Fertility and pregnancy outcomes in women with Turner syndrome: A single centre experience.

OBJECTIVE: Many women with Turner syndrome (TS) will consider fertility options and pregnancy. We wished to examine the fertility and pregnancy outcomes in women with TS undergoing oocyte donation (OD) treatment or spontaneous pregnancy in a large single-centre cohort. General population reference data or data from those with idiopathic premature ovarian insufficiency were used as comparators. DESIGN: A retrospective single-centre cross-sectional study. PATIENTS AND MEASUREMENTS: Seventy-four women with TS underwent OD treatment with a total of 105 pregnancies, and 31 women with TS had 71 spontaneous conceptions. Fertility outcomes included clinical pregnancy and live birth rate. Pregnancy outcomes included miscarriage rate, prevalence of hypertension, gestational diabetes, lower segment caesarean section (LSCS), small for gestational age (SGA), prematurity and vertical transmission of TS. RESULTS: In those with TS, OD pregnancies were associated with increased rates of LSCS and SGA compared to spontaneous pregnancies; LSCS (OR: 4.19, 95% CI: 1.6-10.8, p = .003) and SGA (OR: 2.92, 95% CI: 1.02-8.38, p = .04). There were no recorded cardiac events but 5 (17.2%) cases of vertical transmissions of TS in daughters were identified. OD in those with TS was associated with a lower live birth rate per cycle started (OR: 0.53, 95% CI: 0.34-0.84, p = .008) and a higher rate of miscarriage compared to women with POI (40% vs. 26.2%, p = .04). CONCLUSIONS: We show that pregnancy in women with TS, whether OD or spontaneously conceived, carries obstetric risks, and therefore, women with TS, considering pregnancy, should receive comprehensive pre-pregnancy counselling and optimal obstetric care.

Healthcare and research priorities for women with polycystic ovary syndrome in the UK National Health Service: A modified Delphi method.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is a chronic lifelong condition affecting up to 20% of women worldwide. There is limited input from affected women to guide the provision of healthcare services and future research needs. Our objective was to scope the healthcare and research priorities of women with PCOS in the United Kingdom. DESIGN: A three-staged modified Delphi method, consisting of two questionnaires and a consensus meeting involving lay representatives and healthcare professionals. PATIENTS AND MEASUREMENTS: Lay patient representatives of women with PCOS. Participants were asked to identify and rank healthcare and research priorities for their importance. RESULTS: Six hundred and twenty-four lay participants took part in our Delphi method. Over 98% were diagnosed with PCOS (614/624, 98.4%). More than half experienced difficulties to receive a PCOS diagnosis (375/624, 60%), and the majority found it difficult to access specialised PCOS health services in the NHS (594/624, 95%). The top two healthcare priorities included better education for health professionals on the diagnosis and management of PCOS (238/273, 87.1%) and the need to set up specialist PCOS services (234/273, 85.7%). The top two research priorities focused on identifying better treatments for irregular periods (233/273, 85.3%) followed by better tests for early PCOS diagnosis (230/273, 84.2%). CONCLUSIONS: We identified 13 healthcare and 14 research priorities that reflect the current health needs of women with PCOS in the United Kingdom. Adopting these priorities in future healthcare and research planning will help to optimise the health of women with PCOS and increase patient satisfaction.

Non-oestrogen-based and complementary therapies for menopause.

Women are living a significant portion of their adult lives in the post-reproductive phase, and many seek help for debilitating menopausal symptoms. Every individual's experience of menopausal transition is unique. Adopting a holistic approach to managing the menopause using a combination of lifestyle, hormonal, and non-hormonal interventions is key to maximise the quality of life of affected women. However, many opt to use non hormonal options or have contraindications to using hormonal therapy. Studies have shown that several pharmacological non-hormonal medications such as SSRIs, SSRI/SNRIs, Gabapentin, and Pregabalin are effective for managing vasomotor symptoms as well as other menopausal symptoms. Their main side effects are dry mouth, nausea, constipation, reduced libido, and loss of appetite. Clonidine is the only non-hormonal drug which is licenced for control of vasomotor symptoms in the UK, but has several side effects including dizziness and sleep disturbance. Cognitive Behavioural Therapy is recommended as a treatment for anxiety, sleep problems and vasomotor symptoms related to menopausal transition. Evidence for clinical efficacy and safety of herbal remedies and alternative therapies remains weak. Studies with neurokinin receptor 3 antagonists on women with hot flushes have shown improvement in vasomotor symptoms and results of large-scale studies are awaited.

