Optimising health after early menopause.

The typical age at menopause is 50-51 years in high-income countries. However, early menopause is common, with around 8% of women in high-income countries and 12% of women globally experiencing menopause between the ages of 40 years and 44 years. Menopause before age 40 years (premature ovarian insufficiency) affects an additional 2-4% of women. Both early menopause and premature ovarian insufficiency can herald an increased risk of chronic disease, including osteoporosis and cardiovascular disease. People who enter menopause at younger ages might also experience distress and feel less supported than those who reach menopause at the average age. Clinical practice guidelines are available for the diagnosis and management of premature ovarian insufficiency, but there is a gap in clinical guidance for early menopause. We argue that instead of distinct age thresholds being applied, early menopause should be seen on a spectrum between premature ovarian insufficiency and menopause at the average age. This Series paper presents evidence for the short-term and long-term consequences of early menopause. We offer a practical framework for clinicians to guide diagnosis and management of early menopause, which considers the nature and severity of symptoms, age and medical history, and the individual's wishes and priorities to optimise their quality of life and short-term and long-term health. We conclude with recommendations for future research to address key gaps in the current evidence.

Uterine NK cells underexpress KIR2DL1/S1 and LILRB1 in reproductive failure.

A significant proportion of recurrent miscarriage, recurrent implantation failure and infertility are unexplained, and these conditions have been proposed to have an etiology of immunological dysfunction at the maternal-fetal interface. Uterine Natural Killer cells (uNK) comprise three subsets and are the most numerous immune cells found in the uterine mucosa at the time of implantation. They are thought to play an important role in successful pregnancy by regulation of extravillous trophoblast (EVT) invasion and spiral artery remodelling. Here, we examine the frequency, phenotype and function of uNK1-3 from the uterine mucosa of 16 women with unexplained reproductive failure compared to 11 controls with no reproductive problems, during the window of implantation. We report that KIR2DL1/S1 and LILRB1 expression is lower in the reproductive failure group for both uNK (total uNK, uNK 2 and 3) and pNK. We also show that degranulation activity is significantly reduced in total uNK, and that TNF-α production is lower in all uNK subsets in the reproductive failure group. Taken together, our findings suggest that reproductive failure is associated with global reduction in expression of uNK receptors important for interaction with HLA-C and HLA-G on EVT during early pregnancy, leading to reduced uNK activation. This is the first study to examine uNK subsets during the window of implantation in women with reproductive failure and will serve as a platform to focus on particular aspects of phenotype and function of uNK subsets in future studies. Further understanding of uNK dysregulation is important to establish potential diagnostic and therapeutic targets in the population of women with unexplained reproductive failure.

Exploring the knowledge and attitudes of women of reproductive age from the general public towards egg donation and egg sharing: a UK-based study.

