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BACKGROUND The early onset of menopause is associated with increased risks of cardiovascular disease and osteoporosis. As a woman’s circulating anti-Müllerian hormone (AMH) concentration reflects the number of follicles remaining in the ovary and declines towards the menopause, serum AMH may be of value in the early diagnosis and prediction of age at menopause. OBJECTIVE AND RATIONALE This systematic review was undertaken to determine whether there is evidence to support the use of AMH alone, or in conjunction with other markers, to diagnose menopause, to predict menopause, or to predict and/or diagnose premature ovarian insufficiency (POI). SEARCH METHODS A systematic literature search for publications reporting on AMH in relation to menopause or POI was conducted in PubMed®, Embase®, and the Cochrane Central Register of Controlled Trials up to 31 May 2022. Data were extracted and synthesized using the Synthesis Without Meta-analysis for diagnosis of menopause, prediction of menopause, prediction of menopause with a single/repeat measurement of AMH, validation of prediction models, short-term prediction in perimenopausal women, and diagnosis and prediction of POI. Risk-of-bias was evaluated using the Tool to Assess Risk of Bias in Cohort Studies protocol and studies at high risk of bias were excluded. OUTCOMES A total of 3207 studies were identified, and 41, including 28 858 women, were deemed relevant and included. Of the three studies that assessed AMH for the diagnosis of menopause, one showed that undetectable AMH had equivalent diagnostic accuracy to elevated FSH (>22.3 mIU/ml). No study assessed whether AMH could be used to shorten the 12 months of amenorrhoea required for a formal diagnosis of menopause. Studies assessing AMH with the onset of menopause (27 publications [n = 23 835 women]) generally indicated that lower age-specific AMH concentrations are associated with an earlier age at menopause. However, AMH alone could not be used to predict age at menopause with precision (with estimates and CIs ranging from 2 to 12 years for women aged WIDER IMPLICATIONS The findings of this systematic review support the use of serum AMH to study the age of menopause in population studies. The increased sensitivity of current AMH assays provides improved accuracy for the prediction of imminent menopause, but diagnostic use for individual patients has not been rigorously examined. Prediction of age at menopause remains imprecise when it is not imminent, although the finding of very low AMH values in young women is both of clinical value in indicating an increased risk of developing POI and may facilitate timely diagnosis.

Menstrual cyclicity is a marker of health for reproductively mature women. Absent menses, or amenorrhea, is often the initial sign of pregnancy—an indication that the system is functioning appropriately and capable of generating the intended evolutionary outcome. Perturbations of menstrual regularity in the absence of pregnancy provide a marker for physiological or pathological disruption of this well-orchestrated process. New-onset amenorrhea with duration of 3 to 6 months should be promptly evaluated. Secondary amenorrhea can reflect structural or functional disturbances occurring from higher centers in the hypothalamus to the pituitary, the ovary, and finally, the uterus. Amenorrhea can also be a manifestation of systemic disorders resulting in compensatory inhibition of reproduction. Identifying the point of the breakdown is essential to restoring reproductive homeostasis to maintain future fertility and reestablish reproductive hormonal integrity. Among the most challenging disorders contributing to secondary amenorrhea is primary ovarian insufficiency (POI). This diagnosis stems from a number of possible etiologies, including autoimmune, genetic, metabolic, toxic, iatrogenic, and idiopathic, each with associated conditions and attendant medical concerns. The dual assaults of unanticipated compromised fertility concurrently with depletion of the normal reproductive hormonal milieu yield multiple management challenges. Fertility restoration is an area of active research, while optimal management of estrogen deficiency symptoms and the anticipated preventive benefits of hormone replacement for bone, cardiovascular, and neurocognitive health remain understudied. The state of the evidence for an optimal, individualized, clinical management approach to women with POI is discussed along with priorities for additional research in this population.

Case and Principles of Management The case of a symptomatic, postmenopausal woman is presented and a full discussion of the approach to her management is discussed. Pertinent guidelines and scientific evidence are emphasized as support for the recommendations.

Background: \ud Uterine fibroids, the most common type of tumor among women of reproductive age, are associated with heavy menstrual bleeding, abdominal discomfort, subfertility, and a reduced quality of life. For women who wish to preserve their uterus and who have not had a response to medical treatment, myomectomy and uterine-artery embolization are therapeutic options.\ud Methods: \ud We conducted a multicenter, randomized, open-label trial to evaluate myomectomy, as compared with uterine-artery embolization, in women who had symptomatic uterine fibroids and did not want to undergo hysterectomy. Procedural options included open abdominal, laparoscopic, or hysteroscopic myomectomy. The primary outcome was fibroid-related quality of life, as assessed by the score on the health-related quality-of-life domain of the Uterine Fibroid Symptom and Quality of Life (UFS-QOL) questionnaire (scores range from 0 to 100, with higher scores indicating a better quality of life) at 2 years; adjustment was made for the baseline score.\ud Results: \ud A total of 254 women, recruited at 29 hospitals in the United Kingdom, were randomly assigned: 127 to the myomectomy group (of whom 105 underwent myomectomy) and 127 to the uterine-artery embolization group (of whom 98 underwent embolization). Data on the primary outcome were available for 206 women (81%). In the intention-to-treat analysis, the mean (±SD) score on the health-related quality-of-life domain of the UFS-QOL questionnaire at 2 years was 84.6±21.5 in the myomectomy group and 80.0±22.0 in the uterine-artery embolization group (mean adjusted difference with complete case analysis, 8.0 points; 95% confidence interval [CI], 1.8 to 14.1; P=0.01; mean adjusted difference with missing responses imputed, 6.5 points; 95% CI, 1.1 to 11.9). Perioperative and postoperative complications from all initial procedures, irrespective of adherence to the assigned procedure, occurred in 29% of the women in the myomectomy group and in 24% of the women in the uterine-artery embolization group.\ud Conclusions: \ud Among women with symptomatic uterine fibroids, those who underwent myomectomy had a better fibroid-related quality of life at 2 years than those who underwent uterine-artery embolization. (Funded by the National Institute for Health Research Health Technology Assessment program; FEMME Current Controlled Trials number, ISRCTN70772394).

