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57 WHEN IS PREMATURE OVARIAN FAILURE NOT MENOPAUSE?
9th European Congress on Menopause and Andropause / Maturitas 71, Supplement 1 (2012) S1–S82
Regarless of the mechanisms which require more research including Genome Wide Association Studies, these patients must be treated by Hormone Replacement in order to prevent long term effects of estrogen deficiency: osteoporosis, increase in cardiovascular risk, and cognitive impaiment. Infertility treatment, mainly oocyte donation must be proposed in those women that could not undergo oocyte/embryo or ovarian fragments preservation before menopause.
S13
58 PREMATURE OVARIAN FAILURE: EMAS RECOMMENDATIONS AND NEW PERSPECTIVES S.Z. Vujovic 1 , M. Ivovic 1 , M. Tancic-Gajic 1 , M. Ivanisevic 2 , L. Marina 1 , M. Barac 1 , Z. Arizanovic 1 , D. Micic 3 . 1 Dpt. for Gynecological Endocrinology, Clinical Center of Serbia, Institute of Endocrinology, Faculty of Medicine, University of Belgrade; 2 Clinical Center of Serbia; 3 Center for Metabolic Disorders, Clinical Center of Serbia, Institute of Endocrinology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
56 PREDICTING THE AGE OF MENOPAUSE F.J. Broekmans. Reproductive Medicine & Gynaecology, University Medical Center, Utrecht, The Netherlands Delayed childbearing has resulted in a sharp increase in age related female infertility, as ageing ovaries will progressively affect oocyte quality in the 30s of a woman’s life. Assisted reproduction technology will provide solutions for not more than 50% of couples. Therefore, there is an urgent need for effective preventive campaigns. Menopause is the only hallmark of the ovarian ageing process that can be clearly assessed, marking the reproductive lifespan (RLS) of an individual woman in retrospect. Recent research has identified forecasters for age at menopause. Cross-sectional data have demonstrated that, if age specific variation in antral follicle counts (AFC) and antimullerian hormone (AMH) is projected into future age at menopause, the predicted distribution of menopausal age highly resembles the observed menopausal age distribution in existing population cohorts. Subsequently, follow up studies have identified AMH as a steady decline marker across the years, describing both the process of decay in follicle numbers as well as the final result of it: menopause. Recently, two long term follow up studies have linked age specific AMH to the later timing of menopause, showing the potential to individualise projections of menopause. Ongoing studies now cover a time lapse of 15-20 years and will deliver the final clue as to whether individual predictions of RLS are realistic. If so, the obtained knowledge may offer tools for preventive campaigns, finally altering the need for infertility treatment and associated expenditure, as well as provide tools to identify women that may decide on fertility preservation at young age.
57 WHEN IS PREMATURE OVARIAN FAILURE NOT MENOPAUSE?
Premature ovarian failure (POF) is defined as the menopause before the age of forty. EMAS position statement: Summary recommendations are: • POF may be primary or secondary, in majority of cases the cause is unknown. • Diagnose is confirmed with the FSH >40 IU/L, E2 <50 pmol/L. • Untreated POF increases risk of osteoporosis, cardiovascular diseases, dementia, cognitive decline and Parkinsonism. • The mainstay is estradiol replacement which needs to be continued until the average age of natural menopause. Hormone therapy is not contraceptive. • In the absence of oophorectomy POF is associated with intermittent ovarian function. • Ideally, women with POF are seen in the special units. Trying to find the new approach to aetiology we have investigated subject characteristics in 717 women in Belgrade POF group. Those with idiopathic POF were tested for some typical characteristics. All of them met criteria for idiopathic POF and were otherwise healthy. Noone had hirsutism. They had regular cycles in 83.6%, nulliparous were 73.4%, mostly thin. No family POF was recorded in 71.2% and 45.7% were exposed to stressors, the divorce being the most prominent. In 51% weight increase was detected. Hot flushes were found in 60.3% older women with POF. These data are the base for the new hypothesis of POF aetiology. The role of androgen receptor, steroidogenic pathways, stressors as the triggering factors, protective role of the adipose tissue and the role of aging on neurovascular mechanisms of hot flushes has to be in the focus of the further scientific investigations.
