Svetlana Vujovic

EMAS position statement: Managing women with premature ovarian failure.

INTRODUCTIONnPremature ovarian failure (also known as premature menopause) is defined as menopause before the age of 40. It can be natural or iatrogenic such as after bilateral oophorectomy. It may be either primary or secondary. In the majority of cases of primary POF the cause is unknown. Chromosome abnormalities (especially X chromosome), follicle-stimulating hormone receptor gene polymorphisms, inhibin B mutations, enzyme deficiencies and autoimmune disease may be involved. Secondary POF is becoming more important as survival after treatment of malignancy through surgery, radiotherapy and chemotherapy continues to improve.nnnAIMnTo formulate a position statement on the management of premature ovarian failure.nnnMATERIALS AND METHODSnLiterature review and consensus of expert opinion.nnnRESULTS AND CONCLUSIONSnDiagnosis should be confirmed with an elevated FSH greater than 40 IU/L and an estradiol level below 50 pmol/L in the absence of bilateral oophorectomy. Further assessment should include thyroid function tests, autoimmune screen for polyendocrinopathy, karyotype (less than 30 years of age) and bone mineral density. Untreated early ovarian failure increases the risk of osteoporosis, cardiovascular disease, dementia, cognitive decline and Parkinsonism. The mainstay of treatment is hormone therapy which needs to be continued until the average age of the natural menopause. With regard to fertility, while spontaneous ovulation may occur the best chance of achieving pregnancy is through donor oocyte in vitro fertilization. It is essential that women are provided with adequate information as they may find it a difficult diagnosis to accept. It is recommended that women with POF are seen in a specialist unit able to deal with their multiple needs.

EMAS position statement: Managing obese postmenopausal women

INTRODUCTIONnObesity is a public health problem, with overweight individuals representing approximately 20% of the adult world population. Postmenopausal status is associated with higher prevalence of obesity, as 44% of postmenopausal women are overweight, among whom 23% are obese. Obesity often co-exists with other diseases, the most important being diabetes mellitus, dyslipidemia and hypertension. Furthermore, obesity increases the risk of gynecologic cancer, cardiovascular disease, venous thromboembolism, osteoarthritis and chronic back pain.nnnAIMnTo formulate a position statement on the management of the menopause in obese women.nnnMATERIALS AND METHODSnLiterature review and consensus of expert opinion.nnnRESULTS AND CONCLUSIONSnObese women seeking hormone therapy should be evaluated for their individual baseline risk of developing breast cancer, cardiovascular disease and venous thromboembolism. These risks should be weighed against expected benefit from symptom relief, improved quality of life and osteoporosis prevention. The lowest effective estrogen dose should be used (CEE 0.300-0.400 mg or estradiol 0.5-1 mg orally daily or 25-50 microg estradiol transdermally). With regard to progestogens, although no RCT data exist, there are observational studies showing that micronized progesterone or dydrogesterone may have a better risk profile with respect to breast cancer risk. There are no RCT data comparing various progestogens with regard to VTE risk. There are observational data, however, suggesting that micronized progesterone or pregnane derivatives may be associated with a lower VTE risk in postmenopausal women taking HT compared to nonpregnane derivatives. There is a rationale in suggesting the use of transdermal HT in obese women, since this route of administration has been associated with a lesser risk of venous thromboembolism than oral therapy.

EMAS position statement: Managing menopausal women with a personal or family history of VTE.