A systematic review of randomised clinical trials - The safety of vaginal hormones and selective estrogen receptor modulators for the treatment of genitourinary menopausal symptoms in breast cancer survivors.

Therapies utilised in breast cancer management have been found to induce or worsen the genitourinary symptoms of menopause (GSM), a group of physical symptoms associated with the systemic loss of estrogen. These symptoms are often undertreated due to concerns surrounding cancer recurrence, especially when considering treatments with possible pro-estrogenic effects. As breast cancer prognosis continues to improve, clinicians are increasingly focussing on managing these symptoms amongst survivors. This systematic review primarily aimed to determine the risk of breast cancer recurrence amongst survivors using vaginal hormones and selective estrogen receptor modulator therapies recommended for use in GSM in the United Kingdom amongst currently published randomised clinical trials (RCTs). The secondary aim was to determine whether these RCTs demonstrated a significant rise in serum estrogen levels following the use of these therapies. A literature search revealed three RCTs suitable for assessment, two evaluating vaginal estrogen and one evaluating vaginal DHEA treatment. Our review determined that amongst published RCTs, no studies have aimed to assess for breast cancer recurrence; however among the studies observing for serious adverse effects of vaginal estrogen preparations, none have reported an increased incidence. Furthermore, these studies did not report a persistent or significant increase in serum estrogen levels following the use of vaginal estrogen products and low concentration (3.25 mg/day) DHEA gel. Larger RCTs studying commonly used vaginal preparations and selective estrogen receptor modulator treatments for GSM over longer follow-up periods will be vital to better assess the risk of breast cancer recurrence in survivors receiving these treatments.

Women's knowledge and attitudes to the menopause: a comparison of women over 40 who were in the perimenopause, post menopause and those not in the peri or post menopause.

OBJECTIVES: To evaluate women's knowledge and attitudes towards the menopause by comparing three groups of women: perimenopause, post menopause and those women not in either the peri or post menopause (other). METHODS: A 35 question online survey was advertised on social media to evaluate women's attitudes and knowledge of the menopause. Three groups of women were compared: perimenopause, post menopause and those women not in either the peri or post menopause (other). RESULTS: Most women were completely uninformed or only had some knowledge of the menopause before the age of 40. Most women thought that the menopause should be taught at school, but over 80% had received no menopause education at school themselves. The most popular sources of menopause information were independent websites and friends. Perimenopausal women were significantly more likely than postmenopausal women to use online resources for menopause information. The perimenopausal and postmenopausal groups had more positive attitudes towards the menopause than the other group. 57.5% of postmenopausal women found the menopause difficult or very difficult. Most women were happy about no longer menstruating, although some expressed sadness regarding fertility loss. CONCLUSIONS: Most women had limited knowledge and negative attitudes towards the menopause, leaving them unprepared to cope with the physical and psychological changes associated with this stage of life. Improved menopause education is required to improve quality of life during the menopausal transition and a most positive narrative of life postmenopause.

In praise of ovulation induction for the management of anovulatory subfertility.