STUDY QUESTION: What are the knowledge and views of UK-based women towards egg donation (ED) and egg sharing (ES)? SUMMARY ANSWER: Lacking knowledge of the practices of ED and ES could be an influential factor in donor egg shortages, rather than negative perceptions or lack of donor anonymity and financial incentives. WHAT IS KNOWN ALREADY: The increasing age of women trying to conceive has led to donor egg shortages, with ED and ES failing to meet demand. Indeed, in recent years in the UK, ES numbers have fallen. This results in long waiting lists, forcing patients abroad for fertility treatment to take up cross border reproductive care. Previous research suggests a lack of knowledge of ED among members of the general public; however, no study has yet assessed knowledge or views of ES in the general public. STUDY DESIGN, SIZE, DURATION: Six hundred and thirty-five UK-based women over 18 years were voluntarily recruited from social media community groups by convenience sampling. The recruitment period was from February to April 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants completed a previously validated questionnaire regarding female fertility, ED and ES, including knowledge, perceptions and approval of the practices and relevant legislation. This included ranking key benefits and issues regarding egg sharing. The questionnaire was completed using the online Qualtrics survey software. Statistical analysis was conducted using SPSS. MAIN RESULTS AND THE ROLE OF CHANCE: Regarding knowledge of ED and ES, 56.3% and 79.8%, respectively had little or no prior knowledge. Upon explanation, most approved of ED (85.8%) and ES (70.4%). A greater proportion of respondents would donate to a family member/friend (49.75%) than to an anonymous recipient (35.80%). Overall, ES was viewed less favourably than ED, with ethical and practical concerns highlighted. Women aged 18-30 years were significantly more likely to approve of egg donation practice compared to those aged >30 years (P < 0.0001). Those against ES found fears of financial coercion or negative psychological wellbeing the most concerning. About 35.8% and 49.7% would personally consider anonymous and known ED, respectively, whilst 56.7% would consider ES. Those answering in favour of egg sharing were significantly more likely to give higher benefit ratings compared to those against the practice (P < 0.001). Most agreed (55.8%) with and were not deterred to donate (60.1%) by the 'Disclosure of Donor Identity' legislation. Only 31.6% agreed with the compensatory cap; however, 52.7% would not be more motivated to donate by an increased cap. LIMITATIONS, REASONS FOR CAUTION: There were several limitations of the study, including the use of convenience sampling and the voluntary nature of participation opening the study up to sampling and participation bias. Finally, closed questions were predominantly used to allow the generation of quantitative data and statistical analysis. However, this approach prevented opinion justification and qualitative analysis, limiting the depth of conclusions drawn. WIDER IMPLICATIONS OF THE FINDINGS: To our knowledge, this is the first study to survey the general public's knowledge and views of ED/ES using a previously validated questionnaire. The conclusion that lack of knowledge could be contributing to the current donor shortfall in the UK demonstrates that campaigns to inform women of the practices are necessary to alleviate donor oocyte shortages. STUDY FUNDING/COMPETING INTEREST(S): No external funds were used for this study. The authors have no conflicts of interest. TRIAL REGISTRATION NUMBER: NA.

Cardiovascular health after menopause transition, pregnancy disorders, and other gynaecologic conditions: a consensus document from European cardiologists, gynaecologists, and endocrinologists.

Women undergo important changes in sex hormones throughout their lifetime that can impact cardiovascular disease risk. Whereas the traditional cardiovascular risk factors dominate in older age, there are several female-specific risk factors and inflammatory risk variables that influence a woman's risk at younger and middle age. Hypertensive pregnancy disorders and gestational diabetes are associated with a higher risk in younger women. Menopause transition has an additional adverse effect to ageing that may demand specific attention to ensure optimal cardiovascular risk profile and quality of life. In this position paper, we provide an update of gynaecological and obstetric conditions that interact with cardiovascular risk in women. Practice points for clinical use are given according to the latest standards from various related disciplines (Figure 1).

Should we abandon all conservative treatments for uterine fibroids? The problem with leiomyosarcomas.

Fibroids are the most common tumor in women and many medical and surgical options exist for their management. The incidence of uterine sarcoma in women undergoing treatment for fibroids has previously been thought to be extremely rare, however there has been recent controversy as to whether this risk has been underestimated. This article reviews the literature investigating the incidence of leiomyosarcoma and explores how different treatment modalities may affect risk from occult malignancy. We aim to provide a tool for counseling women who are considering options for the management of their fibroids.

Current concepts in premature ovarian insufficiency.

Premature ovarian insufficiency (POI) is a life-changing diagnosis, with profound physical and psychological consequences. Unfortunately, there are many deficiencies in our understanding of the condition as the underlying etiology and optimum management strategies are poorly understood. Improved awareness of POI and its long-term implications has led to increased research interest in recent years. Current research has allowed a greater understanding of the changing epidemiology in POI, genetic factors in its etiology and randomized controlled trials of hormone therapy are underway to provide evidence for treatment. This article reviews the latest literature on POI to summarize current understanding and future directions.

Laparoscopic treatment of uterine fibroids: a comparison of peri-operative outcomes in laparoscopic hysterectomy and myomectomy.

