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EFFECT OF AGE AND AETIOLOGY OF PREMATURE OVARIAN FAILURE ON SYMPTOMS AT PRESENTATION: DATA FROM THE WEST LONDON POF DATABASE
8th European Congress on Menopause (EMAS) / Maturitas 63, Supplement 1 (2009) S1–S136
Objectives: This study looks at the effectiveness and safety of the ICS procedure for the treatment of vaginal vault prolapse in the first cohort of 25 patients treated at the James Paget University Hospital. Methods: A prospective analysis of 25 ICS procedures performed at James Paget University Hospital between November 2006 and April 2008. The outcome measures were Intra-operative complications, operating time, post-operative complications and length of hospital stay. Patients followed up at 6 weeks, 6 months, 12 months and 18 months. Results: No rectal or visceral injury occurred. Blood loss was minimal. All patients were discharged within 24 hours and post operative pain was minimal. There was one case of tape erosion into the vagina, which was removed under local anaesthesia. The cure rate for vault prolapse was 96% at 12-18 months follow up along with a significant improvement in concomitant urinary symptoms. Conclusions: ICS is a safe and effective day case procedure for the treatment of vaginal vault prolapse. It is easy to perform after training and has good short to medium term results. Long term data on its efficacy and safety is required to compare it with existing procedures but preliminary results are very encouraging. Keywords: Vaginal Vault Prolapse Posterior Infra-Coccygeal Sacropexy.
104 INTRAVAGINAL PRASTERONE (DHEA), A HIGHLY EFFICIENT AND THE ONLY PHYSIOLOGICAL TREATMENT OF VAGINAL ATROPHY F. Labrie 1 , D. Archer 2 , C. Bouchard 3 , M. Fortier 3 , L. Cusan 4 , J.-L. Gomez 4 , G. Girard 5 , M. Baron 6 , N. Ayotte 7 , M. Moreau 8 , R. Dubé 9 , I. Côté 10 , C. Labrie 1 , L. Lavoie 10 , L. Berger 10 , L. Gilbert 11 , C. Martel 10 , J. Balser 12 . 1 Laval University Hospital Research Center (CRCHUL) and Laval University and Endoceutics Inc, Quebec City, Canada; 2 Clinical Research Center, Eastern Virginia Medical School, Norfolk, United States; 3 Clinique de Recherche en Santé des Femmes, Quebec City, Canada; 4 Laval University Hospital Research Center (CRCHUL) and Laval University, Quebec City, Canada; 5 Diex Recherche Inc., Sherbrooke, Canada; 6 Rapid Medical Research Inc., Cleveland, United States; 7 Clinique Gynécologique, Shawinigan, Canada; 8 Montreal Clinical Study Center, Montreal, Canada; 9 Centre Hospitalier Affilié Universitaire de Québec, Quebec City, Canada; 10 Endoceutics Inc., Quebec City, Canada; 11 McGill University Health Center, Royal Victoria Hospital, Montreal, Canada; 12 Veristat Inc., Boston, United States Objective: Since the secretion of dehydroepiandrosterone (DHEA), the exclusive source of sex steroids in postmenopausal women, is already decreased by 60% and continues to decline at time of menopause, this prospective, randomized, double-blind and placebo-controlled phase III clinical trial studied the effect of Prasterone (DHEA) applied locally in the vagina on the signs and symptoms of vaginal atrophy in 216 postmenopausal women. Results: All three doses (0.25%, 0.5% and 1.0%) of DHEA ovules applied daily intravaginally induced a highly significant beneficial change in the % of vaginal parabasal and superficial cells and pH as well as in the most bothersome symptom at 2 weeks. At the standard 12-week time interval, 0.5% DHEA caused a 45.9±5.31 (p<0.0001 versus placebo) decrease in the % of parabasal cells, a 6.8±1.29% (p<0.0001) increase in superficial cells, a 1.3±0.13 unit (p<0.0001) decrease in vaginal pH and a 1.5±0.14 score unit (p<0.0001) decrease in the severity of the most bothersome symptom. Similar changes were seen on vaginal secretions, color, epithelial surface thickness and epithelial integrity. Conclusions: Local Prasterone, through local androgen and estrogen formation, causes a rapid and efficient reversal of all the symptoms and signs of vaginal atrophy with no or minimal changes in serum steroids which remain well within the normal postmenopausal range, This approach avoids the fear of systemic effects and adds a novel physiological androgenic component to therapy. Keywords: Vaginal atrophy, Dehydroepiandrosterone, pH, Maturation index, Intracrinology, Vaginom™.
