Menopause and MHT in 2024: addressing the key controversies - an International Menopause Society White Paper.

The vision of the International Menopause Society (IMS) is that all women across the world will have easy and equitable access to evidence-based knowledge and health care, empowering them to make fully informed midlife health choices. The aim of this White Paper is to provide a well-balanced educational narrative of the menopause and menopause hormone therapy (MHT) from IMS experts, leading into World Menopause Day 2024. This is achieved by exploring the anthropology and history of menopause, the principles and controversies of prescribing MHT, and by placing this into regulatory and menopause society contexts. The White Paper also lays the groundwork for the forthcoming updated IMS recommendations on menopause and will act as a blueprint for the future ethical management of menopause from practical and aspirational perspectives. An important section of the paper is 'The 5Ws of prescribing MHT': WHO is MHT for; WHAT types and doses of MHT; WHEN should MHT be started and stopped; WHY is MHT important; WHERE can MHT be accessed? A key points summary of this information is provided for healthcare professionals and the public. The summary provides 'easy to access' advice regarding several recent controversial MHT prescribing issues in the healthcare and media spotlights.

Elinzanetant for the Treatment of Vasomotor Symptoms Associated With Menopause: OASIS 1 and 2 Randomized Clinical Trials.

Importance: Safe and effective nonhormonal treatments for menopausal vasomotor symptoms (VMS) are needed. Objective: To evaluate the efficacy and safety of elinzanetant, a selective neurokinin-1,3 receptor antagonist, for the treatment of moderate to severe menopausal vasomotor symptoms. Design, Setting, and Participants: Two randomized double-blind phase 3 trials (OASIS 1 and 2) included postmenopausal participants aged 40 to 65 years experiencing moderate to severe vasomotor symptoms (OASIS 1: 77 sites in the US, Europe, and Israel from August 27, 2021, to November 27, 2023, and OASIS 2: 77 sites in the US, Canada, and Europe from October 29, 2021, to October 10, 2023). Intervention: Once daily oral elinzanetant, 120 mg, for 26 weeks or matching placebo for 12 weeks followed by elinzanetant, 120 mg, for 14 weeks. Main Outcomes and Measures: Primary end points included mean change in frequency and severity of moderate to severe vasomotor symptoms from baseline to weeks 4 and 12, measured by the electronic hot flash daily diary. Secondary end points included Patient-Reported Outcomes Measurement Information System Sleep Disturbance Short Form 8b total T score and Menopause-Specific Quality of Life questionnaire total score from baseline to week 12. Results: Eligible participants (mean [SD] age, OASIS 1: 54.6 [4.9] years; OASIS 2: 54.6 [4.8] years) were randomized to elinzanetant (OASIS 1: n = 199; OASIS 2: n = 200) or placebo (OASIS 1: n = 197; OASIS 2: n = 200). A total of 309 (78.0%) and 324 (81.0%) completed OASIS 1 and 2, respectively. For the elinzanetant and placebo groups, the baseline mean (SD) VMS per 24 hours were 13.4 (6.6) vs 14.3 (13.9) (OASIS 1) and 14.7 (11.1) v 16.2 (11.2) (OASIS 2). Baseline VMS severity was 2.6 (0.2) vs 2.5 (0.2) (OASIS 1) and 2.5 (0.2) vs 2.5 (0.2) (OASIS 2). Elinzanetant significantly reduced VMS frequency at week 4 (OASIS 1: -3.3 [95% CI, -4.5 to -2.1], P < .001; OASIS 2: -3.0 [95% CI, -4.4 to -1.7], P < .001) and at week 12 (OASIS 1: -3.2 [95% CI, -4.8 to -1.6], P < .001; OASIS 2: -3.2 [95% CI, -4.6 to -1.9], P < .001). Elinzanetant also improved VMS severity at week 4 (OASIS 1: -0.3 [95% CI, -0.4 to -0.2], P < .001; OASIS 2: -0.2 [95 CI, -0.3 to -0.1], P < .001) and week 12 (OASIS 1: -0.4 [95% CI, -0.5 to -0.3], P < .001; OASIS 2: -0.3 [95% CI, -0.4 to -0.1], P < .001). Elinzanetant improved sleep disturbances and menopause-related quality of life at week 12, and the safety profile was favorable. Conclusions and Relevance: Elinzanetant was well tolerated and efficacious for moderate to severe menopausal VMS. Trial Registration: ClinicalTrials.gov Identifier: OASIS 1: NCT05042362, OASIS 2: NCT05099159.

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).

The European Vulvovaginal Epidemiological Survey (EVES). Impact of history of breast cancer on prevalence, symptoms, sexual function and quality of life related to vulvovaginal atrophy.

OBJECTIVE: Women with history of breast cancer (HBC) frequently suffer from vulvovaginal atrophy (VVA). European Vulvovaginal Epidemiology Survey (EVES) sub-analysis assesses the impact of HBC on VVA, sexual life and quality of life (QoL) in postmenopausal women. MATERIALS AND METHODS: Women with at least one VVA symptom aged 45-75 years were included. EuroQol (EQ-5D-3L) and Day-to-Day Impact of Vaginal Aging (DIVA) questionnaires were filled to investigate QoL. VVA diagnosis was confirmed with objective gynecological examination. Comparison of postmenopausal women with and without HBC, and evaluation of treatment impact on VVA were performed. RESULTS: 1985 postmenopausal women without HBC and 175 with HBC were included. VVA was confirmed in 90.4% of women without HBC and 91.4% of women with HBC. There were no differences in VVA symptoms severity or vulvovaginal discomfort between groups. However, women with HBC who had completed treatment and had surgery 11-20 years previously versus those without HBC presented significantly worse Vaginal Health Index scores, as well as a higher prevalence of VVA objective diagnosis, although their overall symptom severity score was lower. Health status and QoL comparisons were similar. CONCLUSIONS: Results support a similar burden in terms of VVA prevalence and symptoms, QoL and sexual function in postmenopausal women with and without HBC.

