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Hormonal treatment in the perimenopause
TUESDAY,
SEPTEMBER
5
RM2.03 ISSUES IN THE PERIMENOPAUSE RM2.03.01 BIOLOGY AND ENDOCRINOLOGY OF PERIMENOPAUSE Khunving. The Royal Thai College of Obstetricians and Gynaecologists, Bangkok, Thailand Perimenopause should be regarded as a starting of hormone deficient state. Decreased levels of inhibin results in raised levels of folliclestimulating hormone (FSH) which is the first biological change indication of perimenopause. The increased FSH induced rapid follicular development with consequent in shorting of cycles. Inhibin is a non-steroidal inhibitor present in follicular fluid, its peptide moiety is synthesized by the granulosa cells and secreted into the follicular fluid. Near the menopause, the number of follicle is further decreased, decreased in estrogen production, no ovulation occurred or cycle became irregular. The ovary itself continued to loose primordial follicle from intrauterine life and throughout the reproductive year until menopause. This cause the decrease and complete cessation of cyclic function of the female reproductive organ. At age 35, the ovary begins to decrease in weight and size, the follicles start to be atretic and degenerated. The ovarian estradiol and progesterone secretion are sharply reduced but the ovarian stroma cell as well as the adrenal cells still have steroidogenic capacity to produce androstenedione which is converted to estrone. The primary steroidogenic element of the perimenopausal and postmenopausal ovary is the stroma which sometimes there is an island of “theta” cell which response to the stimulus from high LH concentration secrete androgen. In post menopausal women, estrogen is formed by peripheral conversion of androstenedione, which the circulating level is about one-half of that detected prior to menopause, most of the androstenedione derived from adrenal gland. This conversion rate of androstenedione to estrone is significantly correlated with obesity, especially fat at the periphery or skin appendages. The blood level of estradiol is rather low, lo-20 pg/ml or 40-70 pmoln, and mostly this estradiol derived from peripheral conversion. The circulating level of estrone is higher in perimenopause, 30-70 pg/ml, then produce with average of 4.5 cl&24 hr in post menopause. The dramatic endocrine alteration of menopause transition involves the decline in the circulating levels and excretion rates of estrogen. Estrogen production in postmenopausal women is almost exclusively due to extraglandular aromtization of androstenedione.
RM2.03.02 CONTRACEPTIVE ISSUES Carmen Co11 Caudevila, Women’s Health Program of Maresme, Catalan Institute of Health, Matar6, Barcelona, Spain. Contraception it’s a bio psycho socio-cultural and relational problem that needs a special attention during the different period o live. Women in their forties are still potentially fertile, and pregnancy in this age group is attended with increased maternal mortality, spontaneous abortion, foetal anomalies and perinatal mortality. Contraception for women in this age group has special risks and benefits, both should be balanced to choose between the different options available. Recent epidemiological and clinical pharmacology studies have indicated the safety of extending the use of combined oral contraceptives (COCs) beyond the age of 35 years and up to menopause. In March 1996, an international group of recognised authorities in their field met to review the available evidence concerning the effects of COCs and the value of various screening procedures in pre-menopausal women. Current scientific evidence suggests only two pre-requisites for the safe provision of COCs: a careful personal and family medical history with particular attention to cardiovascular risk factors, and an accurate blood pressure measurement. Further assessment is required only if a relevant personal or family history is disclosed or the blood pressure is elevated. The improved picture of COCs has largely resulted from the use of lowdose-formulations, and avoidance of their use in women with risk factors for developing cardiovascular diseases. Besides their high reliability, which is desirable at this age, COCs will prevent the occurrence of climacteric symptoms and menstrual irregularities, which are frequently complained of in the premenopausal years. Moreover, the use of COCs has a substantial protective effect against ovarian and endometrial cancers. The Levonorgestrel IUD has the advantage of reducing the amount of menstrual bleeding. The extent of use of barrier
11
methods will depend upon the availability of a back up by abortion service in case of failure. The condom has the added benefit of protection against STDs. Male or female sterilization is an excellent contraceptive option, provided that this approach is culturally acceptable and available at reasonable cost and low risk.
