EMAS position statement: Predictors of premature and early natural menopause.

INTRODUCTION: While the associations of genetic, reproductive and environmental factors with the timing of natural menopause have been extensively investigated, few epidemiological studies have specifically examined their association with premature (<40 years) or early natural menopause (40-45 years). AIM: The aim of this position statement is to provide evidence on the predictors of premature and early natural menopause, as well as recommendations for the management of premature and early menopause and future research. MATERIALS AND METHODS: Literature review and consensus of expert opinion. RESULTS AND CONCLUSIONS: Strong genetic predictors of premature and early menopause include a family history of premature or early menopause, being a child of a multiple pregnancy and some specific genetic variants. Women with early menarche and nulliparity or low parity are also at a higher risk of experiencing premature or early menopause. Cigarette smoking (with a strong dose-response effect) and being underweight have been consistently associated with premature and early menopause. Current guidelines for the management of premature and early menopause mainly focus on early initiation of hormone therapy (HT) and continued treatment until the woman reaches the average age at menopause (50-52 years). We suggest that clinicians and health professionals consider the age at menopause of the relevant region or ethnic group as part of the assessment for the timing of HT cessation. In addition, there should be early monitoring of women with a family history of early menopause, who are a child of a multiple pregnancy, or who have had early menarche (especially those who have had no children). As part of preventive health strategies, women should be encouraged to quit smoking (preferably before the age of 30 years) and maintain optimal weight in order to reduce their risk of premature or early menopause.

Menopause and diabetes: EMAS clinical guide.

INTRODUCTION: Whether menopause increases the risk of type 2 diabetes mellitus (T2DM) independently of ageing has been a matter of debate. Controversy also exists about the benefits and risks of menopausal hormone therapy (MHT) in women with T2DM. AIMS: To summarise the evidence on 1) the effect of menopause on metabolic parameters and the risk of T2DM, 2) the effect of T2DM on age at menopause, 3) the effect of MHT on the risk of T2DM, and 4) the management of postmenopausal women with T2DM. MATERIALS AND METHODS: Literature review and consensus of experts' opinions. RESULTS AND CONCLUSION: Metabolic changes during the menopausal transition include an increase in and the central redistribution of adipose tissue, as well as a decrease in energy expenditure. In addition, there is impairment of insulin secretion and insulin sensitivity and an increase in the risk of T2DM. MHT has a favourable effect on glucose metabolism, both in women with and in women without T2DM, while it may delay the onset of T2DM. MHT in women with T2DM should be administered according to their risk of cardiovascular disease (CVD). In women with T2DM and low CVD risk, oral oestrogens may be preferred, while transdermal 17ß-oestradiol is preferred for women with T2DM and coexistent CVD risk factors, such as obesity. In any case, a progestogen with neutral effects on glucose metabolism should be used, such as progesterone, dydrogesterone or transdermal norethisterone. Postmenopausal women with T2DM should be managed primarily with lifestyle intervention, including diet and exercise. Most of them will eventually require pharmacological therapy. The selection of antidiabetic medications should be based on the patient's specific characteristics and comorbidities, as well on the metabolic, cardiovascular and bone effects of the medications.

Current management of pelvic organ prolapse in aging women: EMAS clinical guide.

Management of pelvic organ prolapse (POP) is a common and challenging task. Nowadays older women are more active than they were in the past, and the development of POP disrupts quality of life and impairs social and personal activities. The menopausal transition is a time of vulnerability, during which many women start experiencing symptoms and signs of POP. The role of hormonal changes or of hormonal therapies in influencing the development or progression of POP has been explored extensively. The management of POP requires considerable clinical skills. Correct diagnosis and characterization of the prolapse and an identification of the individual woman's most bothersome symptoms are the hallmark of appropriate initial management. Therapy is multimodal and often multidisciplinary, and requires a competence in pelvic medicine and surgery. The integration of hormonal, non-hormonal and surgical strategies is important and needs to be adjusted to changing circumstances on an individualized basis. When surgery is required, optimal management requires clinicians who are familiar with the advantages and disadvantages of all the available strategies and who are able to use these strategies in a tailored manner. Complex cases should be sent to specialist referral centers. Management of POP should be integrated into the practice of healthcare professionals dealing in menopause.

The sexual health approach in postmenopause: The five-minutes study.

