2 Effects of isoflavones combined with Actaea racemosa L. on coronary heart disease risk markers: a randomised, placebo-controlled, study in menopausal women Marieke O Verhoeven1 , T Teerlink2 , P Kenemans1 , SD Zuijdgeest-van Leeuwen3 , MJ van der Mooren1,3 1 VU University Medical Center, Department of Obstetrics and Gynaecology, Amsterdam, The Netherlands; 2 VU University Medical Center, Department of Clinical Chemistry, Amsterdam, The Netherlands; 3 Numico Research BV, Wageningen, The Netherlands Objective: To investigate the effects of a supplement containing soy isoflavones and Actaea racemosa L. on plasma concentrations of asymmetric dimethylarginine (ADMA) and serum concentrations of lipids and Creactive protein (CRP) in menopausal women. Methods: In a multi-centre, double-blind study, 124 healthy menopausal women were randomised to receive daily either placebo (n = 64) or a soy isoflavones and Actaea racemosa L. containing supplement (n = 60) for 12 weeks. Fasting blood samples were collected at baseline and week 12. Results: In the supplement group total cholesterol and low-density lipoprotein cholesterol showed a small reduction at week 12 (−0.2 ± 0.5 mmol/L; p = 0.02 and −0.2 ± 0.5 mmol/L; p = 0.01, respectively). Concentrations of ADMA, triglycerides, lipoprotein(a) and CRP did not significantly change. ANCOVA over the 12-week study period revealed no significant betweengroup differences for all parameters. No significant correlations were found between the plasma isoflavones

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concentrations and the concentrations of the cardiovascular risk markers investigated. Conclusion: Twelve weeks administration of a supplement containing soy isoflavones and Actaea racemosa L. had little or no influence on the coronary heart disease parameters studied. This supplement probably has neither protective nor adverse effects on the cardiovascular system, however, large long-term studies are needed to confirm this. FC07.3 Effects on asymmetric dimethylarginine (ADMA) of HMR 3339, a novel SERM: a randomised, placebo-controlled, double-blind study in healthy postmenopausal women Marieke O Verhoeven1 , T Teerlink2 , P Kenemans1 , TE Vogelvang1 , MJ van der Mooren1 1 VU University Medical Center, Department of Obstetrics and Gynaecology, Amsterdam, The Netherlands; 2 VU University Medical Center, Department of Clinical Chemistry, Amsterdam, The Netherlands Objective: To investigate the short-term effects of three different doses of the novel oestrogen receptor modulator HMR 3339 in comparison with raloxifene and placebo on the nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA), an independent risk factor for coronary heart disease. Methods: In a multi-centre, randomised, placebocontrolled, double-blind, dose-ranging study 94 healthy postmenopausal women received daily placebo (n = 16), HMR 3339 2.5 mg (n = 20), HMR 3339 10 mg (n = 19), HMR 3339 50 mg (n = 20), or raloxifene 60 mg (n = 19) for 12 weeks. Fasting plasma concentrations of ADMA, arginine, and symmetric dimethylarginine (SDMA) were measured at baseline and after 4 and 12 weeks by high-performance liquid chromatography. Results: ANCOVA over the 12-week study period showed significant reductions in ADMA concentrations in the HMR 3339 50 mg group versus placebo (p < 0.01). A reduction was observed in SDMA in all the active treatment groups compared with placebo: HMR 3339 2.5 mg: −8.8% (95% confidence interval (CI) −15.9 to −1.7%); HMR 3339 10 mg: −11.7% (95% CI −19.7 to −3.8%); HMR 3339 50 mg: −16.2% (95% CI −22.4 to −10.0%); raloxifene 60 mg: −7.2% (95% CI −14.1 to −0.2%). Arginine did not change over time in any of the treatment groups versus placebo.

Conclusions: HMR 3339 50 mg reduced both ADMA and SDMA concentrations significantly. The implication of these effects for CHD risk is unclear. FC07.4 The effect of hormone replacement therapy on arterial stiffness Chun Ng1 , R Schiff2 , N Panay1 , C Bulpitt2 , C Rajkumar2 1 Queen Charlotte’s and Chelsea Hospital, London, UK; 2 Hammersmith Hospital, London, UK Introduction: Arterial function measurements are increasingly being used as surrogate markers of cardiovascular disease. It has been shown that an increase in the arterial stiffness is an independent marker of cardiovascular risk. HRT was, until recently, promoted to reduce the risk of cardiovascular disease. However, recent randomised prospective studies have shown no cardiovascular benefit. The present study was conducted to assess the effect of HRT on arterial stiffness, hence the potential risk for cardiovascular disease. Methods: Two studies were performed. Each was a 6 months randomised, double-blind, placebocontrolled, cross-over study using either transdermal 17-␤ oestradiol-only or continuous oestradiol/levonorgestrel. Arterial stiffness was assessed by pulse wave velocity (PWV); and systemic arterial compliance (SAC), measured by simultaneous recording of aortic flow and carotid artery pressure. The principle of PWV is that the pulse pressure wave generated by ventricular ejection is propagated along the arterial tree at a speed determined by the geometric and elastic properties of the arterial wall. Results: Twenty patients completed oestradiol-only trial. SAC improved in the oestradiol group at 6 weeks (0.95 ± 0.6 versus 0.75 ± 0.4, p = 0.056) but not maintained at 12 weeks (0.76 ± 0.5 versus 0.70 ± 0.4, p = 0.532). Carotid-femoral PWV showed improvement in the oestradiol group at 12 weeks (12.1 ± 1.8 versus 12.8 ± 2.1, p = 0.035). In the combined HRT, 17-patients completed the trial. Carotid-femoral PWV showed improvement after 12 weeks (9.48 ± 1.79 versus 8.89 ± 1.19, p = 0.037), the carotid-radial PWV showed non-significant improvement after 12 weeks (10.85 ± 2.07 versus 10.19 ± 1.42, p = 0.177). Conclusion: Short term HRT resulted in a reduction in central arterial stiffness but have no effect on the muscular/peripheral arteries.

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FC07.5 Lipids and women in early and physiological menopause Ljiljana Marina, S Vujovic, Z Penezic, M Stojanovic, M Ivovic, N Drezgic Institute of Endocrinology, Department for Reproductive Endocrinology, Belgrade, Serbia & Montenegro Abnormal lipid levels are important risk factors for developing cardiovascular diseases. The objective of this study was to compare the total cholesterol, high density cholesterol (HDL), low density cholesterol (LDL) and triglycerides in women in early menopause with women in physiological menopause. We evaluated 184 women prior to the hormone replacement therapy or lipid lowering therapy. They were divided in two groups. 1st group: 151 women, mean age 50.90 ± 4.91 years, mean BMI 26.44 ± 4.85 kg/m2 , with laboratory proven menopausal levels of FSH and LH. 2nd group: 33 women, mean age 34.39 ± 7.78 years, mean BMI 23.01 ± 3.25 kg/m2 , with laboratory proven premature ovarian failure. Statistical analysis was performed with Mann–Whitney’s U-test. Mean age of entering physiological menopause in the 1st group was 46.88 ± 3.79 years and in the 2nd group was 28.21 ± 7.03 years. Mean total cholesterol level in the 1st group was 6.10 ± 1.29 nmol/L versus 5.35 ± 0.91 nmol/L in the 2nd group. Mean triglyceride level was 1.65 ± 0.86 nmol/L in the 1st group versus 1.19 ± 0.38 nmol/L in the 2nd group. The difference between the total cholesterol, LDL and triglyceride levels in the tested groups was highly significant, p < 0.01. There was no significant difference between the level of HDL among the tested groups, p > 0.05. According to our study women in physiological menopause have much higher risk of developing cardiovascular diseases than women in early menopause. FC07.6 Obesity and risk of venous thromboembolism among postmenopausal women: differential impact of hormone therapy by route of estrogen administration: the ESTHER study Marianne Canonico, PY Scarabin Inserm, Cardiovascular Epidemiology Unit 780, Villejuif Cedex, France Context: Oral estrogen use and elevated Boby-Mass Index (BMI) increase the risk of venous thromboem-

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bolism (VTE). Recent data suggest that transdermal estrogen might be safe with respect to thrombotic risk. However, the impact of the transdermal estrogen on the association between overweight (BMI > 25 kg/m2 ) or obesity (BMI > 30 kg/m2 ) and the VTE risk has not been investigated. Methods: We did a multicenter case-control study of VTE among postmenopausal women aged 45–70 years, between 1999 and 200, in France. Case population consisted of women with a first documented idiopathic VTE. We recruited 253 cases (191 hospital cases and 62 outpatient cases) matched with 597 controls (416 hospital controls and 181 community controls). Results: The odds ratio for VTE was 2.5 (95% CI: 1.7–3.7) for overweight and 3.9 (95% CI: 2.2–6.9) for obesity. Oral, not transdermal, estrogen was associated with an increased VTE risk (OR = 4.5; 95% CI: 2.6–7.7 and OR = 1.1; 95% CI: 0.7–1.7, respectively). Compared with non-users with normal weight, the combination of oral estrogen use and overweight or obesity enhanced further the VTE risk (OR = 10.2; 95% CI: 3.5–30.2 and OR = 20.6; 95% CI: 4.8–88.1, respectively). However, transdermal users with increased BMI had similar risk as non-users with increased BMI (OR = 2.9; 95% CI: 1.5–5.8 and OR = 2.7; 95% CI: 1.7–4.5, respectively, for overweight; OR = 5.4; 95% CI: 2.1–14.1 and OR = 4.0; 95% CI: 2.1–7.8, respectively, for obesity). Conclusion: In contrast to oral estrogen, transdermal estrogen does not confer additional risk of idiopathic VTE on women with increased BMI. The safety of transdermal estrogen on thrombotic risk has to be confirmed. FC07.7 Phytoestrogens supplementation and clinical cardiovascular risk factors: a placebo controlled studyin overweight postmenopausal women Myl`ene Aubertin-Leheudre, C Lord, A Khalil, IJ Dionne Research Centre on Aging of Sherbrooke, Canada Menopause is recognised to change body composition and increase cardiovascular risk factors. Hormonal replacement therapy (HRT) has been shown to counteract these deleterious changes. However, since the Women’s Health Initiative study, the use of HRT has become controversial. Moreover, several studies

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have shown that phytoestrogen treatment may decrease menopausal symptoms, cholesterol levels and increase bone density. The aim of this study was to verify the effect of 6 months of phytoestrogens supplementation on clinical cardiovascular risk factors in overweight postmenopausal women. Fifty-six overweight postmenopausal women without medication which could influence lipid or glucose metabolism were recruited. Women were randomly assigned to two groups (phytoestrogens versus placebo) and ingested 75 mg/day of isoflavones or a placebo during 6 months. Fat mass and visceral fat mass was measured by DXA, biochemical parameters (lipid profile, insulin sensitivity index, CRP), resting (indirect calorimetry) and total (accelerometry) energy expenditure and energy intake (3× 24 h recalls) were also obtained. No difference was found between the two groups at baseline for any of the variables and no treatment effect was found We observed that 6 months of phytoestrogens did not alter clinical cardiovascular risk factors in overweight postmenopausal women to a greater extent than a placebo. Nevertheless, it is possible that because our population did not present metabolic problems this prevented significant changes. Moreover, 6 months of treatment may not have been enough to observe a change. Further study could also explore a possible interaction of phytoestrogens with exercise or dietary intervention. Tuesday, 6 June 2006 14:15–16:15 FC08—Free Communication Session: Pre- and perimenopause FC08.1 Management of women with premature ovarian failure (POF) at a main teaching hospital Etienne Horner, A Kay, N Panay Queen Charlotte’s & Chelsea Hospital, Department of Gynaecology, London, UK Objective: To update clinicians as to the management of premature ovarian failure. Background: Approximately 1% of women in the general population have premature ovarian failure (POF). In most instances the etiology is unknown. Known causes include genetic aberrations, autoimmune ovarian damage, environmental factors and iatrogenic causes (surgical, radiotherapeutic or chemotherapeutic interventions).

Design: Review of referrals and consensus building amongst gynaecologists, oncologists and haematologists with a special interest in women with premature ovarian failure. Results: Over the last 24 months we have seen 80 women with POF in our department. of these women, 21 were aged under 35 years and 9 women were aged under 30 years. We have divided the patients in our review into idiopathic (n = 52), oncological (n = 21) and haematological (n = 7) causes. Conclusion: Young women with POF experience pathologically high FSH levels with low serum E2 levels. Physiological replacement of ovarian steroid hormones is indicated until the age of normal menopause. Clinicians need to be sensitive to the many emotional aspects of this condition, both at the time of diagnosis and during subsequent management. FC08.2 The climacteric syndrom—a comparison between young and old Christine Bodmer-Hindermann1 , C Limoni2 , K Tschumi1 , M Birkh¨auser1 1 Department of Obstetrics & Gynecology, University of Bern, Switzerland; 2 Biostatistik, Riva San Vitale, Switzerland It is well known, that the climacteric syndrome is a typical phenomenon of the perimenopausal woman. It can be documented with the “Green Climacteric Scale”. The aim of this study was to evaluate the incidence of this syndrome in a group of young women and at the same time to compare with an older perimenopausal population. Nine hundred young women from various consultations of the department of Gynaecology (general outpatient clinic, division of gynaecological endocrinology and family planning) as well as 760 older women of our menopause – centre received a questionnaire – the modified “Greene Climacteric Scale” with the request to fill it in and to return it anonymously. The realization of this survey was accepted by the ethical committee of Bern. Two hundred and ninty five young women with an average age of 28 years as well as 339 perimenopausal women with an average age of 55 years did fill in and return the questionnaire anonymously. The following symptoms were noticed by the young and by the older women more ore less frequently and without signif-

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icant difference: feeling tense or nervous, excitable, difficulty in concentrating, feeling tired or lacking in energy, loss of interest in most things, feeling unhappy or depressed, feeling dizzy or faint, headaches, impression that life is senseless and a rising tendency to brood. Crying spells and irritability are significantly more frequent in young women. The remaining symptoms like hot flushes, sweating at night, heart beating quickly or strongly, difficulty in sleeping, attacks of panic, breathing difficulties, muscle and joint pains, loss of interest in sex, depressions, dry mucosae, urge symptoms, loss of feeling in hands or feet, parts of body feel numb or tingling as well as pressure or tightness in head or body were significantly more frequent in older women. The so-called typical perimenopausal symptoms can occur already in young years. Therefore it is possible to find questions in the Green climacteric Scale, which we shouldn‘t assign specifically to the menopause. FC08.3 Fragile X premutation screening in Romanian women with premature ovarian failure Daniel Tutunaru1 , L Savu2 , MC Dumitrascu3 1 Elias Emergency Hospital, Bucharest, Romania; 2 Genetic Lab Center, Bucharest, Romania; 3 Universitary Emergency Hospital, Bucharest, Romania Premature ovarian failure (POF) is usually defined as menopause before the age of 40 years and occurs in 1% of women. Fragile X (FRAXA) permutation carriers have an increased risk of POF. Aim: To assess the prevalence of FRAXA permutation between genetic causes of POF in Romanian women showing premature menopause. Methods: Prospective, multicentric, 3 years study. Inclusion criteria: phenotipically normal females with cesasion of menses before 40 years, 46XX karyotype. Exclusion criteria: ovarian surgery, chemotherapy, autoimmune affections. We have screened 164 women with premature ovarian failure for fragile X (FRAXA) premutations. Results: There were two cases of family history of mental retardation. Six from of 45 (13%) pedigrees with the familial POF and five from 119 (4.2%) of women with the sporadic form of premature ovarian failure have FRAXA permutations, which is statistically significantly higher than expected in the general

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Caucasian population with an expected prevalence of 1:590. Conclusion: The study has confirmed the link between FRAXA premutation and the pathogenesis of POF. FRAXA screening can be valuable in predicting POF and in the identification of families at risk of transmitting fragile X syndrome. FC08.4 Premature ovarian failure and metabolic syndrome X Svetlana Vujovic, M Stojanovic, Z Penezic, M Ivovic, M Miletic, B Barac, L Marina, M Drezgic Clinical Center of Serbia, Institut of Endocrinology, Department of Gynecological Endocrinology, Beograd, Serbia & Montenegro Premature ovarian failure (POF), as hypoestrogenic status, can increase the preva- lence of the metabolic syndrome X (glycosae intolerance, insulin resistance, central obesity, dislipidaemia, hypertension). Aim: To test the prevalence of the metabolic syndrome X in POF. SUBJECTS: 96 women with POF: (I) 1 year of amenorrhoic period; (II) 2–5 years; (III) 6–10 years; (IV) more than 10 years. They were not on hormone replacement therapy. Methods: Body mass index (BMI), weist/hip, biochemical analysis (glycosae, cholesterol, HDL, LDL, triglyceride) and OGTT were performed. Statistics: Mann–Whitney test, HOMA, Spearman. Results: BMI: (I) 21.28 + 2.53 kg/m2 ; (II) 24.94 + 3.00 kg/m2 ; (III) 25.33 + 2.93 kg/m2 ; (IV) 26.00 + 2.94 kg/m2 . Triglycerides: (I) 1.09 + 0.31; (II) 1.60 + 0.70; (III) 1.35 + 0.68; (IV) 1.51 + 0.44. Significant difference were found between: I and II group for: BMI p < 0.01 and triglycerides p < 0.01); I and III group for: BMI p < 0.01; I and IV group for: BMI (p < 0.01), TR (p < 0.05), glycaemia in 60 min; (5.07 + 2.22 versus 6.61 + 1.86, p < 0.05), 90 min; (4.98 + 1.44 versus 6.27 + 1.43, p < 0.05) 120 min; (4.40 + 0.77 versus 5.33 + 1.24 mmol/L, p < 0.05) and insulin 0 min (10.55 + 3.54 versus 14.30 + 5.30 pmol/L, p < 0.05). Many significant correlations between parameters were found in every group. Conclusion: Even some metabolic changes were observed no metabolic syndrome X was found in POF.

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FC08.5 The impact of hormone therapy and herbal remedies for menopause symptoms on sleep quality: the HALT Trial Katherine Newton1,2 , S Reed1,2 , L Grothaus1 , K Lee3 , K Ehrlich1 , A LaCroix1,2 1 Center for Health Studies, Group Health Cooperative, Seattle, USA; 2 University of Washington, School of Public Health and Community Medicine, Seattle, USA; 3 School of Nursing, University of California, San Francisco, USA Objective: Test the impact of three herbal regimens, hormone therapy, and placebo on sleep quality. Methods: Randomized, controlled trial, Washington state, USA. Participants were 351 women, age 45–55, with >2 vasomotor symptoms/day. Women were randomly assigned to: (1) black cohosh (160 mg daily); (2) multibotanical with black cohosh (200 mg daily) and nine other ingredients; (3) multibotanical plus dietary soy counseling; (4) conjugated equine estrogen 0.625 mg + medroxyprogesterone acetate 2.5 mg daily (HT); or (5) placebo. Main outcomes, measured by self report at baseline, 3, 6, and 12 months, were a nine-item sleep disturbance scale (SDS), number of nighttime awakenings, and a one-item sleep quality measure (1 = very poor to 5 = very good). Results: At 3 months, the SDS decreased 13% with black cohosh, 10% with multibotanical, and 12% with multibotanical plus soy, versus 6% with placebo and 32% with HT (global test for herbs and placebo p = 0.72; HT versus placebo p = 0.3). Number of nighttime awakenings decreased 20% with black cohosh, 2% with multibotanical (p = 0.01 versus placebo), and 31% with multibotanical plus soy, versus 26% with placebo and 51% with HT (global test for herbs and placebo p = 0.02; HT versus placebo p = 0.39). Effects on sleep quality were not significant (p = 0.90 for herbs, p = 0.32 for HT versus placebo). No significant effects were found on any outcome at 6 or 12 months. Conclusions: Hormone therapy lessened sleep disturbances and nighttime awakenings at 3 months but not with longer follow up. Herbal remedies had no effect on sleep quality.

FC08.6 The impact of total hysterectomy (with or without oophorectomy) on the sexual steroids plasma levels and ovarian circulation Decebal Hudita1,2 , A Ursuleanu1,2 , M Russu1,2 , S Nastasia1,2 1 ‘Carol Davila’ University of Medicine and Pharmacy, Bucharest, Romania; 2 Department of Obstetrics and Gynecology, Clincal Hospital ‘Dr. I. Cantacuzino’, Bucharest, Romania Objectives: To assess the effect of the hysterectomy on the plasma levels of the sexual steroids and ovarian circulation. Methods: The plasma levels of the sexual steroids (estradiol, total testosterone and DHEAS) were evaluated in patients which undergone hysterectomy (with or without ovarian conservation) before the procedure and after 48 h. We also assessed the ovarian circulation by Doppler sonography in ovarian arteries before an after total hysterectomy with ovarian conservation. In all cases the hysterectomies were performed for benign uterine pathology or for malignancies without preoperative radiotherapy. The results were analyzed with respect to the patients’ age, menopausal status and body mass index. We concluded that total hysterectomy with ovarian conservation have an appreciable impact on the endocrine ovarian function in premenopausal women. The changes in ovarian arteries Doppler velocimetry might be associated and explain these effects. It can be concluded, also, that in postmenopausal women ovaries remain an important source of androgens. This finding could be an argument for changing the current practice of oophorectomy in all cases of postmenopausal women. Wednesday, 7 June 2006 08:30–09:00 KL07—Keynote Lecture Forever young: are stem cells a possibility? Kutluk Oktay Weill Medical College of Cornell University, The Center for Reproductive Medicine and Infertility, New York, USA Philosophers have searched for the meaning and origin of life from the beginning of conscious times. Just like all complex living beings have all emerged from a

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single cell over the history of our planet, we all emerge from essentially a single “stem cell”. A limited number of multipotential cells in an embryo eventually lead to us. What is aging then? In addition to the preexisting hypotheses on the mechanism of aging, more evidence is emerging on the role of stem cells on this physiological process. Recent evidence suggests aging of stem cells in reproductive and hematopoietic systems. On the reproductive side, recent rodent studies suggested the possibility of the existence of germline stem cells in adult females, and localized these cells to bone marrow. In rodent studies, bone marrow transplantation restored primordial follicles to ovaries devoid of germ cells. In a clinical parallel, we have observed spontaneous pregnancies in a postchemotherapy menopausal patient after we transplanted her cryopreserved ovarian tissue underneath her skin. The latter finding prompted the hypothesis that ovarian transplantation may potentially provide endocrine signals, which may enable germline stem cell recruitment from an unknown niche. Is reproductive aging, in fact all of aging, is due to malfunction of adulthood stem cells? Does aging begin when essentially a system can no longer efficiently regenerate its stem cells? Can stem cells be induced into regeneration to remain forever young? Future research in this century may bring exiting and shocking answers to these provocative questions. Wednesday, 7 June 2006 09:00–09:30 KL08—Keynote Lecture Mechanisms of ovarian failure Sophie Christin-Maitre France Abstract not available at the time of printing. Wednesday, 7 June 2006 10:30–12:30 S09—Symposium: Osteoporosis S09.1 Treatment of osteoporosis: whom, when and how to treat? Mithat Erenus Marmara University, Obstetrics and Gynecology Department, Reproductive Endocrinology and Infertility Unit, Turkey

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Osteoporosis is a public health problem affecting 200 million people worldwide. Thirty percent to 50% of women and 15–30% of men will suffer a fracture related to osteoporosis in their lifetime. Fractures increase morbidity and mortality and impose a financial burden on the community. Osteoporosis is a condition characterized by microarchitectural deterioration of bone tissue leading to decreased bone mass and bone fragility. Bone is remodelled throughout adult life by discrete remodelling units of osteoclasts and osteoblasts. In old age the volume of bone resorbed is greater than the volume replaced in each remodelling unit. In women the rate of remodelling and the negative bone balance increases after menopause. In both women and men, the imperative to intervene pharmacologically incrases with age, as fracture risk incrases exponentially. There is high level of evidence for the anti fracture efficacy of treatment in women with osteoporosis particularly if there is prevalent fracture, the evidence is less compelling for women with osteopenia with or without a fracture. The rigorously investigated drugs reported to reduce vertebral fractures are the biphosphanates alendronate and risedronate, the SERM, raloxifene, the anabolic agent PTH and most recently, strontium ranelate. Only the two biphosphanates and Hormone Treatment have been reported to reduce hip fractures in community-dwelling women and Calcium plus Vitamin D have been reported to reduce hip fractures in elderly people in institutions. HT is not recommended in women for fracture risk reduction alone. Who should be treated and when? In an ideal world in which drugs were 100% efficacious, 100% safe and cost free and patients were 100% compliant, treating everyone could be logical. As this is not the case the most important factor determining whom and when to treat is an individials absolute risk of fracture. If the risk is 2 per 1000 women per year, and a drug halves fracture risk, then one event is prevented, one women will sustain a fracture despite treatment, and 998 who wre not going to have a fracture anyhow had treatment. If the absolute risk is higher, say 2 per 100 women per year again one fracture is prevented but only 99 women are treated. Over 3–5 years of treatment, this equates to a number needed to treat (NNT) to prevent a fracture of 20–25 women, a figure commonly accepted for treatments designed to reduce adverse outcomes in illnesses such as hypertension and hyper-cholesterolaemia. Thus

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knowledge of an individual’s absolute risk is central to making treatment decisions. The absolute risk of fracture depends upon age and life expectancy as well as the current relative risk. In general remaining lifetime risk of fracture increases with age up to the age of 70 years. Thereafter probability plateaus and then decreases since the risk of death with age outstrips the increasing incidence of fracture with age. The ability of BMD to predict fracture is comparable to the use of blood pressure to predict stroke and beter than serum cholesterol to predict myocardial infarction. Accuracy is improved by site specific measurements so that for hip fracture measurements made at the hip. The highest gradient of risk is found at the hip to predict hip fracture where the gradient of risk is 2.6. Thus an individual with a T score of −3 S.D. at the hip would have a 2.6 or greater than 15 fold higher risk than an individual with a T score of 0 S.D. Age contributes to risk independently of BMD. It would be predicted that hip fracture risk might increase four-fold between ages of 50 and 80 years. In reality for hip fracture the risk increases 30-fold, indicating that changes in age are seven-fold more important rhan changes in BMD. It also indicates the independent value of assesing age. Many clinical risk factors for osteoporotic fracture have been reported. A series of recent meta analyses from population based cohorts has shown consistency for low body mass index, a prior history of fracture, a family history of hip fracture, smoking, high intake of alcohol and rheumatoid arthiritis. Intervention thresholds: of all osteoporotic fractures hip fracture confers the greatest morbidity and economic consequences and has been the subject of much research. When hip fracture alone is considered a 10year hip fracture probability of 10% or more is a cost effective threshold for women in Sweden or the UK. When account is taken of other fractures, the threshold for hip fracture probability at which interventions become cost effective decreases. For example, at the age of 50 years the 10-year probability of hip fracture at which intervention becomes cost effective is 1.1 (RR: 3.8). The reason that the threshold probability is lower at younger ages is that many fractures other than hip fractures are contributing to the calculation of cost effectiveness. These thresholds for intervention correspond to a BMD value that lies between −2 and −3 S.D. over all ages (in the absence of other risk factors), it is evident that the consideration of multiple risk

factors improves risk stratification of individuals and enhances a case finding strategy. The interrelationship between BMD, age and a single independent clinical risk factor is now established. The desirable measurement to determine intervention thresholds is 10 years probability of fracture. Many treatments can be given to men and women where hip fracture probability over 10 years ranges from 1 to 10% depending on age. S09.2 Cost-effectiveness in osteoporosis David H Barlow Professor of Reproductive Medicine, University of Glasgow, UK In the management of osteoporosis the primary goal is the prevention of fracture. There is international recognition that the effectiveness of osteoporosis drug interventions must be based on fracture prevention data and not on bone density outcomes. On that basis the strongest evidence base relates to the use of bisphosphonates but there are useful fracture studies involving strontium, raloxifene, PTH and HRT. With the information on the drug costs as well as the effectiveness of the drug interventions it is then possible to begin to understand the cost-effectiveness of the different drugs. This can be expressed as the cost for a specific drug to achieve prevention of one fracture. In studies of this kind the usual method of reporting the cost-effectiveness has been to quote the cost per fracture averted and the sort of standards applied has been to ask if a drug can achieve a cost-effectiveness around £20,000 per fracture averted. This approach provides valuable comparison between drug options but does not permit the cost-effectiveness to be weighed against other competing health interventions. Those who want to compare health interventions across disease areas usually ask that cost-effectiveness be expressed in more comprehensive terms and that impact of quality of life by fracture being prevented is considered. The more comprehensive approach demands that the cost burden of the fractures prevented is considered as well as an indicator of the difference in quality of life over time in a person who sustains a fracture. In terms of the cost burden of osteoporotic fracture the hip fracture is well recognised to be the most important clinical event but there is increasing evidence that the cost burden of clinical vertebral fracture is also important and more significant than was previously recog-

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nised. The extent to which the cost burden of vertebral fracture is recognised internationally varies substantially. Once the treatment costs and costs of fracture management etc have been calculated for a population of patients it is necessary to consider the change in quality of life resulting from fracture so that the cost per quality adjusted life year can be computed. This then permits comparison across health interventions in different diseases. The cost effectiveness expressed in these terms is usually asked to achieve a cost of around £20,000–£30,000 per QALY with the general philosophy that drugs providing benefit at this level of cost-effectiveness are well justified against competing priorities for healthcare funds. In osteoporosis such a threshold results that some treatment situations being cost-effective and others not. This will be an important question in State-funded health services if funding is limited across medicine but will be much less of an issue in private medicine. These issues cut across the general philosophy of osteoporosis management that is in place in most countries and the challenge for the field is to ensure that we have the best possible data on which to make the necessary judgements and to seek to interpret the overall information in a clinically sensible way so that patients can be given optimal management. S09.3 Is there still a role for HRT? Claus Christiansen Denmark Abstract not available at the time of printing. S09.4 Osteoarthritis and estrogens, is there a link? M Christine de Vernejoul, ME Cohen-Solal INSERM U606 and F´ed´eration de Rhumatologie, Hˆopital Lariboisi`ere, Paris, France The link between osteoarthritis (OA) and estrogens has been suggested since 1925. However the data are still controversial. Estrogen receptors (ER) alpha and beta are expressed on human chondrocytes. They are also present in synovial and bone tissues that surround cartilage and impact on the development of OA. Experimental animal models suggest a relationship between gonadal steroids and cartilage. Epidemiological data show that after 50 years old OA become more frequent in women than in men. However there is no association