PURPOSE: To compare peri-operative outcomes between laparoscopic myomectomy (LM) and laparoscopic hysterectomy (LH) for the treatment of uterine fibroids. METHODS: Retrospective cohort study including 400 women who underwent LH or LM for the management of uterine fibroids. RESULTS: LH patients were older, with higher BMI and larger uterine size but LH was associated with shorter operative duration (80.2 vs. 115.7 min, p < 0.0001), lower blood loss (215 vs. 316 ml, p < 0.0001), and shorter hospital stay (1.81 vs. 2.12 days, p = 0.0003). Seven LM patients (3.2%) had blood loss >1000 ml compared with no LH patients and five LM patients (2.3%) required blood transfusion compared to 1 (0.5%) LH patient. Three LM patients (1.9%) and no LH patients required conversion to laparotomy. Bladder injury occurred in three LH cases (1.6%) and no LM cases. When the data was restricted only to women aged 44 years or over, LH was again associated with significantly lower operative duration and estimated blood loss. CONCLUSIONS: Particularly in perimenopausal women, the decision to perform myomectomy can be controversial. These data suggest that there are potential advantages to LH over LM, including reduced operation length, blood loss and hospital stay but increased risk of urinary tract injury.

Co-existence of uterine myomas and endometriosis in women undergoing laparoscopic myomectomy: risk factors and surgical implications.

STUDY OBJECTIVE: To investigate the prevalence of and explore risk factors for the coexistence of uterine myomas and endometriosis and to assess operative outcomes during laparoscopic myomectomy. DESIGN: Retrospective cohort study (Canadian Task Force classification II-2). SETTING: Tertiary referral center in London, England. PATIENTS: Two hundred twelve women undergoing laparoscopic myomectomy to treat symptomatic uterine myomas. INTERVENTION: Laparoscopic myomectomy. MEASUREMENTS AND MAIN RESULTS: Coexisting myomas and endometriosis were identified in 21.2% of patients. Endometriosis was more common in those with subfertility (44% vs 25.7%; p = .02) and less common in those with bleeding disorders (20% vs 45%; p = .003). Parity, location of myoma, and race/ethnicity affected risk of endometriosis, whereas size and number of myomas did not. Of patients with endometriosis, 42% underwent surgical treatment of endometriosis during myomectomy. Significantly more patients with endometriosis also underwent ovarian cystectomy than did those without endometriosis (15.6% vs 3%; p = .004). Operative time was similar in both groups (109.6 minutes vs 116.4 minutes; p = .83), as was estimated blood loss (271 mL vs 327 mL; p = .16). CONCLUSIONS: A diagnosis of concomitant endometriosis should be considered, in particular in patients with subfertility and pain. This enables optimal preoperative counseling and consent for potential additional procedures such as treatment of endometriosis or ovarian cystectomy.

A rare case of small bowel obstruction secondary to ovarian torsion in an IVF pregnancy.

A 39- year-old woman, who conceived following in vitro fertilisation (IVF) treatment, presented at 12 weeks gestation with symptoms of ovarian hyperstimulation syndrome (OHSS), abdominal pain, vomiting and diarrhoea. Subsequent investigations found small bowel obstruction  secondary to ovarian torsion. Surgical management to remove a necrotic ovary and fallopian tube led to a good recovery from the acute illness. A postoperative ultrasound scan confirmed a viable pregnancy and the patient was discharged. Her case demonstrates a rare complication of OHSS and ovarian torsion leading to small bowel obstruction.

A study to evaluate the cause of bone demineralization in gynecological cancer survivors.

BACKGROUND: An association between treatment for gynecological cancers and risk of osteoporosis has never been formally evaluated. Women treated for these cancers are now living longer than ever before, and prevention of treatment-induced morbidities is important. We aimed to distinguish, in gynecological cancer survivors, whether cancer therapy has additional detrimental effects on bone health above those attributable to hormone withdrawal. METHODS: We performed a retrospective cross-sectional analysis of dual energy x-ray absorptiometry (DEXA) scan results from 105 women; 64 had undergone bilateral salpingo-oophorectomy (BSO) followed by chemotherapy or radiotherapy for gynecological malignancies, and 41 age-matched women had undergone BSO for benign etiologies. All were premenopausal prior to surgery. RESULTS: The median age at DEXA scan for the cancer group was 42 years, and 66% had received hormonal replacement therapy (HRT) following their cancer treatment. For the benign group, the median age was 40 years, and 87% had received HRT. Thirty-nine percent of cancer survivors had abnormal DEXA scan results compared to 15% of the control group, with the majority demonstrating osteopenia. The mean lumbar spine and femoral neck bone mineral densities (BMDs) were significantly lower in cancer patients. A history of gynecological cancer treatment was associated with significantly lower BMD in a multivariate logistic regression. CONCLUSIONS: Women treated for gynecological malignancies with surgery and adjuvant chemotherapy have significantly lower BMDs than age-matched women who have undergone oophorectomy for noncancer indications. Prospective evaluation of BMD in gynecological cancer patients is recommended to facilitate interventions that will reduce the risk of subsequent fragility fractures.