Background Progesterone is essential for a healthy pregnancy. Several small trials have suggested that progesterone therapy may rescue a pregnancy in women with early pregnancy bleeding, which is a symptom that is strongly associated with miscarriage. Objectives (1) To assess the effects of vaginal micronised progesterone in women with vaginal bleeding in the first 12 weeks of pregnancy. (2) To evaluate the cost-effectiveness of progesterone in women with early pregnancy bleeding. Design A multicentre, double-blind, placebo-controlled, randomised trial of progesterone in women with early pregnancy vaginal bleeding. Setting A total of 48 hospitals in the UK. Participants Women aged 16–39 years with early pregnancy bleeding. Interventions Women aged 16–39 years were randomly assigned to receive twice-daily vaginal suppositories containing either 400 mg of progesterone or a matched placebo from presentation to 16 weeks of gestation. Main outcome measures The primary outcome was live birth at ≥ 34 weeks. In addition, a within-trial cost-effectiveness analysis was conducted from an NHS and NHS/Personal Social Services perspective. Results A total of 4153 women from 48 hospitals in the UK received either progesterone (n = 2079) or placebo (n = 2074). The follow-up rate for the primary outcome was 97.2% (4038 out of 4153 participants). The live birth rate was 75% (1513 out of 2025 participants) in the progesterone group and 72% (1459 out of 2013 participants) in the placebo group (relative rate 1.03, 95% confidence interval 1.00 to 1.07; p = 0.08). A significant subgroup effect (interaction test p = 0.007) was identified for prespecified subgroups by the number of previous miscarriages: none (74% in the progesterone group vs. 75% in the placebo group; relative rate 0.99, 95% confidence interval 0.95 to 1.04; p = 0.72); one or two (76% in the progesterone group vs. 72% in the placebo group; relative rate 1.05, 95% confidence interval 1.00 to 1.12; p = 0.07); and three or more (72% in the progesterone group vs. 57% in the placebo group; relative rate 1.28, 95% confidence interval 1.08 to 1.51; p = 0.004). A significant post hoc subgroup effect (interaction test p = 0.01) was identified in the subgroup of participants with early pregnancy bleeding and any number of previous miscarriage(s) (75% in the progesterone group vs. 70% in the placebo group; relative rate 1.09, 95% confidence interval 1.03 to 1.15; p = 0.003). There were no significant differences in the rate of adverse events between the groups. The results of the health economics analysis show that progesterone was more costly than placebo (£7655 vs. £7572), with a mean cost difference of £83 (adjusted mean difference £76, 95% confidence interval –£559 to £711) between the two arms. Thus, the incremental cost-effectiveness ratio of progesterone compared with placebo was estimated as £3305 per additional live birth at ≥ 34 weeks of gestation. Conclusions Progesterone therapy in the first trimester of pregnancy did not result in a significantly higher rate of live births among women with threatened miscarriage overall, but an important subgroup effect was identified. A conclusion on the cost-effectiveness of the PRISM trial would depend on the amount that society is willing to pay to increase the chances of an additional live birth at ≥ 34 weeks. For future work, we plan to conduct an individual participant data meta-analysis using all existing data sets. Trial registration Current Controlled Trials ISRCTN14163439, EudraCT 2014-002348-42 and Integrated Research Application System (IRAS) 158326. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 33. See the NIHR Journals Library website for further project information.

Historically, a lack of methodologically strong and generalizable studies has limited policymakers fromrecommending the use of progesterone supplementation to improve outcomes in women at high risk of miscarriage. The PROMISE and PRISM trials were carried out to rectify this and generate robust evidence on the role of progesterone supplementation to prevent miscarriage. This review aims to evaluate the PROMISE and PRISM trials and their impact on collective academic understanding of the use of progesterone supplementation for miscarriage prevention, as well as to provide recommendations for clinical practice. The PROMISE trial was a randomized double-blind, placebo-controlled study that included 836 women from 45 hospitals in the United Kingdom and the Netherlands and found a 3% increase in live birth rate with progesterone supplementation; however, the P value associated with this finding was 0.45. A post hoc subgroup analysis was performed with cohorts stratified according to number of previous miscarriages that revealed a trend for greater benefit with increasing number of previous miscarriages. Small sample sizes in this subgroup analysis resulted in a P value of 0.41; however, these results were hypothesis-generating that a biological gradient existed with respect to improved benefit of progesterone treatment among women with an increasing number of prior miscarriages. The PRISMtrial was a randomized, double-blind, placebo-controlled study that involved 4153 women from48 hospitals in the United Kingdom and noted a 3% increase in live birth rate with vaginal micronized progesterone; however, the P value associated with this finding was 0.08. To followup on the gradient effect observed in the PROMISE trial, this study included a prespecified subgroup analysis analyzing the number of previous miscarriages with population split into 3 subgroups: women with zero prior miscarriages, women with 1 to 2 prior miscarriages, and women with 3 or more prior miscarriages. Among women with 1 or more priormiscarriages and bleeding in the current pregnancy, the live birth rate was 75%with progesterone versus 70% with placebo (risk ratio, 1.09; 95% confidence interval, 1.03 1.15; P = 0.003). Among women with 3 or more prior miscarriages and bleeding in the current pregnancy, live birth rate was 72% with progesterone versus 57% with placebo (risk ratio, 1.28; 95% confidence interval, 1.08 1.51; P = 0.004). Guidelines for interpretation of subgroup analyses translate into 11 criteria to assess credibility and therefore clinical applicability; 5 on design, 2 on analysis, and 4 on context. The PRISM trials subgroup analysis meets all 11 criteria in women with dual risk factors of previous miscarriage and current pregnancy bleeding, suggesting the subgroup effect of a gradient existing in the context of improving live birth rate with progesterone treatment is highly plausible. Given biologic plausibility, lack of short-term safety concerns, and observed positive treatment effect, providers should consider offering women with vaginal bleeding and a history of 1 or more previous miscarriages a course of treatment with vaginal micronized progesterone 400 mg twice daily.