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105 COMPARATIVE TRIAL BETWEEN PROMESTRIENE AND ESTRIOL VAGINAL CREAMS: ANALYSIS AFTER SIX CONTINUOUS MONTHS R. Bruno 1 , F. Silveira 1 , K. Costa 1 , R. Freitas 1 , J. Ormond 1 , D. Postruznik 2 . 1 Gynecology Institute of Federal University of Rio de Janeiro, Endocrinology Gynecology, Rio de Janeiro, Brazil; 2 Merck Theramex International Medical, Monaco-Ville, Monaco Objective: To compare vaginal creams composed of Promestriene and Estriol for use in symptomatic climacteric women, concerning its effectiveness and collateral effects after 6 months. Methods: 40 women were divided and randomized in two groups (promestriene-1 and estriol-2). The patients received a 1g/day dosage of the cream for application via vagina, for six consecutive months. All the patients had their plasma analysis of estradiol and the hormonal vaginal cytology analyzed before and after the study. The patients answered a questionnaire on climacteric/menopausal symptoms and on quality of life. Results: There was no significant variation of the estradiol dosage in the groups. In the promestriene group, there was a significant decrease of basal and parabasal cells, which was not observed in the estriol group. Both groups had a significant increase of superficial cells (promestriene p<0,0001; estriol p<0,002); group 1 had, on the sixth month, a significant variation, when compared to the third month. Both groups had also a significant improvement of the vaginal cytology (group 1 p<0,0001; group 2, p<0,0069). Conclusions: Both creams proved to be efficient for the recovery of vaginal epithelium. Promestriene group presented a relative decrease of 100% on vaginal dryness, while estriol group had a 78,6%. Promestriene group had a larger percentage of proliferation of superficial cells, as well as a larger decrease of basal cells. Promestriene patients declared to be 100% satisfied with the treatment, while only 76,33% of the estriol patients were satisfied. Keywords: Promestriene, estriol and vaginal atrophy.
Free Communications: Premature Menopause
106 EFFECT OF AGE AND AETIOLOGY OF PREMATURE OVARIAN FAILURE ON SYMPTOMS AT PRESENTATION: DATA FROM THE WEST LONDON POF DATABASE J. Nicopoullos 1 , H. Grech 2 , C. Domoney 1 , E. Horner 3 , E. Kalu 4 , C. Bellone 1 , C. Rothon 5 , N. Panay 2 . 1 Chelsea & Westminster Hospital, London, United Kingdom; 2 Queen Charlotte’s & Chelsea & Wesminster Hospitals, West London Menopause & PMS Centre, London, United Kingdom; 3 St Mary’s Hospital, London, United Kingdom; 4 Kingston Hospital, Surrey, United Kingdom; 5 Queen Charlotte’s Hospital, London, United Kingdom Objectives: We present the West London POF database, and assess the effect of age at diagnosis and aetiology on presentation. Methods: A retrospective observational analysis of 239 women diagnosed with POF attending dedicated clinics. Data compiled from history, symptom questionnaire, investigation and ongoing treatment. Results: Mean age at diagnosis was 30.7 years (range 11-40). 107 (44.8%) cases were idiopathic, and 93 (38.9%), 27 (11.3%), 6 (2.5%) and 6 (2.5%) as a consequence of malignant disease, benign gynaecological disease, benign medical disease and genetic causes respectively. Dividing the cases by age at diagnosis (<30, 30-35, >35) there was a statistically significant increase in complaints of loss of libido (10%:25%:10% respectively), vaginal dryness (18%:42%:26%) and depression/anxiety (15%:35%:21%) at presentation in the 30-35 age group compared to both other groups and a significant increase in complaint of memory loss (0%:8%:7%), tiredness (13%:29%:22%) and joint pain (0%:9%:2%) compared to the 20-30 age group. Overall there was a significant increase in the number of symptoms at presentation in the 30-35 age group (3.2 vs. 1.8; all p<0.05). There was also a statistically significant increase in complaints of loss of libido (21%:10%), vaginal dryness (36%:21%) and hot flushes (70%:53%) in those with a malignant compared to those with a non-malignant aetiology. These differences were independent of blood sex hormone levels.