Rapid advances in assisted reproductive technology have revolutionized fertility treatments for couples worldwide seeking a pregnancy. Although this is promising, concerns are emerging over the overuse of unnecessary assisted conception treatments, particularly among couples with anovulatory subfertility. Some experts are calling for the cessation of ovulation induction as the primary treatment of anovulatory subfertility in favour of more sophisticated assisted conception treatments. In the absence of other causes of subfertility, ovulation induction in patients with type 1 and type 2 anovulation disorders can achieve an up to 80% ovulation rate with a 40% cumulative pregnancy rate and few adverse effects. Considering the various risks and high costs associated with assisted reproductive technology treatments, it is hard to argue for their cost-effectiveness when simpler, safer and cheaper pharmacological ovulation induction could achieve comparable pregnancy rates. We argue here for the safe, effective and ethical use of ovulation induction in this population, supplemented by a judicious use of assisted conception treatments. We emphasize the essential role of ovulation induction as a first-line intervention for couples with anovulatory subfertility delivered within a patient-centred multidisciplinary care model and with a clear escalation pathway to use assisted reproductive technology treatments based on the person's response, characteristics and treatment preference.

Hormone replacement therapy in women with history of thrombosis or a thrombophilia.

Findings from the Women's Health Initiative (WHI) randomised placebo-controlled trial (RCT) were published at the beginning of this century. They suggested that hormone replacement therapy (HRT) use increased the risk of cardiovascular disease and venous thromboembolism including pulmonary embolism and deep vein thrombosis The findings led to a decline in HRT prescriptions and negative publicity about the use of HRT for women with significant menopausal symptoms. Subsequent studies have shown that the risk of thrombosis with HRT relates to whether estrogen is combined with a progestogen and the route of administration of estrogen. In healthy women with no background medical problems, transdermal hormone replacement is not associated with an increased risk of thrombosis. However, much less is known about the safety of various HRT preparations in women with a high background risk of thrombosis. These cases can often be challenging for clinicians with uncertainties around testing for thrombophilia, use of anticoagulation and striking a balance between the risks and benefits of prescribing HRT. This article will review the mechanism of thrombosis with differing types of HRT and present the evidence from the relevant trials. The article will also present the evidence that specifically relates to women with a personal history of thrombosis or thrombophilia (heritable and acquired) to enable clinicians to better individualise the risk assessment for each woman requesting HRT and understand the role of thrombophilia screening or concomitant anticoagulation in such situations.

Menopause knowledge and education in women under 40: Results from an online survey.

BACKGROUND: All women experience the menopause, yet education around the topic is limited. Studies conducted in women aged over 40 show that women have limited knowledge about the menopause. OBJECTIVES: This study aims to understand what women under 40 know about the menopause, how they have acquired this knowledge and where they think menopause education should be taught. This data will help to determine how to effectively deliver menopause education. DESIGN: A survey was designed that asked women under 40 what they know of, and their attitudes to, the menopause, using Qualtrics XM software. METHODS: The survey was advertised for 5 weeks on social media. Six questions related to menopause education were analysed. Responses between age groups under 20, 21-30 and over 30 were compared using a chi-square test. A thematic-style analysis was also conducted on a free-text question where answers referred to education. RESULTS: A total of 738 women's responses were included in the analysis; over 80% had no knowledge or just some knowledge of the menopause. Women over 30 used official websites (p = 0.017) and scientific literature (p = 0.047) significantly more than other age groups to learn about the menopause, while women under 20 were more likely to learn from family members (p = 0.002). These women felt education should start in schools. CONCLUSION: Many women under 40 have limited education of the menopause. Women under 20 are more passive in their approach to learning about the menopause compared with those over 30, who are more proactive. Menopause education strategies must start at school and extend beyond schools adopting a multifaceted approach; it is recommended that the workplace, social media and public health campaigns are used to deliver menopause education moving forward.

An online survey of perimenopausal women to determine their attitudes and knowledge of the menopause.