Objective Genitourinary symptoms, such as vaginal dryness and pain with sex, are commonly experienced by postmenopausal women. Comparing treatments for these genitourinary symptoms are restricted by the use of different outcome measures in clinical trials and the omission of outcomes, which may be relevant to women. The aim of this project was to develop a Core Outcome Set (COS) to be reported in clinical trials of treatments for genitourinary symptoms associated with menopause. Methods We performed a systematic review of randomized controlled trials of treatments for genitourinary symptoms associated with menopause and extracted their outcomes. This list was refined and entered into a two-round modified Delphi survey, which was open to clinicians, researchers, and postmenopausal women from November 2019 to March 2020. Outcomes were scored on a nine-point scale from "not important" to "critically important." The final COS was determined following two international consensus meetings. Results A total of 26 unique outcomes were included in the Delphi process, which was completed by 227 participants of whom 58% were postmenopausal women, 34% clinicians, and 8% researchers. Predefined thresholds were applied to the Delphi scores to categorize outcomes by importance, which informed the e consensus meetings, attended by 43 participants from 21 countries. The final COS includes eight outcomes: (1) pain with sex, (2) vulvovaginal dryness, (3) vulvovaginal discomfort or irritation, (4) discomfort or pain when urinating, (5) change in most bothersome symptom, (6) distress, bother or interference of genitourinary symptoms, (7) satisfaction with treatment, (8) side effects of treatment. Conclusion These eight core outcomes reflect the joint priorities of postmenopausal women, clinicians, and researchers internationally. Standardized collection and reporting of these outcomes in clinical trials will facilitate the comparison of different treatments for genitourinary symptoms, advance clinical practice, and ultimately improve outcomes for symptomatic women.

Background There remains uncertainty about the impact of menopausal hormone therapy (MHT) on women’s health. A systematic, comprehensive assessment of the effects on multiple outcomes is lacking. We conducted an umbrella review to comprehensively summarize evidence on the benefits and harms of MHT across diverse health outcomes. Methods and findings We searched MEDLINE, EMBASE, and 10 other databases from inception to November 26, 2017, updated on December 17, 2020, to identify systematic reviews or meta-analyses of randomized controlled trials (RCTs) and observational studies investigating effects of MHT, including estrogen-alone therapy (ET) and estrogen plus progestin therapy (EPT), in perimenopausal or postmenopausal women in all countries and settings. All health outcomes in previous systematic reviews were included, including menopausal symptoms, surrogate endpoints, biomarkers, various morbidity outcomes, and mortality. Two investigators independently extracted data and assessed methodological quality of systematic reviews using the updated 16-item AMSTAR 2 instrument. Random-effects robust variance estimation was used to combine effect estimates, and 95% prediction intervals (PIs) were calculated whenever possible. We used the term MHT to encompass ET and EPT, and results are presented for MHT for each outcome, unless otherwise indicated. Sixty systematic reviews were included, involving 102 meta-analyses of RCTs and 38 of observational studies, with 102 unique outcomes. The overall quality of included systematic reviews was moderate to poor. In meta-analyses of RCTs, MHT was beneficial for vasomotor symptoms (frequency: 9 trials, 1,104 women, risk ratio [RR] 0.43, 95% CI 0.33 to 0.57, p < 0.001; severity: 7 trials, 503 women, RR 0.29, 95% CI 0.17 to 0.50, p = 0.002) and all fracture (30 trials, 43,188 women, RR 0.72, 95% CI 0.62 to 0.84, p = 0.002, 95% PI 0.58 to 0.87), as well as vaginal atrophy (intravaginal ET), sexual function, vertebral and nonvertebral fracture, diabetes mellitus, cardiovascular mortality (ET), and colorectal cancer (EPT), but harmful for stroke (17 trials, 37,272 women, RR 1.17, 95% CI 1.05 to 1.29, p = 0.027) and venous thromboembolism (23 trials, 42,292 women, RR 1.60, 95% CI 0.99 to 2.58, p = 0.052, 95% PI 1.03 to 2.99), as well as cardiovascular disease incidence and recurrence, cerebrovascular disease, nonfatal stroke, deep vein thrombosis, gallbladder disease requiring surgery, and lung cancer mortality (EPT). In meta-analyses of observational studies, MHT was associated with decreased risks of cataract, glioma, and esophageal, gastric, and colorectal cancer, but increased risks of pulmonary embolism, cholelithiasis, asthma, meningioma, and thyroid, breast, and ovarian cancer. ET and EPT had opposite effects for endometrial cancer, endometrial hyperplasia, and Alzheimer disease. The major limitations include the inability to address the varying effects of MHT by type, dose, formulation, duration of use, route of administration, and age of initiation and to take into account the quality of individual studies included in the systematic reviews. The study protocol is publicly available on PROSPERO (CRD42017083412). Conclusions MHT has a complex balance of benefits and harms on multiple health outcomes. Some effects differ qualitatively between ET and EPT. The quality of available evidence is only moderate to poor., In an umbrella review, Guo-Qiang Zhang and colleagues comprehensively summarize evidence on the benefits and harms of menopausal hormone therapy across diverse health outcomes., Author summary Why was this study done? By 2050, it is estimated that worldwide more than 1.6 billion women will have reached menopause or be postmenopausal, up from 1 billion in 2020. Up to 75% of menopausal women are affected by bothersome menopausal symptoms, such as hot flashes and night sweats. Menopausal hormone therapy (MHT) is the most effective treatment for alleviating menopausal symptoms, but its effects on numerous health outcomes remain uncertain. What did the researchers do and find? We included 60 published systematic reviews of MHT use in menopausal women, involving 102 meta-analyses of randomized controlled trials and 38 of observational studies, and synthesized the evidence on 102 health outcomes. Overall, MHT had a complex balance of benefits and harms; for example, beyond alleviation of menopausal symptoms, it was associated with decreased risks of bone fracture, diabetes mellitus, and esophageal, gastric, and colorectal cancer, but increased risks of stroke, venous thromboembolism, gallbladder disease, and breast and ovarian cancer. The available clinical data in support of MHT reducing the risk of coronary heart disease and all-cause mortality in women aged