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8th European Congress on Menopause (EMAS) / Maturitas 63, Supplement 1 (2009) S1–S136
Conclusions: Our data highlights the importance of managing POF within dedicated clinics with appropriate multidisciplinary support allowing care to be tailored to the particular needs of patient group that may vary by age or aetiology. Keywords: Aetiology/Premature Ovarian Failure/Symptoms.
107
Of this symptomatic group on androgen replacement, 50% (14/28) were oophorectomised. Conclusions: In POF, androgen therapy should be considered in conjunction with oestrogen therapy, a necessary part of treatment in young symptomatic women. Oophorectomised status in POF patients is less of a consideration as the initial insult which impaires ovarian function, appears to affect both oestrogen and androgen production. Keywords: Premature Ovarian Failure, Androgen therapy.
TROUBLE SLEEPING DURING THE MENOPAUSAL TRANSITION: RESULTS FROM THE MRC 1946 BIRTH COHORT STUDY S. Tom 1 , J. Guralnik 1 , D. Kuh 2 , G. Mishra 2 . 1 National Institute on Aging, Laboratory of Epidemiology, Demography, and Biometry, Bethesda, United States; 2 Medical Research Council, Unit for Lifelong Health and Ageing and National Survey of Health and Development, London, United Kingdom Objectives: Trouble sleeping affects 43% of women in the United Kingdom and is associated with detrimental outcomes, including depression and stroke. The causes of trouble sleeping require further elucidation. Understanding of how women manage such trouble is limited. The objectives of this paper are 1) to study the relationship between menopausal transition status and trouble sleeping, and 2) to identify how women manage trouble sleeping. Analysis adjusts for current psychological, vasomotor, and somatic symptoms, and other social and lifestyle factors. Methods: The analysis utilized a cohort of 889 British women followed from birth in 1946 through age 54. Generalized estimating equations were utilized for repeated measures of trouble sleeping, menopausal transition status, and health symptoms from ages 48 to 54. Classification trees were used to describe women seeking conventional and alternative/complementary therapies. Results: While current psychological, vasomotor, and somatic symptoms attenuated the relationship between menopausal transition status and trouble sleeping, women who transitioned to postmenopause (adjusted odds ratio [95% CI]: 1.51 [1.08, 2.10]) or had a hysterectomy (1.57 [1.14, 2.15]) were more likely to report trouble sleeping than women who remained premenopausal. Adjustment for other factors did not alter these relationships. Women with greater educational attainment and of non-manual social class were more likely to seek conventional and alternative/complementary therapies. Conclusions: Treatment of psychological, vasomotor, and somatic symptoms may contribute to improved sleep during the menopausal transition. Women may require additional attention for sleep around the time of transition to postmenopause or hysterectomy. Keywords: Menopausal transition, sleep, menopausal symptoms.
108 ANDROGEN REPLACEMENT THERAPY IN PREMATURE OVARIAN FAILURE J. Woodman, H. Gauci Grech, N. Panay. Menopause Unit, Obstetrics and Gynaecology, London, United Kingdom Objectives: 1. To investigate androgen deficiency symptoms in relation to causative factors of premature ovarian failure (POF). 2. To assess uptake of androgen therapy in women diagnosed with POF with androgen deficiency symptoms. Methods: Patients diagnosed with premature ovarian failure under the age of 40 years attending the dedicated POF clinic in a London Teaching Hospital were entered into a database. Patients with symptoms of androgen deficiency i.e lack of libido and fatigue were identified from this database comprising 220 patients. Results: 43% (95/220) of patients were diagnosed with cancer [of which 20 patients had a bilateral salpingo-oophorectomy (BSO)], 44% (97/220) were idiopathic/genetic and 13% (28/220) had a BSO for benign indications. Despite adequate oestrogen replacement therapy 22% (45/205) reported androgen deficiency symptoms. Of this symptomatic group, 13% (17/45) report ed lack of libido, 48% (22/45) report only fatigue and 13% (6/45) reported both lack of libido and fatigue. These androgen deficient symptoms are reported equally among POF patients who have had oophorectomies 35% (16/45), radio/chemotherapy 37% (17/45) or idiopathic 26% (12/45). In symptomatic POF patients, uptake of androgen therapy was 62% (28/45).