Parallel Session: Complementary and Alternative Therapies
S. Kalantaridou. Obstetrics and Gynecology, University of Ioannina, Ioannina, Greece
59 Premature ovarian failure (POF) is a condition characterized by sex-steroid deficiency, amenorrhea, and infertility in women younger than 40 years. POF once was considered irreversible and was described as “premature menopause”. POF is not an early natural menopause. Normal menopause results from ovarian follicle depletion, whereas POF is characterized by intermittent ovarian function in half of affected women. These women produce estrogen intermittently and may ovulate despite the presence of high gonadotropin concentrations. Pregnancies may occur in 5-10% of women after the diagnosis of POF. POF may occur as a result of ovarian follicle dysfunction or ovarian follicle depletion and may present as either primary or secondary amenorrhea. Young women with POF sustain sex steroid deficiency for more years than do naturally menopausal women. This deficiency can result in a significantly higher risk for osteoporosis and cardiovascular disease. Postmenopausal women who take hormone therapy prolong their exposure to estrogen beyond the average age of completion of their reproductive phase. In contrast, women with POF need exogenous sex steroids to compensate for the decreased production by their ovaries. The goal of therapy in young women with POF is to provide a hormone replacement regimen that maintains sex steroid concentrations as effectively as the normal, functioning ovary. Thus, hormone replacement therapy is required at least until these young women reach the age of “natural menopause”.
PHYTOESTROGENS FOR THE MENOPAUSAL WOMAN F. Borrelli. Department of Experimental Pharmacology, University of Naples Federico II, Naples, Italy Phytoestrogens are plant-derived compounds that may display both estrogenic and anti-estrogenic effects. There are three major classes of phytoestrogens: the isoflavones, lignans and coumestans. Numerous systematic reviews have analyzed the therapeutic efficacy of phytoestrogens in relieving vasomotor menopausal symptoms, in reducing the incidence of breast cancer and cardiovascular diseases, and in preventing the loss of bone mineral density in menopausal women. Until now no conclusive evidence has emerged (1). Recent systematic reviews conclude that phytoestrogens should only be used in women with mild to moderate vasomotor symptoms in early natural menopause (1). A recent meta-analysis of 17 RCTs of soy isoflasvones on bone mineral density showed that isoflavones are not effective in decreasing bone loss in perimenopausal and postmenopausal women (2). By contrast, another meta-analysis found a reduction of the loss of bone mineral density and a slight decrease in LDL cholesterol in postmenopausal women taking soy isoflavones (1). Three RCTs out of four RCTs found that flaxseed was not more effective than placebo for reducing hot flashes (1). Contradictory and inconclusive results exist on the efficacy of flaxseed in reducing cholesterol concentration in menopausal women. Results from clinical trials did not show that phytoestrogens cause breast cancer-promoting effects in healthy women or breast cancer survivors. Moreover, a meta-analysis of observational epidemiological studies suggested a decreased risk of breast cancer in women consuming phytoestrogens.
Regarless of the mechanisms which require more research including Genome Wide Association Studies, these patients must be treated by Hormone Replacement in order to prevent long term effects of estrogen deficiency: osteoporosis, increase in cardiovascular risk, and cognitive impaiment. Infertility treatment, mainly oocyte donation must be proposed in those women that could not undergo oocyte/embryo or ovarian fragments preservation before menopause.
S13
58 PREMATURE OVARIAN FAILURE: EMAS RECOMMENDATIONS AND NEW PERSPECTIVES S.Z. Vujovic 1 , M. Ivovic 1 , M. Tancic-Gajic 1 , M. Ivanisevic 2 , L. Marina 1 , M. Barac 1 , Z. Arizanovic 1 , D. Micic 3 . 1 Dpt. for Gynecological Endocrinology, Clinical Center of Serbia, Institute of Endocrinology, Faculty of Medicine, University of Belgrade; 2 Clinical Center of Serbia; 3 Center for Metabolic Disorders, Clinical Center of Serbia, Institute of Endocrinology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
56 PREDICTING THE AGE OF MENOPAUSE F.J. Broekmans. Reproductive Medicine & Gynaecology, University Medical Center, Utrecht, The Netherlands Delayed childbearing has resulted in a sharp increase in age related female infertility, as ageing ovaries will progressively affect oocyte quality in the 30s of a woman’s life. Assisted reproduction technology will provide solutions for not more than 50% of couples. Therefore, there is an urgent need for effective preventive campaigns. Menopause is the only hallmark of the ovarian ageing process that can be clearly assessed, marking the reproductive lifespan (RLS) of an individual woman in retrospect. Recent research has identified forecasters for age at menopause. Cross-sectional data have demonstrated that, if age specific variation in antral follicle counts (AFC) and antimullerian hormone (AMH) is projected into future age at menopause, the predicted distribution of menopausal age highly resembles the observed menopausal age distribution in existing population cohorts. Subsequently, follow up studies have identified AMH as a steady decline marker across the years, describing both the process of decay in follicle numbers as well as the final result of it: menopause. Recently, two long term follow up studies have linked age specific AMH to the later timing of menopause, showing the potential to individualise projections of menopause. Ongoing studies now cover a time lapse of 15-20 years and will deliver the final clue as to whether individual predictions of RLS are realistic. If so, the obtained knowledge may offer tools for preventive campaigns, finally altering the need for infertility treatment and associated expenditure, as well as provide tools to identify women that may decide on fertility preservation at young age.