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between duration of estrogen exposure and OA. Several cross sectional studies have investigated the relationship between HRT and OA. Some of them observed a slight but significant reduced RR of OA in women taking HRT mainly considering knee and hip OA. Only one control prospective study (HERS) looked at prevalence of knee pain and HRT and was negative. There was no relationship between serum estrogens levels and hand OA that is independent of obesity. Finally a cross sectional study could show a relationship between ER alpha polymorphism and radiographic OA of the knee. Independent of progression of OA could be the arthralgia observed after cessation of HRT. Although well known by clinicians, the frequency of these transient symptoms has not been recorded in any study. They could be in the same line as the arthralgia occurring during treatment with aromatase inhibitor. So far no clinical study was designed to conclusively prove or disprove a role for estrogens in OA. This study will not be easy to design. Wednesday, 7 June 2006 10:30–12:30 S10—Symposium: CNS disorders S10.1 Depression Andrea R Genazzani Italy Abstract not available at the time of printing. S10.2 Lifetime cognition function and menopause Diana Kuh, the NSHD team MRC National Survey of Health & Development, Royal Free and University College London, UK A life course perspective has been largely absent from studies of reproductive ageing and women’s health experiences during the menopause transition. Yet, there is growing evidence that women’s reproductive characteristics reveal or have a direct influence on health outcomes in later life, and that both are influenced by risk factors acting from early life, or across generations. For example, in a British birth cohort study, following 1797 women from birth to age 60 years, indicators of poor early growth, cognitive development, and socio-economic circumstances were associated with timing of menopause as well

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as adult performance and chronic disease risk. These potentially common antecedents may lie on the same causal pathways and account for associations between reproductive ageing and later health outcomes. Understanding such pathways may identify women for timely and targeted interventions to improve health in later life. This presentation focuses on intriguing observations from this British cohort study and three other cohort studies showing that early cognitive ability was related to age at menopause, independent of later risk factors. These findings have implications for the interpretation of studies that investigate whether menopause affects cognitive function in middle-aged and older women. To demonstrate this, we show how associations between menopausal characteristics and adult cognitive function were attenuated after adjusting for prior cognitive ability. Early environmental or genetic programming may explain the relationships between lifetime cognitive function and reproductive ageing, perhaps by setting lifelong patterns of hormone release, or causing transient hormonal changes during sensitive periods of development. S10.3 Dementia—oestrogen and testosterone on female brain Declan G Murphy Professor of Psychiatry and Brain Maturation, Institute of Psychiatry, Department of Psychological Medicine, London, UK Background: There is increasing interest in the endocrine determinants of brain development and aging. Also the Western population is aging, and has an increasing prevalence of age-related neuropsychiatric disorders (e.g. Alzheimer’s disease (AD)). Observational studies suggest that in postmenopausal women Hormone Therapy (HT) protects against cognitive decline and AD. However, results from recent randomised controlled trials in women aged 65 years and older were negative. Recent developments: The Women’s Health Inititiative Memory Study (WHIMS; JAMA 2004;291(24):2947–58.) had two study arms – in one postmenopausal women received continuous combined estrogen (conjugated equine estrogen – CEE) plus progestin (medroxyprogesterone acetate, MPA) or placebo. In the other hysterectomised women

were randomised to ‘continuous unopposed’ estrogen (CEE) or placebo. WHIMS reported that CEE ± MPA given to women aged 65 and over does not protect against from, but increases the risk for, all-cause dementia and cognitive decline1 . Where next? WHIMS answered important questions about whether HT can protect against dementia when initiated late in life. However, important questions remain; e.g. the generalisability of WHIMS to perimenopausal and early postmenopausal women with menopausal symptoms for whom HT is indicated, and other routes of delivery and treatment regimens. I will discuss evidence (1) from observational studies that when HRT is started around the menopause brain ageing is modulated, (2) from a new RCT that loss of ovarian function in young women affects brain blood flow and memory, and (3) that testosterone modifies brain development in women. S10.4 Parkinson disease Murat Emre Turkey Abstract not available at the time of printing. Wednesday, 7 June 2006 10:30–12:30 S11—Symposium: Alternative therapies: advisable or unavoidable? S11.1 Phytoestrogens, a serious alternative? Olavi Ylikorkala Department of Obstetrics and Gynecology, Helsinki University, Helsinki, Finland I assessed randomized trials (RCT) (placebo or control) on phytoestrogens in treatment of hot flushes. Eleven trials (including around 1000 women) with soy foods (bars, drinks, powers), nine trials (around 700 women) with soy extracts (isolated isoflavones) and five trials (around 400 women) with red clover were traced. As a mean, women were 53 years and 4 years in menopause; the study regimen had been given on average for 17 weeks. Seven of eight soy food trials, reporting frequency of hot flushes failed to show any decrease in hot flushes. Effect size was negative (favouring placebo) in three,

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and positive (favouring soy) in two trials. Three of five soy extracts trials were negative. Trials on red clover also failed to show any improvement in hot flushes. No marked differences were seen in side-effects, although gastrointestinal complaints were more common during phytoestrogens (17–47%) in some trials. In our own placebo controlled crossed over trial in 62 women with a history of breast cancer, isolated isoflavones (114 mg/day) for 3 months failed to alleviate hot flushes or improve quality of life. Neither had it any effect on the vagina, endometrium or different surrogate markers of cardiovascular disease. Yet bone bone resorption markers slightly reduced (5–9%). Phytoestrogens are not a serious alternative for treatment of menopause. S11.2 Dietary intervention in menopausal prevention J´anos Garai1 , V Moln´ar1 , K Z´amb´o2 , E Schmidt2 , I R´ep´asy3 , S Vil´agi3 , M Hock4 , J B´odis3 1 University of P´ ecs, Department of Pathophysiology, Hungary, Hungary; 2 University of P´ecs, Central Clinical Radioisotope Labratory of Medical School, Hungary; 3 Baranya County Hospital, Department of Obstetrics & Gynecolgy, P´ecs, Hungary; 4 University of P´ecs, Department of Physiotherapy of Healthcare Highschool, Hungary Phytoestrogens have been purported as viable alternatives for menopausal hormone therapy (MHT). Their action might be mediated by the beta estrogen receptor (ER-␤) at least under experimental conditions. Still, there are controversies concerning phytoestrogens’ clinical utility in prevention or treatment of menopausal pathologies like hot flushes, osteoporosis or declining cognitive function. Convincing data have been reported on lipid lowering effects and on cardiovascular benefits derived from consumption of phytoestrogen rich food (soy, linseed and rye bread), but the results with purified phytoestrogens are equivocal. Hence promotion of phytoestrogen rich food seems the best approach for our patients. The available soyfood items, at least in central Europe, nevertheless, are often deficient in their phytoestrogen content or are unacceptable for large masses of consumers. Hence development of novel attractive phytoestrogen rich food items is urgently needed. No clinical estrogenic effect on the genital tract can be expected, however, from food derived phytoestrogens, hence urinary incontinence and vaginal xerosis needs

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local hormone treatment. We have conducted a short term (8 weeks) interventional study to assess efficacy of phytoestrogen rich food items against menopausal hot flushes, nevertheless, pathologies that start with menopause are more often chronic, hence short lived interventions cannot achieve their goals. Our aim was to assess the effect of long-term phytoestrogen rich dietary intervention and of a specific exercise program on the progression of osteoporosis in a menopausal population. Patients and methods: According to the exclusion criteria 72 participants have started the study from the 121 volunteers screened. Of the participants 56 completed the 1-year intervention in the following groups: 1 Control group (no intervention n = 21). 2 Phytoestrogen group (120 g seedcake w. 32% soy and 20% linseed n = 15). 3 Excercise group (3× 1 h weekly, once w. a physiotherapist n = 6). 4 Excercise and phytoestrogen combined group (n = 14). Phytoestrogen serum levels (genistein, daidzein, equol, O-DMA and enterolacton) were monitored quarterly by using the TRFIA (DELFIA) kit of Wallac. Bone density was monitored by DEXA. Results: Those who consumed seedcakes have attained highly elevated serum levels of the phytoestrogens monitored confirming both, acceptable complience and effective absorption, though there is considerable inter-individual variation. Concerning bone density 1-year follow up is insufficient to draw definite conclusion. Although no significant difference between the groups has been detected, however, a tendency toward beneficial effect of the combined intervention is percieved concerning femoral neck density. Longer follow-up is needed to determine wether the effect persists. It is noteworthy, that equol producers’ bone densities seem to benefit the most from the dietary intervention. No serious side-effect or injury has occured during this study. Conclusion: Dietary or excercise intervention might be a useful tool against menopausal pathologies.

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S11.3 Life-style: a sensitive alternative? Martina D¨oren Charit´e-Universit¨atsmedizin Berlin, Clinical Research Center of Women’s Health, Berlin, Germany Evidence-based advice about nutrition, smoking cessation and physical activity, both of which may help with vasomotor symptoms, nutrition and weight control, physical exercise, management of stress, and possibilities to maintain cognitive abilities at old age in order to prevent diseases are the most essential corner stones of preventive medicine. Regular (leisure-time) physical activity decreases the risk of cardiovascular diseases, diminishes the risk of osteoporotic fractures, protects against obesity’s many adverse health outcomes, and eventually may protect against Alzheimer’s disease. Continued mental exercises also appear to be beneficial to maintain cognitive abilities. Nutrition rich in polyunsaturated fatty acids, not necessarily supplemented by calcium and Vitamin D if daily diet provides amounts regarded as sufficient for bone protection, will help to control body weight, is the basis for prevention of cardiovascular diseases, and in more general terms is essential to maintain health. Effects of certain diets to reduction the burden of breast and colon cancer are uncertain. The increasing epidemic of lung cancer in women may be targeted if women stop smoking and do not regard smoking as an expression of possessing equal rights compared to (smoking) men. Women should also be counseled that menopausal hormone therapy is only one option to improve certain aspects of mid-life health. However, most of our present knowledge may be derived at best from prospective, population-based cohort studies, data from controlled randomized trials are very few. Obesity is one of the most challenging health problems. The prevalence of diabetes, which often goes along with obesity, appears to be associated to changing living conditions of women, often living alone when they age in Western societies. However, all non-pharmaceutical approaches are somewhat arduous and demand continuous, essentially lifelong, efforts, which are often not invested in maintenance of health by women and men and not often enough recommended and explained by doctors. To best prevent diseases remains a compelling, growing task given the demographic changes never seen before

in history with rapidly growing numbers of women and men at old and very old ages. S11.4 More alternatives: DHEA; vitamins and antioxidants Michael Klentze Germany Abstract not available at the time of printing. Poster Sessions P01 Cancer P01.01 Black cohosh and breast cancer recurrence-free survival Hans-Heinrich Henneicke-von Zepelin1 , H Meden2 , D Schroeder-Bernhardi3 , K Kostev3 , H Becher4 1 Schaper & Bruemmer GmbH & Co. KG, Salzgitter, Germany; 2 Diakonie-Krankenhaus Rotenburg/W. gGmbH, Rotenburg/W, Germany; 3 IMS Health GmbH & Co. OHG, Frankfurt/Main, Germany; 4 RuprechtKarls-Universitaet, Heidelberg, Germany We investigated the safety of the isopropanolic Cimicifuga racemosa extract (iCR) among breast cancer patients, including estrogen-dependent tumors, regarding the risk of recurrence. This pharmacoepidemiologic retrospective cohort study examined breast cancer patients treated at facilities linked to a medical database in Germany. The main endpoint was diseasefree survival following breast cancer. The impact of treatment with iCR following diagnosis was analysed by Cox proportional hazards models. of 18,861 patients, a total of 1102 had received an iCR therapy. Mean cumulative duration of iCR treatment and observation was 1.5 and 4.5 years. iCR was associated with significantly prolonged disease-free survival. Two years after diagnosis, 14% of the control group had developed a recurrence, while the iCR group reached this proportion after 6.5 years. The primary Cox regression model controlling for age, tamoxifen use and other confounders demonstrated a protractive effect of iCR on the rate of recurrence (hazard ratio 0.83, 95% confidence interval 0.69–0.99). This effect remained consistent throughout all variations of the statistical model. TNM status was unknown but did not bias the iCR-

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treatment decision as investigated separately. Hence, it was assumed to be equally distributed between treatment groups. Correlation analyses showed good internal and external validity of the database. An increase in the risk of breast cancer recurrence for women having had iCR treatment is unlikely. P01.02 An isopropanolic extract of black cohosh (iCR) suppresses the invasive activity of human breast cancer cells Katarina Hostanska1 , T Nisslein2 , J Freudenstein2 , R Saller1 1 University Hospital Zurich, Department of Internal Medicine, Zurich, Switzerland; 2 Schaper and Bruemmer GmbH & Co. KG, Salzgitter, Germany Tumour cell invasion is a frequent prerequisite of metastasis formation and thus a major cause of mortality in breast cancer patients. Previously we showed that iCR, a herbal menopausal preparation, reduces the proliferation and induces apoptosis in breast cancer cells in vitro. In the present study, we investigated the antimetastatic activity of iCR (39–155 ␮g/ml) and its two major fractions triterpene glycosides (TTG; 0.1–5 ␮g/ml) and cinnamic acid esters (CAE; 0.1–5 ␮g/ml) on highly invasive, estrogen receptornegative human breast cancer cells MDA-MB 231. The effect of the compounds was studied in BiocoatMatrigel invasion chambers for 24 h. Invasive cells were quantified microscopically via post-treatment labelling with Giemsa stain. Poorly metastatic MCF-7 cells served as controls and paclitaxel (10 nM) as positive antimetastatic agent. The viability of cells was assessed in flow cytometry by propidium iodide uptake. In contrast to only 4% invasive MCF-7 cells, 41.5% of untreated MDA-MB 231 cells proved to be invasive. at a concentration of 77 ␮g/ml, which retains cell viability at 89%, iCR reduced this cell invasion by 51.8%. Without affecting the cells’ viability, TTG (5 ␮g/ml) and CAE (1 ␮g/ml) fractions inhibited cell invasion, but only by 26% and 19.5%, respectively. Paclitaxel reduced the invasivness of MDA-MB231 cells by 48%. In conclusion it can be said that iCR significantly decreases the invasive capacity of human breast cancer cells. These result together with its low cytotoxicity and known antiproliferative and apoptosis-inducing effects suggest iCR as a secure menopausal treatment with chemopreventive activity.

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P01.03 Co-administration of an isopropanolic extract of black cohosh (iCR) and a steroidal aromatase inhibitor in the DMBA rat model of mammary carcinoma Thomas Nisslein, J Freudenstein Schaper and Bruemmer GmbH & Co KG, Germany Breast cancer patients often seek relief from climacteric complaints triggered or augmented by antihormonal therapy with e.g. aromatase inhibitors. Extracts of black cohosh (Actaea/Cimicifuga racemosa) have been shown to be devoid of estrogen agonistic effects on hormone dependent breast cancer. Here we used a well established rat model of chemically induced, estrogen receptor positive mammary cancer to investigate interactions between iCR – a dose of 60 mg herbal drug per kg body weight – and the steroidal aromatase inhibitor formestane. When mammary tumors occured, four groups of animals were included in the study and the various treatments commenced: group A (n = 14) was treated with 3.5 mg formestane/animal and iCR; group B (n = 13) was treated with 5.0 mg formestane/animal and iCR; group C (n = 13) was treated with 5.0 mg formestane/animal and isopropylic alcohol; group D (n = 14) remained untreated. After 30 days of experimental treatment animals were sacrificed. Initially, animals had an overall mean tumor area of approx. 200 mm2 which increased within 21 days up to 1400 mm2 in animals of group D. Compared to group D, the three formestane test groups showed a significantly retarded tumor growth of up to 700 mm2 within 30 days, but no significant differences between each other. Necropsy data confirmed this observation. Irrespective of iCR-coadministration, levels of serum estradiol in formestane-treated groups B and C were significantly lower than in control group D. Thus, in vivo, iCR does not attenuate the beneficial effects of steroidal aromatase inhibitors, currently propagated as first-line breast cancer therapeutics.

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P01.04 Menopausal hormone therapy and risk of breast cancer—a meta-analysis of epidemiological studies and randomized controlled trials C Greiser1 , E Greiser1 , Martina D¨oren2 1 Institute for Public Helath and Nursng Research, Bremen, Germany; 2 Charit´e-Universit¨atsmedizin Berlin, Germany Objective: We conducted meta-analyses to assess the impact of menopausal hormone therapy on the risk of incident invasive breast cancer (BC) in cohort studies (CS), case-control studies (CCS), and randomized controlled trials (RCT) published 1989–2004. Methods: We used published data providing information upon unopposed estrogen therapy (ET), estrogen progestin therapy (EPT) or all hormone therapy combined (MHT). Major outcomes were MHTassociated overall risk of BC and change of risk per year used. Results: There is a linear increase of overall risk by midterm year of case ascertainment based upon data of all study types for MHT and to a larger extent for EPT, not for ET. Effects are larger in cohort that in case-control studies. Meta-analyses stratified by <1992 versus ≥1992 as midterm year of case ascertainment indicate larger summary risks for the latter period for all MHT analysed, in particular for EPT. Annual increases in breast cancer risk for EPT across study types are 0–9%, for ET 0–3%. In conclusion, there is evidence that relative risks for breast cancer risks by MHT, in particular EPT, and risks have been increasing in recent years. Conclusion: Given the widespread use of MHT, and often long duration, more detailed knowledge about differential breast cancer risks of both estrogens and progestins are necessary in order to minimize breast cancer risk in symptomatic women who consider MHT. P01.05 Ratio of A- and D-ring estradiol metabolites in postmenopausal women with and without breast cancer Alfred O Mueck, H Seeger, J Huober University Women’s Hospital, T¨ubingen, Germany Objectives: Estrogens are involved in the etiology of breast cancer. However, estrogens are hydroxylized to different metabolic products and it is still unclear which estrogen metabolites are most relevant to breast car-

cinogenesis. Preliminary data have shown that D-ring metabolites like 16alpha-hydroxyestrone (16-OHE1) may increase the risk of developing breast cancer (BC), whereas, A-ring metabolites like 2-hydroxyestrone (2OHE1) could be protective. Patients and methods: Urine of 207 postmenopausal BC patients and 206 postmenopausal control patients with no or benign gynecological disorders were collected prior to any breast cancer treatment or surgery. A commercially available ELISA (Estramet, Immunacare) was used to measure the urinary estrogen metabolites 16-OHE1 and 2-OHE1. Predictors for the log ratio of 2-OHE1 to 16-OHE1 were analyzed by analysis of covariance. Results: Mean age of BC and control patients was 62.7 years (S.D. 8.5) and 59.5 years (S.D. 8.1), respectively. In a simple group comparison the mean log ratio of 2-OHE1 to 16-OHE1 was lower in BC patients than in controls (0.11 (S.D. 0.28) versus 0.22 (S.D. 0.29), p = 0.02). The log ratio was inversely related to the BMI (p = 0.04), whereas nicotine consumption had no influence. Conclusion: In our investigation enhanced estrogen metabolism via the D-ring-pathway represented by a low ratio of 2-OHE1 to 16-OHE1 was associated with a higher susceptibility to breast cancer. This ratio could be influenced favouring the D-ring pathway with increasing BMI. P01.06 Study protocol: treatment of the climacterium after breast cancer and interactions with tamoxifen C Antoine, F Liebens, B Carly, A Pastijn, Serge Rozenberg Department of Obstetrics and Gynaecology, Free Universities of Brussels (VUB-ULB) CHU Saint-Pierre, Brussels, Belgium Aim: (1) Evaluate the prevalence and type of treatments to alleviate menopausal symptoms in breast cancer survivors. (2) Evaluate whether pharmaceutical interactions exist between tamoxifen and the most used treatments for menopausal symptoms. Material and methods: (1) Survey to all the patients who had been treated for breast cancer during the last few years in our department, analyzing also demographic characteristics as well as factors influencing the pharmacokinetic of tamoxifen. Patients will be stratified in relation to the type of treatment used. (2)

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Women who use a medication to alleviate menopausal symptoms will be invited to participate to the pharmacinetic study. After written consent, series of blood samples will be collected: after the concomitant intake of tamoxifen and of the menopausal treatment. After a “wash out” period of the menopausal treatment, a new series of blood samples will be collected. DNA of each patient will be extracted and the genotype of cytochrome P450 for the alleles of the genes CYP2D6, CYP2C9 and CYP3A5 will be detremined. Discussion: We hope that this study will contribute to the elaboration of safe treatments in women with breast cancer in order to increase their quality of life. P01.07 Menopause and breast cancer Badr Jellab, Y Sofiane, O Maliki, A Aboulfalah, H Abbassi University Hospital Center Mohammed VI, Marrakech, Morocco In Morocco, the breast cancer represent the first localisation of women’s cancers. The menopause, period of hormonal cancers, can change the classical clinical aspects of this cancer and makes it take specials particularities. Our study deals with a series of 200 cases of breast cancer of menopaused women hospitalised in Ibn Tofail Maternity, Department of Genecology Obstetric A, during the period 2003–2005. Our objective is to emphasize some epidemiologic, diagnosis and therapeutic particularities of breast cancer of Moroccan menopaused patients. We reached the following results: The age is a major identifiable risk factor. More than 70% of breast cancer cases occur in women over 60. At the age of 50, the analysises have shown that one woman among 45 women develop breast cancer. If a woman lives up to 85, the odds of her having breast cancer are one in six. Social and economic factors make it difficult for majority of patients (65%) to get consulted, so they are more likely to be diagnosed at a later stage and less likely to have access to effective treatments (35%). Menopausal hormonal therapy is another risk factor and is not recommended to alleviate menopausal symptoms for women who have had breast cancer. We noticed that mammograms are very effective low-radiation screening methods for breast cancer after menopause. To ameliorate the prognosis of breast cancer of Moroccan menopaused patients, we insist on depicting it at an early stage

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by self-examinations and regular mammography which remain an effective tools against this cancer. P01.08 Mission study: initial results on the prevalence of breast cancer ThierryChevallier 1 , P de reilhac2 , MC Micheletti1 1 Laboratoire Th´ eramex, Monaco; 2 Honorary President of F.N.C.G.M., Nantes, France The MISSION study, “Menopause: Risk of Breast Cancer, Morbidity and Prevalence”, is a national, historico-prospective study, carried out in France by the National Federation of Medical Gynaecology Colleges (F.N.C.G.M.). In the first case (historical approach), the principal objective is to determine the prevalence of breast cancer in menopausal women under gynaecologists’ care, in relation to the presence or absence of Hormone Replacement Therapy (HRT). The originality of the MISSION study is that it studies HRTs commonly prescribed in France: HRT containing estradiol either alone or associated with a natural progesterone or related compound or a norpregnane or pregnane derivative; excluding medroxyprogesterone acetate and 19 nor-testosterone derivatives. This study has been included a total of 6871 randomly selected women: 3509 treated with HRT and 3362 untreated. The mean age of the women is 60.7 years. The women who are (or were previously) on HRT have been (or were) treated for an average of 8 years, and 29.9% have been (or were) treated for more than 10 years. Seventy four percent of the treated women receive cutaneous estradiol. The initial results concerning the prevalence of breast cancer in this population demonstrate the likely importance of the gynaecologists’ selection of women for whom they consider HRT to be appropriate or inappropriate. These results will be presented in full.

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P01.09 Does raloxifene therapy affect mammographic breast cancer screening in postmenopausal patients? Teksin Cırpan 1 , F Akercan1 , I Mete Itil 1 , G Gundem1 , I Bilgen2 , M Sait Yucebilgin2 1 Department of Obstetrics and Gynecology, Ege University Faculty of Medicine, Izmir, Turkey; 2 Department of Radiology, Ege University Faculty of Medicine, Izmir, Turkey Objective: The aim of the study was to determine the mammographic breast density changes during raloxifene therapy in postmenopausal patients. Materials and methods: Fifty-five cases who were using raloxifen therapy were included for this retrospective analysis. Raloxifene was given for osteopenia and osteoporosis according to low bone mineral density measured by DEXA. None of the patients were using hormone replacement therapy 12 months before the initiation of raloxifene treatment and during the study. The mammographic breast density was determined by mammography at before the initiation of raloxifene treatment (baseline) and after 12–16 months of therapy. BI-RADS breast density score was used for the evaluation of mammographic density. Results: There was no change in mammographic breast density when the baseline and the first mammography taken after the initiation of the therapy was compared (p = 0.32). There was no significant correlation between the duration of raloxifene treatment and the mammographic density measured after the raloxifene treatment (r = −0.158, p = 0.25). Only in one patient BI-RADS classification 2 changed to 3 after 12 months of therapy. Conclusions: In conclusion, that in postmenopausal women with low bone mass, raloxifene therapy for 12–16 months does not increase mammographic breast density.

P02.01 Study of the effect of folic acid on the vasomotor symptoms and cardiovascular risk predictors in postmenopausal women Sherief S Gaweesh1 , A Nagaty1 , MN Deusky2 , M Moawed1 1 Alexandria University, Department of Obstetrics and Gynecology, Alexandria, Egypt; 2 Alexandria University, Department of Biochemistry, Alexandria, Egypt Aim of the work: To study the effect of folic acid on the vasomotor symptoms and cardiovascular risk predictors in postmenopausal women. Materials: The study included 65’ women attending the outpatient clinic of El-Shatby Maternity University Hospital. All patients complained of hot flushes occurring for more then four times daily. Flushes were accompanied by profuse perspiration, which was often intolerable. Those women who suffered from any metabolic or cardiovascular disease were excluded. Also, cases taking any hormonal or nonhormonal drugs in last 3 months prior to this study were excluded. The period of study was 4 weeks. The included menopausal women were allocated into three groups: (1) Group I: 23 patients received 5 mg folic acid daily. (2) Group II: 22 patients received 10 mg folic acid daily. (3) Group III: 19 patients received one course of placebo. Methods: (1) Methods of administration: We had planned a schedule that the first comer will take folic acid 5 mg tablet daily, next one will take a double dose of folic acid 5 mg twice daily and the third comer will take starch capsule and will be considered as control. We included more 8 patients after the end of our targeted number for fear of drop out alternatively taking 10 mg and 5 mg folic acid. Only one case (of group II) had dropped out. (2) Clinical examination: Patients were requested to record the frequency of hot flushes per day and its intensity, beginning 1 week before the treatment, and was transcribed at the end of treatment and during the follow up period. (3) Laboratory test: Two specimens were taken from each patient; one was plasma; while the other sample was serum, which was analyzed directly. Results: (1) As regard hot flushes: complete disappearance of flushes in 63.6% of patients receiving 10 mg folic acid, decreased frequency and intensity in 18.2% of patients. Placebo had only a minimal effect on

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improving hot flushes in 5.3–15.8% of patients. (2) As regard MHPG: there was significant lowering in mean plasma levels of MHPG with 10 mg folic acid daily, better than with 5 mg folic acid daily which shows also significant lowering as compared to placebo that had no significant effect on MHPG. Spearman’s r-test for nonparametric correlation between clinical improvement of hot flushes and laboratory changes in MHPG proved that there was definite positive correlation between flushes improvement and lowering in plasma levels of MHPG. (3) As regard lipid profile: Folic acid either in a dose of 5 mg or 10 mg daily had no significant effect on T.G, LDL-cholesterol and HDL-cholesterol. But there was significant decrease in total cholesterol in group II as compared to group I and III, Placebo has nearly no effect on lipid profile. (4) As regard CRP “as an acute phase reactant for increased cardiovascular risk” Mild improvement of CRP occurred with 10 mg folic acid daily, rather than with 5 mg folic acid daily and placebo, but was not significant. Conclusion: 1 Folic acid is capable of improving menopausal hot flushes. 2 Folic acid is a good non-hormonal solution for hot flushes in cases when HRT is contraindicated. 3 Folic acid is capable of reducing cardiovascular risk in postmenopausal women. P02.02 The Herbal Alternatives for Menopause Study (HALT): dietary soy intervention Susan D Reed1,2,3,4 , KM Newton1,2 , L Grothaus1 , K Ehrlich1 , J Schenk4 , AZ LaCroix1,2,4 1 Center for Health Studies, Group Health Cooperative, Seattle, WA, USA; 2 Department of Epidemiology, University of Washington, Seattle, WA, USA; 3 Department of Obstetrics and Gynecology, University of Washington, Seattle, WA, USA; 4 Fred Hutchinson Cancer Research Center, Seattle, WA, USA Objective: Describe impact of the HALT dietary soy intervention on daily soy intake. Methods: We randomized 351 peri- and postmenopausal women to one of five treatment arms: (1) hormone therapy (HT); (2) black cohosh; (3) a multibotanical; (4) the same multibotanical plus soy dietary counseling; (5) placebo. The soy intervention included five telephone calls from a dietitian and a 34-page soy

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booklet recommending two daily soy food servings (12–20 g soy protein). Soy intake was calculated. Results: Among women assigned to the soy food intervention, 77% completed >3 phone calls. At baseline, women averaged 0.6 soy servings per day; 10% reported at least 1.5 servings per day (NSS). Women in the soy intervention increased dietary soy by 1.1 servings/day from baseline to 3 months (p < 1) versus a 0.1 servings/day increase in the other four groups (NSS). Compared to baseline, in the soy intervention group, mean intake of genistein and daidzein increased by 50.7 mg per week (95% CI 33.3–68.1, p < 1) and 43 mg per week (95% CI 28.4–57.7, p < 1), respectively, at 3 months, and by 70.7 mg per week (95% CI 47.0–94.4, p < 1) and 58.4 mg per week (95% CI 39.1–77.7, p < 1), respectively, at 12 months. In other groups, mean changes from baseline to 3 months ranged from −13.7 to 2.9 mg per week for genistein, and from −9.3 to 4.7 mg per week for daidzein (NSS). Discussion: Meticulous attention to study design can maximize completion of successful dietary interventions in randomized controlled trials. P02.03 The effects of raloxifene on serum lipid profiles, C-reactive protein and homocysteine levels in postmenopausal women GA Turan2 , E Dogan1 , Cemal Posaci1 , S Calyskan3 , S Guclu1 , S Altunyurt1 1 Dokuz Eylul University Department of Obstetrics and Gynecology, Izmir, Turkey; 2 Sifa Medical Center, Izmir, Turkey; 3 Dokuz Eylul University Department of Biochemistry, Izmir, Turkey Objective: Menopause is associated with unfavorable lipid modifications and certain inflammation markers are increased which are believed to increase the risk of cardiovascular disease. The aim of the study was to investigate the effects of selective estrogen receptor modulator raloxifene on serum lipid profiles, C-reactive protein and homocysteine levels in postmenopausal women. Materials and methods: A single center, longitudinal, open-labeled, uncontrolled study was performed with 64 postmenopausal women having osteoporosis or osteopenia with fracture risk. The mean age of the patients was 56.53 ± 6.92 years. Patients received daily 60 mg of raloxifene for 6 months. Serum levels of total cholesterol, LDL cholesterol, triglycerides,