INTRODUCTION: Women are not usually taught about the menopause formally, and many general practitioners have relatively little training. The aim of this study was to explore perimenopausal women's attitudes and knowledge of the menopause. METHOD: An online survey was designed to evaluate attitudes and knowledge of the menopause in women older than 40 years. The survey was generated with Qualtrics XM® and promoted via social media. In all, 3150 women started the survey. In this study, data from 947 perimenopausal women were analysed. RESULTS: Regarding women's attitudes to the menopause, 38.8% were accepting of it but more than 30% were dreading it. The women had experienced a number of menopause symptoms including mood swings (68.9%), brain fog (68.3%), and fatigue (66.8%). More than 90% of women had never been taught about the menopause at school, and more than 60% did not feel informed at all about the menopause. School was thought to be the best place for menopause education to start (83.6%). In all, 68.2% of women had only looked for information about the menopause as their symptoms started and they had talked to friends and used a variety of websites to look for information. When asked for their free-text views on the menopause, thematic analysis produced four themes: the overarching knowledge gap, the onset and impact of symptoms, perimenopause: the hidden phenomenon, and managing symptoms: differing schools of thought. CONCLUSION: Lack of education for women and their general practitioners is causing perimenopausal women to go through this important stage in their lives with a lack of knowledge and appropriate medical care. It is essential that women are taught about the menopause, from school onwards and that we offer health professionals appropriate training starting from the medical school curriculum.

An online survey and interview of GPs in the UK for assessing their satisfaction regarding the medical training curriculum and NICE guidelines for the management of menopause.

BACKGROUND: The UK is home to 13 million menopausal women. The aim of this study was to determine the views of GPs on their levels of confidence and comfort when advising or treating menopausal women and assess the need for further training. METHOD: An anonymous online questionnaire was sent out to GPs working within the NHS across the UK between January 2021 and March 2021. The questionnaire was circulated via GP e-mail lists, Facebook, and LinkedIn, and included an option for respondents to volunteer for a semi-structured interview. RESULTS: The questionnaire had 173 responses. 52% of GPs indicated that they were not offered enough support to be able to advise and treat women with menopausal symptoms appropriately. 77.5% of GPs expressed that there is a need to improve training provided on menopause in medical school and GP training. 60.7% of GPs felt comfortable managing menopausal women and offering them management options. 22.5% of the respondents felt that the NICE guidelines are easy and clear guidance for clinical practice. Five GPs were further interviewed, and the analysis of the responses showed the perceived need by the GPs for improvements in medical training regarding menopause. CONCLUSION: There is a need for better support and medical training for GPs to help them advice and treat women with menopausal symptoms. This is key for ensuring that every woman in the UK feels supported in their journey during the menopausal transition and is offered evidence-based advice to help them make informed decisions.

Menopause transition: Physiology and symptoms.

With life expectancy for women on the rise, most women will experience menopausal transition and spend a significant number of years of their life in the menopausal phase. Menopausal transition involves a myriad of physical, endocrine, and psychological changes which are influenced by ethnic, psychological, and socio-cultural factors. Every woman's experience of the menopausal transition is unique, and a one-size-fits-all approach to the management of symptoms does not work. An understanding of the pathophysiology and severity of menopausal symptoms and the benefits and risks associated with both hormonal and non-hormonal treatments is important when individualising treatment options for menopausal symptoms.

Variability of response to early puberty induction demonstrated by transverse uterine diameter measurement and a novel method of 3D breast imaging.

OBJECTIVE: Induction of puberty with exogenous oestrogen results in considerable variability in final uterine and breast volumes. We set out to quantify the variability of these two outcome measures with a view to establishing monitoring methods that could be used to individualise treatment protocols. DESIGN: A prospective observational study. PARTICIPANTS: Sixteen participants with pubertal delay and primary amenorrhoea, due to hypogonadism were recruited from paediatric gynaecology and endocrinology clinics at University College London Hospital. A standardised protocol of transdermal 17ß oestradiol (17ßE) was used (Evorel™), with a starting dose of 12.5 mcg increasing to 25 mcg (patch changed twice weekly) after 4 months. Follow up was every 2 months for a total of 8 months. MEASUREMENTS: Uterine dimensions using ultrasound, oestradiol concentrations and breast development assessed by both Tanner staging and 3D photographic imaging. RESULTS: After 8 months of treatment, the changes in oestradiol concentrations (0-174 pmol), uterine volume growth (4.4-16.4 ml) and breast volume (1.76-140.1 ml) varied greatly between individuals. Of uterine parameters, transverse uterine diameter was most closely associated with serum oestradiol levels at 8 months (beta standardised coefficient = 0.80, p = .001). Change in breast volume was associated with age of treatment initiation (beta standardised coefficient 0.55 p = .04). CONCLUSIONS: We demonstrate variation in response to exogenous oestrogen, emphasising the necessity for individualised dose titration. In the absence of sensitive oestradiol assays, uterine transverse measurements may be used as a surrogate marker of oestrogen sensitivity to guide early dose adjustment. 3D breast imaging may provide a quantitative assessment of breast development to complement Tanner breast staging.

