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Premature ovarian insufficiency: current point of view
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Abstracts / Maturitas 81 (2015) 105–121
Ovarian AMH expression seems to be absent in primordial follicles, theca cells or oocytes, but is highest in granulosa cells of pre-antral and small antral follicles. Interestingly, AMH is expressed in follicles that have undergone recruitment from the primordial follicle pool but have not been selected for dominance. Serum AMH concentrations, being stable and consistent throughout the menstrual cycle, constitute a reliable marker of ovarian reserve; thus, AMH has already found a role in the clinical practice, particularly when combined with classic markers of ovarian reserve such as age, Follicle Stimulating Hormone (FSH) and antral follicle count (AFC). AMH has emerged as a marker of ovarian reserve and a possible surrogate marker of reproductive aging. There is recent evidence that AMH is a strong predictor of time to menopause in women of late reproductive age women (20–49 years). For those who reached menopause, serum AMH concentrations six years before the event provided fairly accurate estimates of the age at menopause. Age and smoking are additional, independent predictors of this event. http://dx.doi.org/10.1016/j.maturitas.2015.02.021 Premature ovarian failure INV10 Premature ovarian insufficiency: current point of view Svetlana Vujovic ∗ , Miomira Ivovic, Milina Tancic-Gajic, Ljiljana Marina, Maja Ivanisevic, Marija Barac, Zorana Arizanovic, Dragana Rakovic, Branko Barac, Dragan Micic Clinic for Endocrinology, Diabetes and Metabolic Disorders, Clinical Center of Serbia, Medical Faculty, University of Belgrade, Belgrade, Serbia Premature ovarian insufficiency (POI) is characterized by a loss of menstruation, FSH >40 IU/L, estradiol <50 pmol/L in women younger than 40 years of age. As no single gene mutation is responsible for the etiology of POI further gene analysis were done in last years. Shorter CA repeat lengths in ESR2 and shorter TA repeat lengths in ESR1 were found more often in POI patients, compare to controls, but the difference is small. Microsatellites AR (CAG)n and (GGN)n have no association with POI in Serbian women. In contrast to Han Chinese patients no association was found between POI in Serbian women and 8q22.3, HK3, ESR1 and BRSK 1. This indicates that ethnically distinct population may show differences in gene-regulating pathways and genes causing POI. In autoimmune POI therapy with estradiol decreases activated T lymphocytes, enhance autoimmunity, activates effector helper T lymphocytes and macrophages, facilitates the maturation of pathogenic B cells, diminishes the product of potentially protective B cells. Doses of estrogens are twice as high as recommended dose for hormone replacement therapy. The pregnancy rates depends not only on the ovarian reserve but the endometrium characteristics. Estroprogestagens are the first line therapy for ovulation induction in POI after testing metabolic and hematologic status. Novel techniques are indicated in well prepared poor responders: cryopreservation, vitrification, ovary transplantation, in vitro activation. After disrupting Hippo signaling pathway Akt signaling pathway is stimulated. In POI women with ovaries real hope for pregnancy never dies thankfully to modern medicine. http://dx.doi.org/10.1016/j.maturitas.2015.02.022
INV11 Premature ovarian insufficiency: modern management Nick Panay 1,2 1 Imperial College London, Consultant Gynaecologist, London, United Kingdom 2 Queen Charlotte’s & Chelsea and Westminster Hospitals, West London Menopause Service, London, United Kingdom
Management: POI is a difficult diagnosis for women to accept, and a carefully planned and sensitive approach is required when informing women of the diagnosis. A dedicated multidisciplinary clinic separate from the routine menopause clinic will provide time and the appropriate professionals to meet the needs of these young women. An International database “www.poiregistry.net” has recently been developed at Imperial College London to collate important information on POI; this will facilitate research on the causes of POI, the impact of various treatments and allow the development of evidence-based management guidelines. Treatment – general principles: Specific areas of management include the provision of counselling and emotional support, diet and nutrition supplement advise, hormone replacement therapy, and reproductive health care, including contraception and fertility issues. Hormone replacement therapy: Hormone replacement therapy (HRT) is recommended to control vasomotor symptoms, minimise risk of cardiovascular disease, osteoporosis, Alzheimer’s and maintain sexual function. HRT in POI is simply replacing ovarian hormones that should normally be produced at this age. The aim is to replace hormones as close to physiological levels as possible using body identical preparations. HRT should continue at least until the estimated age of natural menopause (on average 51 years). Optimising fertility: 50% of women with POI would not consider ovum donation. It is therefore important to explore options such as ultra low dose body identical HRT and DHEA/testosterone which might promote any remaining ovarian reserve. Conclusion: There is an urgent need to develop evidence based guidelines and appropriate research programmes to optimise health in premature ovarian insufficiency. http://dx.doi.org/10.1016/j.maturitas.2015.02.023 Lifestyle and the menopause INV12 Exercise and hot flushes Margaret Rees University of Oxford, Women’s Centre, Oxford, United Kingdom Regular physical activity reduces the risk of coronary heart disease, type 2 diabetes, osteoporotic fracture and breast and endometrial cancer. With regard to hot flushes the evidence is conflicting. In 2007 a Cochrane review found no evidence from randomised controlled trials on whether exercise is an effective treatment relative to other interventions or no intervention in reducing hot flushes and or night sweats in symptomatic women. However the longitudinal Melbourne Women’s Midlife Health Project, in which 438 women were followed over 8 years, those who exercised every day at baseline were 49% less likely to report hot flashes, and those whose exercise levels decreased were more likely