109 CLINICAL AND GENETIC CHARACTERISTICS OF WOMEN WITH PREMATURE OVARIAN INSUFFICIENCY V. Smetnik 1 , L. Marchenko 1 , L. Butareva 1 , N. Chernyshova 1 , G. Tabeeva 1 , V. Nemtcova 2 . 1 Research Center of Obstetrics, Gynecology and Perinatology, Gynecologycal Endocrinology, Moscow, Russian Federation; 2 Reseach Medico-Genetic Center, Moscow, Russian Federation Objectives: We investigated some molecula-genetic cases of premature ovarian insufficiency (POI). Methods: 96 women with POI (karyotype 46,XX) were included in our study (aged 33,2±1,3 years). Serum concentrations of inhibin B, FSH, LH, E2 were analysed by immune-fluorescence assay. Karyotype was examined by Seabright method (G-painting). Skewed X chromosome inactivation (SXCI) was studied using by methyl-sensitive fluorescence PCR. The number of CGG-repeats of gene FMR1 were analysed by methyl-sensation PCR. Results: Average levels of inhibin B were 10,4±1,13pg/ml, FSH - 99,5±4,5 ME/l, LH - 83,4±5,3 ME/l, E2 - 73,3±5,1 pmol/l. SXCI was revealed in 25% patients. The pre-mutation FMR1 gene (number of CGG repeats were 56) were noticed in one woman (1,04%) with sporadic POI. Increasing of the number of CGG repeats in FMR1 gene in the range of “grey zone” (40-51) was detected in 8,3% cases with sporadic and family form POI. Conclusions: We propose that the high frequency of SXCI and the presence of pre-mutation of FMR1 gene confirmed of insufficient function of chromosome X genes probably located in Xq13 or Xq26-28. Keywords: POI, skewed X chromosome inactivation, FMR1 gene.
110 SEX CHROMOSOMAL MOSAICISM IN OVARIAN TISSUE IN WOMEN WITH PREMATURE OVARIAN INSUFFIENCY V. Smetnik 1 , A. Karseladze 2 , L. Marchenko 1 , L. Butareva 1 , N. Chernyshova 1 , G. Tabeeva 1 . 1 Research Center of Obstetrics, Gynecology and Perinatology, Gynecologycal Endocrinology, Moscow, Russian Federation; 2 Reseach Center of Oncology, Moscow, Russian Federation Objectives: We investigated some molecula-genetic cases of premature ovarian insufficiency (POI). Methods: 19 women with POI and normal female karyotype 46,XX were included in our study. Karyotype in lymphocyte was examined by standart cytogenetic analize (G-painting). Patients were performed laparoscopy with biopsy of ovaries. Following interphase fluorescence in situ hybridization (FISH) analysis was performed by the commercial centromeric probes for chromosomes X (CEPX), Y (CEPY) and a centromeric probe for chromosomes 18 (CEP18) as a control from Vysis. Results: FISH analisis of ovarian tissue confirmed the karyotype 46,XX in 100% cells in 31,6% cases (in 6 of 19 patients). Sex-chromosomal mosaicism was revealed in 68,4% cases. Monosomy or trisomy X were found in 2-10% of ovarian cells approximately in the same frequency (21% and 26,3% corresponding). Compound mosaicism was detected in 21% patients: 10,5% with 3 abnormal cell lines consisted in monosomy, trisomy and tetrasomy X in 16-26% cells; 10,5% with 2 abnormal cell lines consisted in the same frequency monosomy X and trisomy X in 13% cells and trisomy and tetrasomy X in 11% cells. Conclusions: We suppose that the high frequency of sex chromosomal tissue mosaicism (68,4%) can be one of the reasons of POI. Keywords: POI, FISH, sex chromosomal mosaicism.