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HDL cholesterol, lipoprotein (a), C-reactive protein and homocysteine were measured at basal and 6th month of therapy. The mean changes in the serum levels were analyzed. Results: Raloxifene significantly lowered total cholesterol (−3.4%; p < 0.05), LDL cholesterol (−11.2%; p < 0.001) and lipoprotein (a) (−3.4%; p < 0.001) levels. HDL-cholesterol levels increased significantly by 11.1% after 6 months of raloxifene treatment (p < 0.001). Raloxifene did not alter serum triglyceride levels significantly. Serum inflammation marker homocysteine decreased by 21% (p < 0.001), but C-reactive protein levels did not change significantly (p > 0.05). Conclusion: Raloxifene treatment favorably alters cardiac risk factor levels by decreasing total cholesterol, LDL cholesterol, lipoprotein (a), and homocysteine and by increasing HDL cholesterol without changing triglyceride and CRP levels. With these beneficial effects raloxifene may reduce the risk of cardiovascular disease in postmenopausal women. P02.04 The effects of raloxifene on serum lipids, C-reactive protein, macrofage colony stimulating factor and interleukin-18 G Kurtay, Efser Oztas Ankara University Faculty of Medicine, Turkey Objective: Our purpose was to investigate the effect of raloxifene, a selective estrogen receptor modulator, on serum lipids, C-reactive protein (CRP) and on macrophage colony stimulating factor M-CSF) and Interleukin-18 (IL-18); cytokines that are presumably involved in the pathogenesis of atherosclerosis. Methods: We studied the effect of raloxifene, a nonsteroidal benzothiphene on serum CRP, M-CSF and IL-18 concentrations in 75 healthy postmenopausal women. Participants were randomly assigned to 60 mg daily raloxifene (40 subjects) for 6 months; thr rest of he subjects were in the control group. Results: Serum concentration of M-CSF were significantly lower (p < 0.05) during the early postmenopausal period (<10 years) than the values in the late postmenopausal period (>10 years). Raloxifene lowered the serum M-CSF and IL-18 concentrations when compared with the baseline but the difference was not statistically significant. Compared with the control group, raloxifene produced a significant decrease

on the serum IL-18 concentrations (27.5%, p < 0.05). Raloxifene treatment resulted in a 26% reduction in serum CRP concentrations (p < 0.05). At 6 months, total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were significantly reduced by 60 mg/day raloxifene (6.8% and 5.6%, respectively) when compared with the control group. Conclusion: The results of our study showed that raloxifene at a dose of 60 mg/day reduces serum TC, LDL-C, CRP and IL-18 levels significantly in healthy postmenopausl women. According to the results of our study we suggest that raloxifene may have a favorable effect on the prevention of cardiovascular disease in healthy postmenopausal women. P02.05 “Advanced oxidation protein products” levels as a new marker for cardiovascular risk in postmenopausal women: comparison with malondialdehyde levels Ahmet Erdem, A Bilgihan, M Erdem, G G¨unaydin, ¨ G¨ulbahar T Cakir, O Gazi University, Department of Obstetrics and Gynecology, Ankara, Turkey Objective: Oxidative stress appears to play a key role in the pathogenesis of atherosclerosis. Lipid peroxidation has long been shown in association with increased cardiovascular risk. Recently, elevated advanced oxidation protein products (AOPP) levels have also been reported to be associated with increased cardiovascular risk. Although an increase in MDA levels in postmenopausal women have been reported in many studies, there is no data about AOPP levels in postmenopausal women. Our aim was to measure the AOPP levels as a new marker for cardiovascular risk in postmenopausal women and to compare these with MDA levels. Methods: The study was conducted with 20 premenopausal and 90 postmenopausal women. Plasma AOPP and MDA levels levels were measured by a spectrophotometric method described by Witko-Sarsat and Valenzuela, respectively. Kruskal–Wallis variance analysis and Mann–Whitney’s U-test were used for statistical analysis (SPSS 10.0 for Windows). Results: AOPP levels of premenopausal and postmenopausal women were found as 61.59 ± 16.42 ␮mol/L and 116.13 ± 52.00 ␮mol/L, respectively. MDA levels of premenopausal and

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postmenopausal women were found as 5.98 ± 0.77 and 6.91 ± 1.30 ␮mol/L, respectively. Plasma AOPP and MDA levels in postmenopausal women were increased when compared with the premenopausal women (p < 0.05). Conclusion: AOPP and MDA are oxidative stress markers that are found to be elevated in postmenopausal women compared to premenopausal women. AOPP levels may also be used as a marker in postmenopausal women for prediction of cardiovascular risk.

radicals and inhibited intracellular hydrogen peroxide production. Conclusion: 17 beta-Estradiol treatments decrease ischemic brain infarction in association with inhibition of apoptotic cell death.

P03

Extracts of black cohosh (Actaea/Cimicifuga racemosa) exert estrogen-agonistic and antagonistic effects. Recent data further propose feedback control of CNS receptor-concentrations in situ, as well as direct neurotransmitter properties as candidate contributors to their clinical efficacy in the treatment of menopausal complaints. We investigated the binding of an isopropanolic extract (iCR, Remifemin® ) of black cohosh to 21 subtypes of three classes of central nervous system receptors (dopamine, serotonin, and GABA). Tests were based on the displacement of radiolabelled natural ligands. A dose dependent decrease in receptor-bound radioactivity corresponding to the displacement of natural ligands by black cohosh was measured with a scintillation counter. iCR showed greatest affinities (IC50 < 15 ␮g herbal dry matter/ml) towards the 5-HT1A, 5-HT1D, 5-HT7, and GABAA receptors: An IC50 of 3 ␮g/mL at the 5-HT1A receptor, an IC50 of 77 ␮g/mL at the 5-HT1B receptor, an IC50 of 15 ␮g/mL at the 5-HT1D receptor, and an IC50 of 4 ␮g/mL at the 5-HT7 receptor. The IC50 at the GABAA receptor was in the same range, i.e. 3 ␮g/mL, while the IC50 at the D4.4 receptor was at a higher concentration, i.e. 368 ␮g/mL. of special interest is the finding that within the wide concentration range (10 ng/ml–1000 ␮g/mL) tested, iCR did not influence serotonin transport, nor did it interfere with serotonin secretion or release. The high affinity of iCR to selected central nervous receptors suggests an association between CNS receptor-mediated effects and an efficacious treatment of menopausal symptoms.

CNS P03.01 Neuroprotective effect of 17 beta-estradiol against focal cerebral ischemic damage via antiapoptotic action in rats Kyu-Sup Lee1 , B-I Lee2 , K-H Hong1 1 Pusan National University Hospital, South Korea; 2 Inha University Hospital, South Korea Objective: Overall incidence of stroke is uniformly higher in men than in women, and rare especially in women during the reproductive stage. A number of studies have demonstrated the reduced infarct size upon administration of estrogen to ovariectomized females in ischemic brain injury models. Design: We aimed to examine the potential neuroprotective effects of 17 beta-estradiol on the cerebral infarct size and then on the apoptotic mechanism after the completion of 2-h occlusion of middle cerebral artery (MCA) and 24-h reperfusion. Results: The ischemic zone with cerebral infarct was consistently observed in the cortex and striatum of the left hemisphere at 24 h of reperfusion after the completion of 2-h occlusion of left MCA. The infarct area and volume were significantly reduced, when rats received 4 and 10 mg/kg 17 beta-estradiol intraperitoneally 24 h before and 5 min after 2-h ischemia. Samples from the regions corresponding to the penumbra showed markedly reduced Bcl-2 protein level and, in contrast, high levels of Bax protein and cytochrome c release. Both increased Bax and cytochrome c were significantly reduced, and decreased Bcl-2 protein was markedly restored by 17 beta-estradiol. 17 betaestradiol (10−7 –10−5 M) potently scavenged hydroxyl

P03.02 In vitro binding of an isopropanolic extract of black cohosh to selected central nervous receptors T Nisslein1 , U Koetter2 , Johannes Freudenstein1 1 Schaper and Bruemmer GmbH & Co KG, Germany; 2 Max Zeller S¨ ohne AG, Romanshorn, Switzerland

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P03.03 Diffusion weighted imaging (DWI) of ovariectomized rats brain following traumatic brain injury Onder Celık, S Hascalik, M Hascalik, A Firat, M Tamser, HM Karakas, M Ozsahın, C Onal Inonu University Medical Faculty, Department of Obstetrics and Gynecology, Radiology and Neurosurgery, Malatya, Turkey; Anesthesiology Clinic, Yesilyurt State Hospital, Malatya, Turkey; Firat University Veterinary Faculty Department of Physiology, Elazig, Turkey Objective: We examined the effects of melatonin treatment on ovariectomized rat brain after traumatic brain injury (TBI) using NMR diffusion-weighted imaging (DWI). Material and method: A total of 24 young Wistaralbino rats, of which 18 animals were submitted to bilateral oophorectomy and six rats were submitted to the same surgical incision but without oophorectomy were studied. After 7 days, rats were assigned to four groups of six animals each. Group 1, sham operated; group 2, ovariectomy; group 3, ovariectomy + TBI; group 4, ovariectomy + TBI + melatonin. Rats in group 3 had only received vehicle (0.1% etanol) whereas melatonin group had received 4 mg/kg melatonin intraperitoneally. Drug administration started before injury and continued for 7 days. DWIs were obtained 1-week postinjury, and apparent diffusion coefficient (ADC) were constructed. Results: There is no significance between the ADC values of sham and ovariectomized rats (p = 0.861). The placebo group revealed a decreasing trend in ADC values compared to sham and ovariectomy groups, which is statistically insignificant. ADC values due to melatonin treatment are significantly higher than the placebo treatment group (p = 0.002) and are similar to sham group (p = 0.062), which implies a physiological state. TBI resulted a decrease in ADC values, which indicates cytotoxic edema. The results after 1 week show a significant increase in ADC values, which is concordant with effective treatment of melatonin. Conclusion: Melatonin administration prevents the disruptive effects of TBI in ovariectomized rat brains.

P04 Hormone therapy P04.01 The effect of low-dose hormone therapy on endometrial thickness and vaginal bleeding Zaidieva Jana, G Alexandre, M Lidija, G Sanijat Zaidievna, Moscow, Russian Federation Objectives: The aim of this study was to evaluate the endometrial safety of low-dose continuous combined estrogen–progestin therapy and incidence of vaginal spotting/bleeding over a 1-year period. Methods: Twenty eight postmenopausal patients with climacteric symptoms underwent on continuous oral administration of 17␤-estradiol 1 mg/didrogesterone 5 mg. The mean age was 52.69 ± 4.02; the time since natural menopause was 2.73 ± 0.4. All patients were assessed at study entry and at 12 months intervals with transvaginal ultrasonography, colour Doppler analysis of blood flow in the uterine arteries and had an endometrial aspiration Pipelle-biopsies for histological assessment. Results: The study was completed by 24 women (85.7%). The drop-out rate due to spotting/bleeding was 14.3%. The mean endometrial thickness at baseline was 3.6 ± 0.85 mm versus 3.3 ± 0.65 mm during the therapy (p > 0.05), in two cases (7.14%) 10 and 11 mm, and one case of endometrial polyp was found. Hystologically, atrophy was found in 22 (78.6%) cases at the time of study entry (with six cases of insufficient tissue sample for histological assessment) and in 20 (83.3%) cases under the cc-HT (in four cases—insufficient tissue sample for histological assessment). The mean pulsatility index (PI) not significantly decreased during the therapy (1.67 ± 0.6 versus 1.49 ± 0.57, χ2 > 0.05). The mean resistance index (RI) at baseline and after 12 months of treatment were 0.79 and 0.74 (χ2 > 0.05). Conclusion: Women received low-dose cc-HT associated with low incidence of vaginal spotting/bleeding and did not appear to associate with significant changes in endometrial thickness during the hormone therapy use.

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P04.02 Efficacy of biorhythmic transdermal bioidentical hormones in releaving vasomotor symptoms associated with menopause Bent Formby, F Schmid, M Faber The Rasmus Institute for Medical Research Department of Reproductive Endocrinology, Santa Barbara, CA, USA Objective: To evaluate the efficacy and tolerability of a combination of low-dose bioidentical 17bestradiol and progesterone transdermal delivery system (lipophilic emulsion type base) administered in a rhythmic 28 days regimen to mimic a normal physiologic ovary secretory pattern in relieving vasomotor symptoms. Design: An open-label, observational evaluation conducted over 8 months in 12 age-matched menopausal women with vasomotor symptoms. Pharmacokinetics were evaluated following percutaneous 0.05–0.3 mg estradiol and 25–100 mg progesterone administration. Results: Improvement in vasomotor symptoms was reported by 11 (92%) of women evaluated. of responders, 10 (83%) characterized symptom relief as complete. No adverse health-related events were attributed to the bioidentical hormone therapy. Time of maximum saliva concentrations (tmax ) was, in all cases, in the neighborhood of 6 h. Baseline values were reached within 24 h. Conclusion: Percutaneous absorption of bioidentical 17b-estradiol correlates with the absorption of transdermal bioidentical progesterone and was associated with a significant reduction in complains of vasomotor symptoms before menpause. The cyclical transdermal delivery system of bioidentical hormones may be advantageous because it mimics the physiological ovary secretory pattern.

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P04.03 Treatment of vasomotor symptoms with tibolone in breast cancer surgery patients—design and baseline data LIBERATE trial Jean-Michel Foidart1 , NJ Bundred2 , P Kenemans3 , E Kubista4 , B von Schoultz5 , P Sismondi6 , R Vassilopoulou-Sellin7 , MW Beckmann8 , CH Yip9 1 Department of Obstetrics and Gynecology, University of Liege, Liege, Belgium; 2 Department of Surgery, University of Manchester, Manchester, United Kingdom; 3 Department of Obstetrics and Gynecology, Free University, Amsterdam, The Netherlands; 4 Department of Special Gynecology, Medical University, Vienna, Austria; 5 Division of Obstetrics and Gynecology, Karolinska Institute, Stockholm, Sweden; 6 Unit of Gynecologica Oncology, University of Turin, Turin, Italy; 7 Anderson Cancer Center, University of Texas, Houston, United States; 8 University Clinic, Erlangen, Germany; 9 University of Malaya Medical Centre, Kuala Lumpur, Malaysia Background: LIBERATE is a randomized, doubleblind trial to evaluate that tibolone 2.5 mg/day (Livial® ) is non-inferior to placebo regarding BC recurrence in women with vasomotor symptoms surgically treated for primary BC within the last 5 years. Methods: Patients had histologically confirmed and surgically treated BC and complained of vasomotor symptoms. In non-hysterectomized women, entry required a normal endometrium as judged by TVUS, defined as absence of endometrial polyps in tamoxifen users and thickness Ø4 mm or 4–8 mm in nontamoxifen users. The primary end-point is breast cancer recurrence rate. Hot flushes, sweating episodes, BMD and QoL will be recorded regularly. The primary analysis will be performed mid 2007, with a follow-up analysis on all data in 2009. Baseline data: 3148 patients were randomized at 245 centers in 31 countries. Based on the data 01/2006, mean age at randomization was 52.6 years, and the mean time since surgery was 2.1 years. The mean daily number of hot flushes and sweating episodes was 7.3 and 6.1, respectively. For the primary tumour, stage IIA or higher was reported for >70% of the patients. In subjects whose receptor status was known, 79% of the tumours were ER+. Prior to or at study entry, tamoxifen was given to 74% of the patients and aromatase inhibitors to 8%.

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Discussion: Regular unblinded safety reviews performed by an independent DSMB have led to recommendations to continue without modification. The LIBERATE trial remains the largest and only ongoing, well-controlled study for treatment of vasomotor symptoms following BC surgery. P04.04 Cholesterolemic levels in post-menopause women treated with Tamoxifen Stefania Zovato1 , Fable Zustovich1 , Mario Trivellato2 , Binato Samuela1 , Pastorelli Davide1 , Artioli Grazia1 , Salmaso Flavia1 , Cartei Giuseppe1 1 U.O. Oncologia Medica, IOV, Padova, Italy; 2 Servizio di Cardiologia, Ulss16 c/o IRA, Padova, Italy Background and purpose: Tamoxifen (T) is an antiestrogen used as adjuvant therapy for breast cancer, with some weak estrogenic properties. A huge number of women in the world are currently using T, usually over 5 years in the adjuvant setting. Moreover, many women in T therapy, are affected by familial type IIb hypercholesterolemia, a common disease considered a risk factor for cardiovascular pathologies. T, as demonstrated by other studies, can influence circulating lipids. Patients and methods: We have prospectively studied haematic lipids in 77 selected postmenopause (physiological or jatrogen) women, aged 33–76 (mean 56.8; median 56.5) who received adjuvant T for 5 years. Thirty PTS belonged to families with IIb. Twenty-three PTS had intermediate total-cholesterol-level (TCL) (200–240 mg/dl), 24 were normocholesterolemic. We have measured cholesterol levels (HDL, LDL and TCL) and other lipids (triglycerids, apolipoproteins type A1 and B) before starting T (b), after 6, 12 and 36 months (m) and 3 months after stopping T (stop). The results of TCL are shown below (Table 1): TCL

Mean S.D. Median

FD IIb (>240 mg/dl)

non-familial dyslipidemia group with a statistical significance (p < 0.01) between the two groups. P04.05 The effect of HT (Hormone Therapy) on BMI (Body Mass Index) on women taking therapy for the first 6 months G¨ulc´yhan Akkuzu1 , K Erogluk2 1 Baskent University, Department of Nursing and Health Services, Ankara, Turkey; 2 Hacettepe University, School of Nursing, Ankara, Turkey Aim: To examine the effect of HT on BMI who women taking therapy for the first 6 months. Method: Total 238 (E:119, C:119) women were being seen (This study was based on a doctoral dissertation. The experimental group was given group education and an educational booklet on the first day they began therapy and counselling in the 3rd and 6th months of therapy. The control group was not given counselling and education.). The data were collected using a questionnaire and monitoring form in the 3rd and 6th months of therapy. Data were analysed using Chi-square test and variance analysis in repeated measures were used to evaluate the data. Results: 5.9% of women were 40–44 year group, 32.8% were in the 45–49 year group and 55.5% were 50 and older. 19.3% of women were illiterate, 60.5% were literate/primary school graduates, and 20.2% were middle school or higher graduates. The mean BMI values were 30.46–4.77 (p > 0.05). The 3rd month follow-up was completed with 110 experimental and 107 control group women (total 217). The 6th month follow-up was completed with 109 experimental and 97 control group women (total 206). The women’s mean BMI did not change over time (p = 0.05).

Hypercholesterolemic (200–240 mg/dl)

Normal (<200 mg/dl)

b

6m

12 m

36 m

Stop

b

6m

12 m

36 m

Stop

b

6m

12 m

36 m

Stop

273 29 268

233 36 230

232 35 236

228 33 231

245 38 235

218 9 217

202 28 195

205 29 210

212 35 208

239 46 220

174 23 179

174 29 172

184 28 181

196 37 183

190 28 205

Conclusions: The effect of T on TCL is unappreciable in the “normal” group. A 15.5% decrease (p < 0.1 Student’s t-test, paired data) was induced in the IIb dyslipidemia group. A lower decrease (5.2) occurred in the

Conclucions: HT did not effect on BMI of women’s for the first 6 months of therapy. It is recommended that studies being conducted to examine a longer-term effect of HT on BMI.

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P04.06 Effect of HRT on glucose and lipid levels in postmenopausal women with Type 2 diabetes and hyperlipidemia Miljanka Vuksanovic1 , T Beljic1 , S Popovic2 1 Zvezdara University Hospital, Departmaent of Endocrinology, Belgrade, Serbia & Montenegro; 2 Clinical Centre of Serbia, Institute of Endocrinology, Diabetes and Diseases of Metabolism, Belgrade, Serbia & Montenegro Objectives: Hormone replacement therapy (HRT) is known to decrease lipid levels in healthy postmenopausal women. However, it is prescribed less frequently to women with diabetes type 2, known to have lipid abnormalites. Subjects and methods: The aim of this study was to assess the effect of oral HRT in postmenopausal women with type 2 diabetes and hyperlipidemia. Continuously combined, estradiol (E2) 2 mg + norethisterone acetate (NETA) 1 mg was given to 30 women with diabetes type 2 and hyperlipidemia and two control groups (30 women with hyperlipidemia only and 30 healthy women) over a 6 month period. Total holesterol (t-HOL), triglycerides (TG), LDL-cholesterol, HDLcholesterol, insulin level and glycated haemoglobin (HbA1c) were evaluated in 3 months intervals. Fasting and postprandial glycose were evaluated monthly. Results: HRT significantly decreased levels of 2 t-HOL (χFriedman = 11, 712; p < 0.01) and LDL2 c (χFriedman = 10, 403; p < 0.01) in postmenopausal women with type 2 diabetes. The effect was more pronaunced in two control groups. TG 2 2 (χFriedman = 5400; p > 0.05) and HDL-c (χFriedman = 1113; p > 0.05) did not change in postmenopausal type 2 diabetic women. Six months of HRT significantly decreased HbA1c (F = 44.693; p < 0.01). There was no 2 significant differences in the insulin leves (χFriedman = 1267; p > 0.05) while fasting and postprandial gly2 caemia decreased but not significantly (χFriedman = 6527; p > 0.05). Conclusion: Six months duration of HRT is effective in lowering lipid levels and HbA1c in postmenopausal women with type 2 diabetes. However, target lipid levels were not achieved.

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P04.07 Breast density and ultra low dose HRT Bo von Schoultz1 , E Lundstr¨om1 , M Bygdeson2 , G Svane2 , E Azavedo2 , E Lang3 , R Gut3 1 Department of Obstetrics and Gynaecology, Karolinska Hospital, Stockholm, Sweden; 2 Department of Radiology, Karolinska Hospital, Stockholm, Sweden; 3 Novo Nordisk FemCare AG, Zurich, Switzerland Objective: The effects of two ultra low dose HRT combinations and placebo on mammography breast density were compared in postmenopausal women. Design: A subpopulation of 255 women from the CHOICE trial were randomly assigned to 0.5 mg E2 + 0.25 mg NETA, 0.5 mg E2 + 0.1 mg NETA or placebo, and treated for 24 weeks. Mammograms were performed prior to start of treatment and at the end of the study after at least 5 months of treatment. All patients who used systemic HRT up to 2 months prior to the screening mammogram were excluded. Finally, 154 women fulfilled the above mentioned criteria and were included in the assessment. The mammographic breast density was evaluated by two independent radiologists, blinded to treatment and order of the mammograms. Two visual assessments (the Wolfe classification and a percentage scale) as well as a digitized quantification of mammographic density were performed. Results: No significant differences were detected between the treatment groups and placebo in the digitized quantification. Visual assessment according to the Wolfe classification and the percentage scale also showed no increase in breast density after 24 weeks of treatment in any study group. Conclusion: In contrast to currently available bleedfree regimens, the new ultra low dose combination of 0.5 mg E2 and 0.1 mg NETA seems to have very little or even a neutral effect on the breast. In both the digitized quantification and the visual assessment breast density was unchanged after 24 weeks of treatment. Larger prospective studies should be performed to confirm this new finding.

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P04.08 Effective relief of menopausal symptoms with ultra low dose HRT Nick Panay1 , O Ylikorkala2 , DF Archer3 , E Lang4 , R Gut4 1 West London Menopause and PMS Centre, London, UK; 2 Department of Obstetrics and Gynecology, Helsinki University, Finland; 3 Institute for Reproductive Medicine, Norfolk, Virginia, US; 4 Novo Nordisk FemCare AG, Zurich, Switzerland Objective: The aim of this study was to assess the efficacy of ultra low doses of estradiol (E2) plus norethisterone acetate (NETA) for the relief of postmenopausal symptoms. Design: A total 577 postmenopausal women with moderate to severe hot flushes were prospectively randomised to a double-blind, 24 weeks, multi-national treatment with 0.5 mg E2 + 0.25 mg NETA, 0.5 mg E2 + 0.1 mg NETA or placebo. The primary endpoint was the change in mean number of moderate to severe hot flushes per week. Additionally a sensitivity analysis was performed to analyse the mean changes in frequency and sever-ity of moderate to severe hot flushes. The secondary efficacy endpoints were the Hot Flush Weekly Weighted Score (HFWWS) and the Greene Climacteric Scale. Results: Postmenopausal women using 0.5 mg E2 + 0.1 mg NETA, presented a rapid and significant reduction in the frequency of moderate to severe hot flushes as well as in the severity score versus placebo (p = 0.1). The same statistically significant improvement was also reported in the HFWWS and the total Green Climacteric Scale. This effect was maintained over the whole study period. During the observation period the treatment was very well tolerated, no difference in adverse events between groups and only 1% of serious adverse events were reported. Conclusion: The new ultra low dose combination with 0.5 mg E2 + 0.1 mg NETA effectively reduces the frequency and severity of hot flushes within the initial weeks of treatment. This effectiveness was also confirmed by the Hot Flush Weekly Weighted Score and the Green Climacteric Scale.

P04.09 Increased incidence of amenorrhea and no bleeding associated with ultra low dose HRT David Sturdee1 , DF Archer2 , E Lang3 , R Gut3 1 Department of Obstetrics and Gynaecology, Solihull Hospital, Solihull, UK; 2 Jones Institute for Reproductive Medicine, Norfolk, Virginia, US; 3 Novo Nordisk FemCare AG, Zurich, Switzerland Objective: To assess the efficacy and the bleeding profile of new ultra low dose combina-tions HRT in postmenopausal women. Design: A total of 577 postmenopausal women, average age 55.5 years, experiencing mod-erate or severe hot flushes were randomly assigned to receive 0.5 mg E2 plus two different doses of NETA or placebo in a double-blind, multi-centre study and treated for 24 weeks. All bleeding and spotting episodes during the treatment period were recorded in a diary card. The incidence of bleeding or spotting by cycle were analysed and compared between each treatment. Results: The rates of amenorrhoea were similar with both ultra low dose combinations. In cycles 1–6 the rate with 0.5 mg E2 + 0.1 mg NETA was: 89%, 89%, 86%, 85%, 89% and 89%, respectively. The percentage of patients with no bleeding per cycle was correspondingly very high: 95%, 94%, 93%, 90%, 95% and 95%. Furthermore, there were only three patients (2%) who dropped-out due to bleeding or spotting in the 0.5 mg E2 + 0.1 mg NETA treatment group. The efficacy results are reported in a separate communication. Conclusion: This new ultra low dose combination of 0.5 mg E2 + 0.1 mg NETA had an extremely high incidence of amenorrhea and no bleeding in postmenopausal women during the 6 months study. Both amenorrhoea and no bleeding rates were consistent from the start of treatment. The new ultra low dose HRT combination was significantly better in terms of the incidence of amenorrhea and bleeding compared to other commonly prescribed standard or low dose HRT.

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P04.10 Optimal tolerability and safety with ultra low dose HRT G¨oran Samsioe1 , L Sch¨onberg2 , E Lang3 , R Gut3 1 Department of Obstetrics and Gynaecology, Lund University Hospital, Lund, Sweden; 2 Praxis Dr. Sch¨onberg & Dr. Lorenbeck, Rheine, Germany; 3 Novo Nordisk FemCare AG, Zurich, Switzerland Objective: The influence of two ultra low dose HRT combinations with 0.5 mg E2 and 0.1 mg or 0.25 mg NETA on lipid and lipoprotein profiles, haemostasis and carbohydrate metabolism in healthy postmenopausal women was assessed. Additionally overall tolerability and safety endpoints were analysed. Design: Metabolic parameters were measured at baseline and after 12 and 24 weeks of treatment in a subpopulation of 120 women from Nordic countries. All adverse events occurring in the study from the first trial related activity, whether related or not related to the study medication were recorded and summarised (n = 575). The severity, seriousness, relationship to treatment and the reason for withdrawal were also reported. Results: Both ultra low dose HRT combinations showed neutral to favourable changes in lipid and lipoprotein, haemostasis parameters and carbohydrate metabolism in healthy postmenopausal women over the whole observation period. Only 1% of serious adverse events were reported in the safety population during the 24 weeks of the trial. The distribution of those events was similar in all treatment groups. No changes in weight gain or blood pressure were reported during the whole 6 months treatment. As a consequence of excellent tolerability and minimal side effects, the total drop out in 0.5 mg E2 + 0.1 mg NETA group was only 9%. Conclusion: The new ultra low dose HRT combinations were tolerated very well over the whole study period. Neutral to favourable changes were observed in metabolic parameters in healthy postmenopausal women. These excellent results open new possibilities for the treatment of menopausal symptoms.

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P04.11 Association between serum estradiol level and intraocular pressure in postmenopausal women Byung Moon Kang1 , C-H Kim1 , S-R Lee1 , H-D Chae1 , S-H Kim1 , H Lee2 , S-H Hong3 , E-J Park4 1 College of Medicine, University of Ulsan, South Korea; 2 College of Medicine, Kang Won National University, South Korea; 3 College of Medicine Chung Buk National University, South Korea; 4 Eul GI Medical Colledge, South Korea Objective: To find out whether any relationship exists between serum estradiol (E2) level and intraocular pressure (IOP) in postmenopausal women. Materials and methods: From January 1999 to December 2000, serum concentration of estradiol and intraocular pressure weremeasured in 2462 postmenopausal women. Serum concentration of estradiol was measured by radioimmunoassay. IOP was measured using Goldmann applanation tonometer. All data were analyzed with Student’s t-test, multiple logistic regression analysis, and multiple linear regression analysis. Results: The mean age of the study subjects was 56.2 ± 5.6. The mean E2 concentration was 13.4 ± 12.9 pg/ml. The mean intraocular pressures were 13.1 ± 2.6 mmHg, 13.0 ± 2.4 and 13.0 ± 2.6 mmHg for the left eyes, right eyes, and the average of both eyes, respectively. When the patients were divided into two groups and once again into four groups according to the E2 concentration, the IOP of each group did not differ significantly. On multiple linear regression analysis, no significant association was found between IOP and age or IOP and serum E2 concentration. Conclusion: This study suggests that in postmenopausal women no direct association exists between serum E2 concentration and IOP. P04.12 The effects of black cohosh root extract on the vasomotor symptom and bone metabolism ofmenopausal women Heung-Yeol Kim1 , B-I Lee2 1 College of Medicine, Kosin University, South Korea; 2 College of Medicine, Inha University, South Korea Introduction: Extract of the rootstock of Cimicifuga racemosa (black cohosh) have a traditional reputation as herbal remedies. for the last four decades case reports

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and clinical research with the socially manufactured C. racemosa extract have shown a good therapeutic efficacy and safe profile in the treatment of neurovegetative climacteric complains. Safety concerns associating 6 months use with climacteric complains and prevention of bone loss, have prompted the search for the effect of BCRE. Objective: To evaluate the effect of black cohosh root extract (BCRE) on vasomotor symptoms and bone metabolism in postmenopausal women. Methods: This prospective randomized clinical trial examined the effects of BCRE on vasomotor symptom and biochemical markers of bone turnover in 90 postmenopausal women. Treatment included BCRE (group I, n = 30) or 0.625 mg CEE (group II, n = 30), control group (group III, n = 30) for 6 months. Kupperman index and biochemical bone marker were measured at 0, 3 and 6 months. Results: Kupperman index decreased significantly at 3 months and 6 months of the treatment in groups I and II (p < 0.05). Urinary deoxypyridinolin decreased significantly at 3 months and 16 months of the treatment in groups I and II (p < 0.05). Conclusion: BCRE appears to be a safe and effective alternate to hormone therapy for vasomotor symptom and may be especially useful in women with intolerance or contraindication to traditional hormone therapy. P04.13 Effects of isoflavone on surgically menopaused women Chan-Hee Han, J-H Kim, H-H Jo, J-H Kim Catholic University of Korea, Department of Obstetrics & Gynecology, Seoul, South Korea Objective: To evaluate the effects of isoflavone intake on estrogen deprivated symptoms in surgically menopaused women. Methods: Premenopausal women who took total hysterectomy with both adnexectomy were randomized into three groups. One group took conjugated equine estrogen 0.625 mg daily for 12 weeks after surgery, the second group took isoflavone 100 mg daily for 12 weeks after surgery, and the third group took no medication for controlled group. Questionnaires about the acute menopausal symptoms, incontinence score, blood lipid profile, bone turnover marker were checked before and 12 weeks after surgery.