OBJECTIVES: To determine whether actively addressing sexuality in a gynaecological consultation with menopausal patients improves the diagnosis of sexual problems. STUDY DESIGN: A multi-centre analytical cross-sectional study was conducted at 12 Spanish hospitals. In gynaecological consultations the usual medical histories were taken, except that, initially, issues relating to sexuality were omitted, unless the patients raised them. Then, after 5min, gynaecologists offered the possibility of talking about sexuality and asked about possible sexual problems. Main outcome measures Observed prevalence of sexual problems. RESULTS: A total of 256 postmenopausal women participated in the study. Of them, 12.1% reported a sexual problem during the first 5 minutes of the interview. The prevalence of patients with a sexual problem increased by 35.9% (from 12.1% to 48.0%) when they were asked about sexuality after 5min (p<0.0001). The main factors associated with having a sexual problem were genitourinary syndrome of menopause (GSM) and having a stable sexual partner. CONCLUSIONS: Asking postmenopausal women about sexuality in gynaecological consultations is an important tool that increases the number of diagnoses of sexual problems. Gynaecologists should routinely ask about sexuality.

Calcium in the prevention of postmenopausal osteoporosis: EMAS clinical guide.

INTRODUCTION: Postmenopausal osteoporosis is a highly prevalent disease. Prevention through lifestyle measures includes an adequate calcium intake. Despite the guidance provided by scientific societies and governmental bodies worldwide, many issues remain unresolved. AIMS: To provide evidence regarding the impact of calcium intake on the prevention of postmenopausal osteoporosis and critically appraise current guidelines. MATERIALS AND METHODS: Literature review and consensus of expert opinion. RESULTS AND CONCLUSION: The recommended daily intake of calcium varies between 700 and 1200mg of elemental calcium, depending on the endorsing source. Although calcium can be derived either from the diet or supplements, the former source is preferred. Intake below the recommended amount may increase fragility fracture risk; however, there is no consistent evidence that calcium supplementation at, or above, recommended levels reduces risk. The addition of vitamin D may minimally reduce fractures, mainly among institutionalised people. Excessive intake of calcium, defined as higher than 2000mg/day, can be potentially harmful. Some studies demonstrated harm even at lower dosages. An increased risk for cardiovascular events, urolithiasis and even fractures has been found in association with excessive calcium intake, but this issue remains unresolved. In conclusion, an adequate intake of calcium is recommended for general bone health. Excessive calcium intake seems of no benefit, and could possibly be harmful.

Drug holidays from bisphosphonates and denosumab in postmenopausal osteoporosis: EMAS position statement.

BACKGROUND: Bisphosphonates and denosumab are used extensively in the treatment of postmenopausal osteoporosis. Despite their proven efficacy in the reduction of vertebral and non-vertebral fractures, their optimal duration of use has not been determined. The occurrence of adverse effects, such as osteonecrosis of the jaw (ONJ) and atypical femoral fractures (AFF), has raised the issue of bisphosphonate or denosumab discontinuation ("drug holiday") after a certain treatment period. AIM: To assess the effect of bisphosphonate and denosumab discontinuation on fracture risk, as well as its possible benefits in reducing the risk of adverse effects. METHODS: Systematic review and consensus of expert opinion. RESULTS AND CONCLUSIONS: Discontinuation of bisphosphonates should be considered in all patients who have beentreated for more than five years with alendronate, risedronate or zoledronic acid. In view of the limited evidence, no robust recommendations can be made for ibandronate and denosumab. If the patient has not experienced fractures before or during therapy and the fracture risk is low, a "drug holiday" canbe recommended. Although there is no solid evidence, 1-2 years for risedronate, 3-5 years for alendronate and 3-6 years for zoledronic acid are suggested. After this time, the patient should be reassessed. If a new fracture is experienced, or fracture risk has increased or BMD remains low (femoral neck T-score ≤-2.5), anti-osteoporotic treatment should be resumed. In the case of denosumab discontinuation, close monitoring is suggested, due to the possibility of rebound fractures.

Interventions to reduce the risk of ovarian and fallopian tube cancer: A European Menopause and Andropause Society Postition Statement.