The safety of postmenopausal testosterone therapy.

Testosterone is increasingly used as part of postmenopausal HRT regimens. Unfortunately, few androgenic preparations designed specifically for use in women have been approved by regulatory authorities. Ongoing concerns exist surrounding the potential long-term effects of testosterone therapy. Here, we review the most recent data on postmenopausal testosterone therapy, focusing particularly on the effects of testosterone on breast, endometrium and cardiovascular health.

Primary prevention of cardiovascular disease with HRT.

Prevention of cardiovascular disease has increasingly important health implications as our population ages. Menopause is associated with the development of cardiovascular risk factors and there are many plausible biological mechanisms through which estrogen may confer cardiovascular protection. Despite a wealth of observational data to support the use of estrogen, large randomized controlled trials failed to demonstrate a benefit. It is now becoming clearer that the beneficial cardiovascular effects of estrogen are greatest in younger women and those closest to menopause. This has led to the development of the timing hypothesis. Use of age-appropriate estrogen doses is crucial to maximize cardiovascular benefits while minimizing risk of adverse effects such as venous thromboembolism and stroke.

Managing low sexual desire in women.

Low sexual desire is a prevalent symptom, but not one frequently volunteered by women. When accompanied by distress, loss of libido is known as hypoactive sexual desire disorder, which can have a significant impact on a woman's wellbeing. The etiology of hypoactive sexual desire disorder is multifactorial and its management requires a combination of psychosocial and pharmacological interventions. This article outlines the assessment of patients presenting with the symptom of low sexual desire and discusses the evidence for pharmacological management.

Premature ovarian failure.

Premature ovarian failure (POF) is the occurrence of amenorrhoea, elevated gonadotrophins and hypoestrogenism in women under 40 years of age. It has important physical and psychological consequences and is increasingly common due to improved survival following treatment for malignancy. Despite this, it remains a poorly understood condition. Here we review the presentation and investigation of POF, discuss recent advances in the management of affected women, and suggest how our knowledge of the condition could be improved.

Frequency, viral loads, and serotype identification of enterovirus infections in Scottish blood donors.

BACKGROUND: Enteroviruses are non-enveloped, frequently pathogenic RNA viruses infecting humans. Infection is potentially transmissible through blood or blood component transfusion from donor in the viremic phase before seroconversion for antibody. To investigate the threat to blood safety from enteroviruses, a large-scale survey of frequency and levels of viremia in blood donors was conducted. STUDY DESIGNS AND METHODS: Blood donations from Scotland over a period of 22 calendar months were screened for enterovirus RNA sequences by PCR. Positive samples were quantified, and serotypes were identified by nucleotide sequencing of VP1. RESULTS: From a total of 3658 pools of 95 donations tested, 73 samples that were enterovirus-positive were identified (corrected annual frequency 0.024% or 1 in 4000). The highest rates of viremia were in late summer months (e.g., 0.055%, 1 in 1800 in July) and lowest from January to May (0.009 and 0.012%). Viral loads ranged from 500 (the lower cutoff of the assay) to greater than 100,000 amplifiable enterovirus template copies per mL. Coxsackievirus A16, echoviruses 11 and 30, and enterovirus 71 were most often identified. CONCLUSIONS: The detection of enterovirus-positive blood units indicates the potential for enteroviral transmission by blood components. Although the infrastructure established for PCR-based screening for HCV RNA would allow parallel screening for enteroviruses, any decision concerning donor testing would require further information on the outcome of transfusion-acquired enterovirus infections.