C. Tamer Erel

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.

EMAS position statement: management of uterine fibroids.

INTRODUCTION Uterine fibroids (also termed leiomyomas or myomas) are the most common tumors of the female reproductive tract. AIM The aim of this position statement is to provide and critically appraise evidence on the management of women with uterine fibroids. METHODS Literature review and consensus of expert opinion. RESULTS AND CONCLUSIONS Many uterine fibroids are asymptomatic and require no intervention, although it is advisable to follow up patients to document stability in size and growth. Fibroid-associated symptoms include heavy menstrual bleeding and pain or pelvic discomfort. The association between infertility and fibroids increases with age. Fibroids do not increase the risk of malignant uterine disease and leiomyosarcomas are extremely rare (less than one in 1000). It is unknown at present whether leiomyosarcoma represents de novo growth or malignant transformation from benign uterine fibroids. Treatment options for symptomatic fibroids include pharmacologic, surgical and radiologically guided interventions. The range of medical treatments allows flexible management of fibroid-related symptoms; the options include tranexamic acid, non-steroidal anti-inflammatory drugs, contraceptive steroids, gonadotropin-releasing hormone analogs, antiprogesterone, and selective progesterone receptor modulators. However, these medical options do not remove the tumors and symptoms may return when treatment is stopped. Surgical and radiologically guided procedures may be tailored to age, general health, and individual patient wishes. Hysterectomy is the most effective treatment, although in some cases myomectomy may be sufficient to control symptoms. Alternatives to surgery include uterine artery embolization, myolysis and ablation by high-intensity focused ultrasound (guided with magnetic resonance imaging or ultrasound). The choice of treatment depends on fibroid size, the underlying symptoms and their severity and the womans desire for subsequent fertility and pregnancy, as well as efficacy and need for repeated interventions.

Role of the mutations Trp8 ⇒ Arg and Ile15 ⇒ Thr of the human luteinizing hormone β-subunit in women with polycystic ovary syndrome

OBJECTIVE To evaluate the clinical significance of LH in the form of a mutant beta-subunit in women with polycystic ovary syndrome (PCOS). DESIGN Prospective, controlled study. SETTING University hospital. PATIENT(S) Thirty healthy women and 30 women with PCOS. INTERVENTION(S) Clinical, ultrasonographic, and hormonal findings were used to define PCOS. Nucleotide mutations within codons 8 and 15 in the LH beta-subunit gene (Trp8 => Arg and Ile15 => Thr) were analyzed with the use of polymerase chain reaction and subsequent restriction fragment length polymorphism. MAIN OUTCOME MEASURE(S) Serum levels of gonadotropins, androgens, E2, and prolactin were determined, and the results of restriction fragment length polymorphism were analyzed. RESULT(S) Five women in the control group and one woman in the PCOS group were found to be affected by the LHbeta gene mutations. No difference was observed in serum androgen and E2 levels between the affected women and 25 healthy women who were homozygous for the wild-type LH. However, women whose serum LH levels were < or = 5.1 mIU/mL had a higher risk of having mutant LH. CONCLUSION(S) The frequency of LH mutations in women with PCOS is similar to that in healthy women. The presence of the variant does not cause any significant change in serum levels of androgens and E2.

EMAS position statement: The ten point guide to the integral management of menopausal health

With increased longevity and more women becoming centenarians, management of the menopause and postreproductive health is of growing importance as it has the potential to help promote health over several decades. Women have individual needs and the approach needs to be personalised. The position statement provides a short integral guide for all those involved in menopausal health. It covers diagnosis, screening for diseases in later life, treatment and follow-up.

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

INTRODUCTION Venous thromboembolism (VTE), including deep venous thrombosis (DVT) and pulmonary embolism (PE), is a serious cardiovascular event whose incidence rises with increasing age. AIMS To formulate a position statement on the management of the menopause in women with a personal or family history of VTE. MATERIAL AND METHODS Literature review and consensus of expert opinion. RESULTS AND CONCLUSIONS Randomized 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: Non-hormonal management of menopausal vasomotor symptoms