Results: Kupperman’s index and insentience score were showed less increased rate than control group. Total cholesterol and triglyceride were increased in all groups and HDL cholesterol was increased in estrogen and isoflavone groups. Osteocalcin was decreased in estrogen and isoflavone groups, ICTP was decreased in estrogen group, and increased in the other groups. Conclusion: Isoflavone was effective to acute postmenopusal symptoms, urogenital atrophy and bone turnover. Keywords: Isoflavone; Kupperman’s index; Incontinence; Bone turenover marker. P04.14 Menopause and determinants of quality of life at midlife and beyond S Schwarz1 , H V¨olzke2 , D Alte2 , C Schwahn2 , HJ Grabe2 , W Hoffmann2 , U John2 , Martina D¨oren1 1 Charit´ e-Universit¨atsmedizin Berlin, Germany; 2 Ernst-Moritz-Arndt-University Greifswald, Germany Objectives: There is an ongoing controversy about the association between menopause and quality of life (QoL). The objective of this study is to investigate to which extent mental and physical symptoms are associated with (a) menopausal status, (b) sociodemographic, psychosocial and lifestyle factors, and (c) menopausal hormone therapy (MHT). Methods: The Study of Health in Pomerania (SHIP) is a population-based, cross-sectional survey in the northeast of Germany. We used computer-aided interviews and questionnaires to capture QoL in 1,119 women, aged 40–-79 years. QoL was assessed using the von Zerssen Symptom List (ZSL). Additionally, the items of the ZSL were factor analyzed (4 factors: mood, pain, gastrointestinal (GI) symptoms and cardiopulmonary symptoms/sensory impairment. We investigated (1) the association between menopausal status and the ZSL, and (2) the association between menopausal status and the factor regression scores for each of the 4 factors after adjustment for confounders [socio-demographic parameters, psychosocial, and lifestyle indicators]. Results: Analyses suggest that menopausal status was not associated with QoL. MHT was associated with the ZSL-score and GI symptoms. Age was a significant predictor for cardiopulmonary symptoms and sensory impairment. The relation between age and the ZSL-score was inverse as was the relation between

Abstracts / Maturitas 54S (2006) S1–S112

age mood and gastrointestinal symptoms. Age, socioeconomic status, abuse, social support, nutrition, body mass index, self-rated health, chronic diseases and MHT modulated QoL. Conclusion: Our findings do not support the hypothesis that QoL is reduced after the menopause. Differences between pre- and postmenopausal women can be explained by socio-demographic, psychosocial and life-style factors. P04.15 The impact of the Women’s Health Initiative Study 2002 on perceived risk, communication and use of postmenopausal hormone therapy in Germany C Heitmann2 , E Greiser2 , Martina D¨oren1 1 Center of Public Health, University of Bremen, Germany; 2 Charit´e-Universit¨atsmedizin Berlin, Germany Objective: The purpose of this representative, nationwide telephone survey was to collect information about postmenopausal hormone therapy (HT) use in relation to women’s knowledge about the Women’s Health Initiative Randomized Controlled Trial 2002 (WHI-RCT) in Germany. Design: During July 2003, telephone interviews were conducted withrandomly selected women aged 45–60 years (n = 10.030; response 59.9%; completed interviews n = 67). They were asked about information sources regarding the WHI-RCT, and use of HT. Results: Most women stated that they knew about the WHI-RCT (88.6%),those with high educational status appeared to be have more information than those with middle or low educational status. Among informed women (uninformed excluded), 46.6% continued, 25.7% stopped, 14.2% ceased use of HT prior the WHI-RCT. The prevalence of lifetime use of HT was higher in West (37.4%) than in East Germany (29.2%), the highest prevalence of use was in the age group 55–59 years. The most common reason to continue HT was the benefit risk assessment by physicians (58%), to stop HT were women’s perceptions that risks of HT exceeded benefits (56%). If information was solely given by physicians, women were more likely to continue HT (60.4%), compared with mass media (46.1%), as source of information. Conclusions: The survey demonstrates the impact of the WHI-RCT in Germany, both media and advice by physicians were important. Women who continued use of HT did so largely because of their physician’s advice.

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Women who discontinued were mainly those who had a negative subjective perception about risk of HT. P04.16 Breast cancer and hormone replacement therapy after menopause Dae Hoon Kim1 , M-R Kim2 1 St. Vincent’s Hospital, The Catholic University of Korea, South Korea; 2 Kangnam St. Mary’s Hospital, The Catholic University of Korea, South Korea Objectives: To evaluate the breast cancer developed after postmenopopal hormone replacement therapy (HRT) and analyze the clinopathologic characteristics of breast cancer including the type of HRT and peroid used. Method: The study included women who were on postmenopausal routine follow-up at Department of Obstetrics & Gynecology, Kangnam St. Mary’s Hospital, Catholic University of Korea, from January 1995 to June 2004 and diagnosed of breast cancer after HRT. Result: Fourteen patients had breast cancer after HRT and their average age was 53.9. ± 3. Average menopause age was 48.2 ± 2, and 8 patients were naturally menopaused wherease 6 patients received hysterectomy and bilateral adnexectomy. HRT used before discovery of cancer were Premarin (n = 6), Livial (n = 2) and estrogen + progesterone (n = 2, Premarin + Dupaston, Climen). Four patients used more than 2 HRT medications. Average HRT period was 41.1 ± .9 months (1–132 months). Breast cancer stage are: stage 0, one patient; stage I, seven patients; stage IIA, three patients; stage IIB, two patients; stage IV, one patient. ER PR status were: ER(−)PR(−), five cases; ER(+)PR(+), two cases; ER(+)PR(−), two cases; ER(−)PR(+), one case. Modified radical mastectomy (MRM) was performed on seven cases and the combination of MRM and postoperative chemotherapy or radiation was done on seven cases. Disease free survival period was 38.4 ± 7 months and all patients are currently in disease free status. Conclusions: Number of breast cancer cases relate with HRT was 14 cases for 10 years. In our study, most patients were in early stage of breast cancer and the patient prognosis was relatively good.

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P04.17 Preparation of endometrium for egg donation and cryo/thawed embryo transfer programs with transdermal estradiol Oleg Berestovoy, V Zinchenko, V Veselovsky Isida Hospital, IVF Department, Kiev, Ukraine Background: Today cryo/thawed embryo transfer (CThET) and egg donation (ED) programs is a well established methods of assisted reproduction and offers the unique opportunity to treat patients with various clinical indications. The aim of this part of investigation was researching of effectiveness of transdermal estrogen endometrium preparing protocol with Divigel. Methods: We have analyzed outcomes of 51 cycles of CThET and 39 ED with Divigel protocol in compaison with 38 cycles of CThET and 21 ED with oral tablets route step-up protocol. Divigel protocol: under agonist desensitization from the 3rd to 5th cycle day start 2 mg Divigel daily for 10–11 days, then dose increase till 3 mg daily for 3–4 days when we make US exam to make decision either increase Divigel for a few days or start progesteron synchronization and ET four-cells embryo on the 3rd day of progesteron. Adequate progesterone concentrations were achieved with 50 mg i.m. injection and 300 mg progesterone vaginaly starting synchronization from 12 h before day “0” – day OR. Results: for CThET cycles pregnancy rate per embryo transfer was 28.1% for Divigel protocol versus 30.2% for oral route step-up protocol. for ED cycles pregnancy rate per embryo transfer was 45.7% for Divigel protocol versus 50.2% for oral route step-up protocol. Conclusion: Thus according to results today we have good established posibility in order to bypass the gastrointestinal tract thus avoiding first pass metabolism and prepare endometrium for ED and CThET programs with Divigel.

P04.18 Tibolone and its estrogenic metabolites have positive effects on biochemical markers surrogating on vascular tone and atherogenesis Alfred Mueck1 , L Kloosterboer2 , M Studen2 , H Seeger1 1 University Women’s Hospital, T¨ ubingen, Germany; 2 NV Organon, The Netherlands Objectives: Tibolone is a synthetic steroid used for the treatment of postmenopausal symptoms and osteoporosis. After absorption, tibolone is rapidly metabolized into two estrogenic metabolites, the 3␣- and 3␤-hydroxy tibolone, as well as into a progestogenic/androgenic metabolite, the delta4-isomer. Few experimental data have shown that tibolone and its metabolites may have beneficial direct effects on the vasculature. Methods: Endothelial cell cultures from human female coronary artery were used at passages 3–5. Tibolone and its metabolites 3␣-tibolone, 3␤-tibolone and delta4-tibolone were tested at the concentrations of 0.1 and 1 ␮M. for comparison, estradiol combined with norethisterone or medroxyprogesterone acetate, estradiol alone, norethisterone and medroxyprogesterone acetate alone were tested at the same concentrations. The biochemical markers eNO-synthase, prostacyclin, endothelin, pro-MMP-1, a precursor of MMP-1, PAI1, MCP-1, ICAM-1 and E-Selectin were measured by enzyme immunoassay. Results: Tibolone and its estrogenic metabolites were able to positively influence all markers. The effects were, however, less pronounced than those of estradiol combined with norethisterone or estradiol alone. Only the combination of estradiol with medroxyprogesterone acetate sometimes showed a lower activity than tibolone or its estrogenic metabolites. Conclusion: In the present study tibolone and its estrogenic metabolites positively influenced biochemical markers surrogating on vascular tone and atherogenesis. Long-term clinical studies are necessary to prove a beneficial effect of tibolone on the cardiovascular system.

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P04.19 Interpreting the Million Women Study: primary care prescribing of Tibolone in 2000 Sarah Gray1 , H Lambert2 , L Nutt2 , E Roberts2 1 Central Cornwall PCT, UK; 2 Peninsula Medical School, UK Objective: The Million Women Study (MWS) related breast cancer and endometrial cancer to usage of hormone replacement therapy. The results are observational, derived from a questionnaire completed by women attending the UK National Breast Screening Program. Usage was classified by the last used HRT. Primary care prescribing was audited to validate this assumption. Method: The MWS questionnaire asked for total HRT usage, most recent type of HRT and duration of use. The comparison audit focussed on the use of Tibolone in a primary care population during a 6-month period in 2000. During this time all 50–65-year-old women were invited for breast screening at a participating screening centre. All women who were prescribed Tibolone during the index period were identified from computerised prescribing records. Both computerised and paper versions of their lifelong health record were searched to identify all hormone therapy regimes, noting changes of regime and duration of use. Results: Twenty three women were identified. Three were excluded being outside the range of the MWS. Their average age was 56.9 (range 51–63) and they had taken an average of 25.3 (range 1–99) cycles of Tibolone. They had previously used 2.4 (0–9) different regimes of conventional hormone therapy for total of 60.5 cycles (0–203). Conclusion: The Tibolone users matched the MWS population but average Tibolone use appears too short to have significant effect on tumour incidence. Previous use of conventional regimes for over twice as long as Tibolone throws doubt on the association previously reported for this product.

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P04.20 Evaluation of coronary artery atherosclerosis using CACS in postmenopausal women on hormone therapy Da Jung Chung1 , JS Koo1 , KH Park1 , BS Lee1 , HS Moon2 1 Department of obstetrics and gynecology, Yonsei University College of Medicine, Seoul, Republic of Korea; 2 Department of Obstetrics and Gynecology, Good Moonhwa Hospital, Busan, South Korea Objective: To determine whether current hormone therapy (HT) in postmenopausal women with no coronary artery disease (CAD) risk factors is associated with subclinical coronary artery plaque burden assessed by coronary artery calcium score (CACS), whether any association varies by duration of HT, and whether known CAD risk factors are independently associated with CACS. Methods: A retrospective study was conducted of medical records of 120 postmenopausal women on HT without history or symptoms of CAD whose CACS were evaluated by multidetector row spiral computed tomography, from March 2003 until July 2005. CACS was analyzed according to age and duration of HT, and the association between CACS and CAD risk factors was evaluated. Results: CACS increased with age, especially from 60 years, and rapidly from 65 and thereafter. The prevalence rate of CACS higher than 0 also increased with age. CACS was significantly associated with age and obesity. CACS also showed weak correlation with total cholesterol, high density lipoprotein and blood pressure. No association between duration of HT and CACS was observed. Conclusion: Prevalence and severity of atherosclerosis in postmenopausal women on HT increased with age, and known CAD risk factors such as age, obesity, blood sugar levels and family history were significantly associated with CACS. However, there was no correlation between HT duration and CACS. A larger clinical study should be conducted to elucidate the role of HT on coronary artery calcium plaque.

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P04.21 Advances of tibolon therapy in women with surgical menopause Liberis Vasilios, T Panagiotis, G Georgios, T Ioannis, F Asterios, G Xenophon, Z Stefhanos, M Georgios University of Thrace, Department of Obstetrics and Gynaecology, Alexandapolis, Greece Introduction: Replacement of deficient hormones (HRT) is the main treatment modality in menopause. In this study we aimed to explore the effects of tibolone on symptoms of women with surgical menopause. Material and methods: During the period from 1 April 2000 to 31 October 2004, tibolone 2.5 mg daily was prescribed to women with climacteric symptoms in our Menopause centre. In a group of 40 women receiving tibolone one tablet of 2.5 mg daily for 4 years. The mean age was 47.5 years old. These women had abdominal or vaginal hysterectomy with bilateral oophorectomy for benign conditions were recruited into study after the operation. The frequency of menopausal complaints and instrumental tests (mammography, bone densitometry), as well as efficacy and side effects of the therapy were studied after 2, 4, 12 months of treatment. Results: During the 36-months follow up tibolone therapy effectively reduced menopausal complaints especially hot flushes and night sweats, caused no increase in the anamnestic risk factors, or serious side effects. Only 20% of the women reported adverse effects (breast tenderness and nausea), which turned out to be transitional. Tibolone treats protects against bone loss, without inducing significantly increased mammographic density or neoplasmatic disease of the breast. Conclusion: Tibolone is a valuable treatment option for women with climacteric complaints. Additional studies will determine whether the promise of increased safety with tibolone will be realized. P04.22 Comparison of transvaginal ultrasonography and endometrial biopsy findings in postmenopausal HRT users of tibolon Panagiotis Tsikouras, V Liberis, G Galazios, I Triantafyllidis, S Fotos, X Grapsas, N Koutlaki, G Maroulis University of Thrace, Department of Obstetrics and Gynaecology, Alexandrapolis, Greece

Introduction: The aim of this study was to estimate the efficacy of ultrasonography as a non-invasive method in detection of endometrial pathology in postmenopausal women with the use of Tibolone. Material and methods: A prospective investigation has been performed in 57 postmenopausal women not menstruating for more than a year, and who reported to Menopause centre, for strong climacteric ailments. Age of women ranged 44–49 years, mean 46.5 years. They received 2.5 mg-Tibolone/day for 4 years (01.05.2000 to 01.05.2004). Each woman underwent ultrasonographic examinations by a 5-MHz vaginal probe maintaining a 3-month interval and only once in a fraction curettage after 1 year of the treatment. Results: Endometrial thickness (double layer) was determined bytransvaginal ultrasonography (thinnest = 3 mm, the thickest was 12 mm) and compared with histological findings. During the Tibolone treatmentthe change in endometrial thickness was no differentpreviously. If endometrial thickness was <6 mm, the endometrial biopsy sample was either inactive/atrophic (78%) or insufficient for histological diagnosis (22%). In 8% of the cases ranged endometrial thickness was from 6–12 mm and endometrial biopsy showed endometrial polyp. Hyperplastic or malignant changes were not reported. Conclusion: Transvaginal ultrasonographic endometrial thickness measurement alone may allow adequate endometrial assessment and could safety decrease the number of curettages in detection of endometrial pathology. According to our view, transvaginal endometrial examination can be of distinct value in the detection of (pre)malignant endometrium. P04.23 Divigel and Divina in the rehabilitation and treatment of patients with Terner syndrome Ludmila Bondarenko1 , E Ivaschenko2 , 1 V Povoroznjuk 1 Research Institute for Endocrinology and Metabolism of the Academy of Medical Science, Ukraine; 2 Institute of Gerontology of The Academy of Medical Science, Ukraine Background: The work was aimed at a study of the efficacy of administration of Divigel and Divina in patients with Terner syndrome.

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Methods: Divigel was administered by 15 girls of 13–18 years of age with Terner syndrome (TS) once every 7th day for 2–2.5 years. In 2 years following the beginning of the study therapy, the second exam was performed, including the standard methods of analysis for TS patients. After such exam, Divina was administered in compliance with the selected scheme. The third examination of such patients was performed in 2 years. Results: In the beginning height of patients was on average 134.6 cm, mean weight 34.1 kg; BWI 18.7 kg/m2 . US densitometry was on average 78.8. Menses-like reactions were observed on the 2nd or 3rd cycle following the administration of Divina. Development of secondary sexual characters by the end of the second year following the beginning of administration of Divina corresponded to Ma III in 87.5% of patients, to Ds III in 100% and to Ax II–III in 87.5% of patients. Index of density of the bone tissue in the study group of patients was on average 77.3. Conclusion: Further administration of Divina favours the formation of female phenotype with a satisfactory development of the mammary glands and sex-related pilosis and onset of menses-like discharge providing for the maximum sexual and social adaptation of the patients. P04.24 Optimisation of administration of Fareston in females with diffuse fibrous cystic mastopathy and survived ovarian function Ludmila Bondarenko, E Ivashenko Research Institute for Endocrinology and Metabolism of the Academy of Medical Science, Ukraine Background: A study of the efficacy of Fareston in the treatment of diffuse fibrous cystic mastopathy (DFCM) and of the tolerance and incidence of side effects of the administered therapy with Fareston in females with the survived ovarian function (SOF). Methods: Ninteen patients of 37–48 years of age with DFCM and SOF received Fareston in the doses of 30 mg daily for 6 months continuously starting from the 5th day of the cycle and 5 mg of Levonorgestrel daily on days 16 through 24 of the cycle during 6 consecutive cycles. All patients underwent exam before and in 3 and 6 months of the study treatment. Standard clinical tests were performed. All patients were under supervision of mammologist.

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Results: After 6 months of the study treatment, a substantive improvement was noticed:alleviation of breast pain, reduction of diameter cysts is noted on the average about 13 cm up to 5 cm, decrease in the number of small cysts (less than 5 mm), by 28.6%, and a reduction of the breast hardness. During the two phase of the cycle, the size of the ovary did not change, menses were regular, non-heavy and painless. Reduction of endometrium height is noted on the average about 11.4 mm up to 8.1 mm after the treatment. Conclusion: The obtained results suggest an efficacy and safety of administration of Fareston in the treatment of DFCM in women with SOF according our scheme. P04.25 The relationship between the concentration of plasma estradiol and antioxidant in ovariectomised rats Hyuk Jung Chosun University Hospital, Department of Obstetrics & Gynecology, Gwang Ju, South Korea Objective: To observe whether any relationship exists between the concentration of plasma estradiol (E2) and the plasma concentration of malondialdehyde (MDA) or whether a relationship exists between the concentration of plasma E2 and the activity of erythrocyte enzymes, superoxide dismutase (SOD) and catalase, in ovariectomized female Sprague–Dewley rats. Materials and method: We used 40 ovariectomized Sprague–Dewley rats randomly assigned to four groups. The first group (group A) was allowed to evolve freely with no estrogen supply. A gel containing 17␤estradiol was administered transdermally to the other three groups at dose of 5 (group B), 10 (group C) and 15 ␮g/day (group D). After 2 weeks of recovery date from operation and 4 weeks of estrogen treatment, blood samples were obtained from the four groups. The concentrations of plasma E2 and MDAand the concentrations of erythrocyte catalase and SOD were determined. Results: There were significant correlations between the plama E2 concentrations and the concentrations of erythrocytes catalase and SOD in the group C, D. Whereas, catalase and SOD activities in erythrocytes was decreased in hormone replacement group. Any relationship wasn’t found between the

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E2 concentrations and the plasma MDA levels in all groups. Conclusion: This result suggested that the catalase and SOD in erythrocytes should be related the plasma E2 concentration. This model may explain the contradictory findings presented by estrogens with respect to their pro- or antioxidant action. The further study will be needed to evaluate the effect of estrogen induced plasma lipid peroxidation. P04.26 Effect of postmenopausal hormone replecement therapy on leptin level and body composition Sung-Ha Lee, J-H Kim, J-H Kim, Y-O Rew, D-H Kim Catholic University Medical College, Department of Obstetrics & Gynecology, Seoul, South Korea Objective: To compare the women who use postmenopausal hormone replacement therapy to never user for the serum leptin level and degree of obesity, then evaluate the precausing factor of postmenopausal obesity. Method: We checked the serum leptin level, blood chemistry and body composition in three groups, two groups are postmenopause groups which is HRT user (n = 125) and HRT never user (n = 194), and the other is premenopause groups (n = 82). We used SPSS and Excel for analyzed the difference between the groups. Result: BMR is decreased after menopause, body fat ratio, abdominal fat ratio, BMI, leptin, sugar, and cholesterol level are increased after menopause. There is no difference between the postmenopausal HRT group and non-HRT group in body fat composition, abdominal fat ratio, BMI,BMR,AMC and leptin levels. Serum sugar level shows positive correlation with the leptin level in pre and postmenopausal women after exclude the effect of body fat ratio. Serum estradiol and leptin level shows positive correlation.(correlation coefficient 0.68 in postmenopausal non-HRT group and 0.735 in postmenopausal HRT group). Conclusion: Serum estradiol and sugar level have some correlation with leptin level and leptin resistance in postmenopausal women, and decreased estradiol level caused obesity through increased leptin resistance.

P04.27 Lipid profile on oral and non-oral hormone therapy in menopause Manuela Russu1 , S Nastasia1 , N Mubarak2 , D Hudita1 1‘ Carol Davila’ University ofMedicine and Pharmacy, Bucharest, Romania; 2 Titan Center of Diagnosis and Treatment, Romania Objective: Assessment of oral and non-oral hormone therapy (HT) on lipid profile in menopause. Patients and methods: There are retrospectively analyzed at 6, 12, 24 months LDL-, HDL-, total cholesterol, triglycerides in 50 postmenopausal women on 5 types of sequential HT (estrogens-oral/transdermal, and progesterone/progestins-oral/vaginal, duration of progesterone/progestins-12/14 days/month and cyclic 14 days at every 3 months) compared to 10 controls, untreated postmenopausal patients. We appreciated as protective for atherosclerosis: total cholesterol <200 mg/dl, LDL-c <130 mg/dl, HDL-c >65 mg/dl, triglycerides <150 mg/dl. Results: After 6 months of HT: increased total cholesterol: seven treated (14%), four untreated (40%); HDL-c in normal limits: 12 treated (2.4%), no one control; HDL-c of 50–64 mg/dl: 34 (68%) studied, eight (80%) controls; HDL-c <50 mg/dl: four (8%) studied and two (20%) controls; triglycerides >150 mg/dl: 10 (20%) treated, six (60%) controls. After 12 months of HT: total cholesterol >200 mg/dl: five (10%) treated, four (40%) controls; increased LDL-c: four treated (8%), eight (80%) controls; high triglycerides: 10 (20%) studied, six (60%) controls. We registereda reduction of: total cholesterol (with 12%, 15–18%, and 18% at 6, 12 and respectively at 24 months), of LDL-c (with 20%, 25% at 6 and respectively at 12, 24 months) in all treated groups, triglycerides (only with transdermal estrogens: with 14%, 15% at 6 and respectively at 12, 24 months), the increase of HDL-c (with 8–10%, 14–18% at 6, and respectively at 12, 24 months, the greatest values being on vaginal micronised progesterone). Conclusions: The lipid profile was positively influenced after the first 6 months, with best values at 12 months (p < 0.05), maintained at 24 months. Oral estrogens induced a light raise of triglycerides. The best antiatherogenic results were with vaginal and cyclic at 3 months micronised progesterone (p = 0.01 for cholesterol, 0171 for HDL-c, 00002 for LDL-c).

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P04.28 HRT version of immobilisation in the surgical practice of a gynaecologist Stanislav Leush1 , G Roshina, V Terentyuk, P Karpuk Kiev Medical Academy of Postgraduate Education, Ukraine Background: A validation of and a report on the results of implementation in the gynaecological clinical practice of HRT versions in 1051 postmenopausal women before and after surgical intervention because of prolapse and urogenital disorders (UGD), that has authentically provided quality of a life of patients. Methods: An analysis of 1051 cases of postmenopausal patients who have underwent surgery for prolapse and UGD makes it possible to substantiate the scope of intervention and a choice of agents and methods for prevention of purulo-inflammatory complications. Receptors of sex hormones are available in all urogenital structures, which makes it possible to select a correct configuration of dissection and splitting, assess the course of wound process in case of a surgical correction of descents and foresee HRT effects in target organs and results of corrective surgery. Results: A success of an intervention depends also on the choice of HRT determining a mild course of reparative processes. Conclusion: We recommend to administer estrogencontaining transdermal gels during preoperative treatment for a month or even longer. HRT agents are valuable components of surgery for prolapse and UGD. HRT administered during a perioperative period substantially improve the characteristics of the activity of a gynaecological hospital and the quality of life of a woman. P04.29 Isoflavones:effects on haemostasis and lipid profile in postmenopausal women Danyelle Romana Rios1 , SA Franceschini2 , MBA Montes1 , F Barbosa1 , LHD Costa1 , MRT Toloi1 1 Faculty of Pharmaceutical Sciences of Ribeir˜ ao Preto/USP, Sao Paulo, Brazil; 2 Integrated Services for Health-USP/SISUSP, Sao Paulo, Brazil Introduction: Cardiovascular disease (CVD) is associated with unfavorable alterations of lipid profile and haemostasis, proceeding from decrease of the estrogenic activity in postmenopausal women. Hor-

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monal Replacement Therapy (HRT) has been much debated because some studies show HRT increases breast cancer predisposition and it does not protect against cardiac diseases. attempting to reach treatment to menopause symptoms, minimizing side effects, we suggest isoflavone, a natural compound extracted from soy (Glycine max) protein that has a effect estrogen like. Objective: To evaluate the effects of the isoflavone on haemostasis and lipids levels in healthy postmenopausal women. Methods: In this double blind placebo-controlled study, 35 postmenopausal women of age 47–66 years received 40 mg isoflavone-GALENA® (n = 20) or 40 mg casein placebo (n = 15). Levels of hemostatic factors [PT, APTT, activity factors VII and X, and ® ) and lipids [total choles` fibrinogen (BIOMERIEUX terol/TC, triglycerides/TG (BAYER® ), High Density Lipoprotein/HDL (LABTEST® ), Low Density Lipoprotein/LDL and Very Low Density Lipoprotein/VLDL] were measured at baseline and 6 months. Results: Levels of hemostatic variables did not change significantly throughout the study in isoflavone group; however placebo group experienced statistically significant reduction in plasma concentration of fibrinogen (11.6%). Levels of lipids (LDL and TC) decreased no significant similarly in both groups. HDL decreased significantly in the isoflavone group (7.4%), but the change was not different to the placebo group (11.9%). Furthermore, in both groups were increased no significant of levels VLDL and TG. Conclusion: The results of the current study do not support biologically significant estrogenic effects of isoflavone on coagulation and lipid profile. P04.30 Post-menopause hormonal therapy: the continuity after the menopause consultation Alexandra Sofia, I Marques, A Cruz, F Geraldes, ´ F Ventura, F Aguas Maternidade Bissaya-Barreto, Department of Gynecology, Coimbra, Portugal The results of the recent studies about the use of hormonal therapy (HT) and the way they were interpreted and revealed, led to a rethinking of its therepeutical use, as well a drastic reduction of its use. In order to evaluate the impact of this situation, a group of 879 women was questioned. This group had been followed

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and had been discharged fom the consultation, with the indication to continue being followed by their Family’s Doctor. Through a survey, which was posted, we tryed to know if they were maintaining the prescribed HT, how it was watched, if there was any significant modifications in their health and if they knew about the news spread by the media. The analises of the 506 answers revealed that only 34% of the women mantained the HT, 65% of those who suspended said that besides economical difficulties, they were afraid of cancer and heart diseases. Concerning health modifications there is only a register of four cases of breast cancer (1%) and the aggravation of bone problems in 54 cases. After this suspension 67% of the questioned women showed symptoms related to the lack of estrogen. Out of this sample only 22% refer to having heard the news. These results show a very significant reduction of the use of the HT, although less than 1/3 of the women seem to have given special importance to the divulged news. P04.31 Estradiol replacement influence on lipids metabolism in women with surgical menopause A Andreyev, N Izmozherova, Artem Popov, A Akimova, N Tagiltseva Department of Internal Medicine No. 2, Ekaterinburg, Russian Federation Aim: Assessment of estradiol replacement influence on lipids metabolism in women with surgical menopause. Methods: The main group consisted of 48 females with surgical menopause who received estradiol (Proginova 2 mg) replacement for at least 6 months after surgical menopause. The control group included 48 females with surgical menopause who had decided not to take estrogenes. The groups were matched by age, age of total hysterectomy and body-mass index. Total cholesterol, high density lipoproteins (HDLP), low density lipoproteins (LDLP), triglycerides (TG), apolipoproteines A1 and B (apoA1 and ApoB) were measured in blood sera after 14 h fasting. Results: Those who received estradiol had significantly higher levels of HDLP (1.47; 95% CI: 1.22–1.8 mmol/l) and ApoA1 (187.5; 95% CI: 143.3–199.9) than control group (1.29; 1.02–1.51 and 126.35; 119.2–154.7, respectively). Aterogenic index was also significantly lower in estradiol group.