Study question In men and women undergoing IVF are preconceptual circulating metabolites associated with ongoing pregnancy rates? Summary answer Preconceptual serum histidine levels, in both women and men were associated with ongoing pregnancy. Several amino acids and lipoproteins exhibited possible sex-specific associations. What is known already Preconceptual maternal health has been associated with pregnancy outcomes after IVF. The extent to which this is because of pre-existing metabolic factors related to infertility and the role of paternal metabolic health is unclear. Study design, size, duration Cohort of 398 women and 325 male partners prospectively recruited between 1 April 2017 and 31 March 2019. Participants/materials, setting, methods Women and their male partners intending to undergo assisted conception at a University Hospital, had detailed pre-treatment phenotyping including non-fasting serum lipids, lipoprotein subclasses, and low-molecular weight metabolites (including amino acids, glycolysis and inflammatory markers) (155 metabolites) quantified by NMR spectroscopy. Multivariable linear and logistic regression were used to examine the associations of pre-treatment serum metabolic profiles, with ongoing pregnancy at 20 weeks gestation with adjustment for confounders. Main results and the role of chance 392 women and 322 men proceeded to IVF treatment, with an overall ongoing pregnancy rate of 47.2% (95% CI 0.42, 0.52) per cycle started and a multiple pregnancy rate of 1.1% (95%CI 0.0, 0.04). In both females and males in confounder adjusted analyses histidine was associated with the chance of ongoing pregnancy, with similar magnitudes in each parent (OR 1.28 (95% CI 1.03, 1.60) per one standard deviation (SD) increase for males and OR 1.26 (95% CI 0.99, 1.60) per one SD increase for females). In females Alanine (OR = 1.31 (1.05, 1.64)), Isoleucine (OR = 1.28 (1.02, 1.61)) and Leucine (OR = 1.24 (0.99, 1.55)) had a positive association with ongoing pregnancy, while in males, pyruvate (OR = 1.30 (1.02,1.66)) exhibited a positive association with ongoing pregnancy. In both parents, associations of lipids, lipoproteins sub-particles and fatty acids with pregnancy were closer to the null. Limitations, reasons for caution Suggestive parental differences could be due to chance. Patients were relatively homogenous undertaking their first IVF cycle and the results may not be generalisable to other clinical populations. Wider implications of the findings: This study provides data on a range of metabolic pathways and their association with ongoing pregnancy following IVF. The identification of potentially relevant clinical effect sizes in both men and women warrants further exploration. Trial registration number Not applicable

Background There is substantial variation in how menopausal vasomotor symptoms are reported and measured among intervention studies. This has prevented meaningful comparisons between treatments and limited data synthesis. Objectives To review systematically the outcome reporting and measures used to assess menopausal vasomotor symptoms from randomised controlled trials of treatments. Search strategy We searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials from inception to May 2018. Selection criteria Randomised controlled trials with a primary outcome of menopausal vasomotor symptoms in women and a sample size of at least 20 women per study arm. Data collection and analysis Data about study characteristics, primary vasomotor-related outcomes and methods of measuring them. Main results The search identified 5591 studies, 214 of which were included. Forty-nine different primary reported outcomes were identified for vasomotor symptoms and 16 different tools had been used to measure these outcomes. The most commonly reported outcomes were frequency (97/214), severity (116/214), and intensity (28/114) of vasomotor symptoms or a composite of these outcomes (68/214). There was little consistency in how the frequency and severity/intensity of vasomotor symptoms were defined. Conclusions There is substantial variation in how menopausal vasomotor symptoms have been reported and measured in treatment trials. Future studies should include standardised outcome measures which reflect the priorities of patients, clinicians, and researchers. This is most effectively achieved through the development of a Core Outcome Set. This systematic review is the first step towards development of a Core Outcome Set for menopausal vasomotor symptoms. Tweetable summary Menopausal hot flushes and night sweats have been reported in 49 different ways in clinical research. A core outcome set is urgently required.

Objective: We sought to examine the association of menopausal hot flashing with vascular reactivity in two different vascular beds in the same cohort of postmenopausal women and explore the relationship between hot flashing and cardiovascular disease (CVD) risk profile. Methods: A cross-sectional study of 79 healthy postmenopausal women, 23 of whom have never had menopausal hot flashes and 56 of whom have reported hot flashes. Endothelial function at a microvascular level was measured with Laser Doppler Imaging with Iontophoresis which assesses the response to both acetylcholine (Ach, endothelium dependent) and sodium-nitroprusside (SNP, endothelium independent). Reactive Hyperemia Index (RHI) was measured with peripheral arterial tonometry as a marker of endothelial function mainly at a macrovascular level. Metabolic biomarkers including insulin sensitivity were assessed. Results: Women with hot flashes had enhanced microvascular response to Ach by ∼30% (P = 0.04) and to SNP by ∼31% (P = 0.02), but lower RHI by ∼13% (P = 0.05) compared with women without flashes. Hot flashing was associated with enhanced response to SNP and lower RHI after adjustment for confounders and conventional CVD risk factors. Women with hot flashes were more insulin resistant than nonflashers (HOMAIR: 1.9 (1.2-2.6) vs 1.4 (0.8-1.9), P = 0.03). Conclusions: Our data support the association of hot flashing with greater insulin resistance and lower macrovascular response. The paradoxical enhanced microvascular response in hot flashers could be the result of the net effect of thermoregulatory and nonnitric oxide-related pathways rather than of endothelial integrity.

The consequence of treatment for gynaecological cancers can cause sudden onset of intense menopausal symptoms, such as vasomotor symptoms, sexual dysfunction and emotional instability. Hormone replacement therapy (HRT) is often effective and can overcome these unpleasant and severe symptoms. However, data regarding its safety remains controversial. The big question therefore is whether HRT in gynaecological cancer survivors is possible. This is due to the fear of disease relapse. So, the purpose of this study was to review the evidence regarding cancer recurrence or death following use of HRT in survivors of gynaecological cancers. For endometroid endometrial cancer, most of the retrospective studies concluded that there was no increase in recurrence rate of endometrial cancers in HRT versus non-HRT users. HRT should be particularly avoided in epithelial ovarian tumours particularly serous cancers and serous borderline tumours due to expression of oestrogen receptors. Given the lack of evidence on the impact of HRT on recurrence and disease-free survival in survivors of cervical cancers, it would seem perfectly reasonable to prescribe HRT, particularly if they are premenopausal. Many clinical guidelines would consider the use of HRT to be contraindicated in breast cancer survivors based on limited RCT evidence. Current scientific data, comprising mainly of retrospective studies, suggest that recurrence rates and survival are comparable between HRT users and non-users. Women should know the paucity of safety data regarding the use of HRT. Wherever possible, non-hormonal alternatives to HRT should be considered in all women. If non-hormonal alternatives fail to achieve adequate control of symptoms, then it is possible to consider the HRT after careful counselling of the patient as well as involvement of the oncology team in the decision-making process. However, more robust randomised controlled trials are needed to get convincing data regarding the safety of HRT in gynaecological cancer survivors.