INTRODUCTIONnVenous thromboembolism (VTE), including deep venous thrombosis (DVT) and pulmonary embolism (PE), is a serious cardiovascular event whose incidence rises with increasing age.nnnAIMSnTo formulate a position statement on the management of the menopause in women with a personal or family history of VTE.nnnMATERIAL AND METHODSnLiterature review and consensus of expert opinion.nnnRESULTS AND CONCLUSIONSnRandomized controlled trials have shown an increased risk of VTE in oral hormone therapy (HT) users. There are no randomized trial data on the effect of transdermal estrogen on VTE. Recent observational studies and meta-analyses suggest that transdermal estrogen does not increase VTE risk. These clinical observations are supported by experimental data showing that transdermal estrogen has a minimal effect on hepatic metabolism of hemostatic proteins as the portal circulation is bypassed. A personal or family history of VTE, especially in individuals with a prothrombotic mutation, is a strong contraindication to oral HT but transdermal estrogen can be considered after careful individual evaluation of the benefits and risks. Transdermal estrogen should be also the first choice in overweight/obese women requiring HT. Observational studies suggest that micronized progesterone and dydrogesterone might have a better risk profile than other progestins with regard to VTE risk. Although these findings should be confirmed by randomized clinical trials, they strongly suggest that both the route of estrogen administration and the type of progestin may be important determinants of the overall benefit-risk profile of HT.

EMAS position statement: Managing the menopause in women with a past history of endometriosis

INTRODUCTIONnEndometriosis is a common disease in women of reproductive age. The symptoms usually disappear after a natural or a surgical menopause. Estrogen-based hormone therapy is required in women with premature or early menopause until the average age of the natural menopause and should be considered in older women with severe climacteric symptoms. However use of hormone therapy raises concerns about disease recurrence with pain symptoms, need for surgery and possibly malignant transformation of residual endometriosis.nnnAIMnTo formulate a position statement on the management of the menopause in women with a past history of endometriosis.nnnMATERIALS AND METHODSnLiterature review and consensus of expert opinion.nnnRESULTS AND CONCLUSIONSnThe data regarding hormone therapy regimens are limited. However it may be safer to give either continuous combined estrogen-progestogen therapies or tibolone in both hysterectomised and nonhysterectomised women as the risk of recurrence may be reduced. The risk of recurrence with hormone therapy is probably increased in women with residual disease after surgery. Management of potential recurrence is best monitored by responding to recurrence of symptoms. Women not wanting estrogen or those who are advised against should be offered alternative pharmacological treatment for climacteric symptoms or skeletal protection if indicated. Herbal preparations should be avoided as their efficacy is uncertain and some may contain estrogenic compounds.

EMAS position statement: managing the menopause in women with epilepsy.

INTRODUCTIONnEpilepsy is a major public health problem worldwide which is clinically characterized by recurrent seizures.nnnAIMnThe aim of this position statement is to provide evidence-based advice on management of the menopause in postmenopausal women derived from the limited data available.nnnMATERIALS AND METHODSnLiterature review and consensus of expert opinion.nnnRESULTS AND CONCLUSIONSnWomen with epilepsy may undergo an earlier natural menopause, between 3 and 5 years depending on seizure frequency, but the data are limited. Data regarding the effects of the perimenopause and menopause on epilepsy are conflicting: some studies show an increased risk of seizures but others do not. With regard to hormone therapy (HT) one study has shown an increase in seizures with oral therapy with conjugated equine estrogens and medroxyprogesterone acetate, but no data are available for other regimens. Women starting HT should be closely monitored as their antiepileptic drug (AED) needs may change. As vitamin D and calcium metabolism can be affected by AEDS, supplements should be considered. Herbal preparations should be avoided as their efficacy is uncertain and they may interact with AEDs.

EMAS clinical guide: Selective estrogen receptor modulators for postmenopausal osteoporosis

Osteoporosis and the resulting fractures are major public health issues as the world population is ageing. Various therapies such as bisphosphonates, strontium ranelate and more recently denosumab are available. This clinical guide provides the evidence for the clinical use of selective estrogen modulators (SERMs) in the management of osteoporosis in postmenopausal women.

EMAS position statement : bone densitometry screening for osteoporosis

INTRODUCTIONnOsteoporosis and its consequent fractures is a major public health problem.nnnAIMnTo formulate a position statement on the use of bone densitometry in screening postmenopausal women for osteoporosis and in their management.nnnMATERIALS AND METHODSnLiterature review and consensus of expert opinion.nnnRESULTS AND CONCLUSIONSnBone densitometry has an important role in screening postmenopausal women for osteoporosis. For higher sensitivity and specificity, there may be a stronger case for screening in later life, depending on the extent to which risk factors add to the value of bone mineral density tests.