Conclusion: In patients with surgical menopause, estrogen replacement has a positive influence on lipids metabolism. P04.32 Low dose estrogen replacement therapy and symptoms in postmenopausal women Yesica Navarrete2 , M Fajardo1 , J Malacara1 1 Universidad de Guanajuato, Instituto de Investigaciones Medicas, Mexico; 2 Instituto Mexicano del Seguro Social, Mexico Aim: To compare the effect of low dose estrogen treatment (LE) with the conventional dose estrogen (CE), estrogen + progesterone (CE + P), and placebo (P) on symptoms in postmenopausal women. Methods: A prospective, randomized, doubleblind, placebo-controlled trial was carried out for 3 months. Postmenopausal women without diabetes, smoking habit, or HRT during the 3 previous months were invited to participate. Seventy volunteers (52.2 ± 4.4 years of age) were randomly assigned to 4 treatments: (1) CE + P, conjugated equine estrogens 0.625 mg/d + micronized progesterone 2.5 mg/d (n = 20); (2) CE, estrogens 0.625/d mg (n = 20); (3) LE, estrogens, 0.315 mg/d; (4) P (B vitamin complex) (n = 10). A questionnaire recording vasomotor symptoms, depressive mood, anxiety, sleep disturbances, and vaginal dryness was applied before and after 3 months of treatment. Results: After 3 months, the LE treatment induced a greater decrease in the hot flashes scores (p < 0.006) than the CE and CE + P groups. The LE treatment also permitted a similar reduction in the anxiety index (p < 0.002). We found a significant decrease in depression with the LE treatment (p < 0.0006) and with the CE (p < 0.0006), but not with CE + P treatment (p = 0.12). Improvement of sleep alterations was only found in the CE group (p < 0.001). Vaginal dryness improved after LE (p < 0.002), CE (p < 0.02), and CE + P (p < 0.015). The placebo group induced only a marginal improvement in vaginal dryness (p = 0.02). Conclusions: We found that low dose estrogens have similar effect on symptoms at menopause than using conventional doses with or without progesterone. Our results support further investigation comparing their long-term side.

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P04.33 The effect of low-dose hormone therapy on endometrial thickness and vaginal bleeding Jana Z Zaidieva, A Glus, LS Minasyan, S Gasanova Research Centre of Obstetrics, Gynaecology & Perinathology, Russian Academy of Medical Science, Department of Gynaecological Endocrinology, Moscow, Russia Objectives: The aim of this study was to evaluate the endometrial safety of low-dose continuous combined estrogen–progestin therapy and incidence of vaginal spotting/bleeding over a 1-year period. Methods: Twenty-eight postmenopausal patients with climacteric symptoms underwent on continuous oral administration of 17␤-estradiol 1 mg/didrogesterone 5 mg. The mean age was 52.69 ± 4.02; the time since natural menopause was 2.73 ± 0.4. All patients were assessed at study entry and at 12 months intervals with transvaginal ultrasonography, colour Doppler analysis of blood flow in the uterine arteries and had an endometrial aspiration Pipelle-biopsies for histological assessment. Results: The study was completed by 24 women (85.7%). The drop out rate due to spotting/bleeding was 14.3%. The mean endometrial thickness at baseline was 3.6 ± 0.85 mm versus 3.3 ± 0.65 mm during the therapy (p > 0.05), in two cases (7.14%): 10 and 11 mm, and one case of endometrial polyp was found. Hystologically, atrophy was found in 22 (78.6%) cases at the time of study entry (with six cases of insufficient tissue sample for histological assessment) and in 20 (83.3%) cases under the cc-HT (in four cases, insufficient tissue sample for histological assessment). The mean pulsatility index (PI) not significantly decreased during the therapy (1.67 ± 0.6 versus 1.49 ± 0.57, p > 0.05). The mean resistance index (RI) at baseline and after 12 months of treatment were 0.79 and 0.74 (p > 0.05). Conclusion: Women received low-dose cc-HT associated with low incidence of vaginal spotting/bleeding and did not appear to associate with significant changes in endometrial thickness during the hormone therapy use.

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P04.34 Effects of tibolone on sulfatase pathway of estrogens metabolism and on growth of MCF-7 human breast tumours implanted in ovariectomised nude mice Jo¨elle Desreux1 , H Kloosterboer2 , A No¨el1 , F Frankenne1 , M Lemaire3 , M Putman4 , J-M Foidart1 1 CHU Sart-Tilman, Laboratory of Biology of Tumors and Development, Li`ege, Belgium; 2 Organon, Research and Development Laboratories, Oss, The Netherlands; 3 Organon Belgium, Bruxelles, Belgium; 4 Xendo Laboratories, Groningen, The Netherlands Background: The benefits of estrogen plus progestin in healthy postmenopausal women remain uncertain. Tibolone, with its in vitro documented inhibitory effects on estrogens metabolism and its selective action on breast, may be an alternative that could favourably influence the health benefit of hormone replacement therapy (HT). Methods: We studied the effect of tibolone on the tumour growth of MCF-7 cells implanted in 40 ovariectomised nude mice, receiving subcutaneous pellets of 17␤-estradiol, estrone, estrone-sulfate or placebo, and daily gavages of tibolone or placebo. Results: Tibolone, although used at high dose, did not stimulate nor inhibit the estrogens-induced tumours, nor the tumours in estrogens deprived mice. Plasma levels of estrogens indicated that tibolone reduced steroid sulfatase activity and even more potently stimulated sulfotransferase activity, but intratumour levels of estrogens were not significantly modified by tibolone. Conclusions: This in vivo study performed with high dose of orally administered tibolone that allowed its hepatic conversion into active metabolites has shown no significant effect on breast tumours growth. Tibolone modified, by its activity on the sulfatase pathway of estrogens, the circulating but not the intratumour levels of estrogens. P04.35 Treatment with a levonorgestral-releasing intrauterine device in women affected by adenomyosis associated menorragia Semih Mun, FH Celymly, G Deryn Aegean Maternity and Teaching Hospital, Department of Obstetrics and Gyneacology, Izmir, Turkey Objective: To evaluate the efficiacy of treatment with a levonorgestral-releasing intrauterine device in

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women affected by adenomyosis associated menorragia. Material and method: Forty-two women aged 42–48 years old with recurrent menorragia associated with adenomyosis diagnosed with transvaginal ultrasonography were participated in this study. Intrauterine device releasing levonorgestral 20 ␮g/day was inserted to all patients. All patients were examined by transvaginal ultrasonography, serum hemoglobin levels were assessed and menstrual patterns of them were asked. Results: Forty-two patients were followed for a year. P04.36 Current HRT use among Norwegian women Anita Øren1 , MH Moen2 , N Fjellvang3 , F Egil Skjeldestad1 1 Department of Epidemiology, SINTEF Health Research, Trondheim, Norway; 2 Department of Obstetrics and Gynecology, St. Olavs University Hospital, Trondheim, Norway; 3 Novo Nordisk Skandinavia AS, Oslo, Norway Introduction: After publication of the WHI study, HRT use has been significantly reduced in several countries. In Norway, the sales of HRT fell by 50% from 2002 to 2005. We wanted to study which Norwegian women who utilised HRT in 2005. Material and methods: A questionnaire about use, attitudes and knowledge of HRT was undertaken during 2005. A representative sample of 4988 Norwegian women 45–64 years of age was asked to participate, among whom 2325 responded (47%). Chi-square test and logistic regression analyses were performed. Results: In total 40% of the women were ever-users of HRT, while 14% were current users. Women having a positive attitude in recommending HRT to a friend had higher knowledge about symptom relief and diseases associated with HRT-usage compared to women who would not recommend HRT to a friend. Current users had more often a positive attitude to recommend HRT to a friend; usage increased by increasing age and was negatively correlated to self-defined health status (good vs. poor) when compared with never users. Variables such as marital status, education, income, smoking, pregnancy history, or OC usage did not predict current use of HRT. Conclusion: A typical HRT-user in Norway has higher knowledge about symptom relief and diseases associated with HRT, and has therefore a much more

positive attitude to recommend HRT to a friend than a non-user. Education on health benefits and provision of realistic information on diseases associated with usage of HRT are important issues in creating positive attitudes towards HRT usage. P04.37 Continuous-combined HRT improves quality of life in early postmenopausal women Stiina Ylikangas, Writing Group for the Indivina Orion Pharma AB, Sollentuna, Sweden Objectives: We assessed the effects of continuouscombined HRT (Indivina® , Orion Pharma, Finland) on health-related quality of life (HRQoL) in early postmenopausal women. Methods: Subjects were randomised to receive 1 or 2 mg of estradiol valerate (E2V) combined to 2.5 or 5 mg medroxyprogesterone acetate (MPA) for 12 months in a double-blind multicentre trial. HRQoL was measured at baseline and 12, 24, 36 and 52 weeks. Two validated and self-administered measures, generic 15D and menopause-specific Women’s Health Questionnaire (WHQ), were used. Results: Four hundred and fifty nine women (mean age 51.5 years) started, and 401 (87%) completed the study. With both measures the HRQoL improved significantly in all treatment groups after 12 weeks (p < 0.0001), and this improvement was maintained until the end of the study. The 15D score representing the overall HRQoL increased by 0.06, which indicates a clinically relevant improvement. The benefits of HRT were significant in multiple dimensions of the 15D, being largest in the dimension ‘sleeping’. Other 15D dimensions where major improvements were observed included, e.g., sexual activity, distress, vitality and depression. The results were consistent with the WHQ; the largest improvements after 52 weeks of treatment were found in the subscales ‘sleep problems’ and ‘vasomotor symptoms’. No significant differences were observed in change of overall HRQoL, different dimensions of 15D or subscales of the WHQ between the three treatment groups at any time. Conclusions: Both generic and specific HRQoL measures demonstrated that continuous-combined HRT improves all aspects of HRQoL when used by early postmenopausal women for the relief of climacteric symptoms.

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P04.38 Continuous-combined HRT improves quality of life in early postmenopausal women Mika Mustonen, Writing Group for the Indivina Orion Pharma, Espoo, Finland Objectives: We compared the safety profile of three continuous-combined estradiol valerate/medroxyprogesterone acetate (E2V/MPA) regimens (Indivina® , Orion Pharma, Finland) in early postmenopausal women. Methods: Subjects randomised to three parallel groups received 1 mg E2V with either 2.5 or 5 mg MPA, or 2 mg E2V with 5 mg MPA in this 12-month, double-blind multicentre study. Endometrial biopsies were performed at baseline, week 24 (if endometrial thickness was >4 mm) and week 52. Subjects recorded any bleeding/spotting in diaries. Adverse events were recorded at each visit. Results: Of 459 subjects (mean 51.5 years, range 30–63 years), 401 (87%) completed the study, with fewer women discontinuing in the lowest dose group (13 versus 22/23). Atrophy/inactive endometrium was seen in >88% of baseline samples. No relevant changes were observed during study as >92% of samples were atrophic/inactive/insufficient at 52 weeks. No endometrial hyperplasias were detected. Most patients had no bleeding during the study. Mean number of bleeding days at cycle 4 was significantly lower for lowdose options (1.53 days for 1 mg E2V + 2.5 mg MPA; 0.99 days for 1 mg E2V + 5 mg MPA) compared to the higher E2V/MPA dose option (2.37 days) (p < 0.005). Potentially drug-related adverse events were generally mild and those commonly reported with HRT. More events, 46.7% of all reported, occurred in the higher E2V/MPA group compared to 26–27% in the low-dose groups (p = 0.0001). No serious cardiac or vascular events or breast cancers occurred during study. Conclusions: All doses provided excellent bleeding control and endometrial protection and were well tolerated, with a more favourable profile for lower doses. P04.39 Low dose HRT sufficient for severe hot flushes in early postmenopausal women Mika Mustonen, Writing Group for the Indivina Orion Pharma, Espoo, Finland

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Objectives: We compared the efficacy of three dose options of continuous-combined estradiol valerate/medroxyprogesterone acetate (E2V/MPA) regimens (Indivina® , Orion Pharma, Finland) on climacteric symptoms in women close to menopause who are most likely to experience severe hot flushes. Methods: Subjects were randomised to receive 1 mg E2V with 2.5 mg or 5 mg MPA, or 2 mg E2V with 5 mg MPA for 12 months in a double-blind fashion. Subjects recorded severity and frequency of hot flushes daily, and assessed all climacteric symptoms using a Visual Analoque Scale (0–100 mm, severe symptoms ≥ 60 mm). Results: A total of 459 women (mean age 51.5 years; 30–63 years) from eight European countries started the study treatment, and 401 (87%) completed the study. Majority of women had severe hot flushes (66%), sweating (65%) or sleeping problems (55%) at baseline. Median VAS scores for these symptoms ranged from 63 to 70 at baseline. A lower number of women reported severe moodiness (35%) or vaginal dryness (29%) at baseline and the median scores for these symptoms were also lower, 50 and 43, respectively. Significant improvement was apparent for all symptoms from the first 1–2 weeks onwards in all dose groups. After 4 weeks, no differences were seen between the doses, and improvement in the frequency and severity of moderate to severe vasomotor symptoms was highly significant (p < 0.0001) at 12 weeks with all treatments. Conclusions: Low-dose HRT is sufficient to relieve also very severe climacteric symptoms in early postmenopausal women. P04.40 A retrospective analysis of side effects observed in menopausal women using hormone treatment (HT) Hikmet Hassa1 , HM Tanir1 , S Kahraman1 , T Oge1 , F Sahin Mutlu2 1 Eskisehir Osmangazi University School of Medicine, Department of Obsbterics and Gynecology, Turkey; 2 Eskisehir Osmangazi University School of Medicine, Department of Biostatistics, Turkey Objective: This study was performed to assess side effects of different HT regimens. Methods: One thousand one hundred and forty five women with established menopausal signs and symptoms were admitted to our menopause clinic between

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2001 and 2004. HT was initiated in 604 cases. Types of HT regimens consisted of oral cyclic- or continouscombined E + progestin (P) and tibolone. Results: Mean age of women with HT was 49.2 ± 5.7 years. In cyclic-combined E + P (n:112), and continous-combined E + P (n:204) group, 24 (11.7%) women have with side effects of edema and weight gain (n:15), nausea and vomiting (n:3), allergic reaction (n:3) and irregular vaginal bleeding episodes (n:3). However elevated liver enzymes (n:1), development of hypertension (n:1) and libido loss (n:1) were only seen in continous-combined HT group. Among tibolone users (n:128), In 10 (7.8%) cases had side effects like weight gain (n:3), vaginal bleeding (n:3), elevated liver enzymes (n:1), state of nervousness (n:1), nausea (n:1) and allergic reaction (n:1). Conclusion: Adverse effect for various forms of HT is one of the leading factors for HT discontinuation and poor treatment compliance. Hence, every efforts should be made to tailor appropriate HT regimen on individual basis and to reassess, regularly, the treatment effect as to obtain a better and long-term drug compliance. P04.41 Attitudes of menopausal women towards hormone treatment (HT) during first admission to the menopause clinic Hikmet Hassa1 , HM Tanir1 , B Tekin1 , S Kahraman1 , T Oge1 , F Sahin Mutlu2 1 Eskisehir Osmangazi University School of Medicine, Department of Obsbterics and Gynecology, Turkey; 2 Eskisehir Osmangazi University School of Medicine, Department of Biostatistics, Turkey Objective: This retrospective study was performed to elucidate the attitudes and feeling of menopausal women first admitted to our clinic, prior to any form of HT regimen application. Methods: One thousand one hundred and forty five women with established menopausal signs and symptoms were admitted to our menopause clinic between 2001 and 2004. Results: Of 1145 cases, 296 (25.8%) women were unaware of the presence of any form of HT regimen, while, 849 (74.2%) women have heard it. Of 849 women, the origin of knowledge were from: male physicians (44.8%), female physicians (20%), nurses (2%) family relatives (9.7), television (10.7%), journals (6.9%). Past HT use was present in 231 (20%) of

women, while in 633 (55%) cases. Main rationale of 559 women with non-compliance were as follows: lack of adequate counselling (30.1%, n:168), fear of cancer (23.4%, n:131), pressure from surroundings (9.8%, n:55), presence of medical problems (8.8%, n:49), weight gain (4.8%, n:27), bleeding (3.8%, n:21), financial reasons (15.2%, n:85), allergic reactions (0.9%, n:5), being useless (2.3%, n:13). Conclusion: Given the results of the study, majority of menopausal women still have doubts on whether to initiate or continue HT. Furthermore, lack of adequate counselling and fear of cacer remained the two main issues leading to poor compliance. Therefore, in addition to counselling efforts of health workers, a mass campaign covering all institutions should be currently planned to overcome the low rate of HT use. P04.42 Demographic characteristics of menopausal women using hormone therapy (HT) in an university hospital of mid-Anatolian region of Turkey Hikmet Hassa1 , HM Tanir1 , A Yildirim1 , S Kahraman1 , T Oge1 , F Sahin Mutlu2 1 Eskisehir Osmangazi University School of Medicine, Department of Obsbterics and Gynecology, Turkey; 2 Eskisehir Osmangazi University School of Medicine, Department of Biostatistics, Turkey Objective: This retrospective study was an attempt to document the various demographic characteristics of menopausal women for better counselling with regard to appropriate hormone therapy regimens. Methods: One thousand one hundred and forty five women with established menopausal signs and symptoms were admitted to our menopause clinic between 2001 and 2004. HT was initiated in 604 cases. Demographic characteristics of them were evaluated. Types of HT regimens consisted of oral conjugated equine estrogen (CEE) only, transdermal E, oral cyclic- or continous-combined E + progestin (P), nasal E, vaginal E tablet and tibolone. Results: Oral CEE only (n:85), transdermal E (n:61), Cyclic-combined E + P (n:112), continous-combined E + P (n:204) nasal E (n:5), vaginal E tablets (n:9) and tibolone (n:128) were used. Mean age of women with HT was 49.2 ± 5.7 years. Mean gravidity, parity and living children were, 4.1 ± 3.2, 2.5 ± 1.3, 2.2 ± 0.6, respectively. Mean age at menopause was 45.7 ± 6.8 years. Seventy-two percent (n:435) women

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harbored natural menopause, while surgical and premature menopause were seen in 24.2% (146) and 3.8% (n:23) cases, respectively. In 48.5% of women in whom HT was initiated, no history of sport activities was obtained. Medical problems were present in 48.5% of cases. Conclusion: Prior to initiation of an appropriate form of HT, demographic characteristics of menopausal women should be contemplated and counselling should be performed accordingly.

sity). In continous-combined HT group, all 13 women had mammographic abnormalities, including increased parenchymal density (n:8), microcalcifications (n:3), presence of pathological lymph node (n:1) and the presence of opacity (n:1). One case (2.5%) in tibolone group (n:40) harbored increased parenchymal density. Conclusion: In menopausal women, mammographic changes with different HT regimens should be carefully investigated for the presence of benign or malignant breast lesions.

P04.43 Do different forms of hormone treatment (HT) have an impact on mammographic findings of menopausal women? Hikmet Hassa1 , HM Tanir1 , SS Ozalp1 , OT Yalcin1 , S Kahraman1 , T Oge1 , F Sahin Mutlu2 1 Eskisehir Osmangazi University School of Medicine, Department of Obsbterics and Gynecology, Turkey; 2 Eskisehir Osmangazi University School of Medicine, Department of Biostatistics, Turkey

P04.44 Weak oestrogens and the antioxidant effect Gabor Beksi, Z Tulassay, J Feher, B Szekacs, R Kakucs, E Riss, Z Magyar, J Rigo, K Racz Semmelweis University and Maecenator Foundation, Budapest, Hungary

Objective: The effects of different forms of HT regimens on mammographic findings of menopausal women at 12 months following the drug initiation were evaluated. Methods: HT was initiated in 529 cases, all of whom were mammographically normal at the start of the treatment. Mean age at menopause, types of HT regimen consisted of oral cyclic-, continous-combined E + progestin (P) and tibolone were analyzed after 12 months. Abnormal mammographic findings were categorized as the presence of increased symmetrical or asymmetrical parenchymal density, presence of unilateral or bilateral microcalcifications, mass lesion or presence of any opacity. Results: Oral CEE (n:85), cyclic-combined E + P (n:112), continous-combined E + P (n:204) and tibolone (n:128) were used. Mean age of women was 49.2 ± 5.7 years. Of 529 women, 94 (17.8%) women were reassessed 12 months following the first admission. Out of 94 women, Thirty-one (32.9%) women had mammographic abnormalities. Of all women admitted to the clinic, in 16 cases with oral CEE, nine (56.2%) revealed mammographic abnormalities, most of which were increased parenchymal density (n:6). In 24 cyclic-combined HT group, 8 (33.3%) women harbored suspicious mammographic findings (two microcalcifications; six increased parenchymal den-

In our in vitro experiment we intended to test whether beyond the known antioxidant effect of 17␤-oestradiol, such a property is also possessed by the two weak oestrogens oestrone and oestriol. Blood samples were obtained from five healthy volunteers and neutrophil granulocytes were separated for measurement of superoxide anion generation after incubation with 10−7 , 10−6 and 10−5 M concentrations of oestrone, oestriol and as a reference with 10−7 M of 17-␤-oestradiol. Superoxide anion production of isolated neutrophil granulocytes was quantified by photometry and using the reduction of ferricytochrome-C. When adding oestrone and oestriol to neutrophil granulocyte suspensions, the production of superoxide anion fell (10−5 M: 84.17 ± 3.14%; 88.77 ± 1.98% of control production; p < 0.01 and p < 0.05, respectively). Oestradiol produced an antioxidant effect expectedly at lower (10−7 M) concentration (72.91 ± 7.94% of control production; p < 0.001). Oestrone and oestriol, similarly to oestradiol, also are able (in greater concentration, than the stronger oestrogen 17-␤-oestradiol) to reduce the superoxide anion release in our experimental model. This may have importance in the antioxidant defence of biological systems. An interesting point is the difference between the powers of the effect of certain oestrogenic compounds relating to antioxidant capability. Minimal changes in the chemical structure (only one extra OH group in the case of oestriol, for example) can lead to a modified degree of superoxide inhibition. On the basis of these

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considerations important conclusions can be deduced in connection with the effect-structure relationship, and thus newer aspects might be illuminated in the field of innovative pharmacology. Thus, these data provide further arguments for the investigation of the theoretical possibility of using oestrogenic compounds or their derivates for treatment of several free radical mediated illnesses in a combined manner together with other effective and established agents. P04.45 The effects of once-weekly alendronate 70 mg, risedronate 35 mg, and raloxifene 60 mg daily in the treatment of postmenopausal osteoporosis in Turkish population Mesut Oktem, P Akkaya, D Eroglu, HB Zeyneloglu Department of Obstetrics and Gynecology, Faculty of Medicine, Baskent University, Ankara, Turkey Objective: To compare the efficacy and tolerability of once-weekly alendronate (ALN) 70 mg, risedronate (RSD) 35 mg and raloxifene (RLX) 60 mg daily in the treatment of postmenopausal osteoporosis. Methods: Two hundred and sixteen postmenopausal women with osteoporosis were evaluated retrospectively those were received ALN (70), RSD (74), and RLX (72) for 24 months. Additionally, all patients received 600 mg Calcium + 400 IU Vitamin D daily. Bone mineral density (BMD) was measured by dual X-ray absorptiometry. Efficacy measurements included lumbar spine (LS), total hip, neck, and trochanter at baseline and 24 months. Results: The baseline characteristics were comparable in all groups. Over 24 months, ALN significantly increased LS (11.2%), total hip (15.1%), neck (11.4%) and trochanter BMD (20%) in patients (p < 0.001, p < 0.03, p < 0.02, p < 0.001, respectively). RSD significantly increased only LS BMD (7.4%, p < 0.003). RLX did not produce a significant increase in any BMD measurements. The mean percentage change from baseline in BMD in the ALN group was significantly higher from those in RSD and RLX at each site. Five fractures in the ALN group, five fractures in RLX group, and only one fracture in ALN group were occurred in women. There was a tendency for low fracture incidence in ALN group. No significant differences in the incidence of vasomotor symptoms were seen among groups. The overall incidence of side effects was less in RLX group (2.7%).

Conclusions: ALN 70 mg was well tolerated and produced significantly greater increases BMD than other drugs with low fracture incidence. P04.46 The factors affecting sexual functions and the effects of hormonal therapy on postmenopausal woman in Turkey S¨uleyman E Akhan, U Oskay, E Alici, F G¨ung¨or, ¨ Yalcin O Deartment of Obstetrics and Gynecology, Istanbul University Medical Faculty, Turkey Introduction: The aim of this study is: 1 to evaluate the sexual life and sexual behavior manners of postmenopausal women who applied to a university clinic in Turkey, 2 to test the validity of Female Sexual Function Index (FSFI) in Turkish language, and 3 to evaluate the effects of age, education, experience before marriage, relation with the partner, sexual performance of the partner, menopause type and PHT on postmenopausal women sexual function. Materials and methods: Prepared questionnairre form and FSFI are applied to total of 561 postmenopausal cases. Results: The validity of FSFI was found as in Cronbach’s alfa reliability coefficient domains between 0.80 and 0.91 and 0.92 for total scale. Five hundred and four cases were evaluated totally. The average age was 50.89 ± 4.31. 77.3% of these 504 cases were in natural and 22.7% of them were in surgical menopause. Twenty seven percent of them were having postmenopausal hormonal therapy. Thirty five percent of the cases were never talking about the sexual matters with the partner. For the women who have attended the research 11% were masturbating. 36.5% of the partners had sexual dysfunction. Not taking PHT was a negatively affecting factor to desire (p = 0.05; RR = 0.662), lubrication (p = 0.036; RR = 0.638) ve pain (p = 0.043; RR = 0.661) scores. But two factors appeared as main the negative factors affecting all of the domains: Woman not talking about the sexual matters with his partner (in other words, lack of communication) and man having sexual dysfunction. Especially, premature ejaculation and erection problems occuring together had a very negative effect on woman’s sexuality.

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Conclusion: The most important factors affecting women sexuality in menopause are woman’s relationship with the partner and the sexual performance of the partner. PHT has a positive effect on desire, lubrication and pain scores for woman sexuality in menopause. P04.47 The comparison of the effects of hormone replacement therapy with pulse estrogene, oral conjugated estrogene and estradiol hemihydrate on vasomotor symptoms and Kupperman index on surgical menopausal patients ¨ Fuat Akercan, M Cosan Terek, S Ozsener, T Cirpan, ¨ P Solmaz Yildiz, K Oztekin Department of Obstetrics and Gynecology, Ege University Faculty of Medicine, Izmir, Turkey Objective: The comparison of the effects of hormone replacement therapy with pulse estrogene, oral conjugated estrogene and estradiol hemihydrate on vasomotor symptoms and Kupperman index on surgical menopausal patients. Methods: Total 110 surgical menopausal women who applied to Ege University Medical Faculty Gynecology Department’s menopause clinic between January 2001 and January 2004 included this retrospective study. The hormone replacement therapy preperates, which was the subject of this study are; estradiol hemihydrate (aerodiol, 150 mg, Servier) as pulse estrogene and oral conjugated estrogene (Premarin, 0.625 mg, Wyeth) and estradiol hemihydrate (Estrofem, 2 mg, Novo-Nordisk) as physiological estrogene. There were 30 cases in pulse estrogene group, 50 cases in conjugated estrogene group and 30 cases in physiological estrogene group. The frequency of hot flushes and Kupperman indexes compared between the groups. Results: The average age of the patients was 51.5 ± 3.6 years. There were no statistical difference viewpoint of age, menopausal age and body-mass index (BMI) between the groups (p > 0.05). However, the postmenopausal period of the pulse estrogene group was significantly high than the other groups (p = 0.001). The frequency of hot flushes were: 5.9 ± 3.78; 0.60 ± 0.49; 0.50 ± 0.50 in pulse estrogene group; 6.2 ± 2.07; 0.56 ± 0.64; 0.48 ± 0.50 in oral conjugated estrogene group; 6.1 ± 2.05; 0.50 ± 0.50; 0.43 ± 0.50 in physiological menopausal patients group in initial, 3th and 6th months, respectively.

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The improvement in hot flushes was similar in each groups (p > 0.05). The effects on Kupperman indexes were 23.3 ± 3.3; 8.4 ± 2.5; 8.1 ± 2.4 in pulse estrogene group; 24.4 ± 4.3; 8.1 ± 2.9; 7.6 ± 2.6 in oral conjugated estrogene group and 25.1 ± 4.6; 7.8 ± 3.3; 7.3 ± 2.6 in oral estradiol hemihydrate group in initial, 3th and 6th months, respectively. There were no significant difference between each three groups (p > 0.05). Conclusion: Pulse estrogene therapy is an effective and high tolerable therapeutic choice and does not needed to be combined with progesterone in surgical menopausal patients. This can be used as an effective alternative to the conventional oral therapies in such patients. P04.48 The comparison of the effects on Kupperman indices, hot flushes and changes of endometrial thickness at transvaginal sonography after the therapy of tibolone, estradiol hemihydrate-neta and conjugated estrogene-MPA combinations Fuat Akercan, M Cosan Terek, T Cirpan, P Solmaz ¨ Yildiz, S Ozsener, O Bilgin Department of Obstetrics and Gynecology, Ege University Faculty of Medicine, Izmir, Turkey Objective: To compare the changes of endometrial thickness at transvaginal sonography, frequency of hot flushes and the Kupperman indices after the therapy of tibolone, estradiol hemihydrate-NETA and conjugated estrogene-MPA combinations. Methods: One hundred and sixty four patients who have physiological menopause and taking hormonotherapy were selected from the medical records of Menopause Clinic of Ege University, Medical Faculty, Gynecology Department, between January 2002 and January 2004 for this retrospective study. The first, second, third and sixth months of endometrial thicknesses and the changes in the climacteric complaints of the patients are evaluated. The HRT drugs, which were used in this study were: Tibolone (Livial 2.5 mg, Organon), the combination of estradiol hemihydrate and norethisteron acetate (NETA) (Activelle film tablet, estradiol hemihydrate 1 mg and norethisteron acetate 0.5 mg, Novo Nordisc) and conjugated estrogene–medroxyprogesterone acetate combination (Premelle 2.5 pills, cojugated estrogene 0.625 mg and medroxyprogesterone acetate (MPA) 2.5 mg, Wyeth).