Background: Phenotype-based assortative mating is well established in humans, with the potential for further convergence through a shared environment. To assess the correlation within infertile couples of physical, social, and behavioural characteristics and 155 circulating metabolic measures. Methods: Cross sectional study at a tertiary medical center of 326 couples undertaking IVF. Serum lipids, lipoprotein subclasses, and low-molecular weight metabolites as quantified by NMR spectroscopy (155 metabolic measures). Multivariable and quantile regression correlations within couples of metabolite profiles.Results: Couples exhibited statistical correlations of varying strength for most physical, social, and behavioural characteristics including age, height, alcohol consumption, education, smoking status, physical activity, family history and ethnicity, with correlation coefficients ranging from 0.22 to 0.73. There was no evidence of within couple associations for BMI and weight, where the correlation coefficients were -0.03 (95%CI -0.14, 0.08) and 0.01 (95%CI -0.10, 0.12), respectively. Within spousal associations of the metabolite measurements were all positive but with weak to modest magnitudes, with the median correlation coefficient across all 155 measures being 0.12 (range 0.01 to 0.37 and interquartile range 0.10 to 0.18). With just four having associations stronger than 0.3: docosahexaenoic acid (0.37, 95%CI 0.22, 0.52), omega-3 fatty acids (0.32, 95%CI 0.20, 0.43) histidine (0.32, 95%CI 0.23, 0.41) and pyruvate (0.32, 95%CI 0.22, 0.43). Conclusions: Infertile couples exhibit spousal similarities for a range of demographic and serum metabolite measures, supporting initial assortative mating, with diet-derived metabolites suggesting possible subsequent convergence of their individual metabolic profile.

OBJECTIVE Genitourinary symptoms, such as vaginal dryness and pain with sex, are commonly experienced by postmenopausal women. Comparing treatments for these genitourinary symptoms are restricted by the use of different outcome measures in clinical trials and the omission of outcomes, which may be relevant to women. The aim of this project was to develop a Core Outcome Set (COS) to be reported in clinical trials of treatments for genitourinary symptoms associated with menopause. METHODS We performed a systematic review of randomized controlled trials of treatments for genitourinary symptoms associated with menopause and extracted their outcomes. This list was refined and entered into a two-round modified Delphi survey, which was open to clinicians, researchers, and postmenopausal women from November 2019 to March 2020. Outcomes were scored on a nine-point scale from "not important" to "critically important." The final COS was determined following two international consensus meetings. RESULTS A total of 26 unique outcomes were included in the Delphi process, which was completed by 227 participants of whom 58% were postmenopausal women, 34% clinicians, and 8% researchers. Predefined thresholds were applied to the Delphi scores to categorize outcomes by importance, which informed the e consensus meetings, attended by 43 participants from 21 countries. The final COS includes eight outcomes: (1) pain with sex, (2) vulvovaginal dryness, (3) vulvovaginal discomfort or irritation, (4) discomfort or pain when urinating, (5) change in most bothersome symptom, (6) distress, bother or interference of genitourinary symptoms, (7) satisfaction with treatment, (8) side effects of treatment. CONCLUSION These eight core outcomes reflect the joint priorities of postmenopausal women, clinicians, and researchers internationally. Standardized collection and reporting of these outcomes in clinical trials will facilitate the comparison of different treatments for genitourinary symptoms, advance clinical practice, and ultimately improve outcomes for symptomatic women.

Premature ovarian insufficiency (POI) refers to the loss of ovarian activity before the age of 40 years, which leads to hypoestrogenism and amenorrhea. The diagnosis of POI in a young woman has potentially life-changing physical and emotional consequences for both the patient and her family. Therefore, it is very important that the diagnosis is correct and that it is made in a timely manner. Unfortunately, the diagnosis and therefore the effective treatment of POI are often delayed, which underlines the need for education of the broad medical community on the issue. A panel of menopause experts reviewed and critically appraised the literature, and present: (1) the diagnostic approach to POI, (2) the investigation of the etiology of this condition, (3) the therapeutic strategy regarding both hormone replacement therapy and fertility, and (4) the long-term follow-up and management for ensuring quality of life, as well as urogenital, cardiovascular, bone and mental health. The ultimate goal of this article is to provide a complete toolkit for the primary care physician to have easy access to all the information needed for the optimal management of women with POI, in the context of evidence-based and personalized medicine. HIGHLIGHTS Premature ovarian insufficiency occurs in 1% of the female population of reproductive age, yet the diagnosis is often delayed, with severe physical and emotional consequences for the patient. Primary care physicians should be aware of the possibility of premature ovarian insufficiency in young women presenting with menstrual irregularity. Prompt initiation of hormone replacement therapy ensures quality of life and prevents osteoporosis and cardiovascular disease. Women seeking fertility should be referred to specialists to discuss assisted reproduction options.

This study investigated the efficacy of participation in culture-specific dancing to meet current physical activity recommendations and increase cardio-respiratory fitness in postmenopausal women. Sedentary postmenopausal women (n = 24), aged 63 &plusmn, 8 years and with BMI of 28 &plusmn, 3 kg/m2 completed a 4-week Scottish dancing study. The dancing sessions of approximately 75 min were performed twice a week and each session was based on five Scottish dances performed in 3 sets. Heart rate (HR) measurements were obtained during all dances to evaluate whether the intervention achieves the criteria of moderate to vigorous aerobic exercise intensity. Body composition, waist circumference, and HR during Chester Step test were measured before and after dancing intervention. HR achieved during individual dances ranged from 64 &plusmn, 5% to 80 &plusmn, 5% of HRmax and the mean HR of the five dances corresponded to 72 &plusmn, 7% of HRmax. Post-intervention mean HR was lower throughout Level 2 (Pre, 112 &plusmn, 13 bpm, Post, 106 &plusmn, p = 0.005) and Level 3 (Pre, 122 &plusmn, 14 bpm, Post, 115 &plusmn, p = 0.006) of the Chester test compared with baseline values. The intervention had no impact on body weight or body fat but reduced waist circumference (Pre, 94 &plusmn, 8 cm, Post, 91 &plusmn, 9 cm, p = 0.006). Thus, traditional Scottish dancing should be advocated to sedentary postmenopausal women, emphasising its potential in meeting current physical activity recommendations in relation of weekly duration and exercise intensity and improving cardiorespiratory fitness.

This chapter explores the role of progesterone and progestogens in the management of abnormal uterine bleeding (AUB). Progestogens are used to regulate intermenstrual bleeding and decrease heavy menstrual bleeding (HMB) in women of reproductive age or who are perimenopausal. In menopausal women, progesterones and progestogens prevent endometrial hyperplasia and aim to reduce the development of endometrial cancer. We hope to make clear current best practice including preparation, specific benefits and risks. Progesterone also acts in concert with other hormones to affect breast, cardiovascular system, lipid profile and bone. We hope to explain how its unintended side effects may be used beneficially or may cause intended side effects.