Could Perimenopausal Estrogen Prevent Breast Cancer? Exploring the Differential Effects of Estrogen-Only Versus Combined Hormone Replacement Therapy.

Breast cancer is the commonest cancer among women in the western world, accounting for up to 30% of all cancers in women. There is a long-standing controversy about the potential link to hormone replacement therapy (HRT), with large observational studies suggesting that HRT increases the risk, while the Women's Health Initiative (WHI), a prospective, randomized placebo-controlled trial, has reported several times over a period of 20 years that combined (estrogen and progestogen) HRT increases the risk, while estrogen-only HRT given to women who have had a prior hysterectomy, is associated with a significantly reduced risk of developing breast cancer. Evidence from the randomized trial shows a significant reduction in both incidence of and mortality from breast cancer in women who took estrogen replacement therapy; this message needs to be presented clearly and robustly so that it can help women with decision making when considering HRT for menopause.

Clinical Practice Guidelines on the Diagnosis and Management of Polycystic Ovary Syndrome: A Systematic Review and Quality Assessment Study.

CONTEXT: Clinical practice guidelines (CPGs) are key instruments to implement the practice of evidence-based medicine. We aimed to evaluate the methodological quality and variations in CPGs recommendations on the diagnosis and management of polycystic ovary syndrome (PCOS). EVIDENCE ACQUISITION: We searched MEDLINE, EMBASE, and CENTRAL until December 2020 for all evidence-based CPGs and consensus statements on PCOS. We extracted data in duplicate to map clinical recommendations across prespecified disease domains and assessed CPGs methodological quality of using the Appraisal of Guidelines, Research & Evaluation II tool. EVIDENCE SYNTHESIS: We included 13 PCOS CPGs published between 2007 and 2018. CPGs recommendations were mostly focused on screening for and managing metabolic disease (12/13, 92%), followed by cardiovascular risk assessment (10/13, 77%). Mental health (8/13, 62%) and diagnosis in adolescents (7/13, 54%) were the least reported domains. Most CPGs had a high quality for scope and purpose description (12/13, 92%) while stakeholder's involvement and applicability of recommendations to clinical practice were appropriate in only 2 CPGs (2/13, 15%). We identified inconsistency in recommendations on PCOS diagnosis in adolescents, optimal lifestyle interventions, hirsutism and acne treatments, interventions to reduce the risk of ovarian hyperstimulation syndrome, the frequency and screening criteria for metabolic and cardiovascular disease, and optimal screening tools for mental health illness in women with PCOS. CONCLUSION: Current CPGs on the diagnosis and management of PCOS vary in their scope and methodological quality, which may hinder evidence translation into clinical practice. We identified disease domains with existing evidence gap to guide future research and guideline updates.

Medical Therapy for Fibroids: What Next for Ulipristal Acetate?

Ulipristal acetate (UPA) was introduced as a novel progesterone receptor modulator as effective therapy for symptomatic fibroids. Randomised clinical trials established its effectiveness in the management of heavy menstrual bleeding due to uterine leiomyomas. The trials did not find any significant evidence of clinical harm to the participants. Recently, however, there have been reports of liver injury necessitating liver transplant in women who have had UPA treatment. This has led to the suspension of UPA as one of the medical therapies in the treatment for uterine fibroids while the European Medicines Agency (EMA) conducts a review of liver injury risk with its use. The European Medicine Agency safety committee has advised that women should stop taking 5 mg UPA and that no new patients should commence treatment with the medicine until the ongoing review is completed. In this article, we review the rise of UPA as one of the emerging medical therapies for symptomatic uterine fibroids and the subsequent reports of adverse events leading to the suspension of its use.