RM2.03.03 HORMONAL TREATMENT IN THE PERIMENOPAUSE Thomas Rabe, University Womens’ Hospital; Heidelberg, Germany Perimenopause = time of transition with increase in cycle irregularities, decreased fertility and higher rate of chromosomal defects. Fertility: decreases with age; no contraception in patients with amenorrhoea > 2 years before age 50 and > 1 year thereafter. Onset of menopause can only be determined by high FSH and low E2 in progestinonly and copper IUD users but not in OC takers. Abortions: 51% of unwanted pregnancies (total 6.3 millions) in the US in age 40+ (abortions 65%); 47% in noncontraceptors. Sterilization versus OC in US: age 40-44: 26%/11%; age 45-50: 27%/4%. Tubal sterilization: quite common in older patients; method-related high cummulative pregnancy rate in US (up to 5% up to 10 years) in Europe: 1-2 per 1000 women (total rate). Low dose oral hormonal contraceptives (OC) can be used in healthy patients without OC contraindications (e.g. cigarette smoking) until age 55 followed by HRT (higher acceptance rate in switchers). Additional benefits on bone mineral density, lower hip fracture risk, dysfunctional uterine bleedings, dysmenorrhoea and estrogen deficiency symptoms (e.g. hot flushes). Low OC acceptance by elder patients due to a fear of hormone related side effects (e.g. cancer and cardiovascular diseases), belief that long-term use increases health risks and concerns regarding weight gain. Long-term contraception: injectables, copper IUDs, intrauterine levonorgestrel intrauterine releasing system, hormone implants, vaginal rings*), contraceptive patches*) *) not yet available. Counceling of patients about different choices of contraception or hormone therapy including benefits, side effects, costs etc. will increase acceptance and continuation rates. Furthermore cancer sreening, lifestyle modification (smoking cessation, diet, weight control, aecrobic exercise) and serum cholesterol or fasting coronary risk profile every 5 years is recommended.
RM2.04 REVIEW
OF IU DEVICES
RM2.04.01 WHO MULTI-CENTRED STUDIES P. World Health Organization,
Geneva, Switzerland
The UNDP/UNFP&WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction was establisehd in 1972 with one of its objectives being the evaluation of the safety and efficacy of existing methods of fertility regulation. The initial randomized multicentre studies undertaken by the Programme showed the first generation copper IUDs (Tcu200, Tcu220C and 017) to be comparable to the plain plastic Lippes Loop IUD a device then in widescale use especially in developing country family planning. programmes. The second series of trial compared the Tcu220C with other copper IUDs such as the Nova T and Multiload 250, both of which were found to have pregnancy rates between 1.0 and 2.0 per 100 women at one year of use, whereas the Tcu220C device pregnancy rates at one year were less than 1.0 per 100 women. In subsequent WHO studies, the Tcu380A had significantly lower pregnancy rates at five, eaight and eleven years of use compared to the Tcu220C and the Tcu380A was adopted as the reference device in subsequent WHO trials. In the randomized study of the Mutiload 375 and the Tcu380A, the pregnancy rates at nine years of use were 5.0 (kO.7SE) and 3.2 (kO.5SE) (p=
SEPTEMBER
5
RM2.03 ISSUES IN THE PERIMENOPAUSE RM2.03.01 BIOLOGY AND ENDOCRINOLOGY OF PERIMENOPAUSE Khunving. The Royal Thai College of Obstetricians and Gynaecologists, Bangkok, Thailand Perimenopause should be regarded as a starting of hormone deficient state. Decreased levels of inhibin results in raised levels of folliclestimulating hormone (FSH) which is the first biological change indication of perimenopause. The increased FSH induced rapid follicular development with consequent in shorting of cycles. Inhibin is a non-steroidal inhibitor present in follicular fluid, its peptide moiety is synthesized by the granulosa cells and secreted into the follicular fluid. Near the menopause, the number of follicle is further decreased, decreased in estrogen production, no ovulation occurred or cycle became irregular. The ovary itself continued to loose primordial follicle from intrauterine life and throughout the reproductive year until menopause. This cause the decrease and complete cessation of cyclic function of the female reproductive organ. At age 35, the ovary begins to decrease in weight and size, the follicles start to be atretic and degenerated. The ovarian estradiol and progesterone secretion are sharply reduced but the ovarian stroma cell as well as the adrenal cells still have steroidogenic capacity to produce androstenedione which is converted to estrone. The primary steroidogenic element of the perimenopausal and postmenopausal ovary is the stroma which sometimes there is an island of “theta” cell which response to the stimulus from high LH concentration secrete androgen. In post menopausal women, estrogen is formed by peripheral conversion of androstenedione, which the circulating level is about one-half of that detected prior to menopause, most of the androstenedione derived from adrenal gland. This conversion rate of androstenedione to estrone is significantly correlated with obesity, especially fat at the periphery or skin appendages. The blood level of estradiol is rather low, lo-20 pg/ml or 40-70 pmoln, and mostly this estradiol derived from peripheral conversion. The circulating level of estrone is higher in perimenopause, 30-70 pg/ml, then produce with average of 4.5 cl&24 hr in post menopause. The dramatic endocrine alteration of menopause transition involves the decline in the circulating levels and excretion rates of estrogen. Estrogen production in postmenopausal women is almost exclusively due to extraglandular aromtization of androstenedione.