Objectives To assess the cost‐effectiveness of progesterone compared with placebo in preventing pregnancy loss in women with early pregnancy vaginal bleeding. Design Economic evaluation alongside a large multi‐centre randomised placebo‐controlled trial. Setting Forty‐eight UK NHS early pregnancy units. Population Four thousand one hundred and fifty‐three women aged 16–39 years with bleeding in early pregnancy and ultrasound evidence of an intrauterine sac. Methods An incremental cost‐effectiveness analysis was performed from National Health Service (NHS) and NHS and Personal Social Services perspectives. Subgroup analyses were carried out on women with one or more and three or more previous miscarriages. Main outcome measures Cost per additional live birth at ≥34 weeks of gestation. Results Progesterone intervention led to an effect difference of 0.022 (95% CI −0.004 to 0.050) in the trial. The mean cost per woman in the progesterone group was £76 (95% CI −£559 to £711) more than the mean cost in the placebo group. The incremental cost‐effectiveness ratio for progesterone compared with placebo was £3305 per additional live birth. For women with at least one previous miscarriage, progesterone was more effective than placebo with an effect difference of 0.055 (95% CI 0.014–0.096) and this was associated with a cost saving of £322 (95% CI −£1318 to £673). Conclusions The results suggest that progesterone is associated with a small positive impact and a small additional cost. Both subgroup analyses were more favourable, especially for women who had one or more previous miscarriages. Given available evidence, progesterone is likely to be a cost‐effective intervention, particularly for women with previous miscarriage(s). Tweetable abstract Progesterone treatment is likely to be cost‐effective in women with early pregnancy bleeding and a history of miscarriage., Tweetable abstract Progesterone treatment is likely to be cost‐effective in women with early pregnancy bleeding and a history of miscarriage.

In the United Kingdom, menopause occurs in women at around the age of 51 years, and is part of the normal ageing process. It occurs as a result of a decrease in the number of primordial follicles after the age of 40 years, but can occur prematurely in 1% of women secondary to a number of aetiologies. This chapter covers the definition, and staging, of menopause and, using recently published guidance from the National Institute for Health and Care Excellence, gives recommendations on making a diagnosis. Hot flushes and night sweats (vasomotor symptoms) are the most commonly reported symptoms, but menopause may also be associated with urogenital atrophy, and long-term consequences include osteoporosis, cardiovascular disease, and dementia. Hormone therapy is effective in reducing flushing, but it is not suitable for all women and the evidence for its benefit and long-term consequences is controversial. Non-hormonal therapies are available, but best evidence must be considered when suggesting these alternatives.

Abnormal uterine bleeding is one of the commonest presenting complaints encountered in a gynecologist's office or primary-care setting. The wider availability of diagnostic tools has allowed prompt diagnosis and treatment of an increasing number of menstrual disorders in an office setting. This White Paper reviews the advantages and disadvantages of transvaginal ultrasound, blind endometrial sampling and diagnostic hysteroscopy. Once a proper diagnosis has been established, appropriate therapy may be embarked upon. Fortunately, only a minority of such patients will have premalignant or malignant disease. When bleeding is sufficient to cause severe anemia or even hypovolemia, prompt intervention is called for. In most of the cases, however, the abnormal uterine bleeding will be disquieting to the patient and significantly affect her 'quality of life'. Sometimes, reassurance and expectant management will be sufficient in such patients. Overall, however, in cases of benign disease, some intervention will be required. The use of oral contraceptive pills especially those with a short hormone-free interval, the insertion of the levonorgestrel intrauterine system, the incorporation of newer medical therapies including antifibrinolytic drugs and selective progesterone receptor modulators and minimally invasive treatments have made outpatient therapy increasingly effective. For others, operative hysteroscopy and endometrial ablation are proven therapeutic tools to provide both long- and short-term relief of abnormal uterine bleeding, thus avoiding, or deferring, hysterectomy.

Objective: \ud Review evidence to guide management of menopausal signs and symptoms in women after breast cancer and make recommendations accordingly.\ud Evidence: \ud Randomized controlled clinical trials, observational studies, evidence-based guidelines, and expert opinion from professional societies.\ud Background: \ud Symptoms and clinical problems associated with estrogen depletion—sleep disorders, vulvovaginal atrophy (VVA), vasomotor symptoms (VMS), mood changes, depressive symptoms, cardiovascular disease, osteopenia, and osteoporosis—confront the estimated 9.3 million breast cancer survivors globally.\ud Recommendations: \ud Following breast cancer, women should not generally be treated with menopausal hormone therapy or tibolone but should optimize lifestyle. Women with moderate to severe symptoms may benefit from mind–brain behavior or nonhormone, pharmacologic therapy. The selective serotonin/noradrenaline reuptake inhibitors and gabapentenoid agents improve VMS and quality of life. For osteoporosis, nonhormonal agents are available. Treatment of VVA remains an area of unmet need. Low-dose vaginal estrogen is absorbed in small amounts with blood levels remaining within the normal postmenopausal range but could potentially stimulate occult breast cancer cells, and although poorly studied, is not generally advised, particularly for those on aromatase inhibitors. Intravaginal dehydroepiandrosterone and oral ospemiphene have been approved to treat dyspareunia, but safety after breast cancer has not been established. Vaginal laser therapy is being used for VVA but efficacy from sham-controlled studies is lacking. Therapies undergoing development include lasofoxifene, neurokinin B inhibitors, stellate ganglion blockade, vaginal testosterone, and estetrol.\ud Conclusions: \ud Nonhormone options and therapies are available for treatment of estrogen depletion symptoms and clinical problems after a diagnosis of breast cancer. Individualization of treatment is essential.