BACKGROUND: Ovarian cancer is a leading cause of female gynecological cancer-related death, and there are no effective screening procedures or early diagnostic approaches. AIMS: To examine risk factors and risk-reducing strategies for both sporadic and familial tumors. MATERIALS AND METHODS: Literature review and consensus of expert opinion. RESULTS AND CONCLUSIONS: In women with a genetic predisposition to ovarian cancer, salpingo-oophorectomy reduces the risk of ovarian malignancy, and to a lesser degree of breast cancer. Opportunistic bilateral salpingo-oophorectomy and bilateral salpingectomy may also prevent epithelial ovarian cancer. In premenopausal women, bilateral salpingectomy should be preferred to tubal ligation, and be performed when hysterectomy is carried out for benign uterine disease. Hysterectomy and the use of combined oral contraceptives and non-steroid anti-inflammatory drugs are also recognized to reduce the risk of ovarian cancer, as do the prevention of obesity and smoking cessation.

Osteoporosis management in patients with breast cancer: EMAS position statement.

Aromatase inhibitors (AIs) are the first-line recommended standard of care for postmenopausal estrogen receptor-positive breast cancer. Because they cause a profound suppression of estrogen levels, concerns regarding their potential to increase the risk of fracture were rapidly raised. There is currently a general consensus that a careful baseline evaluation is needed of the risk of fracture in postmenopausal women about to start treatment with AIs but also in all premenopausal women with early disease. Bisphosphonates have been shown in several phase III trials to prevent the bone loss induced by cancer treatment, although no fracture data are available. Even though they do not have regulatory approval for this indication, their use must be discussed with women at high risk of fracture. Accordingly, several guidelines recommend considering treatment in women with a T-score ≤-2 or those with two or more clinical risk factors. Moreover, recent data suggest that bisphosphonates, especially intravenous zoledronic acid, may have an anticancer effect, in that they reduce bone recurrence as well as extra-skeletal metastasis and breast cancer mortality in postmenopausal women. The anti-RANK ligand antibody denosumab is also emerging as a new adjuvant therapeutic option to prevent AI-induced bone loss. It has been shown to extend the time to first fracture in postmenopausal women treated with AIs. Several issues still need to be addressed regarding the use of these different agents in an adjuvant setting. The purpose of this position statement is to review the literature on antifracture therapy and to discuss the current guidelines for the management of osteoporosis in women with early breast cancer.

A model of care for healthy menopause and ageing: EMAS position statement.

Worldwide, the number of menopausal women is increasing. They present with complex medical issues that lie beyond the traditional scope of gynaecologists and general practitioners (GPs). The European Menopause and Andropause Society (EMAS) therefore provides a holistic model of care for healthy menopause (HM). The HM healthcare model's core consists of a lead clinician, specialist nurse(s) and the woman herself, supported by an interdisciplinary network of medical experts and providers of alternative/complementary medicine. As HM specialist teams are scarce in Europe, they are also responsible for structuring and optimizing processes in primary care (general gynaecologists and GPs) and secondary care (HM specialists). Activities for accreditation of the subspecialty Women's Health are encouraged.

Maintaining postreproductive health: A care pathway from the European Menopause and Andropause Society (EMAS).

This position statement from the European Menopause and Andropause Society (EMAS) provides a care pathway for the maintenance of women's health during and after the menopause. It is designed for use by all those involved in women's health. It covers assessment, screening for diseases in later life, treatment and follow-up. Strategies need to be optimised to maintain postreproductive health, in part because of increased longevity. They encompass optimising diet and lifestyle, menopausal hormone therapy and non-estrogen-based treatment options for climacteric symptoms and skeletal conservation, personalised to individual needs.

EMAS recommendations for conditions in the workplace for menopausal women.

Women form a large part of many workforces throughout Europe. Many will be working throughout their menopausal years. Whilst the menopause may cause no significant problems for some, for others it is known to present considerable difficulties in both their personal and working lives. During the menopausal transition women report that fatigue and difficulties with memory and concentration can have a negative impact on their working lives. Furthermore, hot flushes can be a source of embarrassment and distress. Some consider that these symptoms can impact on their performance. Greater awareness among employers, together with sensitive and flexible management can be helpful for women at this time. Particular strategies might include: fostering a culture whereby employees feel comfortable disclosing health problems, allowing flexible working, reducing sources of work-related stress, providing easy access to cold drinking water and toilets, and reviewing workplace temperature and ventilation.

EMAS position statement: Testosterone replacement therapy in the aging male .