Objectives: This study looks at the effectiveness and safety of the ICS procedure for the treatment of vaginal vault prolapse in the first cohort of 25 patients treated at the James Paget University Hospital. Methods: A prospective analysis of 25 ICS procedures performed at James Paget University Hospital between November 2006 and April 2008. The outcome measures were Intra-operative complications, operating time, post-operative complications and length of hospital stay. Patients followed up at 6 weeks, 6 months, 12 months and 18 months. Results: No rectal or visceral injury occurred. Blood loss was minimal. All patients were discharged within 24 hours and post operative pain was minimal. There was one case of tape erosion into the vagina, which was removed under local anaesthesia. The cure rate for vault prolapse was 96% at 12-18 months follow up along with a significant improvement in concomitant urinary symptoms. Conclusions: ICS is a safe and effective day case procedure for the treatment of vaginal vault prolapse. It is easy to perform after training and has good short to medium term results. Long term data on its efficacy and safety is required to compare it with existing procedures but preliminary results are very encouraging. Keywords: Vaginal Vault Prolapse Posterior Infra-Coccygeal Sacropexy.
104 INTRAVAGINAL PRASTERONE (DHEA), A HIGHLY EFFICIENT AND THE ONLY PHYSIOLOGICAL TREATMENT OF VAGINAL ATROPHY F. Labrie 1 , D. Archer 2 , C. Bouchard 3 , M. Fortier 3 , L. Cusan 4 , J.-L. Gomez 4 , G. Girard 5 , M. Baron 6 , N. Ayotte 7 , M. Moreau 8 , R. Dubé 9 , I. Côté 10 , C. Labrie 1 , L. Lavoie 10 , L. Berger 10 , L. Gilbert 11 , C. Martel 10 , J. Balser 12 . 1 Laval University Hospital Research Center (CRCHUL) and Laval University and Endoceutics Inc, Quebec City, Canada; 2 Clinical Research Center, Eastern Virginia Medical School, Norfolk, United States; 3 Clinique de Recherche en Santé des Femmes, Quebec City, Canada; 4 Laval University Hospital Research Center (CRCHUL) and Laval University, Quebec City, Canada; 5 Diex Recherche Inc., Sherbrooke, Canada; 6 Rapid Medical Research Inc., Cleveland, United States; 7 Clinique Gynécologique, Shawinigan, Canada; 8 Montreal Clinical Study Center, Montreal, Canada; 9 Centre Hospitalier Affilié Universitaire de Québec, Quebec City, Canada; 10 Endoceutics Inc., Quebec City, Canada; 11 McGill University Health Center, Royal Victoria Hospital, Montreal, Canada; 12 Veristat Inc., Boston, United States Objective: Since the secretion of dehydroepiandrosterone (DHEA), the exclusive source of sex steroids in postmenopausal women, is already decreased by 60% and continues to decline at time of menopause, this prospective, randomized, double-blind and placebo-controlled phase III clinical trial studied the effect of Prasterone (DHEA) applied locally in the vagina on the signs and symptoms of vaginal atrophy in 216 postmenopausal women. Results: All three doses (0.25%, 0.5% and 1.0%) of DHEA ovules applied daily intravaginally induced a highly significant beneficial change in the % of vaginal parabasal and superficial cells and pH as well as in the most bothersome symptom at 2 weeks. At the standard 12-week time interval, 0.5% DHEA caused a 45.9±5.31 (p<0.0001 versus placebo) decrease in the % of parabasal cells, a 6.8±1.29% (p<0.0001) increase in superficial cells, a 1.3±0.13 unit (p<0.0001) decrease in vaginal pH and a 1.5±0.14 score unit (p<0.0001) decrease in the severity of the most bothersome symptom. Similar changes were seen on vaginal secretions, color, epithelial surface thickness and epithelial integrity. Conclusions: Local Prasterone, through local androgen and estrogen formation, causes a rapid and efficient reversal of all the symptoms and signs of vaginal atrophy with no or minimal changes in serum steroids which remain well within the normal postmenopausal range, This approach avoids the fear of systemic effects and adds a novel physiological androgenic component to therapy. Keywords: Vaginal atrophy, Dehydroepiandrosterone, pH, Maturation index, Intracrinology, Vaginom™.