Could Estrogen Protect Women From COVID-19?

The apparent gender differences in favor of women in the risk of contracting and dying from coronavirus disease 2019 (COVID-19), and the fact that such trends have also been observed in recent epidemics including severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), have prompted the obvious question: Are the reasons life-style or biological? True, women generally make healthier lifestyle choices as compared to men. Women do not smoke or drink as much as men, and they have a lower burden of those diseases (heart disease, diabetes or chronic lung conditions) that are known to be significant factors in the higher death rates among men with COVID-19. But there is compelling evidence for a role for biological factors. Genes are likely to play an important role. The X chromosome, of which women possess two, contains the largest number of immune-related genes of the whole human genome, theoretically giving women double the advantage over men in mounting an efficient and rapid immune response. A fundamental difference between women and men is their hormonal milieu, and it is not unreasonable to suppose that the dominant female hormone estrogen could influence the response to infection. In this paper we evaluate the evidence and mechanisms by which estrogen could provide protection to women from a variety of viruses, perhaps including the coronavirus that causes COVID-19.

Relationship and sexual experiences in women with early-onset oestrogen deficiency: Comparison between women with Turner syndrome and premature ovarian insufficiency.

OBJECTIVE: Age at first date and sexual intercourse have been observed to be delayed in women with Turner syndrome (TS), with delayed puberty being the main factor. We sought to assess relationship and sexual experiences comparing women with TS and premature ovarian insufficiency (POI). DESIGN: Cross-sectional observational study. PATIENTS: 302 women with TS and 53 women with karyotypically normal POI (median age 33.0 [15.0-78.4] and 26.3 [17.8-52.3], respectively). MEASUREMENTS: A self-reporting questionnaire was used to collect data on relationship and sexual experiences. RESULTS: Women with TS were older than women with POI (P = .002). Compared to women with POI, a smaller proportion of women with TS had ever had vaginal sexual intercourse (VSI) (40 [78.4%] vs 169 [58.1%], respectively, P = .006) and women with TS exhibited a delay in the median age at first relationship and VSI (POI 19.3 ± 0.4 vs TS 22.2 ± 1.1, P = <.001). Start of oestrogen replacement therapy at ≤ 14 years of age compared with > 14 years did not result in earlier relationship and sexual debut. After adjusting for age and diagnosis, induction of puberty, as opposed to spontaneous puberty, was associated with a delay in the median age at first relationship and VSI and a reduced probability of having VSI (Hazard ratio = 0.44 [95% confidence interval: 0.32-0.60], P = <.001). CONCLUSIONS: Turner syndrome and induction of puberty are associated with a reduced likelihood and a delay in relationship and sexual experiences. Women needing puberty induction and women with TS more than POI have a delayed mean age at first VSI compared to the general population.

It is all in the name: The importance of correct terminology in hormone replacement therapy.

The global increase in life expectancy to 74 years for women, while the median age of the menopause remains at 51 years, means that an increasing number of women will live a significant portion of their adult lives in the menopause. The WHI publications in 2003/4 reported on the dangers of hormone replacement therapy, in particular with respect to breast cancer and dementia risk. This resulted in a dramatic reduction in hormone replacement therapy prescription and use. However, the findings from the WHI studies have been re-appraised, and the new perspective is reflected in the guidance published by NICE in 2015 in which they recommended that more women be offered hormone replacement therapy as the benefits are now perceived to outweigh the risks for most women. However, controversy continues to surround hormone replacement therapy, and there are probably few areas in medicine where the misuse of terminology causes quite as much confusion as in hormone replacement therapy. Commonly used terms such as 'menopausal hormone therapy' and 'hormone replacement therapy' lack specificity and there is an urgent need for correct terminology to accurately describe the hormones replaced.