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The distribution of the groups were as follows: 70 out of 164 cases were using Tibolone, 34 cases were using Estradiol hemihydrate-NETA and 60 cases were using conjugated estrogene-MPA in the study. Endometrial thickness of the patients were measured by transvaginal sonography. Results: There was no significant difference between the HRT groups in the beginning of therapy and after 3 months with regard to frequency of hot flushes. However, at the end of 6 months the frequency of hot flushes was significantly low in tibolone and conjugated estrogene-MPA groups than estradiol hemihydrate-NETA group (p = 0.02). The effect on Kupperman index were not different between the groups (p > 0.05). There was also no significant difference between the endometrial thickness measurements of the groups (p > 0.05). Conclusion: Tibolone is an effective therapeutic choice in the treatment of climacteric symptoms when compared with the conventional combined HRT drugs and has no significant effect on endometrial thickness. P04.49 The comparison of the effects of hormone replacement therapy with the combination of pulse estrogene–medroxyprogesterone acetate and the conjugated estrogene–medroxyprogesterone acetate on vasomotor complaints and uterine bleeding patterns in physiologic menopausal patients ¨ Serdar Ozsener, F Akercan, T Cirpan, M Cosan Terek, I Mete Itil, S Y¨ucebilgin Department of Obstetrics and Gynecology, Ege University Faculty of Medicine, Izmir, Turkey Objective: The comparison of the effects of hormone replacement therapy with pulse estrogene–medroxyprogesterone acetate and conjugated estrogene–medroxyprogesterone acetate on vasomotor complaints and uterine bleeding patterns in physiologic menopausal patients. Methods: Total 80 cases who applied to Ege University, Medical Faculty, Gynecology Department’s menopause clinic between January 2002 and January 2004 and who were using this hormonotherapies included this retrospective study. The hormone replacement therapy preperates, which was the subject of this study are; the combination of estradiol hemihydrate (aerodiol, 150 mcg, Servier) and medroxyproges-

terone acetate (Farlutal, 5 mg, Deva) preperates as pulse estrogene-MPA and estrogene 0.625 mg and medroxyprogesterone acetate 5 mg (Premelle Cycle, Wyeth) as conjugated estrogene-MPA. There were 30 cases in pulse estrogene-MPA group and 50 patients in conjugated estrogene-MPA group. Results: The average age of the patients was 50, 9 ± 2.5 years. There were no statistical difference viewpoint of age, menopausal age, body-mass index (BMI) and postmenopausal period between the groups (p > 0.05). There were no statistical difference in hot flush frequencies (average 8.60 ± 3.23) (p > 0.05). Kupperman index values on initial, 3th and 6th months were 27.3 ± 4.8; 10.2 ± 2.9; 9.8 ± 2.7 in pulse estrogene-MPA group and 7.9 ± 3.9; 10.5 ± 2.3 and 10.2 ± 2.1 in conjugated estrogene-MPA group; any statistical difference were found between the groups (p > 0.05). The withdrawal bleeding was seen in oral conjugated estrogene-MPA more than the other. But the difference was not have statistical meaning (p = 0.061). In the same way, the irregular bleeding episodes were seen in conjugated estrogene-MPA group more than the second group but, the difference was not significant (p = 0.426). Conclusion: The efficacy and tolerability of pulse estrogene-MPA therapy in physiological menopausal patients was similar to oral conjugated estrogene-MPA therapy and can be used as an effective therapeutic choice. P04.50 The effect of hormone replacement therapy on serum copper levels Ahmet Erdem, C Taskiran, E Biberoglu, K Biberoglu Gazi University, Department of Obstetrics and Gynecology, Ankara, Turkey Purpose: The purpose of this study was to evaluate the change in serum copper levels in postmenopausal women using only estrogen or estrogen–progestin combination treatments. Method: In this study, three different groups of patients were compared with each other: postmenopausal women with intact uteri-amenorrheic for at least 1 year without any treatment (group 1, n = 69), surgically menopausal and hysterectomized women who are on estrogen only treatment for at least 6 months (group 2, n = 45), and women with intact ovaries and uteri, who have been taking combined estrogen and

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progestin treatment for at least 6 months (group 3, n = 52). These groups were compared with respect to age, duration of menopause, duration of hormone treatment, and laboratory parameters such as serum copper, Apo A, Apo B, PAI-1, Factor VII, HDL, and LDL concentrations. Results: The serum copper levels with respect to groups 1, 2, and 3 were 108.37 ± 33.73, 141.23 ± 40.59, and 138.29 ± 36.77, respectively (p < 0.001). In post hoc analysis the differences between groups 1 and 2, and groups 1 and 3 were significant (p < 0.001 for both), but no significant variance was noted between groups 2 and 3 (p = 0.51). There was a significant variance among the groups with respect to age, duration of menopause, Apo A, and LDL. Serum copper concentrations were only significantly correlated with Apo A levels (p < 0.001, r = 0.325). Conclusion: Serum copper levels were found to be increased by either of estrogen-only or estrogen plus progestin regimens. Addition of progestins to the replacement therapy did not change the effect of estrogens. P04.51 The effect of hormone replacement therapy on homocysteine levels Ahmet Erdem, C Taskiran, E Biberoglu, K Biberoglu Gazi University, Department of Obstetrics and Gynecology, Ankara, Turkey Purpose: The purpose of this study was to evaluate the change in serum homocysteine levels in postmenopausal women using only estrogen or estrogen–progestin combination treatments. Method: Overall three groups of women were enrolled to this study: postmenopausal women with intact uteri-amenorrheic for at least 1 year without any treatment (group 1, n = 69), surgically menopausal and hysterectomized women who are on estrogen only treatment for at least 6 months (group 2, n = 45), and women with intact ovaries and uteri, who have been taking combined estrogen and progestin trreatment for at least 6 months (group 3, n = 52). Clinical and epidemiological parameters such as age, body mass index (BMI), duration of menopause, duration of hormone treatment, smoking and Turkish and instant coffee drinking habits, and laboratory parameters such as serum homocysteine, Apo A, Apo B, PAI-1, Factor VII, HDL, and LDL concentrations were evaluated to com-

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pare the effects of exogenous estrogen and progestin administration. Results: No patient had abnormal liver or kidney function tests, or abnormal serum vitamin B12 or folic acid levels. No significant variance was noted with respect to smoking and Turkish and instant coffee drinking habits. Duration of hormone treatment was not significantly different, but the duration of menopause for group 3 was significantly longer than both of the groups 1 and 2. The mean homocysteine concentrations with respect to groups 1–3 were 10.67 ± 3.96, 12.33 ± 7.26, and 12.83 ± 5.94. It was somewhat higher in patients taking hormonotherapy, but it did not reach to a significant value (p = 0.22). Although age (p = 0.005), BMI (p = 0.007), Apo A (p < 0.001) and LDL (p = 0.05) levels were significantly different among the groups, no significant variance was noted for Apo B (p = 0.39), HDL (p = 0.27), FVII (p = 0.92), and PAI-1 (p = 0.96). Conclusion: In this study, we did not observe any significant change in serum homocysteine levels among the postmenopausal women taking only estrogen or estrogen plus progestin, and women who are not on any hormonotherapy. P04.52 Effect of hormone therapy on sexual life: different routes compared S Erbay, H Karabay, F Kara, T Sipahi, N Yesildaglar Z¨ubeyde Hanim Women’s Hospital, Ankara, Turkey Objectives: Sexual dysfunction is common in postmenopausal women. We carried out this study to compare the effects of a continuous combined hormone medication (2 mg of estradiol valerat and 2 mg of dienogest), which was administered orally, and a vaginal cream of conjugated equine estrogens (0.625 mg/g) on sexual life in this group. Methods: One hundred forty-three postmenopausal women, between 50 and 53 years old, were included in the study. Their main complaint was sexual dysfunction. Vaginal hormone therapy was started in women who refused oral hormone administration. Subjects were asked about sexual desire, sexual excitement, orgasm capacity, intercourse frequency and vaginal lubrication during sexual activity and dyspareunia before and after the treatment. Results: After 6 months of treatment, all the patients were called back to hospital and their sexual functions

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were re-evaluated using the same sexual inventory. Significantly higher scores were found for the items assessing sexual desire, sexual excitement, orgasm capacity, intercourse frequency and vaginal dryness (p < 0.01) in the oral hormone group compared with those in the vaginal hormone group. Conclusion: Oral hormone therapy was more beneficial than vaginal hormone therapy in terms of solving problems of sexual dysfunction in menopause. P04.53 Hormone therapy does not alter the severity of depression in menopause ¨ ul, N Yesildaglar S Erbay, H Karabay, S Turgut, Y Onc¨ Z¨ubeyde Hanim Women’s Hospital, Ankara, Turkey Objectives: Estrogens used in postmenopausal women have a positive effect on menopausal symptoms; however, the relation between hormone therapy and depression in these women is not clear. This study evaluated whether hormone therapy had any beneficial effect on the severity of depression in the postmenopausal period. Methods: One hundred seventeen postmenopausal patients with depressive symptoms were included in the study. At the beginning of the study, the Beck depression inventory was used to assess the level of depression before the onset of hormone therapy. All the patients were non-smokers and between 49 and 53 years old and they were free of any internal diseases. All the patients had a similar body mass index (p > 0.05). None of the patients had used hormone therapy previously. Those who had used anti-depressants were not included in the study. They were prescribed the same medication (2 mg of estradiol valerat and 2 mg of dienogest daily) for hormone therapy at the beginning of the study. After 6 and 12 months of therapy, patients were called back to hospital and their depression levels were re-evaluated. Results: After 6 and 12 months, depression scores of patients were not significantly different than their scores at the beginning of the study. Conclusion: Hormone therapy did not affect the severity of depression either positively or negatively in postmenopausal patients.

P04.54 Attitudes of menopausal women towards hormone treatment (HT) during first admission to the menopause clinic H Hassa1 , HM Tanir1 , B Tekin1 , S Kahraman1 , T Oge1 , F Sahin-Mutlu2 1 Eskisehir Osmangazi University School of Medicine, Department of Obstetrics and Gynecology, Turkey; 2 Eskisehir Osmangazi University School of Medicine, Department of Biostatistics, Eskisehir, Turkey Objective: This retrospective study was performed to elucidate the attitudes and feeling of menopausal women first admitted to our clinic, prior to any form of HT regimen application. Methods: One thousand one hundred and forty five women with established menopausal signs and symptoms were admitted to our menopause clinic between 2001 and 2004. Results: Of 1145 cases, 296 (25.8%) women were unaware of the presence of any form of HT regimen, while, 849 (74.2%) women have heard it. Of 849 women, the origin of knowledge were from: male physicians (44.8%), female physicians (20%), nurses (2%) family relatives (9.7), television (10.7%), journals (6.9%). Past HT use was present in 231 (20%) of women, while in 633 (55%) cases. Main rationale of 559 women with non-compliance were as follows: Lack of adequate counselling (30.1%, n:168), fear of cancer (23.4%, n:131), pressure from surroundings (9.8%, n:55), presence of medical problems (8.8%, n:49), weight gain (4.8%, n:27), bleeding (3.8%, n:21), financial reasons (15.2%, n:85), allergic reactions (0.9%, n:5), being useless (2.3%, n:13). Conclusion: Given the results of the study, majority of menopausal women still have doubts on whether to initiate or continue HT. Furthermore, lack of adequate counselling and fear of cacer remained the two main issues leading to poor compliance. Therefore, in addition to counselling efforts of health workers, a mass campaign covering all institutions should be currently planned to overcome the low rate of HT use.

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P04.55 Demographic characteristics of menopausal women using hormone therapy (HT) in an University hospital of mid-Anatolian region of Turkey H Hassa1 , HM Tanir1 , A Yildirim1 , S Kahraman1 , T Oge1 , F Sahin-Mutlu2 1 Eskisehir Osmangazi University School of Medicine, Department of Obstetrics and Gynecology, Turkey; 2 Eskisehir Osmangazi University School of Medicine, Department of Biostatistics, Eskisehir, Turkey

P04.56 Do different forms of hormone treatment (HT) regimens have an impact on mammographic findings of menopausal women? H Hassa1 , HM Tanir1 , S Ozalp1 , YO Talcin1 , S Kahraman1 , T Oge1 , F Sahin-Mutlu2 1 Eskisehir Osmangazi University School of Medicine, Department of Obstetrics and Gynecology, Turkey; 2 Eskisehir Osmangazi University School of Medicine, Department of Biostatistics, Eskisehir, Turkey

Objective: This retrospective study was an attempt to document the various demographic characteristics of menopausal women for better counselling with regard to appropriate hormone therapy regimens. Methods: One thousand one hundred and forty five women with established menopausal signs and symptoms were admitted to our menopause clinic between 2001 and 2004. HT was initiated in 604 cases. Demographic characteristics of them were evaluated. Types of HT regimens consisted of oral conjugated equine estrogen (CEE) only, transdermal E, oral cyclic- or continous-combined E + progestin (P), nasal E, vaginal E tablet and tibolone. Results: Oral CEE only (n:85), transdermal E (n:61), Cyclic-combined E + P (n:112), continous-combined E + P (n:204) nasal E (n:5), vaginal E tablets (n:9) and tibolone (n:128) were used. Mean age of women with HT was 49.2 ± 5.7 years. Mean gravidity, parity and living children were, 4.1 ± 3.2, 2.5 ± 1.3, 2.2 ± 0.6, respectively. Mean age at menopause was 45.7 ± 6.8 years. Seventy two percent (n:435) women harbored natural menopause, while surgical and premature menopause were seen in 24.2% (146) and 3.8% (n:23) cases, respectively. In 48.5% of women in whom HT was initiated, no history of sport activities was obtained. Medical problems were present in 48.5% of cases. Conclusion: Prior to initiation of an appropriate form of HT, demographic characteristics of menopausal women should be contemplated and counselling should be performed accordingly.

Objective: The effects of different forms of HT regimens on mammographic findings of menopausal women at 12 months following the drug initiation were evaluated. Methods: HT was initiated in 529 cases, all of whom were mammographically normal at the start of the treatment. Mean age at menopause, types of HT regimen consisted of oral cyclic-continous-combined E + progestin (P) and tibolone were analyzed after 12 months. Abnormal mammographic findings were categorized as the presence of increased symmetrical or asymmetrical parenchymal density, presence of unilateral or bilateral microcalcifications, mass lesion or presence of any opacity. Results: Oral CEE (n:85), cyclic-combined E + P (n:112), continous-combined E + P (n:204) and tibolone (n:128) were used. Mean age of women was 49.2 ± 5.7 years. Of 529 women, 94 (17.8%) women were reassessed 12 months following the first admission. Out of 94 women, thirty-one (32.9%) women had mammographic abnormalities. Of all women admitted to the clinic, in 16 cases with oral CEE, nine (56.2%) revealed mammographic abnormalities, most of which were increased parenchymal density (n:6). In 24 cyclic-combined HT group, 8 (33.3%) women harbored suspicious mammographic signs, of whom microcalcification and increased parenchymal density were seen in two and six cases, respectively. In continous-combined HT group, all 13 women had mammographic abnormalities, including increased parenchymal density (n:8), microcalcifications (n:3), presence of pathological lymph node (n:1) and the presence of opacity (n:1). One case (2.5%) in tibolone group (n:40) harbored increased parenchymal density.

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Conclusion: In menopausal women, mammographic changes with different HT regimens should be carefully investigated for the presence of benign or malignant breast lesions. P04.57 A retrospective analysis of side effects observed in menopausal women using hormone treatment (HT) H Hassa1 , HM Tanir1 , S Kahraman1 , T Oge1 , F SahinMutlu2 1 Eskisehir Osmangazi University School of Medicine, Department of Obstetrics and Gynecology, Turkey; 2 Eskisehir Osmangazi University School of Medicine, Department of Biostatistics, Eskisehir, Turkey Objective: This study was performed to assess side effects of different HT regimens. Methods: One thousand one hundred and forty five women with established menopausal signs and symptoms were admitted to our menopause clinic between 2001 and 2004. HT was initiated in 604 cases. Types of HT regimens consisted of oral cyclic- or continouscombined E + progestin (P) and tibolone. Results: Mean age of women with HT was 49.2 ± 5.7 years. In cyclic-combined E + P (n:112), and continous-combined E + P (n:204) group, 24 (11.7%) women have with side effects of edema and weight gain (n:15), nausea and vomiting (n:3), allergic reaction (n:3) and irregular vaginal bleeding episodes (n:3). However elevated liver enzymes (n:1), development of hypertension (n.1) and libido loss (n:1) were only seen in continous-combined HT group. Among tibolone users (n:128), In 10 (7.8%) cases had side effects like weight gain (n:3), vaginal bleeding (n:3), elevated liver enzymes (n:1), state of nervousness (n:1), nausea (n:1) and allergic reaction (n:1). Conclusion: Adverse effect for various forms of HT is one of the leading factors for HT discontinuation and poor treatment compliance. Hence, every efforts should be made to tailor appropriate HT regimen on individual basis and to reassess, regularly, the treatment effect as to obtain a better and long-term drug compliance.

P04.58 Effects of HRT on the renal artery Doppler indices in natural menopause Aykan Yucel, N Sagsoz, V Noyan, S Altan Kara, Y Mirace Karadeniz Nevin Sagsoz, Yasemin Mirace Karadeniz, Turkey Objective: The aim of the study was to determine the effects of hormone replacement therapy on the renal artery Doppler indices in natural menopause. Methods: Twenty-seven postmenopausal women (mean age: 49.44 ± 4.07) were randomly assigned to receive Premelle® cycle 5 mg (n = 11), Divitren® (n = 9) or Livial® (n = 7). Doppler ultrasound of the left renal interlobar artery was performed before the commencement of HRT and 70 days after the therapy. The one-way ANOVA and Kruskal–Wallis tests were used to compare the groups. Wilcoxon signed rank test and the paired-samples t-test procedures were used to compare the relation of two variables for a single group. Results: The pulsatility index (PI) and resistivity index (RI) values were comparable before the commencement of the therapy. After 70 days of treatment, CEE + MPA group had no significant change. In the tibolone group, PI and left RI decreased, but only the decrease in RI was statistically significant (p < 0.001). In the estradiol valerate group, PI (p = 0.028) and RI (p = 0.047) decreased significantly. Table 1 Pulsatility and resistivity indices after different hormone replacement therapy applications in natural menopause CEE + MPA (n = 11) PI-0 PI-1 RI-0 RI-1 a b c

1.03 0.91 0.61 0.62

± ± ± ±

0.16 0.21 0.05 0.11

Tibolon (n = 9) 1.04 0.94 0.63 0.59

± ± ± ±

0.13 0.06 0.03b 0.03b

Estradiol (n = 7) 0.97 0.87 0.60 0.56

± ± ± ±

0.06a 0.11a 0.03c 0.04c

p NS NS NS NS

p = 0.028. p = 0.001. p = 0.047.

PI-0: PI-1: RI-0: RI-1:

Baseline pulsatility index value Pulsatility index value after 70 days treatment Baseline resistivity index value Resistivity index value after 70 days treatment

Conclusion: Tibolon and estradiol valerate have favorable effects on the renal artery blood flow and com-

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bining MPA with CEE attenuates the estrogen-induced vascular effects in natural menopause. P04.59 Abstract No.: 291 Presentation Preference: Free communication— poster presentation Keyword: 05—Hormone Therpay Effects of raloxifene and low dose hormone therapy on blood chemistry and Kupperman index in postmenopausal women AY Karageyim Karsidag1 , N Aydogdu2 , Nevriye Alkan1 , R Dansuk1 , B Kars1 , O Unal1 , M Cem Turan1 1 Dr Lutfi Kirdar Kartal Education and Research Hospital, Department of Obstetrics and Gynecology, Istanbul, Turkey; 2 Dr Lutfi Kirdar Kartal Education and Research Hospital, Department of Family Medicine, Istanbul, Turkey

Changes from baseline

Group 1

Endometrial line thickness (mm) Kupperman index TSH Plasma glucose %HbA1C Cholesterol

−0.36 −9.56 −0.53 −2.26 −0.13 −30.03

± ± ± ± ± ±

Results: All groups did not significantly differ regarding age, age at menopause, years after menopause and BMI. Endometrial thickness was significantly reduced in group 1 at the end point. Decrease in Kupperman Index at the end of 3 months was statistically significant in all groups. Free T3 level was significantly increased in group 1 at the end of 3 months, fasting plasma glucose, % HbA1C, HDL and triglycerides were all significantly reduced in group 2. Reductions in cholesterol and LDL were significant in both groups 1 and 2. Endometrial thickness was reduced in group 1 at the end of 3 months, whereas KI scores were significantly reduced in both groups 1 and 2, compared with the controls. Reductions in %HbA1C and cholesterol were significant in both groups 1 and 2. Although LDL seemed increased and HDL decreased in group 1, it was not statistically significant. Table: Comparison of statistically significant changes from baseline in three groups Group 2

0.83 6.67 2.72 21.66 0.41 36.96

Objective: To compare the efficacy of raloxifene and low dose HT on blood chemistry and Kupperman index (KI). Methods: Women treated with low dose HT (1 mg E2/0.5 mg NETA) formed group 1 (n = 30), with raloxifene (60 mg/d) formed group 2 (n = 30) and controls were group 3 (n = 30). KI measurements of all participants are investigated. Baseline and end point measurements of full blood chemistry were performed. Statistical analyses were performed using Tukey’s multiple comparison test, χ2 -test, Kruskal–Wallis test and Dunn’s multiple comparison test besides descriptive statistical analysis.

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0.03 −8.9 −0.15 −8.2 −0.13 −30.83

± ± ± ± ± ±

Group 3 0.28 4.32 1.48 11.63 0.33 42.37

0.24 −2.93 0.21 −3.3 0.11 −7.63

± ± ± ± ± ±

p 0.37 3.78 0.65 13.67 0.26 23.33

0.0001 0.0001 0.029 0.037 0.002 0.007

Conclusions: Both low dose HRT and raloxifene are safe treatment alternatives with minimal side effects and without adverse effects on blood chemistry results. P04.60 The perception of menopause and hormone therapy among women in Turkey 1, G ¨ Yesim Uncu1 , Z Alper1 , G Sadikoglu1 , H Ozdemir 2 Uncu 1 Uludag UniversityFaculty of Medicine, Department of Family Medicine, Turkey; 2 Uludag UniversityFaculty of Medicine, Department of Obstetrics & Gynecology, Turkey Objectives: Everyday, the world population ages and the length of time that women live in menopause

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is increasing. During menopause, nearly one-third of women consult a doctor annually due to menopauserelated symptoms. The aim of the study is to investigate the influence of sociodemographic characteristics and menopause perception on self-reported menopause related symptoms among Turkish women and analyze their knowledge and attitudes toward menopause and hormone therapy. Methods: Our study was a population-based study. Women, from two primary health care clinics, who were accepted, gave written informed consent to join the study. Each woman completed a questionnaire and had an interview to investigate their current health problems. Results: 80.6% of the women suffered from different problems, mainly hot flashes. The women who perceived menopause as a pathological period had more complaints than others did. Twelve percent of women were taking a hormonal treatment. Conclusion: While examining women’s complaints, individual differences, different perceptions of menopause among women from the same society, and social facts caused by cultural differences must be considered as they affect the frequency and characteristics of menopausal problems. P04.61 Mammography category changes by hormone therapy in postmenopausal women attending to Marmara University Menopause Clinic Meltem Uygur, P Y¨or¨uk, B Yildizhan, M Erenus, F Durmusoglu Marmara University, Obstetrics and Gynecology Department, Reproductive Endocrinology and Infertility Unit, Turkey Objective: Breast cancer is the most frequently diagnosed cancer and is the second leading cause of cancer death among women. It has been demonstrated that postmenopausal estrogen–progestin therapy (ERT) increases mammography density. The aim of this study is to evaluate mammography findings between postmenopausal estrogen–progestin therapy users or nonuser in our clinic. Methods: All women attending to Marmara University menopause outpatient clinic, and who have undergone mammography were enrolled into this retrospective study. Women were divided into two groups according to HRT use (group 1 = no HRT use or 6

months prior HRT use; group 2 = current HRT user). Mammography findings were evaluated according to the BI-RADS Assessment System (category 0, need additional imaging evaluation; category 1, negative; category 2, benign finding; category 3, probably benign finding: short interval follow-up suggested; category 4, suspicious abnormality: biopsy should be considered; category 5, highly suggestive of malignancy: appropriate action should be taken) by specialist radiologists. Both groups were compared according to benign mammographic categories. Results: Of the 2500 women enrolled, 85.2% (n = 2129) are current HRT user, 14.8% (n = 371) were non-users. The mean age at menopause was significantly different between users and non-users of HRT (39.9 ± 8.7 and 47.1 ± 4.7, respectively, p < 0.01). In group 1, 58.1% (n = 1236) women and in group 2, 53.9% (n = 200) had category 1 mammography findings (p < 0.001). Both groups were similar in terms of category 2 (39.8% and 39.9%, respectively). Women in group 1 had 2.2% (n = 46) and women in group 2 had 6.2% (n = 23) category 3 mammographic findings (p < 0.001). According to categories 4 and 5 findings, both groups were similar. Conclusion: The results of this study further prove that current HRT use results in increased mammographic category in women who attend to our clinic. Women who are current users of HRT have earlier menopause age. P04.62 Effects of intranasal 17 beta-estradiol and raloxifene on lipid profile and fibrinogen in hypercholesterolemic postmenopausal women: a randomized, placebo controlled clinical trial Yaprak Engin-Ustun, Y Ustun, M Mutlu Meydanli, A Kafkasli ˙ on¨u University Medical Faculty, Department of In¨ Gynecology and Obstetrics, Turkey Aim: To compare the effects of intranasal 17 betaestradiol and raloxifene on the serum lipid profile and fibrinogen in hypercholesterolemic postmenopausal women. Materials and methods: The study population consisted of 46 women after menopause. The placebo group (n = 11) was given calcium, while interventional groups were given intranasal 17 beta-estradiol (Aerodiol, Servier, Chambray-les-Tours, Franceor) (n = 16)

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and raloxifene (n = 19). Blood lipids and fibrinogen were compared between groups at baseline and after 3 months of treatment. Results: 17 beta-estradiol group showed a significant decrease in triglyceride levels (p < 0.05) and a marked increase in high density lipoprotein-cholesterol levels (p < 0.05). No changes in lipid profile were observed in raloxifene and placebo groups. Raloxifene caused a significant decrease in fibrinogen levels (p < 0.05). Conclusion: 17 beta-estradiol exerts significant effects on lipid profile in hypercholesterolemic postmenopausal women. P04.63 Impact of 5-years HRT usage on vaginal maturation in postmenopausal women Pinar Y¨or¨uk, M Uygur, B Yildizhan, M Erenus, F Durmusoglu Marmara University, Obstetrics and Gynecology Department, Reproductive Endocrinology and Infertility Unit, Turkey Objective: Vaginal maturation value (MV) is a useful marker to examine vaginal maturation and reveal vaginal estrogen deficiency regardless of the presence of inflammation. The objective of this study was to evaluate the absolute difference in MV of postmenopausal women after 5-years of HRT usage. Methods: Postmenopausal women who are using HRT for at least 5 years and attending to Marmara University menopause outpatient clinic were enrolled into this retrospective case controlled study. For determination of vaginal MV, pap smear from lateral vaginal wall was obtained and evaluated. Vaginal maturation index were calculated according to Meisels formula. Pap smear reports of the women at the first visit and last visit were noted and the difference between the first and last MV were evaluated statistically. Results: Of 202 women enrolled mean age was 56.6 ± 5.0. Significant difference was detected between percentages of basal cells (30.2 ± 33.5 and 6.0 ± 12.8, p < 0.001), intermediate cells (55.7 ± 26.2 and 73.2 ± 20.7, p < 0.001), superficial cells (14.0 ± 16.0 and 21.1 ± 21.7, p < 0.001) and MV (41.9 ± 22.8 and 57.9 ± 14.3, p < 0.001) of pap smears obtained at first visit and last visit. The absolute differences in scores of basal cells, intermediate cells and superficial cells were −24.2,

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17.6 and 7.1. The absolute increase in MV was 15.9. Conclusion: The results of this study demonstrate a significant increase in vaginal maturation with HRT administration. This is probably due to the improvement in vaginal estrogen status in women using HRT. These results demonstrate a clinical benefit of HRT in postmenoopausal women with atrophic vaginitis. P04.64 Advances of tibolon therapy in women with surgical menopause V Liberis, Panagiotis Tsikouras, G Galazios, I Triantafyllidis, S Fotos, X Grapsas, S Zervoudis, G Maroulis Department of Obstetrics and Gynecology Democritus University of Thrace, Greece Introduction: Replacement of deficient hormones (HRT) is the main treatment modality in menopause. In this study, we aimed to explore the effects of tibolone on symptoms of women with surgical menopause. Material and methods: During the period from 1 April 2000 to 31 October 2004, tibolone 2.5 mg daily was prescribed to women with climacteric symptoms in our Menopause centre. In a group of 40 women receiving tibolone one tablet of 2.5 mg daily for 4 years. The mean age was 47.5 years old. These women had abdominal or vaginal hysterectomy with bilateral oophorectomy for benign conditions were recruited into study after the operation. The frequency of menopausal complaints and instrumental tests (mammography, bone densitometry), as well as efficacy and side effects of the therapy were studied after 2, 4, 12 months of treatment. Results: During the 36 months follow up tibolone therapy effectively reduced menopausal complaints especially hot flushes and night sweats, caused no increase in the anamnestic risk factors, or serious side effects. Only 20% of the women reported adverse effects (breast tenderness and nausea), which turned out to be transitional. Tibolone treats protects against bone loss, without inducing significantly increased mammographic density or neoplasmatic disease of the breast. Conclusion: Tibolone is a valuable treatment option for women with climacteric complaints. Additional studies will determine whether the promise of increased safety with tibolone will be realized.