INTRODUCTION: Late-onset hypogonadism (LOH) represents a common clinical entity in aging males, characterized by the presence of symptoms (most usually of a sexual nature, such as decreased libido, decreased spontaneous erections and erectile dysfunction) and signs, in combination with low serum testosterone concentrations. Whether testosterone replacement therapy (TRT) should be offered to those individuals is still under extensive debate. AIMS: The aim of this position statement is to provide and critically appraise evidence on TRT in the aging male, focusing on pathophysiology and characteristics of LOH, indications for TRT, available therapeutic agents, monitoring and treatment-associated risks. MATERIALS AND METHODS: Literature review and consensus of expert opinion. RESULTS AND CONCLUSIONS: Diagnosis and treatment of LOH is justified, if a combination of symptoms of testosterone deficiency and low testosterone is present. Patients receiving TRT could profit with regard to obesity, metabolic syndrome, type 2 diabetes mellitus, sexual function and osteoporosis and should undergo scheduled testing for adverse events regularly. Potential adverse effects of TRT on cardiovascular disease, prostate cancer and sleep apnea are as yet unclear and remain to be investigated in large-scale prospective studies. Management of aging men with LOH should include individual evaluation of co-morbidities and careful risk versus benefit assessment.

Adenomyosis: what is new?

Adenomyosis is described as the benign invasion of endometrium into the myometrium, with endometrial glands and stroma surrounded by the hypertrophic and hyperplastic myometrium. It may affect 20% of female population and most widely seen among perimenopausal and multiparous women. Its etiopathogenesis, diagnosis, clinical findings and current various treatment options will be discussed in this article.

Diagnosis of Polycystic Ovary Syndrome: AMH in combination with clinical symptoms.

PURPOSE: We assessed the utility of using anti-Müllerian hormone (AMH) and clinical features of polycystic ovary syndrome (PCOS), polycystic ovarian morphology (PCOM), oligo/amenorrhea (OA), and hyperandrogenism (HA) for diagnosing PCOS, and compared their diagnostic accuracy with those of classical diagnostic systems. METHODS: A total of 606 females were admitted to a university hospital with menstrual irregularities or symptoms of hyperandrogenism were enrolled in this cross-sectional study. Fasting blood samples were collected. Pelvic and/or abdominal ultrasonography and clinical examination were performed. Patients were evaluated for the presence of PCOS according to conventional diagnostic criteria. The diagnostic performance of using serum AMH levels alone and in various combinations with the clinical features of PCOM, OA, and HA were investigated. RESULTS: For the diagnosis of PCOS, the combination of OA and/or HA with AMH showed 83% sensitivity and 100% specificity according to the Rotterdam criteria; 83% sensitivity and 89% specificity according to the National Institutes of Health (NIH) criteria; and 82% sensitivity and 93.5% specificity according to the Androgen Excess Society (AES) criteria. CONCLUSIONS: The serum AMH level is a useful diagnostic marker for PCOS and is correlated with conventional diagnostic criteria. The combination of AMH level with OA and/or HA markedly increased the clinical scope for PCOS diagnosis and can be introduced as a possible objective criterion for the diagnosis of this disease.

Serum anti-müllerian hormone, follicle stimulating hormone and antral follicle count measurement cannot predict pregnancy rates in IVF/ICSI cycles.

PURPOSE: To investigate whether serum anti-müllerian hormone (AMH), follicle stimulating hormone (FSH), or antral follicle count (AFC) are predictive for clinical pregnancy in in vitro fertilization (IVF) patients. METHODS: Serum AMH, inhibin B, FSH, luteinizing hormone (LH), estradiol (E2), prolactin, and thyroid stimulating hormone (TSH) levels and AFC of 189 women under 40 years of age were investigated. Pregnant and non-pregnant women were compared. RESULTS: Forty-seven (24.8 %) clinical pregnancies were observed in 189 women. There was no significant difference in terms of mean age, duration of infertility, body mass index, AMH, LH, FSH, E2, TSH, Inhibin B, AFC and total oocyte number between women who did and who did not become pregnant. Additionally, there was no significant difference in clinical pregnancy rates between the quartiles of AMH, FSH and AFC. (P values were 0.668, 0.071, and 0.252, respectively.) CONCLUSION: Serum AMH and FSH, and AFC cannot predict clinical pregnancy in IVF patients under 40; the pregnancy rate tends to increase as AMH increases, although this remains non-significant.

Serum anti-müllerian hormone concentrations in reproductive age women with and without polycystic ovary syndrome: the influence of body mass index.

