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.

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.

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.

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.

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.

Is laparoscopy necessary before assisted reproductive technology?

PURPOSE OF REVIEW: Laparoscopy is widely used during infertility work-up, although it is sometimes unnecessary. This review highlights when laparoscopic intervention should be used in women undergoing assisted reproductive technology cycles. RECENT FINDINGS: There is no evidence for an increase in pregnancy rates in assisted reproductive technology cycles following surgical treatment of pelvic adhesions or endometriosis with laparoscopy. If the patient has bilateral visible hydrosalpinges, laparoscopy may be an option for evaluation of the tubes and treatment with salpingectomy in order to enhance the chance of pregnancy before commencing an assisted reproductive technology cycle. Laparoscopic ovarian drilling before assisted reproductive technology may be considered a therapeutic option in polycystic ovary disease patients who previously had severe ovarian hyperstimulation syndrome. Finally, laparoscopy may be useful in replacing the transposed ovaries to their original sites in the pelvic cavity in previously treated cancer patients so that monitoring of the controlled ovarian hyperstimulation and the oocyte aspiration would be much easier during the assisted reproductive technology cycles. SUMMARY: Laparoscopy should be considered before assisted reproductive technology cycles if the procedure diagnoses and treats a pelvic pathology at the same time and if laparoscopic intervention increases the chance of pregnancy following these cycles.