Background Vasomotor symptoms (VMSs) are the hallmarks of menopause, occurring in approximately 75% of postmenopausal women in the UK, and are severe in 25%. Objectives To identify which treatments are most clinically effective for the relief of VMSs for women in natural menopause without hysterectomy. Search strategy English publications in MEDLINE, Embase, and The Cochrane Library up to 13 January 2015 were searched. Selection criteria Randomised controlled trials (RCTs) of treatments for women with a uterus for the outcomes of frequency of VMSs (up to 26 weeks), vaginal bleeding, and discontinuation. Data collection and analysis Bayesian network meta-analysis (NMA) using mean ratios (MRs) and odd ratios (ORs). Main results Across the three networks, 47 RCTs of 16 treatment classes (n = 8326 women) were included. When compared with placebo, transdermal estradiol and progestogen (O+P) had the highest probability of being the most effective treatment for VMS relief (69.8%; MR 0.23; 95% credible interval, 95% CrI 0.09–0.57), whereas oral O+P was ranked lower than transdermal O+P, although oral and transdermal O+P were no different for this outcome (MR 2.23; 95% CrI 0.7–7.1). Isoflavones and black cohosh were more effective than placebo, although not significantly better than O+P. Not only were selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) found to be ineffective in relieving VMSs, but they also had significantly higher odds of discontinuation than placebo. Limited data were available for bleeding, therefore no conclusions could be made. Conclusion For women who have not undergone hysterectomy, transdermal O+P was the most effective treatment for VMS relief. Tweetable abstract Which treatment best relieves menopause flushes? Results from the #NICE guideline network meta-analysis.

The hot flush is the most characteristic and often the most distressing symptom of the menopause. It is a unique feature and yet the mechanism and health implications are still not fully understood. This review summarizes some of the current thoughts on factors contributing to flushing, the physiological, vascular and neuroendocrine changes associated with flushing and the possible cardiovascular and other health implications for women experiencing hot flushes. Therapy is not discussed.

The recent Collaborative Group on Hormonal Factors in Breast Cancer (CGHFBC) publication calculated the attributable risk of breast cancer from use of estrogen alone and estrogen plus a synthetic progestogen for less than 5 to 15 or more years of use. This CGHFB report calculated attributable risk based on their findings of relative risk from pooled data from 58 studies. Notably, neither the CGHFBC nor other previous studies have examined the effect of underlying risk of breast cancer on attributable risk. This omission prompted us to determine the magnitude of the effect of underlying risk on attributable risk in this perspective. Meaningful communication of the potential risk of menopausal hormonal therapy requires providing women with the estimated risk above their existing underlying risk (ie, attributable risk). Therefore, we have estimated attributable risks from the data published by the CGHFBC, taking into account varying degrees of underlying risk. Based on the Endocrine Society Guideline on Menopausal Hormone Therapy (MHT), we divided groups into 3 categories of risk: low (1.5%), intermediate (3.0%), and high (6.0%) underlying risk of breast cancer over 5 years. In women taking estrogen plus a synthetic progestogen for 5 to 9 years, the attributable risks of MHT increased from 12, to 42, to 85 additional women per 1000 in the low-, intermediate-, and high-risk groups, respectively. The attributable risks for estrogen alone were lower but also increased based on underlying risk. Notably, the attributable risks were amplified with duration of MHT use, which increased both relative risk and breast cancer incidence.

BACKGROUND\ud Bleeding in early pregnancy is strongly associated with pregnancy loss. Progesterone is essential for the maintenance of pregnancy. Several small trials have suggested that progesterone therapy may improve pregnancy outcomes in women who have bleeding in early pregnancy.\ud \ud METHODS\ud We conducted a multicenter, randomized, double-blind, placebo-controlled trial to evaluate progesterone, as compared with placebo, in women with vaginal bleeding in early pregnancy. Women were randomly assigned to receive vaginal suppositories containing either 400 mg of progesterone or matching placebo twice daily, from the time at which they presented with bleeding through 16 weeks of gestation. The primary outcome was the birth of a live-born baby after at least 34 weeks of gestation. The primary analysis was performed in all participants for whom data on the primary outcome were available. A sensitivity analysis of the primary outcome that included all the participants was performed with the use of multiple imputation to account for missing data.\ud \ud RESULTS\ud A total of 4153 women, recruited at 48 hospitals in the United Kingdom, were randomly assigned to receive progesterone (2079 women) or placebo (2074 women). The percentage of women with available data for the primary outcome was 97% (4038 of 4153 women). The incidence of live births after at least 34 weeks of gestation was 75% (1513 of 2025 women) in the progesterone group and 72% (1459 of 2013 women) in the placebo group (relative rate, 1.03; 95% confidence interval [CI], 1.00 to 1.07; P=0.08). The sensitivity analysis, in which missing primary outcome data were imputed, resulted in a similar finding (relative rate, 1.03; 95% CI, 1.00 to 1.07; P=0.08). The incidence of adverse events did not differ significantly between the groups.\ud \ud CONCLUSIONS\ud Among women with bleeding in early pregnancy, progesterone therapy administered during the first trimester did not result in a significantly higher incidence of live births than placebo. (Funded by the United Kingdom National Institute for Health Research Health Technology Assessment program; PRISM Current Controlled Trials number, ISRCTN14163439. opens in new tab.)

The females of most species die soon after ceasing to reproduce, their purpose in life being to ensure survival of their kin. Human females may live more than one-third of their lives after they cease to reproduce, a property shared by few species, one of which is Orca whales. Orcas have been extensively studied because families live together in stable units or pods and individual whales have distinctive markings, enabling them to be identified. The females survive long after the menopause, one possible reason for this being that the older females provide a survival advantage since they are seen to lead the pods more often than younger females or males, thus providing a survival advantage in times of food shortage. The female lifespan is increasing in most countries worldwide, principally due to decreased infection and maternal mortality. Women are now more active through middle and into older age. Whatever sort of life they wish to lead, women need to be as fit as possible to facilitate healthy aging. Chronic diseases that affect millions of women are cardiovascular disease, osteoporosis, cancer, and dementia. The incidence of all these is increased by obesity, the prevention of which is a major challenge in our society. Hormone therapy may have a place for some women but for many others taking control of their health by lifestyle intervention is a major contributor to disease prevention. It is our duty as doctors to encourage this at every opportunity to help all women live a fruitful and healthy old age.

Cardiovascular events are the main cause of death in women, particularly in those over the age of 70 years. However, one third of all non-fatal cardiovascular events before age 80 occur in women below age 60 (Writing Group [1]).

Cancer treatment may result in loss of ovarian function through surgical removal of the ovaries, chemotherapy or radiation. While menopausal symptoms, such as hot flushes, night sweats, sleep disturbance, memory concerns and mood issues can be extremely bothersome to some women going through menopause naturally, women who undergo an induced menopause usually experience more sudden and severe symptoms. Pain and vaginal dryness can occur whether a woman has a sexual partner or not. In women with breast cancer, the aetiology of impaired sexual functioning, and lowered sexual desire, is often multifactorial, and may be related to physical and/or psychological reasons. Pain and vaginal dryness in women without a history of breast cancer can usually be safely treated with vaginal estrogens, in the form of a cream, pessary or ring, and simple lubricants or vaginal moisturisers. Safe usage of vaginal estrogen replacement therapy in breast cancer patients has not been studied within randomised clinical trials of long duration; the guidelines below reflect a clinical consensus.