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105 COMPARATIVE TRIAL BETWEEN PROMESTRIENE AND ESTRIOL VAGINAL CREAMS: ANALYSIS AFTER SIX CONTINUOUS MONTHS R. Bruno 1 , F. Silveira 1 , K. Costa 1 , R. Freitas 1 , J. Ormond 1 , D. Postruznik 2 . 1 Gynecology Institute of Federal University of Rio de Janeiro, Endocrinology Gynecology, Rio de Janeiro, Brazil; 2 Merck Theramex International Medical, Monaco-Ville, Monaco Objective: To compare vaginal creams composed of Promestriene and Estriol for use in symptomatic climacteric women, concerning its effectiveness and collateral effects after 6 months. Methods: 40 women were divided and randomized in two groups (promestriene-1 and estriol-2). The patients received a 1g/day dosage of the cream for application via vagina, for six consecutive months. All the patients had their plasma analysis of estradiol and the hormonal vaginal cytology analyzed before and after the study. The patients answered a questionnaire on climacteric/menopausal symptoms and on quality of life. Results: There was no significant variation of the estradiol dosage in the groups. In the promestriene group, there was a significant decrease of basal and parabasal cells, which was not observed in the estriol group. Both groups had a significant increase of superficial cells (promestriene p<0,0001; estriol p<0,002); group 1 had, on the sixth month, a significant variation, when compared to the third month. Both groups had also a significant improvement of the vaginal cytology (group 1 p<0,0001; group 2, p<0,0069). Conclusions: Both creams proved to be efficient for the recovery of vaginal epithelium. Promestriene group presented a relative decrease of 100% on vaginal dryness, while estriol group had a 78,6%. Promestriene group had a larger percentage of proliferation of superficial cells, as well as a larger decrease of basal cells. Promestriene patients declared to be 100% satisfied with the treatment, while only 76,33% of the estriol patients were satisfied. Keywords: Promestriene, estriol and vaginal atrophy.
Free Communications: Premature Menopause
106 EFFECT OF AGE AND AETIOLOGY OF PREMATURE OVARIAN FAILURE ON SYMPTOMS AT PRESENTATION: DATA FROM THE WEST LONDON POF DATABASE J. Nicopoullos 1 , H. Grech 2 , C. Domoney 1 , E. Horner 3 , E. Kalu 4 , C. Bellone 1 , C. Rothon 5 , N. Panay 2 . 1 Chelsea & Westminster Hospital, London, United Kingdom; 2 Queen Charlotte’s & Chelsea & Wesminster Hospitals, West London Menopause & PMS Centre, London, United Kingdom; 3 St Mary’s Hospital, London, United Kingdom; 4 Kingston Hospital, Surrey, United Kingdom; 5 Queen Charlotte’s Hospital, London, United Kingdom Objectives: We present the West London POF database, and assess the effect of age at diagnosis and aetiology on presentation. Methods: A retrospective observational analysis of 239 women diagnosed with POF attending dedicated clinics. Data compiled from history, symptom questionnaire, investigation and ongoing treatment. Results: Mean age at diagnosis was 30.7 years (range 11-40). 107 (44.8%) cases were idiopathic, and 93 (38.9%), 27 (11.3%), 6 (2.5%) and 6 (2.5%) as a consequence of malignant disease, benign gynaecological disease, benign medical disease and genetic causes respectively. Dividing the cases by age at diagnosis (<30, 30-35, >35) there was a statistically significant increase in complaints of loss of libido (10%:25%:10% respectively), vaginal dryness (18%:42%:26%) and depression/anxiety (15%:35%:21%) at presentation in the 30-35 age group compared to both other groups and a significant increase in complaint of memory loss (0%:8%:7%), tiredness (13%:29%:22%) and joint pain (0%:9%:2%) compared to the 20-30 age group. Overall there was a significant increase in the number of symptoms at presentation in the 30-35 age group (3.2 vs. 1.8; all p<0.05). There was also a statistically significant increase in complaints of loss of libido (21%:10%), vaginal dryness (36%:21%) and hot flushes (70%:53%) in those with a malignant compared to those with a non-malignant aetiology. These differences were independent of blood sex hormone levels.