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P04.65 Effect of simvastatin together with hormonal therapy on lipid levels in postmenopausal women Inci Davas, T Yoldemir, S Leloglu, A Yazgan, A Varolan, A Akyol Sisli Etfal Research and Training Hospital, 2nd Obstetrics and Gynecology Clinic, Istanbul, Turkey Objective: To determine the efficiency of hormonal therapy with simvastatin on serum lipid levels in hypercholestorelemic postmenopausal women. Study design: Women with postmenopausal complaints attending to the S¸is¸li Etfal Research and Training Hospital 2nd Obstetrics and Gynecology Menopause Out-patient Clinic were enrolled to the study. Each women had no contraindications for receiving hormonal therapy and antihyperlipidemic treatment. Forty women with high blood total cholesterol and LDL cholesterol levels were informed about the study and consents were obtained. Patients gave blood for total cholesterol, LDL cholesterol, HDL cholesterol and triglyceride measurements at the beginning, after 6 months and after 12 months of therapy. Patients received continuous combined 0.625 mg conjugated estrojen plus 5 mg medroxyprogesterone acetate in the first 6 months. In the following 6 months 10 mg simvastatin was added. Results: At the end of the 6th month serum total cholesterol and LDL cholesterol levels significantly lowered (p < 0.001) however this was not enough to lower the coronary heart disease risk. At the end of the 12th month serum total cholesterol and LDL cholesterol levels were significantly lowered compared either to the levels before the treatment or the levels at the end of the 6th month (p < 0.001). Conclusion: Simvastatin caused synergistic effect on lowering serum total and LDL cholesterol levels when added to hormonal therapy in postmenopausal women.

P04.66 The atherogenic index of plasma in healthy postmenopausal women: effect of hormone therapy and tibolone GE Christodoulakos1 , Irene V Lambrinoudaki1 , EV Economou2 , C Papadias1 , CP Panoulis1 , EE Kouskouni2 , SA Vlachou1 , GC Creatsas1 1 2nd Department of Obstetrics and Gynecology, University of Athens, Aretaieio Hospital, Athens, Greece; 2 Hormonal and Biochemical Laboratory, University of Athens, Aretaieio Hospital, Athens, Greece The cardiovascular effect of hormone therapy (HT) varies according to the regimen, the dose and the properties of the progestin employed. In the present study, we aimed to assess the effect of various regimens and doses of hormone therapy and tibolone on the Atherogenic Index of Plasma (AIP). Five hundred and nineteen postmenopausal women attending our Menopause Clinic were studied in a prospective design. Women with climacteric symptoms were randomly assigned to receive one of the following regimens: (1) tibolone 2.5 mg (2) conjugated equine estrogens 0.625 mg plus medroxyprogesterone acetate 5 mg (CEE/MPA), (3) 17␤-estradiol 2 mg plus norethisterone acetate 1 mg (E2/NETA) or (4) 17␤-estradiol 1 mg plus norethisterone acetate 0.5 mg (low E2 /NETA). Serum parameters were assessed at baseline and after 6 months and included: Total cholesterol, LDL-cholesterol, HDLcholesterol, triglycerides, Apolipoprotein A1 and Apolipoprotein B. The AIP was assessed as the log [triglycerides (mmol/L)/HDL-c (mmol/L)]. CEE/MPA treatment associated with lower mean LDL-cholesterol but higher mean triglyceride levels (−15.5 mg/dl ±3.6, p = 0.0001; +12.6 mg/dl ±4.8, p = 0.01). Furthermore, CEE/MPA treatment resulted in higher AIP levels (+0.073 ± 0.021, p = 0.001). On the contrary, both E2/NETA regimens and tibolone associated with lower mean triglyceride and HDL-c levels (E2/NETA, triglycerides: −9.8 mg/dl ±5.0, p = 0.049; HDL-c: −4.9 mg/dl ±1.8, p = 0.01, low E2/NETA triglycerides: −12.5 mg/dl ±4.1, p = 0.003; HDL-c: −4.7 mg/dl ±1.3, p = 0.001; tibolone, triglycerides: −21.9 mg/dl ±2.7, p = 0.0001; HDL-c: −12.7 mg/dl ±1.1, p = 0.0001). None of the three regimens had any effect on AIP. In conclusion, the effect of a particular regimen of hormone therapy on the lipid-lipoprotein profile dif-

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fers depending on the parameter assessed. LDL-c and AIP are differently modulated by HT. The concurrent assessment of the therapy effect on both LDL-c and AIP may be more dependable in evaluating the cardiovascular impact of a given regimen. P05 Osteoporosis P05.01 Association of the osteoprotegerin gene polymorphisms with bone mineral density in postmenopausal Korean women Jung-Gu Kim1 , D-O Lee1 , J-Y Kim1 , B-C Jee2 , S-Y Ku1 , C-S Suh2 , S-H Kim1 , Y-M Choi1 , S-Y Moon1 , H-M Park3 H Choi4 1 Seoul National University Hospital, South Korea; 2 Seoul National University Bungdang Hospital, South Korea; 3 ChoongYang Medical School Yongsan Hospital, South Korea; 4 Sange Paik Hospital, South Korea Objective: The objective of this study were to investigate the relationship between the osteoprotegerin (OPG) gene polymorphisms and bone mineral density (BMD) in 287 postmenopausal Korean women. Methods: The A163G, G209A, T245G, and G1181C polymorphisms in OPG gene were analyzed by restriction fragment length polymorphism (RFLP). The BMD at the lumbar spine and proximal femur by dual energy X-ray absorptiometry. Results: The A163G, G209A, and T245G polymorphisms in OPG gene were in complete linkage. Significant association between the OPG gene G1181C polymorphism and BMD at the lumbar spine and femoral neck was observed. the BMD in women with the CC genotype was higher than in women with the GC or GG genotype, with C allele dose effect, and the prevalence of CC genotype in osteoporotic postmenopausal women was lower compared to osteopenic or normal postmenopausal women. However, no significant association between adjusted BMD at any skeletal site and the OPG gene T245G polymorphism was observed. Conclusion: OPG G1181C polymorphism is one of genetic factors which affect BMD of lumbar spine andfemoral neck in Korean women.

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P05.02 Changes of bone mineral density, bone markers and serum leprin after GnRH agonist in endometriosis Sung-Tack Oh1 , K-S Lee2 1 Chonnam University Medical School, South Korea; 2 Pusan University Medical School, South Korea Objective: The aim of this study was to examine the changes of bone mineral density (BMD), biochemical bone markers and serum leptin after GnRH agonist treatment in endometriosis patients and to investigate the relationship between serum leptin concentrations and bone markers and BMD. Methods: Thirty two patients, who were confirmed as endometriosis by laparoscopic operations from March 2004 to February 2005 were enrolled. Goserelin acetate (Zoladex, 3.6 mg) was administered subcutaneously at 28 days interval for 6 months. BMD, biochemical markers and leptin were measured before treatment and after 6 months of treatment. Bone mineral density of lumbar spine and femur was measured by dual energy X-ray absorptiometry. Serum leptin was measured by radioimmunoassay. Serum osteocalcin (OC) and carboxy-terminal telopeptide of type 1 collagen (ICTP) were measured by ELISA method. Results: Patients treated with goserelin for 6 months showed 0.040 ± 0.035 g/cm2 (3.39%) decrease of BMD in lumbar spine, 0.024 ± 0.021 g/cm2 (2.64%) decrease in femur neck, 0.024 ± 0.018 g/cm2 (2.93%) decrease in Ward triangle and 0.016 ± 0.020 g/cm2 (2.11%) in femoral trochanter. These data had statistical significance (p < 0.05). Serum OC (9.20 ± 7.21 ng/mL, 94.74%) and ICTP (0.10 ± 0.12 ng/mL), 38.46%) were significantly increase and serum leptin was also increased significantly (3.06 ± 2.27 ng/mL, 42.27%). However, no correlation was found between serum leptin concentrations and bone markers and BMD. Leptin correlated positively with body mass index (r = 0.571, p < 0.05). Conclusion: BMD was significantly decreased and biochemical bone markers were significantly increased in endometriosis patient after 6 months GnRH agonist treatment. Serum leptin was also significantly increased. However, leptin was not correlated with BMD or with biochemical markers.

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P05.03 Relationship of beta-adrenergic nervous system activity and bone density in menopaused women Jing-Hong Kim, E-J Kim, H-H Jo, J-H Kim Catholic University of Korea, Department of Obstetrics & Gynecology, Seoul, South Korea Objective: To evaluate the effect beta adrenergic nervous system activity has on the relationship between plasma levels of leptin and bone mineral density in women who are in their post-menopause and have taken hormone replacement therapy. Methods: This study was conducted on women who visited the St. Mary’s hospital and took hormone replacement therapy for a period of more than 1 year. We checked the bone mineral density, bone turnover markers and plasma levels of leptin prior to commencing hormone replacement therapy and also after 1 year of medication. In evaluating the beta adrenergic nervous system activity, we used a packaged survey questionnaires and the results were evaluated used Excel and SPSS. Results: After the hormone therapy, the beta adrenergic nervous system activity was in proportion to the decreased in the plasma levels of leptin and inversely proportionate tothe decrease in osteocalcin and UDP. That is of the central nervous system, a decrease in the level of control over beta adrenergic nervous system activity showed a more drastic decrease in the bone mineral density. Conclusion: In the case where the bone mineral density of women in menopause who took the hormone replacement therapy did not increase, the more beta adrenergic nervous system activity, the greater the decrease in the plasma levels of leptin and bone mineral density. P05.04 Estimated prevalence of osteoporosis in Ansan, Korea Tak Kim, S-E Chung, S-H Park, N-W Lee, H-J Kim, S-H Kim, K-W Lee Korea University Ansan Hospital, Department of Obstetrics and Gynecology, Ansan-Si, Kyonggi-Do, South Korea Osteoporosis is a metabolic bone disease characterized by low bone mass and micro-architectural deterioration of bone tissue. It is a major public health

problem because of its association with age-related fractures. We investigated the prevalence of osteoporosis in Ansan, Korea. The prevalence of osteoporosis was evaluated for the 3 years from 1999 to 2001 on the basis of the Ansan Health Clinic (in Korea University Hospital) database. Data from 156 men (44.9%) and 191 women (55.1%) were evaluated. In this study, osteoporosis means a value for lumbar or femur BMD, tested by DEXA, that is more than 2.5 S.D. below the young adultmean value (T ≤ −2.5). It is follow the WHO definition. The results showed a trend toward increasing proportions of osteoporosis & osteopenia with age, more predominantly in the male population. The averaged prevalence of osteoporosis & osteopenia, between 1999 and 2001, in those aged 40–59 years was 41.6% for men and 28.8% for women. These estimates were higher than those reported elsewhere. Findings of the present study showed that in the elderly population in Ansa, Korea, osteoporosis & osteopenia is more popular in male than in women. This suggests that much attention should be paid to male osteoporosis and more consistent osteodensitometric examinations should be performed in male. P05.05 Osteopenic syndrome and cardiovascular diseases risk in postmeonopausal women N Izmozherova, Artem Popov, Y Kozulina, M Fominykh, N Tagiltseva, A Andreyev Department of Internal Medicine No. 2, Ekaterinburg, Russian Federation Aim: assessment of main cardiovascular diseases risk factors prevalence among postmenopausal women with normal and low bone mineral density (BMD). Methods: Three groups of a case-control study included 50 postmenopausal women each. The first ˆ group included persons with normal AMD, the second consisted of osteopenic patients. Women with osteoporosis were in the third group. BMD was assessed by dual energy X-ray absorptiometry of lumbar spine. Cardiovascular risk factors were registered. Ten years cadiovascular risk (Score) was calculated. Results: Lipid metabolism parameters were similar in all groups. Arterial hypertension and increased 10years SCORE fatal risk were more frequent in patient with normal BMD. Osteoporosis is an independent risk factor for cardiovascular diseases development.

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Conclusion: Diagnosis of low BMD requires declaration of more higher individual cardiovascular risk level as the standard risk assessment scales do not take BMD in consideration. P05.06 Mission Study: prevalence of osteoporotic fractures in France, in 6841 menopausal women with or without hormone replacement therapy P De Reilhac1 , Mc Micheletti2 , Thierry Chevallier2 , JY Reginster3 1 Honorary President of F.N.C.G.M., Nantes, France; 2 Laboratoire Th´ eramex, Monaco; 3 World Heath Organisation (WHO) Collaborating Centre for Public Health Aspects of Rheumatic Diseases and Osteoporosis, Li`ege, Belgium This study is being performed with a group of experts and in collaboration with Theramex-Merck Laboratories. Its aims are to determine in France: in the first instance (historical approach), the prevalence of breast cancer and of diseases such osteoporotic fractures, etc., in menopausal women under gynaecologists’ care and treated or not treated with a “French” type of Hormone Replacement Therapy (HRT); then, secondly (prospective phase), the incidence of these pathologies during a follow-up period. Here we present the results of the historical phase concerning osteoporotic fractures. Six thouand eight hundred and forty one menopausal women have been recruited: 3509 treated and 3362 untreated. The mean age is 60.7 years old. The average age of menopause onset is 50 years old. The mean BMI is similar in the two groups (25).The mean duration of HRT is 8 years. Seventy four percent of the treated women receive cutaneous estradiol (E). Of the women taking a progestative supplement to E, 37.4% receive progesterone and 62.6% receive retroprogesterone or a nor-pregnane or pregnane derivative (excluding MPA and nor-testosterone derivatives). Prevalence of osteoporotic fractures. Type

Treated group, n (%)

Untreated group, n (%)

p Femoral

Neck Wrist Lumbar spine

7 (0.2) 48 (1.4) 17 (0.5)

14 (0.4) 97 (2.9) 37 (1.1)

0.1 <0.0001 0.005

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There were significantly less osteoporotic fractures (wrist and lumbar spine) in the treated group than in the untreated. In the MISSION study, the possible protective anti-fracture role of “French” HRT will only be able to be demonstrated in the prospective phase which is currently ongoing. P05.07 Bone mass effects of the BMP-2 and BMP-4 gene polymorphisms in postmenopausal women Z Sema Deveci1 , B Demir1 , D Deveci2 , E Etem2 , H Y¨uce2 , A Haberal1 1 Ankara Etlik Maternity and Women’s Health and Teaching Research Hospital, Turkey; 2 F´yrat University, School of Medicine, Ankara, Turkey Introduction: Bone morphogenetic proteins (BMPs) induce the formation of bone cartilage and bone. Peak bone mass is primarily determined by environmental factors and genetic components. In order to investigate the roles of BMP-2 and BMP-4 genes in regulating the bone mineral density (BMD) in humans, we analyzed the frequency of a single nucleotide polymorphisms (SNP) of BMP-2 and BMP-4 genes. Materials and methods: We analyzed the frequency of SNP of BMP-2 and BMP-4 genes on 72 osteoporotic-postmenopausal women and 50 postmenopausal women with high bone mineral density (T score > +1.0) who were selected from our menopausal out-patient clinic between October 2004 and March 2005. Results: The mean ages of osteoporotic and nonosteoporotic groups were 57.8 ± 6.7 years, 53.5 ± 5.4, years, respectively. The mean menopausal period of osteoporotic group was 12.2 ± 7.5 years and nonosteoprotic group was 5.3 ± 4.5 years. The mean body mass index of the groups were 27.0 ± 4.5 kg/m2 and 31.3 ± 4.7 kg/m2 , respectively. The osteoporotic women showed lower (19.4%) and non-osteoporotic women showed higher (34%) “C” allel proportion for BMP-4 (p = 0.04). But there were no difference of polymorphism proportion on BMP-2 in the groups for T and A alleles. Conclusions: According to our results, BMP4 gene polymorphism is associated with high bone density in postmenopausal women.

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P05.08 Incidence of osteopenia and osteoporosis in postmenopausal women attending to Marmara University Menopause Clinic Pınar Y¨or¨uk, M Uygur, B Yildizhan, M Erenus, F Durmusoglu Marmara University, Department of Obstetrics and Gynecology, Reproductive Endocrinology and Infertility Unit, Turkey Objective: Osteoporosis is a highly prevalent skeletal disorder in elderly women characterized by compromised bone density predisposing women to an increased risk of fractures. The aim of this study is to determine the incidence of osteoporosis and osteopenia in postmenopausal women attending to Marmara University Menopause Clinic. Methods: The records of all postmenopausal women who attended to Marmara University menopause outpatient clinic between years 1995 and 2005 were evaluated retrospectively. Women who underwent bone mineral density (BMD) measurement by dual energy X-ray absorptiometry were enrolled into this study. Osteoporosis was defined by a loss of either lumbar or hip BMD greater than 2.5 S.D. below average peak BMD of young adult women. Results: In all 1506 women 74.4% (n = 1121) had normal BMD, 19.6% (n = 294) had osteopenia, and the remaining 6.0% (n = 91) were osteoporotic. The mean age was 52.4 ± 6.4 and the mean age at menopause was 47.0 ± 6.7. The mean S.D. of BMD values for femoral, lumbar vertebral (L2–4) and total was −1.3 ± 2.5; −1.1 ± 2.2; −0.8 ± 1.6, respectively. All the demographic and BMD parameters were similar between normal, osteopenic and osteoporotic individuals except body mass index, 26.5 ± 3.8; 25.2 ± 3.6; 24.3 ± 3.2, respectively (p < 0.0001). Conclusion: The results of this study demonstrate that 6% of women attending to our menopause outpatient clinic have established osteoporosis, and approximately 20% have osteopenia. High rates of osteopenia and osteoporosis in postmenopausal women attending to menopause clinics has to be considered in terms of screening and management guidelines.

P05.09 Evaluation of the effects of alendronate, risedronate and oestradiol hemihydrate-norethisterone acetate combinations on bone mineral density Teksin Cirpan, F Akercan, F Sendag, M Cosan Terek, ¨ S Ozsener Department of Obstetrics and Gynecology, Ege University Faculty of Medicine, Izmir, Turkey Objective: To evaluate the effects of Alen¨ dronate, Risedronate and Ostradiol hemihydrateNorethisterone acetate combinations on bone mineral density. Methods: Totally 175 postmenopausal women who was taking the one of these three drugs and applied to Ege University Medical Faculty Gynecology Department’s Menopause Clinic between January 2002 and January 2004 were included in this retrospective study. Initial and 12th month vertebral bone mineral density values of all cases were compared. The drugs, which was the subject of this study are; Alendronate (Fosamax, MSD), Risedronate (Actonel, 5 mg, Aventis) and the combination of Estradiol hemihydrateNorethisterone acetate (NETA) (Activelle film tablet, Estradiol hemihydrate 1 mg and Norethisterone acetate 0.5 mg, Novo Nordisk). Eighty out of 175 cases were Alendronate group, 35 out of 175 were Estradiolhemihydrate-NETA group and 60 of them were Risedronate group. The vertebral bone mineral density, which considered with DEXA were compared in the study. Results: The average age of the patients was 52.8 ± 4.1 years. There were no statistical difference with regard to age, menopausal age, body-mass index (BMI) and postmenopausal period between the groups (p > 0.05). There was also no difference on basic vertebral mineral density values by variance analysis in each three groups (p > 0.05). It was seen that all groups could enhance the vertebral bone mineral density significantly 12 months after the beginning. (Alendronate from 0.730 to 0.774, p = 0.01; estradiol hemihydrateNETA from 0.730 to 0.761, p = 0.01; risedronate from 0.725 to 0.750, p = 0.01). There was a significant difference between the Alendronate and Risedronate on 12-month-vertebra bone mineral density values at variance analysis (0.774 and 0.750 respectively, p = 0.02). Conclusion: Alendronate, Risedronate and ¨ Ostradiol hemihydrate-NETA combination caused

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significant increase on vertebral bone mineral density. A significant difference occures between Alendronate and Risedronate at the end of 1-year therapy. P05.10 Effects of exogenous melatonin administration on bone mineral density in ovariectomized and pinealectomized rats Onder Celik, M Ozsahin, S Hascalik, H Parlakpinar, E Kekilli, S Cengiz Inonu University Medical Faculty, Department of Obstetrics and Gynecology, Pharmacology, and Nuclear Medicine, Malatya, Turkey Objective: There is evidence that pineal melatonin is an anti-aging hormon and that the menopause is associated with a substantial decline in melatonin secretion and increased rate of pineal calcification. We proposed that pinealectomy induced melatonin deprivation in ovariectomized rats may be the contributary factor in the development of postmenopausal osteoporosis. Material and method: A total of 49 young Wistaralbino rats were included to study. Chosen groups submitted to bilateral ovariectomy. Pinealectomy was performed as described by Hoffman and Reiter. After pinealectomy and ovariectomy, melatonin was administered intraperitoneally. We measured bone mineral density of the femur by using dual energy X-ray absorptiometry (DXA; 4500 W, Hologic, USA). The BMD of femur named as proximal 1/3 (R2); middle 1/3 (R1); distal 1/3 (R3); total (R4). Results: Compared with the sham group, PX + MLT group had significantly higher BMD values at R3 subregion. There is no statiscally significant relationship between PX + OVX group and sham group at subregions. Compared with the sham group, PX group had significantly higher BMD value at R3 subregion. There is no statiscally significant relationship between PX group and PX + MLT group at subregions. Compared with the OVX + MLT group, PX + OVX + MLT group had significantly higher BMD values at R1, R3, R4 subregions. Compared with the OVX group, OVX + MLT group had significantly lower BMD values at R3, R4 subregions. Conclusion: In aging model which is formed by pinealectomy and ovariectomy administering a pharmacological amount of melatonin could be prevent the osteoporosis.

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P05.11 The effect of clomiphene citrate on osteoporosis in ovariectomized rats Yildiz Uyar1 , SO Koltan1 , S P¨og¨un2 , S Vatansever3 , H Caglar1 1 Department of Obstetrics and Gyenocology, Faculty of Medicine, Celal Bayar University, Manisa, Turkey; 2 Department of Fizyology, Faculty of Medicine, Ege University, Izmir, Turkey; 3 Department of Histology and Embryology, Faculty of Medicine, Celal Bayar University, Manisa, Turkey Objective: The aim of this study is to investigate whether clomiphene citrate (CC) administration could be a new therapeutic agent in case of contrendication of estrogen therapy for hormone-dependent osteoporosis and to show the changes in bone structure by histomorphometric analysis in ovariectomized rats administered CC. Study design: This study was carried out in Experimental Surgery Laboratory of Brain Research Center, Medical Faculty, Ege University. Three months old female rats were divided into six groups: Group 1 (n = 8): nonovarictomized control group, were injected subcutaneously with serum fizyolojik (1 mg/kg) daily for 6 weeks (SF). Group 2 (n = 8): nonovariectomized control group, were injected subcutaneously with CC (1 mg/1 ml/kg) daily for 6 weeks (CC-1). Group 3 (n = 8): ovariectomize group, were injected subcutaneously with CC (1 mg/1 ml/kg) daily for 6 weeks (OVX + CC-1). Group 4 (n = 8): ovariektomize group, were injected subcutaneously with CC (10 mg/1 ml/kg) daily for 6 weeks (OVX + CC-10). Group 5 (n = 8): ovariectomize group, were injected subcutaneously with 17␤-estradiol (50 ␮g/1 ml/kg, within susame oil) daily for 6 weeks (OVX + E). Group 6 (n = 8): ovariectomize group, were injected subcutaneously with susame oil daily for 6 weeks (OVX). Animals were killed by decapitation at the end of the study. Bone-specific serum alkali phosphatase (ALP) levels were measured from collected bloods and statistical analysis was made by using Kruskal–Wallis test. Left femur bone histomorphometric were done in the six groups. Uterus were taken out to measure their

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weight and ANOVA was used to show the differences of the weight. Results: The level of ALP in group 3 was significantly higher than other five groups. Bone histomorphometric examination showed that total bone volume in groups 3–5 was higher than group 6 and 4 had the highest level of bone volume among studied group. Uterus weights in group Uterus weights in group 1 were significantly higher than group 3 and 6 (p = 0.02, p = 0.06) and uterus weights in group 5 also were significantly higher than group 3 and 4 (p = 0.00, p = 0.01). Conclusion: CC administration effective as estrogen therapy to prevent postmenopausal osteoporosis, without causing uterin hyperstimultion. Nevertheless, it needs further more investigations using more amounts of rats to be alternative treatment method of CC.

activity by Hoechst staining. However, by treating with another phytoestrogen, Daidzein, cellular apoptosis by H2 O2 was not inhibited and pretreatment by 17 ␤-estradiol decreased the apoptotic activitity to 3.5 ± 2.4%. Intracellular ROS increased by 11.2 ± 0.7% in H2 O2 group compared with control group. However, in pretreated 0.5 ␮M-Equol group, ROS decreased significantly by 2.2 ± 0.6% (p < 0.05). Conclusions: Pretreatment by Equol on Bovine aortic endothelial cells demonstrated antioxidative effect on oxidative damage by H2 O2 . But Daidzein did not show the antioxidative protection and this finding suggests that bacterial metabolism phytoestrogens is significantly important.

P06

Symptomatology

Preventive medicine P06.01 Antioxidant effect of phytoestrogen equol on bovine aortic endothelial cells Mee-Ran Kim, B-A Choi, S Kim, H-H Jo, S-J Hwang, Y-O Lew, J-H Kim, Y-T Lim, E-J Kim, J-W Lee, J-H Kim The Catholic University of Korea, Seoul, South Korea Objectives: This study is designed to demonstrate the antioxidant effect of Equol on Bovine endothelial cells damaged by oxidation and to clarify the process of antioxidative effects of phytoestrogens. Methods: Cellular apoptosis was evaluated by MTT assay and FACS analysis. Morphological evaluation of apoptosis was demonstrated by Hoechst staining. Intracellular reactive oxygen species was measured by DCFDA oxidation method, and the expression of P38 was evaluated by Western blotting. SB203580 was used as inhibitor of P38. Results: Bovine aortic endothelial cells showed increased apoptosis according to increasing concentration and exposure time of 1 mM of H2 O2 . After treated with 1 mM for 3 h, 48.8 ± 2.4% of endothelial cell underwent apoptosis. However, when pretreated with 0.5 ␮M-Equol for 30 min, endothelial cellular apoptosis decreased significantly to 0.7 ± 0.4% (p < 0.05). Pretreatment of Equol demonstrated decreased numbers of apoptotic cells and nuclear condensation

P07

P07.01 Vaginal findings from a randomized placebocontrolled trial of black cohosh, multibotanical herbs and dietary soy for hot flashes: the Herbal Alternatives (HALT) Study Susan D Reed1,2,3,4 , KM Newton1,3 , L Grothaus1 , K Ehrlich1 , V Grieco5 , AZ LaCroix1,3,4 1 Center for Health Studies, Group Health Cooperative, Seattle, WA, USA; 2 University of Washington, Department of Obstetrics and Gynecology, School of Medicine, Seattle, WA, USA; 3 University of Washington, Department of Epidemiology, School of Medicine, Seattle, WA, USA; 4 Fred Hutchinson Cancer Research Center, Public Health Sciences Division, Seattle, WA, USA; 5 University of Washington, Department of Pathology, School of Medicine, Seattle, WA, USA Background: Black cohosh (Cimicifuga racemosa) is one of the most commonly used herbal alternatives to hormonal therapy for the menopause. Although recent findings suggest that black cohosh does not significantly diminish the number or severity of hot flashes in early postmenopausal women and women in the menopausal transition, its use for genitourinary symptoms and its effect on the vaginal tissues has not been appropriately evaluated in clinical trials to date. Methods: Peri- and postmenopausal women, ages 45–55, were recruited in western Washington state for a randomized placebo controlled trial investi-

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gating alternative therapies for menopause. Interventions included: (1) conjugated equine estrogen + medroxyprogesterone acetate for women with or without a uterus; (2) black cohosh; (3) a multibotanical preparation that contained black cohosh; (4) the same multibotanical preparation plus soy diet counseling; (5) placebo. The primary outcomes, change in percent parabasal vaginal cells, presence of dyspareunia and vaginal dryness, were assessed at baseline, 3 and 12 months. Results: The five groups did not vary in baseline vaginal cytology profiles, dyspareunia or vaginal dryness. The HT group had significant decrease in the percentage of parabasal cells at 3 months (p = 0.2) and 12 months (p = 0.010) as compared with baseline; no other interventions showed significant changes in vaginal cytology at any time points. Dyspareunia and vaginal dryness did not significantly change from baseline in any of the groups. Conclusion: Herbal remedies containing black cohosh did not change vaginal cytology profiles or affect symptoms of dyspareunia or vaginal dryness. P07.02 Inflammatory diseases of the lower parts of genitals and menopause LV Grigorovich Institute Gerontology of Ukraine, Kiev, Ukraine Presently 54% of population of Ukraine are women. Out of them 24% are women in preclimacterium or menopause periods. The first place after inflammatory diseases of genitals is taken by non-cancerous and cancerous growth. The second place is taken by colpoptosis and metroptosis accompanied by disorders of adjacent organs such as enuresis. Inflammatory diseases of the lower parts of genitals during menopause are of bacterial origin and often they are accompanied by allergic component. Infections transmitting by sexual way affect the three following structures of vagina and cervix of the uterus: epithelium, stroma of conjunctive tissue and blood vessels, which later on leads to the development of atrophic, hyperplastic and degenerate changes provoking pretumor states of the lower part of genitals and leading to presenile sclerotic and dystrophic changes of the both conjunctive tissue and muscles of genitals. This promotes the development of dystopia of walls of vagina and uterus. The appearance of dystrophic and atrophic changes of epithelium

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and conjunctive tissue of cervix of the uterus, endocervix and mucous layer of vagina causes increase in necrotic changes in comparison with apoptosis in genitals. This leads to irreversible process of ageing and atrophy. Therefore elaboration of algorithm of checkup and tactics of individual treatment is conductive to restraining of dystrophic and nectrotic processes and prevents the developments of pathogenesis of pretumor and tumor transformation in the lower parts of genitals such as vulva, cervix of the uterus. The accurate approach and algorithm of checkup contribute to improvement of treatment of enuresis and dystopia of walls of vagina and uterus. P07.03 Collagenopathy and menopause LV Grigarovich Institute Pediatrics, Obstetric and Gynecology, Kiev, Ukraine With increasing quality of methods of treatments the higher number of women with hereditary diseases achieve reproductive age. The manifestations of the most hereditary defects reducing or even keeping normal women fertility are changed with conception. Many hereditary diseases damage child bearing as a result of direct or indirect influence of pathology on a mother or fetus. Therefore child bearing and delivery in women with hereditary diseases present complicated problem from the both medicinal and genetic point of view. The contradictory evidences about the course of pregnancy and delivery in women with hereditary diseases and their interrelations are poorly reflected in literature because of the lack of corresponding studies. This was the reason of our investigations. Spontaneous raptures of blood vessels in women with syndrome of Marfan, ruptures of arteries at syndrome of ElersDallos due to deficiency of collagen structures, which manifest during enzymatic overloads caused by sexual maturation or pregnancy. Thus, the pregnancy in such patients is extremely dangerous and delivery requires excluding of delivery activity, e.g. Caesarean section under anesthesia and controlled breathing. The delay of gestation and failure of fetus bearing are frequently observed. Such women could be sterile and address physicians about hormonal disorders and sterility. In women with hereditary abnormalities the syndrome of ovary dystrophy is often observed. Therefore, the pregnancy in such patients is undesirable. The possibility

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of pregnancy at various types of hereditary pathologies, the possibility of maintaining of pregnancy or the way of its interruption during early stages for the sake of the both mother and child, mutual effect of pregnancy, delivery and hereditary pathology, organizational forms of obstetrical aid are very urgent problems requiring complex investigation by obstetricians, therapists, genetics and physicians with various specialization. The first and the most important stage in the treatment of such patients is the establishment of pathology diagnosis and well-timed adequate treatment. P08 Miscellaneous P08.01 Polycystic ovaries and the menopause Yair Frenkel, H Carp Department of Obstetrics & Gynecology, Sheba Medical Center Tel-Hashomer, Ramat-Gan, Israel There is little information describing the effects of polycystic ovaries (PCO) after the menopause. PCO is accompanied by hormonal and metabolic changes which lead to menstrual irregularity, anovulation, hyperandrogenemia, acne, hirsutism, and obesity. The metabolic alterations include insulin resistance and altered lipid levels such as raised serum triglycerides and low-density lipoprotein and lower serum concentrations of high-density lipoproteins. These are risk factors for diabetes and cardiovascular disease which may become clinically apparent after the menopause. Longterm anovulation predisposes to endometrial cancer due to the effect of unopposed estrogen, and indeed a higher incidence of endometrial cancer has been reported in women with PCO. However, the incidence of breast cancer is not increased. Postmenopausal women with PCO seem to have the same features as premenopausal women. The ovaries are enlarged and contain more follicles, and there is hyperandrogenemia resulting in hirsutism. There is also hypertriglyceridemia with its unwanted metabolic effects. As the proportion of women using HRT is similar in PCO women and non-PCO women after the menopause, there is no difference in vasomotor or other menopausal symptoms between women with and without PCO.