RM2.03.02 CONTRACEPTIVE ISSUES Carmen Co11 Caudevila, Women’s Health Program of Maresme, Catalan Institute of Health, Matar6, Barcelona, Spain. Contraception it’s a bio psycho socio-cultural and relational problem that needs a special attention during the different period o live. Women in their forties are still potentially fertile, and pregnancy in this age group is attended with increased maternal mortality, spontaneous abortion, foetal anomalies and perinatal mortality. Contraception for women in this age group has special risks and benefits, both should be balanced to choose between the different options available. Recent epidemiological and clinical pharmacology studies have indicated the safety of extending the use of combined oral contraceptives (COCs) beyond the age of 35 years and up to menopause. In March 1996, an international group of recognised authorities in their field met to review the available evidence concerning the effects of COCs and the value of various screening procedures in pre-menopausal women. Current scientific evidence suggests only two pre-requisites for the safe provision of COCs: a careful personal and family medical history with particular attention to cardiovascular risk factors, and an accurate blood pressure measurement. Further assessment is required only if a relevant personal or family history is disclosed or the blood pressure is elevated. The improved picture of COCs has largely resulted from the use of lowdose-formulations, and avoidance of their use in women with risk factors for developing cardiovascular diseases. Besides their high reliability, which is desirable at this age, COCs will prevent the occurrence of climacteric symptoms and menstrual irregularities, which are frequently complained of in the premenopausal years. Moreover, the use of COCs has a substantial protective effect against ovarian and endometrial cancers. The Levonorgestrel IUD has the advantage of reducing the amount of menstrual bleeding. The extent of use of barrier
11
methods will depend upon the availability of a back up by abortion service in case of failure. The condom has the added benefit of protection against STDs. Male or female sterilization is an excellent contraceptive option, provided that this approach is culturally acceptable and available at reasonable cost and low risk.
RM2.03.03 HORMONAL TREATMENT IN THE PERIMENOPAUSE Thomas Rabe, University Womens’ Hospital; Heidelberg, Germany Perimenopause = time of transition with increase in cycle irregularities, decreased fertility and higher rate of chromosomal defects. Fertility: decreases with age; no contraception in patients with amenorrhoea > 2 years before age 50 and > 1 year thereafter. Onset of menopause can only be determined by high FSH and low E2 in progestinonly and copper IUD users but not in OC takers. Abortions: 51% of unwanted pregnancies (total 6.3 millions) in the US in age 40+ (abortions 65%); 47% in noncontraceptors. Sterilization versus OC in US: age 40-44: 26%/11%; age 45-50: 27%/4%. Tubal sterilization: quite common in older patients; method-related high cummulative pregnancy rate in US (up to 5% up to 10 years) in Europe: 1-2 per 1000 women (total rate). Low dose oral hormonal contraceptives (OC) can be used in healthy patients without OC contraindications (e.g. cigarette smoking) until age 55 followed by HRT (higher acceptance rate in switchers). Additional benefits on bone mineral density, lower hip fracture risk, dysfunctional uterine bleedings, dysmenorrhoea and estrogen deficiency symptoms (e.g. hot flushes). Low OC acceptance by elder patients due to a fear of hormone related side effects (e.g. cancer and cardiovascular diseases), belief that long-term use increases health risks and concerns regarding weight gain. Long-term contraception: injectables, copper IUDs, intrauterine levonorgestrel intrauterine releasing system, hormone implants, vaginal rings*), contraceptive patches*) *) not yet available. Counceling of patients about different choices of contraception or hormone therapy including benefits, side effects, costs etc. will increase acceptance and continuation rates. Furthermore cancer sreening, lifestyle modification (smoking cessation, diet, weight control, aecrobic exercise) and serum cholesterol or fasting coronary risk profile every 5 years is recommended.
RM2.04 REVIEW
OF IU DEVICES
RM2.04.01 WHO MULTI-CENTRED STUDIES P. World Health Organization,
Geneva, Switzerland
The UNDP/UNFP&WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction was establisehd in 1972 with one of its objectives being the evaluation of the safety and efficacy of existing methods of fertility regulation. The initial randomized multicentre studies undertaken by the Programme showed the first generation copper IUDs (Tcu200, Tcu220C and 017) to be comparable to the plain plastic Lippes Loop IUD a device then in widescale use especially in developing country family planning. programmes. The second series of trial compared the Tcu220C with other copper IUDs such as the Nova T and Multiload 250, both of which were found to have pregnancy rates between 1.0 and 2.0 per 100 women at one year of use, whereas the Tcu220C device pregnancy rates at one year were less than 1.0 per 100 women. In subsequent WHO studies, the Tcu380A had significantly lower pregnancy rates at five, eaight and eleven years of use compared to the Tcu220C and the Tcu380A was adopted as the reference device in subsequent WHO trials. In the randomized study of the Mutiload 375 and the Tcu380A, the pregnancy rates at nine years of use were 5.0 (kO.7SE) and 3.2 (kO.5SE) (p=