PURPOSE: To evaluate the correlation between anti-müllerian hormone (AMH) and body mass index (BMI) in patients with and without polycystic ovarian syndrome (PCOS). METHODS: Serum AMH levels of 332 women in their reproductive period and below 45 years of age who were admitted to our reproductive endocrinology clinic with infertility were investigated in a cross-sectional study. Patients were divided into two groups as BMI under and equal or over 25 kg/m2. Both groups were divided into two subgroups as PCOS and non-PCOS. AMH levels of patients were analyzed for each group. RESULTS: Mean AMH values of BMI <25 and ≥25 kg/m2 groups were 3.87 ± 2.95 and 3.58 ± 2.93 ng/mL, respectively (P > 0.05) in all patients. Means of AMH were not significantly different in BMI quartiles (r = -0.008401, P = 0.96). Among 107 patients with PCOS, means of AMH were 6.85 ± 2.95 ng/mL in 56 patients with BMI <25 kg/m2 and 6.66 ± 3.18 ng/mL in 51 patients with BMI ≥25 kg/m2 (P > 0.05). In the group of 225 non-PCOS patients, means of AMH were 2.27 ± 1.12 ng/mL in 104 patients with BMI <25 kg/m2 and 2.28 ± 1.49 ng/mL in 121 patients with BMI ≥25 kg/m2 (P > 0.05). CONCLUSIONS: Body mass index does not seem to have an effect on serum AMH levels in reproductive age women both with and without PCOS.

Thin endometrium in assisted reproductive technology.

PURPOSE OF REVIEW: To review the etiology, diagnosis and clinical importance of thin endometrium during assisted reproductive technology cycles and to find out better ways to deal with it. RECENT FINDINGS: Precise and specific endometrial maturational development is crucial in allowing implantation following assisted reproduction. As endometrial biopsy is invasive and hormonal milieu assessment inaccurate, the need to evaluate endometrial development encouraged the use of high-resolution ultrasonography as an alternative non-invasive method of assessment for uterine receptivity. Ultrasonographic endometrial thickness measurement, endometrial pattern investigation, endometrial volume computation, uterine and subendometrial blood flow analysis by Doppler sonography are just some of the methods that we can utilize to have an idea of uterine receptivity and consequently to better predict pregnancy outcome following assisted reproductive technology cycles. There is a lot of debate on the administration of low-dose aspirin, estrogen, vaginal sildenafil citrate, pentoxifylline, vitamin E, and gonadotropin-releasing hormone agonist for the management of thin endometrium with an aim to increase the pregnancy and implantation rates in assisted reproductive technology cycles. SUMMARY: Various recent modalities proposed for the treatment of thin endometrium seem to be useless and inefficient from an evidence-based medicine point of view. At the moment, evaluation of endometrium using different ultrasonographic markers seems to be superior to all those therapies.

Effect of different hormonal therapies on thyroid function in surgical menopause: short-term results.

OBJECTIVE: To determine the effects of different hormone replacement therapy (HRT) regimens on thyroid function in surgical menopause. STUDY DESIGN: In a randomized, controlled study, 59 euthyroid women with surgical menopause were randomized to an estrogen-only (n=20), tibolone (n=20) or calcium-only (n=19) group. On the 5th postoperative day and 4th and 12th weeks, serum E2, TSH, free T3 and free T4 levels were determined. RESULTS: Although the initial and week 4 serum E2, TSH, free T3 and free T4 levels were comparable, the week 12 serum E2 and TSH levels were different between the subjects on estrogen therapy and those receiving tibolone or calcium only (p=0.008 and 0.000, respectively). Serum E2 levels were higher and TSH levels lower in subjects receiving estrogen. Moreover, serum TSH levels correlated negatively with serum E2 levels in the 12th week of estrogen use (r=-0.354, p=0.006). TSH increased in the tibolone group as compared to the estrogen group but was still lower than in the calcium-only group; however, the differences were not statistically significant. CONCLUSION: Irrespective of different regimens, HRT does not have an important short-term effect on thyroid function in women with surgical menopause.

Tibolone and breast cancer.

Tibolone is a relatively new drug for postmenopausal women, which is structurally related to 19-nortestosterone derivatives and exhibits weak oestrogenic, progestogenic and androgenic activities. The effect of tibolone on breast tissue is still obscure. In vitro studies have shown conflicting results regarding the effects of tibolone on breast cells. On the other hand, although epidemiological studies show an increase in the risk of breast cancer among women treated with tibolone, accumulation of data obtained from radiological studies presents promising results. However, the safety of tibolone with regard to breast tissue needs to be investigated further, especially through well-designed, large-scale, randomised-controlled trials.