P08.02 Compliance and quality of life of postmenopausal women on hormone replacement therapy T Beljic1 , N Knezevic2 , Z Terzic3 , Jelena Vukcevic1 1 Zvezdara University Hospital, Belgrade, Serbia & Montenegro; 2 Department of Clinical Pharmacology, Belgrade, Serbia & Montenegro; 3 Institute of Social Medicine, Belgrade, Serbia & Montenegro Hormone replacement therapy (HRT) is effective in treatment of climacteric symptoms. It may also increase quality of life in postmenopausal women with symptoms. The aim of our study was to investigate the effect of HRT on quality of life (QoL) and factors that may contribute to compliance. Methods: This was a retrospective study. Some 411 women attending the menopause clinic of the Zvezdara Hospital, during the period 1992–2000, were included in the study. of these, 77 had no climacteric symptoms, 132 had climacteric symptoms but discontinued HRT after 3–6 months, while 202 with symptoms continued HRT for an average of 3.5 years. All women were asked to fill in a Health Status Questionaire (SF-36). The SF-36 consisted of 36 questions divided into eight subscales and two domains of QoL (physical and mental). Results: Quality of life was significantly better in all subscales, except body pain, in postmenopausal women with no symptoms than in postmenopausal women with symptoms but on no HRT (general health F = 14.6, p < 0.01; role-physical F = 7.16, p < 0.01; physical functioning F = 15.8, p < 0.01; vitality F = 20.68, p < 0.01, social functioning F = 19.9, p < 0.01; role-emotional F = 20.5, p < 0.01, mental health F = 28.29, p < 0.01). Quality of life was also significantly better in women on long term HRT than in postmenopausal women not taking HRT because of no indication (general health F = 5.86, p < 0.01; role-physical F = 4.14, p < 0.01; physical functioning F = 6.49, p < 0.01; vitality F = 16.48, p < 0.01, social functioning F = 16.55, p < 0.01; role-emotional F = 18.9, p < 0.01, mental health F = 21.82, p < 0.01). Conclusion: Increased quality of life of postmenopausal women with climacteric symptomes on HRT may increase compliance to HRT.

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P08.03 The effect of black cohosh with St. John’s wort (Feramin-Q) on climacteric symptoms: multicenter randomized double-blind placebo-controlled trial Hyoung Moo Park1 , JG Kim2 , BK Yoon3 , BI Lee4 , H Choi5 , SH Seo6 , BS Lee7 , KH Park7 1 Department of Obstetrics & Gynecology, ChungAng University, South Korea; 2 Department of Obstetrics & Gynecology, Seoul National University, South Korea; 3 Department of Obstetrics & Gynecology, Sungkyunkwan University, South Korea; 4 Department of Obstetrics & Gynecology, Inha University, South Korea; 5 Department of Obstetrics & Gynecology, Inje University, South Korea; 6 Department of Obstetrics & Gynecology, Dong-Guk University, South Korea; 7 Department of Obstetrics & Gynecology, Yonsei University, South Korea Objective: After WHI results, more postmenopausal women (PMW) want to try more natural and safer ways of treating their climacteric symptoms. Black cohosh with St. John’s wort (Feramin-Q) may be effective in climacteric symptoms alternative to hormone therapy. This multicenter RCT was carried out to evaluate the effect of Feramin-Q on the general climacteric symptoms, hot flushes (HF) and depression. Methods: Eighty PMW having moderate to severe climacteric symptoms were randomly allocated to receive Feramin-Q (n = 40) or placebo (n = 40) daily for 12 weeks. Fifty eight subjects completed clinical study. The primary endpoint, the relief of general climacteric symptom and HF was evaluated by Kupperman index and the secondary endpoint, the relief of climacteric depression by Beck Depression Inventory. Results: Both groups showed significant decline of Kupperman index and BDI scores compared with baseline, but Kupperman index and BDI scores between the groups were not significantly different at 12 weeks. HF scores of Feramin-Q groups were significantly decreased after 12 weeks, which showed borderline significance (p = 0.07) compared with placebo. There was no statistical difference in change of HF scores from the baseline between the groups. Among the 45 PMW with moderate to severe HF, Feramin-Q group showed significantly different decrease of HF scores compared with placebo. Conclusion: Feramin-Q was not significantly different concerning the effect on general climacteric symp-

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toms and depression but more effective than placebo in relieving of HF in PMW with moderate to severe HF. Therefore, Feramin-Q seems to be effective alternative to hormone therapy. P08.04 The role of ceramide to apoptosis in germ cells of aged mice Young-Oak You1 , M-R Kim2 1 St. Vincent’s Hospital, The Catholic University of Korea, Seoul, South Korea; 2 Kang Nam St. Mary’s Hospital, The Catholic University of Korea, South Korea Objective: To investigate the role of ceramide and spingolipid regulation in the age-dependent acceleration of apotosis in germ cells of female mice and further to elucidate the menopausal process in women. Materials and methods: Collected oocytes from young and aged mice were divided into cumulus celloocyte complexs (COC) and denuded oocytes (DO). Ten micromolars of Spingosine-1-phosphate or 15 g/ml of BH4 was incubated to determine of those agents could prevent apoptosis in oocyt and granulosa cells. Cytochrome c secretion was measured by Quantikine assay. Results: The incidence of apoptosis of oocyte in COCfrom aged micewas 56.9 ± 6.8%. In contrast, denuded ooocytes was 14.5 ± 5.7% which was significantly low and comparable to that in young mice (p < 0.05). High levels of ceramide were present in COC from mice whereas relatively low levels were detected. After 3 h incubation, ceramide level increased in adjacent oocytes whereas it decreased in cumulus cells. DO from aged mice failed to show any increase in ceramide levels after incubation. Incubation with 10 ␮M spingosine-1-phosphte in COC of aged mice demonstrated 0% apotosis and after incubation with 15 g/ml of BH4, 22.7 ± 6.7% apoptosis was noted in comparison with 44.4 ± 11.6% apoptosis in control group (p < 0.05). After incubating granulosa cells in spingosine-1-phosphate for 48 h, apoptosis decreased from 12.7 ± 2% to 8.1 ± 0.2%. Conclusion: This study showed that ceramide is translocated from cumulus cells into the oocytes and induced germ cell apotosis that be prevented by spingosine-1-phosphate. These findings may help to elucidate the mechanism for the accelerated rate of oocyte depletion in women with premature menopause.

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P08.05 Susceptibility to diphtheria in women and men: prevalence and relation to sex and social variables H V¨olzke1 , S Schwarz2 , W Hoffmann3 , Martina D¨oren2 1 University of Greifswald, Institute of Epidemiology & Social Medicine, Germany; 2 Charit´eUniversit¨atsmedizin Berlin, Germany; 3 University of Greifswald, Institute for Community Medicine, Germany Background and objective: Recent outbreaks of diphtheria have drawn attention to the re-emergence of this disease. We undertook the present study to investigate the prevalence of susceptibility to diphtheria in Northeast Germany and its relation to sex and social factors. Methods: A study population of 4275 individuals recruited for the Study of Health in Pomerania was available for analyses. IgG antibodies against diphtheria toxin were determined by ELISA and used to define immunity, basic immunity and susceptibility to diphtheria. Results: The proportions of immunity, basic immunity and susceptibility to diphtheria were 10.3%, 57.3% and 32.4%, respectively. Multivariable analyses revealed a 45% increased risk of being susceptible to diphtheria for women. Females without a diphtheria toxoid vaccination during the past 10 years had a fourfold increased risk to be susceptible to diphtheria toxin compared to unvaccinated men. None of the social factors were associated with the susceptibility status. Conclusions: There is a high proportion of middleaged adults who are susceptible to diphtheria. Women are more often without seroprotection than men which might be partly explained by sex-specific immune responses after vaccinations. There is a need for information campaigns which are aimed to improve the public awareness with respect to these problems. P08.06 Overcoming the difficulties of endometrium for egg donationand cryo/thawed embryo transfer programs with Finoptin Oleg Berestovoy, V Zinchenko, V Veselovsky Isida Hospital, IVF Department, Kiev, Ukraine Background: The aim of this part of investigation was researching of effectiveness of overcoming the dif-

ficulties of endometrium for egg donation (ED) and cryo/thawed embryo transfer (CThET) programs with Finoptin for improving of estrogen-mediated endometrial proliferation and IVF outcome in infertile women with recurrent IVF failure attributed to poor endometrial development. Methods: We have analyzed quality of endometrium growing of four cycles of CThET and four ED with transdermal estradiol (Divigel) protocol with not adequately increasing of endometrium thickness. In these cases Finoptin was added 40 mg twice daily for 5 days when we made US exam to make decision either to keep the patient under observation for a few days with the same regimen or start progesterone synchronization. Doppler estimation of subendometrial and endometrial blood flow was made exactly before Finoptin start and on last day of Finoptin treatment. Results: Qualitative and quantitative characteristics of endometrium growing was statistically better. Qualitative (doppler scores) and quantitative doppler characteristics (peek systolic velocity and PI) was better also. Conclusion: Thus according to results today we can think about good possibility of overcoming the difficulties of endometrium for ED and CThET programs with not expensive regimen with old powerful calcium channel-blocking agent Finoptin. P08.07 Women’s attitudes towards menopause among Turkish women 2 , R Kecialan3 ¨ Orsal ¨ G¨ulcyhan Akkuzu1 , O 1 Department of Nursing and Health Services, Faculty of Health Sciences, Baskent University, Ankara, Turkey; 2 Department of Community Health Nursing, School of Nursing, Hacettepe University, Ankara, Turkey; 3 RN., MsN. In Pediatric Nursing, Turkey Aim: To determine attitudes towards menopause and influencing factors in survey. Method: Two phases stratified cluster systematic random sampling in 42 women subjects with an age range of 40–55 who live in neighbourhoods registered to Ankara, the Hilal Primary Health Center. The data was collected by interview at the home of women using a questionnary form and a Neugarten and Clanires’s Attitudes Towards Menopause Scale that validity and reliability study had performed by Uc¸anok on Turk-

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ish women. Data were analysed using Chi-square and Tukey tests. Results: This research showed that nearly overall (88.1%) women didn’t work, and nearly overall (85.7%) married and almost two-three of women have a third (38.1%) or fourth (31.0%) child. The 50.0% of women was in premenopausal period, 4.8% of them in menopausal period and 45.2% of postmenopausal periods. 64.3% of women did not go to a health center and did not have knowledge about medical therapy. 7.1% of women who are being use any theraphy know that it is calsium therapy and perceive their theraphy is effective. Almost half of them determine the menopause as ‘problem’. However mean score of women (61.80) was related pozitive attitude towards menopause. There were significant differences between education level (F = 4.964, p = 0.012) and work situation (F = 7.141, p = 0.011) attitude towards menopause. There were also significant differences between ic¸e kapanma (F = 535.048, p = 0.020) and scratching (F = 8.948, p = 0.005) from menopausal semptoms and attitude towards menopause. Conclusions: Women should be strengthened with education and counseling about menopausal life periods from child to perimenopausal ages. P08.08 Incidence of dyslipidemia in postmenopausal women attending to Marmara University Menopause Clinic Pınar Y¨or¨uk, M Uygur, B Yildizhan, M Erenus, F Durmusoglu Marmara University, Department of Obstetrics and Gynecology, Reproductive Endocrinology and Infertility Unit, Turkey Objective: During the reproductive period, women generally have lower low-density lipoprotein (LDL) cholesterol and higher high-density lipoprotein cholesterol than age- and diet-matched men. However, these possibly antiatherogenic characteristics of lipoproteins are changed to a potentially atherogenic profile after menopause. The aim of this study is to evaluate the incidence of dyslipidemia in postmenopausal women attending to Marmara University Menopause Unit. Methods: Lipid profile is one of the components of menopausal workup in our menopause outpatient clinic. In this retrospective study records of women attending to Marmara University menopause outpa-

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tient clinic between years 1995 and 2005 were evaluated and serum lipid profiles and medications were noted. Women with LDL-cholesterol >140 mg/dl, total cholesterol >200 mg/dl and triglycerides >200 mg/dl were accepted to have dyslipidemia. Results: In 2267 women enrolled only 36% of women had cholesterol levels within the normal range, and the remaining 64% had high LDL-cholesterol, total cholesterol or triglyceride levels. The mean LDLcholesterol, total cholesterol and triglyceride levels in normo-lipidemic women were 98 ± 22.0, 176.0 ± 23.0 and 107.4 ± 61.2 mg/dl, respectively. The mean LDLcholesterol, total cholesterol and triglyceride levels in dyslipidemic women were 145 ± 29.7, 238.2 ± 29.1 and 195.4 ± 74.5 mg/dl, respectively. Both normolipidemic and dyslipidemic women were similar according to age (51.8 ± 6.7 and 52.2 ± 6.1), age at menopause (45.8 ± 4.7 and 46.4 ± 4.3), and body mass index (26.4 ± 4.0 and 26.1 ± 3.5). Conclusion: Results of this study demonstrate a high incidence of hyperlipidemia (64%) in postmenopausal women attending to Marmara University Menopause Unit. Since increased cholesterol levels are strongly correlated with atherogenic events, it might be appropriate to screen all postmenopausal women attending to health centers for any reason for serum lipid disturbances. P08.09 The relation of thick endometrial lining with increased body mass index in postmenopausal women Meltem Uygur, P Y¨or¨uk, B Yildizhan, M Erenus, F Durmusoglu Marmara University, Department of Obstetrics and Gynecology, Reproductive Endocrinology and Infertility Unit, Turkey Objective: It has been demonstrated that obesity is associated with increased serum E2 levels and related complications in postmenopausal women. The aim of this study is to determine the relation between body mass index and endometrial thickness more than 4 mm in postmenopausal women. Methods: The records of all postmenopausal women who attended to Marmara University menopause outpatient clinic between years 1995 and 2005 were evaluated retrospectively. Women who underwent TVUSG for determination of endometrial thickness

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were enrolled into this study. Four millimeters was used as the cut-off value to determine thick endometrial lining. Results: Of the all 567 women enrolled 26.8% (n = 124) had endometrial lining >4 mm. The remaining 78.2% (n = 443) had normal endometrial thickness. Both groups of women were similar according to demographic factors. On the other hand body mass index were significantly different in women with endometrial lining >4 mm and in women with endometrial lining ≤4 mm (28.6 ± 5.3 and 25.6 ≤ 3.5, respectively). A weak correlation was calculated between body mass index and endometrial thickness (r = 0.431, p < 0.001). Conclusion: The results of this study demonstrate a positive correlation between endometrial thickness and body mass index of postmenopausal women attending to our clinic. These results reflect the increased peripheral estrogen production due to obesity resulting in increased endometrial thickness. It might be suitable to screen postmenopausal women with increased BMI values for increased endometrial thickness. P08.10 The importance of endometrial thickness considered with transvaginal ultrasonography in postmenopausal asemptomatic women Ismail Mete Itil, T Cirpan, F Akercan, P Solmaz Yildiz Department of Obstetrics and Gynecology, Ege University Faculty of Medicine, Izmir, Turkey Objective: To investigate the importance of the measurement of endometrial thickness by transvaginal ultrasound in diagnosis of endometrial pathologies in postmenopausal asemptomatic women. Methods: Total 57 cases, who were being in postmenopausal period and had endometrial thickness (>5 mm) in TVUSG without complaints like bleeding or spotting, admitted to Ege University Gynecology outpatient clinic between January 2004 and January 2005 included the study. The study design was retrospective. The acceptance criterions of the patients were not taking any HRT drugs, 6 months amenorhea at least, had no complaints of vaginal bleeding. Results: The average age of the 57 patients were 55.6 ± 7.5 years. Hypertension was seen in two (63.2%) and diabetes was seen in five (8.8%) of the patients. Thirteen (22.8%) of the patients had diagnosed breast cancer and all of them were taking chemotherapy with tamoxiphene. In conclusion,

endometrial hyperplasia was seen in four (7.0%) of the patients and 53 cases (93.0%) had benign endometrial pathology. Conclusion: The endometrial hyperplasia rates were similar between the patients with breast cancer or not in asemptomatic postmenopausal patients who had increased endometrial thickness (>5 mm) in TVUSG. P08.11 The effect of menopause on serum copper concentrations, and its’ relation with homocysteine, apolipoprotein A, and apolipoprotein B levels Ahmet Erdem, C Taskiran, E Biberoglu, K Biberoglu Gazi University, Department of Obstetrics and Gynecology, Ankara, Turkey Purpose: The purpose of this study was to evaluate the change in serum copper levels after menopause, and also to investigate its’ relation with serum homocysteine, apolipoprotein A (Apo A), and apolipoprotein B (Apo B) levels. Method: To observe the effect of menopause, both the eumenorrheic or oligomenorrheic premenopausal women (n = 42), and postmenopausal women with intact uteri-amenorrheic for at least 1 year without any treatment (n = 69) were included. To decrease the effect of age, only the candidates between 45 and 55 years were recruited to the study. Additionally, factor VII (FVII), plasminogen activator inhibitor 1 (PAI-1), and HDL-LDL cholestrol levels were also analyzed. Results: Serum copper levels were 122.71 ± 37.74 and 108.37 ± 33.73 for premenopausal and postmenopausal groups, respectively, with a significant variance (p = 0.04). Serum homocysteine, Apo A, and Apo B levels were 9.16 ± 4.56 and 10.67 ± 3.96 (p = 0.07); 119.35 ± 18.21 and 135.20 ± 27.85 (p = 0.003); 99.21 ± 23.12 and 110.58 ± 24.02 (p = 0.02), respectively, in pre- and postmenopausal women. Copper levels were significantly correlated with homocysteine concentrations (p = 0.03, r = 0.741). Although it was near to significance, copper was not correlated with Apo A and B levels (p = 0.08, r = 0.410; and p = 0.07, r = 0.479, respectively). LDL cholestrol levels increased significantly, but no variance was seen in HDL, FVII, and PAI-1 levels. Copper concentrations were significantly correlated with PAI-1 levels. Conclusion: In this study, it is demonstrated that serum copper levels were decreased after menopause,

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and this decrement was found to be related with the increase in serum homocysteine levels. P08.12 The effect of raloxifene treatment on immune system ¨ Korucuo¨olu2 , B Ciftci2 , BA Aydan Biri2 , A Y¨ucel1 , U 1 Buyrukcu , K Biberoglu2 1 Gazi Universitesi ¨ Tip Fak¨ultesi, Imuunology AD, Ankara, Turkey; 2 Kadin Hastaliklari ve Do¨oum AD, Beþevler, Ankara, Turkey Objective: Aim was to detect the effect of raloxifene treatment on serum levels of IL-4, IL-10, IL-8/NAP1, TIMP-1, MMP-3, sE-selectin and resistin levels in postmenopausal women and consequently deduce the possible effect of raloxifene on the immune system. Materials and methods: The study was performed in Gynecology and Obstetrics outpatient clinics of Gazi University Faculty of Medicine, Ankara, Turkey, between January 2004 and January 2005. Twenty postmenopausal women suffering from osteoporosis were included in this study. They were treated with raloxifene for 12 months. As a control group, twenty nonosteoporotic postmenopausal women matched with the patient group for age, postmenopausal years, smoking status and other health parameters (full-matched), without any medication were chosen. Serum IL-4, IL-10, IL-8/NAP-1, MMP-3, TIMP-1, sE-selectin and resistin levels were studied in the two groups by using commercial ELISA kits. Results: There was no statistically significant difference between the two groups with respect to the serum IL-4, IL-8/NAP-1, MMP-3, TIMP-1 and sE-selectin levels. Serum IL-10 and resistin levels were below the measurable levels in both groups. Conclusion: Raloxifene use for 12 months seemed not to affect serum levels of IL-4, IL-10, IL-8/NAP1, TIMP-1, MMP-3, sE-selectin and resistin in this study. However, it is not possible to deduce a definite result that raloxifene has no adverse impact on the immune system with a prolonged use, because studies with higher number of patients taking more parameters of the immune system into consideration and comparing the serum levels of the immune parameters before and after the raloxifene treatment are needed.

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P08.13 The comparison of the visual field properties of the migrainous and the healthy menopausal women Omur Taskin, M Erman Akar, I Yucel, M Uner, Y Akar Purpose: To compare the visual field analysis of the migraineous and normal women. Material and methods: Healthy menopausal women and migraineous women were included in the study. Subjects underwent the perimetric analysis twice. Visual field mean sensitivities (MS) and mean deviation (MD) values of the each subject were assessed. MS of the different regions of the same eye were compared. Results: The mean age of the normal and the migraine subjects were 51.2 ± 10.2 and 52.3 ± 10.4 years, respectively (p > 0.05). The visual field mean MS value of the migraine women was found to be significantly lower than that of the normal subjects (p < 0.05). Glaucoma- like visual field defect risks were found to be 3.67 and 4.34 times higher in those with a family history of the glaucoma and those who are older than 35 years of age, respectively. Conclusion: Migrainous women are under more risk for glaucoma with respect to the healthy menopausal women. Migraine duration, patient age and the familial glaucoma history were found to be the major risk factors in development of glaucomatous visual field defects. P08.14 Optic nerve head topography and visual field sensitivity of the migrainous menopausal women with or without glaucoma Y Akar, I Yucel, O Taskin, B Dora, M Erman Akar, M Uner Aim: To compare the optic nerve head topography of the migrainous menopausal women with those of the glaucoma and the normal menopausal population, and to determine the reproducibility of perimetric tests. Material and methods: Migrainous menopausal women, who are followed up by Neurology department at least for 3 years, and the normal menopausal subjects, with no systemic and the ocular problems other than the refractive error, and the primary open angle glaucoma patients are included in the study. The optic nerve head

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topographic measurements were performed using the HRT II (Heidelberg Retinal Tomograph II). Subjects underwent at least two perimetric analysis with the Humphrey visual field analyser central 30-2 program full threshold strategy. The perimetric analyses were repeated in case of the presence of the glaucomatous visual field defects. Regional visual field mean sensitivity (MS), coefficient of variation values in four different visual field quadrants (upper temporal, lower temporal, upper nasal and the lower nasal) of randomly selected normal (n = 26) and migrainous women (n = 23) were compared using five separate tests during a 4-week period. The disc area, topography standart deviation, a total of 11 topographic parameters and the MS, mean deviation (MD) and the corrected patern standard deviation (CPSD) values of the each subject were assessed. Results: The mean age of the migrainous menopausal (n:83), glaucoma (n:88), and the healthy menopausal women (n:91) were not found to be significantly different (p > 0.05). The mean disc area of the three groups were found to be 2.41, 2.17 and 2.09 mm2 , respectively (p < 0.05). All of the optic nerve head topographic parameters of the migrainous patients were found to be significantly different than the glaucoma and the normal subjects. Migraine patients were found to be significantly different than the glaucoma cases for all the parameters studied when the subjects with the disc areas changing only between 2 and 2.25 mm2 , whereas, there were no significant difference in between migraine and the normal cases other than cup shape measure than. The visual field MS coefficient of variation values were found to be statistically higher in migrain patients (p < 0.05). Conclusion: Migrainous women were found to have an optic disc area, which is similar to those of the glaucoma, and is significantly larger than that of the normal cases. The clinicians should take the present finding into consideration that the visual field sensitivitity and its reproducibility of the migraine patients were significantly worse than that of the normal subjects in the clinical follow-up of migrainous women followed with glaucoma suspicion. The parameter cup shape measure can be used for the assessment of such patients for the normal tension glaucoma.

P08.15 Is mammographic density different in women with premature menopause? Cemal Tamer Erel, LM Sent¨urk, MH Yilmaz, G Esen, ¨ Gelen, S Kaleli, H Seyisoglu, E Oral, S Sahmay, E O Ert¨ungealp Istanbul University Cerrahpasa School of Medicine, Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology, Istanbul, Turkey Objective: Women with premature menopause may receive HRT for a longer period of time than the women with natural menopause. There should be many differences between women with premature menopause and natural menopause in terms of breast changes. In this retrospective study, we have compared mammographic density changes among these two groups of women. Materials and methods: In this retrospective study, we included 48 women with premature menopause and 88 women with normal menopause. We confirmed that all of the women included into the study were in menopause by taking their history, performing clinical examination and detecting serum E2 and FSH levels. Two senior radiologists, independently, compared their initial (before starting HRT) and the last (still on HRT) mammographies and classified them according to the BIRADS system. One-way ANOVA was used for statistical analysis. Results: As expected, the average age and the BMI scores were significantly lower in women with premature menopause. Average duration of HRT use was found to be comparable between the two groups. While the mammographic density increase between the first and last mammograms was not significant in women with normal menopause (p = 0.092), this was significantly different in women with premature menopause (p = 0.003). The women with premature menopause had significantly denser breast parenchyma (p = 0.000) both in their first and last mammograms when compared with those in normal menopause. In addition, 41.7% of women with premature menopause had their BIRADS scores increased, while this was seen in only 15.9% of women with normal menopause. Conclusions: Women with premature menopause had denser breast parenchyma. The effect of HRT on breast parenchyma was more significant and prominent in women with premature menopause. Therefore,

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we should closely monitor the breast parenchyma in women with premature menopause on HRT. Table 1 Characteristics of women in the two groups are summarized

Age (years) BMI (kg/m2 ) Duration of HRT E2 (pg/mL) FSH (IU/mL) Initial BI-RADS Last BI-RADS Density increase n (%)

Premature menopause (n = 48)

Normal menopause (n = 88)

36.21 ± 3.20 26.61 ± 3.14 60.00 ± 37.70 23.25 ± 18.90 63.90 ± 29.98 2.54 ± 0.58 2.92 ± 0.65 20 (41.67%)

53.24 ± 5.51 28.82 ± 4.87 57.64 ± 31.58 30.26 ± 15.58 58.00 ± 30.89 2.14 ± 0.63 2.31 ± 0.70 14 (15.91%)

P08.16 The effect of intrauterine levonorgestrel device and oral medroxyprogesterone acetate on endometrial thickness and uterine blood circulation in postmenopausal women ¨ urk Turhan, D Dogan Nilg¨un Ozt¨ Fatih University School of Medicine, Turkey Objectives: A prospective randomized, parallelgroup study was conducted to compare the effects of continuous intrauterine release of levonorgestrel (LNG-IUS) and oral medroxy- progesterone acetate (MPA) on uterine blood circulation and endometrial thickness in women on postmenopausal hormone replacement therapy (HRT). Methods: Women received transdermal estradiol (50 ␮m/day) in combination with LNG-IUS (n = 40, group I, LNG-IUS/EE group) or MPA 10 mg/day for 10 days/month (n = 40, group II, MPA/EE group). Results: Systolic and diastolic blood pressures of the patients were significantly higher in LNG-IUS/EE group before starting therapy but these differences disappeared 1 year after treatment. A significant decrease was observed both in systolic and diastolic blood pressures in LNG-IUS/EE group, while a significant increase was observed in MPA/EE group after a year of treatment. The mean values of the S/D and RI of the uterine arteries, radial arteries and spiral arteries

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were significantly higher in LNG-IUS/EE group compared to MPA/EE group both before starting and after 1 year of treatment. A significant increase in S/D and RI of these arteries and a significant decrease in mean endometrial thickness was observed after 1 year treatment in both groups. Conclusion: Progesteron therapy might have vazoconstriction effects on vessels, might trigger suppression of endometrial proliferation as well as endometrial vascular changes that include thickening of the arterial walls, suppression of spiral arterioles and capillary thrombosis but these local effects by the LNG-IUS is more reasonable and useful compared to that in the oral MPA therapy. P08.17 Menopausal pregnancy, a case report Melahat D Kesim, Y Aydin, A Atis, S Ozdemir, G Ozdemir Sisli Etfal Training and Research Hospital, 3rd Obstetrics and Gynecology Clinics Introduction: After advances in HRT, old year pregnancies have increased but pregnancy complications in older years have also increased. Here we present a 54year-old patient who have undergone IVF with oocyte donation abroad and attended to our clinic. Case: A 54-year-old woman, LMP: 3 years ago, has attended to our clinic with a 31 gestationel week twin pregnancy, with premature contractions and abdominal cramps. She had undergone IVF with oocyte donation abroad. We started tocolysis with premature labour signs. After 1 week, she had symptoms of preeclampsia with very high liver enzymes and one of the fetuses had signs of fetal distress on NST. So she has been undertaken to cesarean section urgently. Two fetuses 1500 and 1400 g each with Apgar scores 8 and 6 were extracted. She had massive uterine bleeding answered to uterine massage and oxitosin induction. One of the babies had laser therapy for the eyes because of premature retinopathy. Discussion: Women in the perimenopausal years are at increased risk of aging-related problems such as cardiovascular disease and diabetes, genetic defects in offspring, morbidity with a pregnancy, and mortality

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from a pregnancy. Pregnancies in advanced age carry both risk of maternal and fetal morbidity. Maternal mortality between ages of 40 and 44 is four times fold compared to ages of 20–25, and 10 times fold above 45 years. Besides, the risk of congenital anomalies and

miscarriages increase at thisages. When forcing older women’s body to pregnancy environment with IVF, we should think all the complications in mind in order not to increase maternal mortality.