Abstracts / Maturitas 81 (2015) 105–121
Ovarian AMH expression seems to be absent in primordial follicles, theca cells or oocytes, but is highest in granulosa cells of pre-antral and small antral follicles. Interestingly, AMH is expressed in follicles that have undergone recruitment from the primordial follicle pool but have not been selected for dominance. Serum AMH concentrations, being stable and consistent throughout the menstrual cycle, constitute a reliable marker of ovarian reserve; thus, AMH has already found a role in the clinical practice, particularly when combined with classic markers of ovarian reserve such as age, Follicle Stimulating Hormone (FSH) and antral follicle count (AFC). AMH has emerged as a marker of ovarian reserve and a possible surrogate marker of reproductive aging. There is recent evidence that AMH is a strong predictor of time to menopause in women of late reproductive age women (20–49 years). For those who reached menopause, serum AMH concentrations six years before the event provided fairly accurate estimates of the age at menopause. Age and smoking are additional, independent predictors of this event. http://dx.doi.org/10.1016/j.maturitas.2015.02.021 Premature ovarian failure INV10 Premature ovarian insufficiency: current point of view Svetlana Vujovic ∗ , Miomira Ivovic, Milina Tancic-Gajic, Ljiljana Marina, Maja Ivanisevic, Marija Barac, Zorana Arizanovic, Dragana Rakovic, Branko Barac, Dragan Micic Clinic for Endocrinology, Diabetes and Metabolic Disorders, Clinical Center of Serbia, Medical Faculty, University of Belgrade, Belgrade, Serbia Premature ovarian insufficiency (POI) is characterized by a loss of menstruation, FSH >40 IU/L, estradiol <50 pmol/L in women younger than 40 years of age. As no single gene mutation is responsible for the etiology of POI further gene analysis were done in last years. Shorter CA repeat lengths in ESR2 and shorter TA repeat lengths in ESR1 were found more often in POI patients, compare to controls, but the difference is small. Microsatellites AR (CAG)n and (GGN)n have no association with POI in Serbian women. In contrast to Han Chinese patients no association was found between POI in Serbian women and 8q22.3, HK3, ESR1 and BRSK 1. This indicates that ethnically distinct population may show differences in gene-regulating pathways and genes causing POI. In autoimmune POI therapy with estradiol decreases activated T lymphocytes, enhance autoimmunity, activates effector helper T lymphocytes and macrophages, facilitates the maturation of pathogenic B cells, diminishes the product of potentially protective B cells. Doses of estrogens are twice as high as recommended dose for hormone replacement therapy. The pregnancy rates depends not only on the ovarian reserve but the endometrium characteristics. Estroprogestagens are the first line therapy for ovulation induction in POI after testing metabolic and hematologic status. Novel techniques are indicated in well prepared poor responders: cryopreservation, vitrification, ovary transplantation, in vitro activation. After disrupting Hippo signaling pathway Akt signaling pathway is stimulated. In POI women with ovaries real hope for pregnancy never dies thankfully to modern medicine. http://dx.doi.org/10.1016/j.maturitas.2015.02.022
INV11 Premature ovarian insufficiency: modern management Nick Panay 1,2 1 Imperial College London, Consultant Gynaecologist, London, United Kingdom 2 Queen Charlotte’s & Chelsea and Westminster Hospitals, West London Menopause Service, London, United Kingdom
Management: POI is a difficult diagnosis for women to accept, and a carefully planned and sensitive approach is required when informing women of the diagnosis. A dedicated multidisciplinary clinic separate from the routine menopause clinic will provide time and the appropriate professionals to meet the needs of these young women. An International database “www.poiregistry.net” has recently been developed at Imperial College London to collate important information on POI; this will facilitate research on the causes of POI, the impact of various treatments and allow the development of evidence-based management guidelines. Treatment – general principles: Specific areas of management include the provision of counselling and emotional support, diet and nutrition supplement advise, hormone replacement therapy, and reproductive health care, including contraception and fertility issues. Hormone replacement therapy: Hormone replacement therapy (HRT) is recommended to control vasomotor symptoms, minimise risk of cardiovascular disease, osteoporosis, Alzheimer’s and maintain sexual function. HRT in POI is simply replacing ovarian hormones that should normally be produced at this age. The aim is to replace hormones as close to physiological levels as possible using body identical preparations. HRT should continue at least until the estimated age of natural menopause (on average 51 years). Optimising fertility: 50% of women with POI would not consider ovum donation. It is therefore important to explore options such as ultra low dose body identical HRT and DHEA/testosterone which might promote any remaining ovarian reserve. Conclusion: There is an urgent need to develop evidence based guidelines and appropriate research programmes to optimise health in premature ovarian insufficiency. http://dx.doi.org/10.1016/j.maturitas.2015.02.023 Lifestyle and the menopause INV12 Exercise and hot flushes Margaret Rees University of Oxford, Women’s Centre, Oxford, United Kingdom Regular physical activity reduces the risk of coronary heart disease, type 2 diabetes, osteoporotic fracture and breast and endometrial cancer. With regard to hot flushes the evidence is conflicting. In 2007 a Cochrane review found no evidence from randomised controlled trials on whether exercise is an effective treatment relative to other interventions or no intervention in reducing hot flushes and or night sweats in symptomatic women. However the longitudinal Melbourne Women’s Midlife Health Project, in which 438 women were followed over 8 years, those who exercised every day at baseline were 49% less likely to report hot flashes, and those whose exercise levels decreased were more likely