57 WHEN IS PREMATURE OVARIAN FAILURE NOT MENOPAUSE?
Premature ovarian failure (POF) is defined as the menopause before the age of forty. EMAS position statement: Summary recommendations are: • POF may be primary or secondary, in majority of cases the cause is unknown. • Diagnose is confirmed with the FSH >40 IU/L, E2 <50 pmol/L. • Untreated POF increases risk of osteoporosis, cardiovascular diseases, dementia, cognitive decline and Parkinsonism. • The mainstay is estradiol replacement which needs to be continued until the average age of natural menopause. Hormone therapy is not contraceptive. • In the absence of oophorectomy POF is associated with intermittent ovarian function. • Ideally, women with POF are seen in the special units. Trying to find the new approach to aetiology we have investigated subject characteristics in 717 women in Belgrade POF group. Those with idiopathic POF were tested for some typical characteristics. All of them met criteria for idiopathic POF and were otherwise healthy. Noone had hirsutism. They had regular cycles in 83.6%, nulliparous were 73.4%, mostly thin. No family POF was recorded in 71.2% and 45.7% were exposed to stressors, the divorce being the most prominent. In 51% weight increase was detected. Hot flushes were found in 60.3% older women with POF. These data are the base for the new hypothesis of POF aetiology. The role of androgen receptor, steroidogenic pathways, stressors as the triggering factors, protective role of the adipose tissue and the role of aging on neurovascular mechanisms of hot flushes has to be in the focus of the further scientific investigations.
Parallel Session: Complementary and Alternative Therapies
S. Kalantaridou. Obstetrics and Gynecology, University of Ioannina, Ioannina, Greece
59 Premature ovarian failure (POF) is a condition characterized by sex-steroid deficiency, amenorrhea, and infertility in women younger than 40 years. POF once was considered irreversible and was described as “premature menopause”. POF is not an early natural menopause. Normal menopause results from ovarian follicle depletion, whereas POF is characterized by intermittent ovarian function in half of affected women. These women produce estrogen intermittently and may ovulate despite the presence of high gonadotropin concentrations. Pregnancies may occur in 5-10% of women after the diagnosis of POF. POF may occur as a result of ovarian follicle dysfunction or ovarian follicle depletion and may present as either primary or secondary amenorrhea. Young women with POF sustain sex steroid deficiency for more years than do naturally menopausal women. This deficiency can result in a significantly higher risk for osteoporosis and cardiovascular disease. Postmenopausal women who take hormone therapy prolong their exposure to estrogen beyond the average age of completion of their reproductive phase. In contrast, women with POF need exogenous sex steroids to compensate for the decreased production by their ovaries. The goal of therapy in young women with POF is to provide a hormone replacement regimen that maintains sex steroid concentrations as effectively as the normal, functioning ovary. Thus, hormone replacement therapy is required at least until these young women reach the age of “natural menopause”.
PHYTOESTROGENS FOR THE MENOPAUSAL WOMAN F. Borrelli. Department of Experimental Pharmacology, University of Naples Federico II, Naples, Italy Phytoestrogens are plant-derived compounds that may display both estrogenic and anti-estrogenic effects. There are three major classes of phytoestrogens: the isoflavones, lignans and coumestans. Numerous systematic reviews have analyzed the therapeutic efficacy of phytoestrogens in relieving vasomotor menopausal symptoms, in reducing the incidence of breast cancer and cardiovascular diseases, and in preventing the loss of bone mineral density in menopausal women. Until now no conclusive evidence has emerged (1). Recent systematic reviews conclude that phytoestrogens should only be used in women with mild to moderate vasomotor symptoms in early natural menopause (1). A recent meta-analysis of 17 RCTs of soy isoflasvones on bone mineral density showed that isoflavones are not effective in decreasing bone loss in perimenopausal and postmenopausal women (2). By contrast, another meta-analysis found a reduction of the loss of bone mineral density and a slight decrease in LDL cholesterol in postmenopausal women taking soy isoflavones (1). Three RCTs out of four RCTs found that flaxseed was not more effective than placebo for reducing hot flashes (1). Contradictory and inconclusive results exist on the efficacy of flaxseed in reducing cholesterol concentration in menopausal women. Results from clinical trials did not show that phytoestrogens cause breast cancer-promoting effects in healthy women or breast cancer survivors. Moreover, a meta-analysis of observational epidemiological studies suggested a decreased risk of breast cancer in women consuming phytoestrogens.