S30
8th European Congress on Menopause (EMAS) / Maturitas 63, Supplement 1 (2009) S1–S136
Conclusions: Our data highlights the importance of managing POF within dedicated clinics with appropriate multidisciplinary support allowing care to be tailored to the particular needs of patient group that may vary by age or aetiology. Keywords: Aetiology/Premature Ovarian Failure/Symptoms.
107
Of this symptomatic group on androgen replacement, 50% (14/28) were oophorectomised. Conclusions: In POF, androgen therapy should be considered in conjunction with oestrogen therapy, a necessary part of treatment in young symptomatic women. Oophorectomised status in POF patients is less of a consideration as the initial insult which impaires ovarian function, appears to affect both oestrogen and androgen production. Keywords: Premature Ovarian Failure, Androgen therapy.
TROUBLE SLEEPING DURING THE MENOPAUSAL TRANSITION: RESULTS FROM THE MRC 1946 BIRTH COHORT STUDY S. Tom 1 , J. Guralnik 1 , D. Kuh 2 , G. Mishra 2 . 1 National Institute on Aging, Laboratory of Epidemiology, Demography, and Biometry, Bethesda, United States; 2 Medical Research Council, Unit for Lifelong Health and Ageing and National Survey of Health and Development, London, United Kingdom Objectives: Trouble sleeping affects 43% of women in the United Kingdom and is associated with detrimental outcomes, including depression and stroke. The causes of trouble sleeping require further elucidation. Understanding of how women manage such trouble is limited. The objectives of this paper are 1) to study the relationship between menopausal transition status and trouble sleeping, and 2) to identify how women manage trouble sleeping. Analysis adjusts for current psychological, vasomotor, and somatic symptoms, and other social and lifestyle factors. Methods: The analysis utilized a cohort of 889 British women followed from birth in 1946 through age 54. Generalized estimating equations were utilized for repeated measures of trouble sleeping, menopausal transition status, and health symptoms from ages 48 to 54. Classification trees were used to describe women seeking conventional and alternative/complementary therapies. Results: While current psychological, vasomotor, and somatic symptoms attenuated the relationship between menopausal transition status and trouble sleeping, women who transitioned to postmenopause (adjusted odds ratio [95% CI]: 1.51 [1.08, 2.10]) or had a hysterectomy (1.57 [1.14, 2.15]) were more likely to report trouble sleeping than women who remained premenopausal. Adjustment for other factors did not alter these relationships. Women with greater educational attainment and of non-manual social class were more likely to seek conventional and alternative/complementary therapies. Conclusions: Treatment of psychological, vasomotor, and somatic symptoms may contribute to improved sleep during the menopausal transition. Women may require additional attention for sleep around the time of transition to postmenopause or hysterectomy. Keywords: Menopausal transition, sleep, menopausal symptoms.
108 ANDROGEN REPLACEMENT THERAPY IN PREMATURE OVARIAN FAILURE J. Woodman, H. Gauci Grech, N. Panay. Menopause Unit, Obstetrics and Gynaecology, London, United Kingdom Objectives: 1. To investigate androgen deficiency symptoms in relation to causative factors of premature ovarian failure (POF). 2. To assess uptake of androgen therapy in women diagnosed with POF with androgen deficiency symptoms. Methods: Patients diagnosed with premature ovarian failure under the age of 40 years attending the dedicated POF clinic in a London Teaching Hospital were entered into a database. Patients with symptoms of androgen deficiency i.e lack of libido and fatigue were identified from this database comprising 220 patients. Results: 43% (95/220) of patients were diagnosed with cancer [of which 20 patients had a bilateral salpingo-oophorectomy (BSO)], 44% (97/220) were idiopathic/genetic and 13% (28/220) had a BSO for benign indications. Despite adequate oestrogen replacement therapy 22% (45/205) reported androgen deficiency symptoms. Of this symptomatic group, 13% (17/45) report ed lack of libido, 48% (22/45) report only fatigue and 13% (6/45) reported both lack of libido and fatigue. These androgen deficient symptoms are reported equally among POF patients who have had oophorectomies 35% (16/45), radio/chemotherapy 37% (17/45) or idiopathic 26% (12/45). In symptomatic POF patients, uptake of androgen therapy was 62% (28/45).