AIM To review non-hormonal therapy options for menopausal vasomotor symptoms. The current EMAS position paper aims to provide to provide guidance for managing peri- and postmenopausal women who cannot or do not wish to take menopausal hormone therapy (MHT). MATERIAL AND METHODS Literature review and consensus of expert opinion. RESULTS Non-hormonal management of menopausal symptoms includes lifestyle modifications, diet and food supplements, non-hormonal medications and application of behavioral and alternative medicine therapies. There is insufficient or conflicting evidence to suggest that exercise, supplements or a diet rich in phytoestrogens are effective for vasomotor menopausal symptoms. Selective serotonin-reuptake inhibitors (SSRIs), serotonin norepinephrine-reuptake inhibitors (SNRIs) and gabapentin could be proposed as alternatives to MHT for menopausal symptoms, mainly hot flushes. Behavioral therapies and alternative medicine interventions have been tried, but the available evidence is still limited. CONCLUSIONS A number of interventions for non-hormonal management of menopausal vasomotor symptoms are now available. For women who cannot or do not wish to take estrogens, non-hormonal management is now a realistic option.

EMAS clinical guide: Vulvar lichen sclerosus in peri and postmenopausal women

INTRODUCTION Vulvar lichen sclerosus (LS) is a chronic inflammatory disease which affects genital labial, perineal and perianal areas, producing significant discomfort and psychological distress. However there may be diagnostic delay because of late presentation and lack of recognition of symptoms. AIMS The purpose of this clinical guide is to provide advice on early recognition and treatment. MATERIAL AND METHODS Literature review and consensus of expert opinion. RESULTS AND CONCLUSIONS The etiology of LS in peri and postmenopausal women is unknown, although autoimmune, genetic and infectious factors have been implicated. Definitive diagnosis of non-malignant disorders depends on the histology of biopsied tissue. LS associated with cellular atypia should be classified as intraepithelial neoplasia. Topical corticosteroids are the most effective treatment, although prolonged treatment may be associated with dermal atrophy. Topical calcineurin inhibitors, such as tacrolimus or pimecrolimus, may be a safe and effective alternative treatment without risk of corticosteroid-related vulvar atrophy since they do not affect collagen synthesis. LS recurrences are frequent, and can lead to significant physical discomfort and emotional distress that affect mood and sexual relationships. Anatomical changes may require surgical management.

Leptin levels in women with hyperemesis gravidarum

Hyperemesis gravidarum(HEG) has been defined as vomiting so severe as to produce weight loss, dehydration, acidosis from starvation, alkalosis from hydrochloric acid loss, and hypokalemia. Leptin, believed to be produced exclusively by adipocytes, is responsible for regulating metabolic processes by interacting with other factors such as cortisol, thyroid hormones, and insulin. Maternal serum leptin levels increase progressively in the first two trimesters of pregnancy and is well correlated with total body fat. A change in serum leptin levels may therefore be expected in cases of decreased body fat mass and metabolic disorders in HEG. We believe that this is the first prospective controlled study aiming to determine serum leptin levels among women who have HEG during the first trimester of pregnancy. We investigated the leptin levels of 40 pregnant women with HEG and 30 pregnant women without HEG. The women in the study group presented with symptoms of hyperemesis and positive ketonuria (qqqq) on dip-

EMAS position statement: Individualized breast cancer screening versus population-based mammography screening programmes

INTRODUCTION Breast cancer is the most prevalent cancer in women, with slightly more than ten percent developing the disease in Western countries. Mammography screening is a well established method to detect breast cancer. AIMS The aim of the position statement is to review critically the advantages and shortcomings of population based mammography screening. MATERIALS AND METHODS Literature review and consensus of expert opinion. RESULTS AND CONCLUSION Mammography screening programmes vary worldwide. Thus there are differences in the age at which screening is started and stopped and in the screening interval. Furthermore differences in screening quality (such as equipment, technique, resolution, single or double reading, recall rates) result in a sensitivity varying from 70% to 94% between studies. Reporting results of screening is subject to different types of bias such as overdiagnosis. Thus because of the limitations of population-based mammography screening programmes an algorithm for individualized screening is proposed.

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

INTRODUCTION Epilepsy is a major public health problem worldwide which is clinically characterized by recurrent seizures. AIM The 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. MATERIALS AND METHODS Literature review and consensus of expert opinion. RESULTS AND CONCLUSIONS Women 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.