The objective of this document is to generate a practice guideline for the management and treatment of symptoms of the menopause.The Treatment of Symptoms of the Menopause Task Force included six experts, a methodologist, and a medical writer, all appointed by The Endocrine Society.The Task Force developed this evidenced-based guideline using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe the strength of recommendations and the quality of evidence. The Task Force commissioned three systematic reviews of published data and considered several other existing meta-analyses and trials.Multiple e-mail communications, conference calls, and one face-to-face meeting determined consensus. Committees of The Endocrine Society, representatives from endorsing societies, and members of The Endocrine Society reviewed and commented on the drafts of the guidelines. The Australasian Menopause Society, the British Menopause Society, European Menopause and Andropause Society, the European Society of Endocrinology, and the International Menopause Society (co-sponsors of the guideline) reviewed and commented on the draft.Menopausal hormone therapy (MHT) is the most effective treatment for vasomotor symptoms and other symptoms of the climacteric. Benefits may exceed risks for the majority of symptomatic postmenopausal women who are under age 60 or under 10 years since the onset of menopause. Health care professionals should individualize therapy based on clinical factors and patient preference. They should screen women before initiating MHT for cardiovascular and breast cancer risk and recommend the most appropriate therapy depending on risk/benefit considerations. Current evidence does not justify the use of MHT to prevent coronary heart disease, breast cancer, or dementia. Other options are available for those with vasomotor symptoms who prefer not to use MHT or who have contraindications because these patients should not use MHT. Low-dose vaginal estrogen and ospemifene provide effective therapy for the genitourinary syndrome of menopause, and vaginal moisturizers and lubricants are available for those not choosing hormonal therapy. All postmenopausal women should embrace appropriate lifestyle measures.

Premature ovarian failure is associated with decreased bone mass and fractures, and an increased risk of premature death from cardiovascular disease. There is also fertility compromise associated not only with the loss of ovarian function but, in those with pre-pubertal POF, inadequate uterine morphology. A wide variety of hormone replacement regimes are reported, but there is no clear evidence of best practice. Hormone replacement therapy (HRT) and the combined oral contraceptive pill (COCP) will suppress menopausal symptoms; however neither is designed to achieve physiological replacement of oestrogen and progesterone. There is evidence that physiological sex steroid replacement is superior to standard hormone replacement, in improving uterine volume as well as an improved blood pressure profile and bone mineral density. Sex steroid replacement therapy is long-term in these women, and therefore it is essential that the risk benefit ratio is optimal to maximise longer term health.

Background Although 70% of postmenopausal women suffer from hot flashes the pathophysiology is poorly understood. The serotonin and noradrenaline reuptake inhibitor (SNRI) venlafaxine provides relief of flushing although the mechanism is unknown and could involve a central effect and/or a peripheral effect. Using single photon emission computed tomography (SPECT) we studied the central serotonin transporter (SERT) in vivo using [ 123 I]-beta-carbomethoxy-3-β-(4-iodophenyl)tropane (beta-CIT) and, as previous studies have shown that reactivity of the skin blood vessels is enhanced in those who flush, we examined cutaneous microvascular perfusion. Methods Cutaneous microvascular perfusion was assessed in 31 postmenopausal women, with flushing, using laser Doppler imaging with iontophoresis (LDI + ION), before and after 8 weeks of treatment with venlafaxine. A sub-group of 14 of these women also had SPECT imaging at both time points to evaluate the availability of SERT in the brain. Flush frequency and score was recorded, and Beck Depression Inventory (BDI) II scores were assessed before and after treatment. Results Following treatment with venlafaxine, there was a significant reduction in the [ 123 I]-beta-CIT binding ratio, BDI scores, flushing and endothelial dependent perfusion response. [ 123 I]-Beta-CIT reduction was associated with BDI reduction ( r 2 = 0.54; F = 8.8; p = 0.004), but not flushing reduction or perfusion reduction. Conclusions Venlafaxine resulted in a decrease in BDI II scores with an associated reduction in [ 123 I]-beta-CIT binding in a group of non-depressed women. It also improved flush frequency and severity which may be as a result of decreases seen in enhanced cutaneous microvascular perfusion.

When I became President of the International Menopause Society (IMS) in October 2016, I thought 20 months would be a long time, but it has gone past incredibly quickly. It has been very busy, but I...

Vasomotor symptoms are the most common indication for the prescription of hormone replacement therapy since it is effective in over 80% of cases. In 1995, 37% of American women took hormone replacement therapy, principally for this purpose. However, following the publication of results from the Women's Health Initiative, as many as half of these women in the US and in the UK and New Zealand discontinued hormone therapy. Discontinuation of estrogen is often accompanied by a return of vasomotor symptoms; however, only a small number (18%) of women report restarting hormone therapy. Alternatives are available, but limited knowledge on etiology and mechanisms of hot flushing represents a major obstacle for the development of new, targeted, non-hormonal treatments, and no current alternatives are as effective as estrogen.

Uterine fibroids are common benign tumours that occur in women of reproductive age. They are frequently associated with symptoms that impact on quality of life and require treatment. Up until mid-1990s, this was usually surgical with either hysterectomy or myomectomy being performed. Although myomectomy conserves the uterus, it is associated with complications that might not enhance the chance of pregnancy and for those concerned about fertility, alternatives are being developed. The most widely used of these is uterine artery embolization (UAE), which is a very successful treatment in terms of treating symptoms such as heavy menstrual bleeding but the impact on fertility is, as yet, unclear. Other exciting developments are high intensity focussed ultrasound and MRI guided focussed ultrasound. These allow a more directed approach. However, these techniques require sophisticated equipment which is not yet generally available. New medical treatments are being evaluated – the most popular currently are the progesterone receptor modulators that induce amenorrhoea and a degree of fibroid shrinkage whilst having minimal effect on ovarian function. One has recently been licensed for short term use in the UK and Europe and it is hoped that longer term use will be possible in the future. This review summarizes the information available on these techniques and also provides suggestions for further reading.