109 CLINICAL AND GENETIC CHARACTERISTICS OF WOMEN WITH PREMATURE OVARIAN INSUFFICIENCY V. Smetnik 1 , L. Marchenko 1 , L. Butareva 1 , N. Chernyshova 1 , G. Tabeeva 1 , V. Nemtcova 2 . 1 Research Center of Obstetrics, Gynecology and Perinatology, Gynecologycal Endocrinology, Moscow, Russian Federation; 2 Reseach Medico-Genetic Center, Moscow, Russian Federation Objectives: We investigated some molecula-genetic cases of premature ovarian insufficiency (POI). Methods: 96 women with POI (karyotype 46,XX) were included in our study (aged 33,2±1,3 years). Serum concentrations of inhibin B, FSH, LH, E2 were analysed by immune-fluorescence assay. Karyotype was examined by Seabright method (G-painting). Skewed X chromosome inactivation (SXCI) was studied using by methyl-sensitive fluorescence PCR. The number of CGG-repeats of gene FMR1 were analysed by methyl-sensation PCR. Results: Average levels of inhibin B were 10,4±1,13pg/ml, FSH - 99,5±4,5 ME/l, LH - 83,4±5,3 ME/l, E2 - 73,3±5,1 pmol/l. SXCI was revealed in 25% patients. The pre-mutation FMR1 gene (number of CGG repeats were 56) were noticed in one woman (1,04%) with sporadic POI. Increasing of the number of CGG repeats in FMR1 gene in the range of “grey zone” (40-51) was detected in 8,3% cases with sporadic and family form POI. Conclusions: We propose that the high frequency of SXCI and the presence of pre-mutation of FMR1 gene confirmed of insufficient function of chromosome X genes probably located in Xq13 or Xq26-28. Keywords: POI, skewed X chromosome inactivation, FMR1 gene.
110 SEX CHROMOSOMAL MOSAICISM IN OVARIAN TISSUE IN WOMEN WITH PREMATURE OVARIAN INSUFFIENCY V. Smetnik 1 , A. Karseladze 2 , L. Marchenko 1 , L. Butareva 1 , N. Chernyshova 1 , G. Tabeeva 1 . 1 Research Center of Obstetrics, Gynecology and Perinatology, Gynecologycal Endocrinology, Moscow, Russian Federation; 2 Reseach Center of Oncology, Moscow, Russian Federation Objectives: We investigated some molecula-genetic cases of premature ovarian insufficiency (POI). Methods: 19 women with POI and normal female karyotype 46,XX were included in our study. Karyotype in lymphocyte was examined by standart cytogenetic analize (G-painting). Patients were performed laparoscopy with biopsy of ovaries. Following interphase fluorescence in situ hybridization (FISH) analysis was performed by the commercial centromeric probes for chromosomes X (CEPX), Y (CEPY) and a centromeric probe for chromosomes 18 (CEP18) as a control from Vysis. Results: FISH analisis of ovarian tissue confirmed the karyotype 46,XX in 100% cells in 31,6% cases (in 6 of 19 patients). Sex-chromosomal mosaicism was revealed in 68,4% cases. Monosomy or trisomy X were found in 2-10% of ovarian cells approximately in the same frequency (21% and 26,3% corresponding). Compound mosaicism was detected in 21% patients: 10,5% with 3 abnormal cell lines consisted in monosomy, trisomy and tetrasomy X in 16-26% cells; 10,5% with 2 abnormal cell lines consisted in the same frequency monosomy X and trisomy X in 13% cells and trisomy and tetrasomy X in 11% cells. Conclusions: We suppose that the high frequency of sex chromosomal tissue mosaicism (68,4%) can be one of the reasons of POI. Keywords: POI, FISH, sex chromosomal mosaicism.