Purified and specific cytoplasmic pollen extract: a non-hormonal alternative for the treatment of menopausal symptoms.

Research into non-hormonal, alternative therapies is necessary for women for whom menopausal hormone therapy is contraindicated or for women who do not wish to take hormones. This review focuses on one such non-hormonal option, namely, purified and specific cytoplasmic pollen extract, or PureCyTonin®. This extract has been evaluated in several preclinical and clinical studies, where it demonstrated its value as a safe and non-estrogenic alternative for menopause. This review presents the beneficial effects of PureCyTonin® in the treatment of menopausal symptoms (e.g. hot flushes) in healthy women, as well as in premenstrual syndrome. We discuss the mechanism of action of PureCyTonin®, an SSRI-'like' therapy. The lack of estrogenic effect demonstrated in preclinical studies suggests that PureCyTonin® may also be a suitable option for the management of menopausal symptoms in women with breast cancer.

Sleep disturbance associated with the menopause.

IMPORTANCE AND OBJECTIVES: Sleep disturbance is one of the most common and debilitating symptoms experienced by women during the menopause transition. However, there are currently no therapies specifically approved for sleep disturbance associated with the menopause. Here, we consider how to characterize sleep disturbance associated with the menopause and discuss its etiology, including the latest advances in our understanding of the neuronal circuits that regulate reproduction, body temperature, sleep, and mood; and reflect on its impact on women's health and well-being. We also examine the current treatment landscape and look to the future of treatment for this condition. METHODS: We conducted a review of the literature and combined this with discussion with experts in the fields of sleep and menopause as well as experiences from our own clinical practices. DISCUSSION AND CONCLUSIONS: Sleep disturbance associated with the menopause is characterized by frequent night-time awakenings and increased awake time after sleep onset. Its impacts are wide-ranging, negatively affecting health as well as personal and social relationships, productivity, and work performance. There is currently an unmet need for effective, safe, and well-tolerated treatments to address this important symptom, and wider recognition of the association between sleep disturbances and the menopause is needed. Sleep disturbances associated with the menopause can result from hormone changes as well as vasomotor and mood symptoms. Growing research has contributed to our knowledge of the role of hypothalamic estrogen-sensitive kisspeptin/neurokinin B/dynorphin neurons. These neurons are thought to integrate the gonadotropin-releasing hormone pathway and the pathways responsible for the homeostatic control of body temperature and the circadian regulation of sleep-wake cycles. Understanding these neurons offers the potential to create treatments that target a key cause of sleep disturbance associated with the menopause. Further research to understand their etiology and characterize the neuronal circuits responsible could benefit the development of these targeted treatment approaches.

Exploring the potential for a set of UK hormone replacement therapy eligibility guidelines: A suggested proposal on the topic of venous thromboembolism.

OBJECTIVE: To explore the feasibility for a set of hormone replacement therapy (HRT) eligibility guidelines that follow a similar structure and appearance to the UKMEC guidance for contraception. To enable non-specialists to feel confident in safely prescribing HRT and to aid selection of the most appropriate first line treatment. METHODS: A literature review was undertaken with evidence summarised on the topic of venous thromboembolism (VTE) which is an area frequently considered a barrier to prescribing. Medical eligibility tables which separated HRT by type were then produced for a set of VTE-related topics. RESULTS: The literature search confirmed the importance of distinguishing between different types and routes of administration when considering the suitability of HRT. Much of the evidence has been based on older synthetic types of HRT and whilst they still have a role in management, these medications carry different risks to the now more accepted use of body identical types. The search also highlighted the nuances involved, increasing the complexity of forming guidelines, with the need for consideration to be given to an individual's own perception of risks and benefits. CONCLUSION: The demand for HRT has risen in recent years and there is a need for this to be managed effectively, particularly for patients in primary care. The production of this type of guidance will enable the non-specialist to feel confident in safe and evidence-based prescribing. The guidelines are also designed to demonstrate to prescribers which complex patients should be referred onto menopause specialists.

Design of OASIS 1 and 2: phase 3 clinical trials assessing the efficacy and safety of elinzanetant for the treatment of vasomotor symptoms associated with menopause.

OBJECTIVE: Elinzanetant is a selective neurokinin-1,3 receptor antagonist in development for the treatment of vasomotor symptoms (VMS) associated with menopause. The pivotal, double-blind, randomized, placebo-controlled phase 3 studies Overall Assessment of efficacy and Safety of elinzanetant In patients with vasomotor Symptoms (OASIS) 1 and 2 will assess the efficacy and safety of elinzanetant in women with VMS. METHODS: The OASIS 1 and 2 pivotal studies are designed in accordance with regulatory guidance. Postmenopausal women with moderate/severe VMS are randomized to receive 120 mg elinzanetant or placebo once daily for 12 weeks, followed by a 14-week active treatment extension. Primary endpoints are the mean change in frequency and severity of moderate/severe VMS from baseline to weeks 4 and 12. Key secondary endpoints will assess the onset of action and effects on sleep disturbance and menopause-related quality of life. Primary and key secondary endpoints will be analyzed using a mixed model with repeated measures. Feedback from postmenopausal women with VMS was used during protocol development. RESULTS: Women confirmed the relevance of endpoints that assess the impact of VMS, sleep disturbance, and mood changes, and the need for new nonhormone treatments. Educational materials around study design, conduct and expected assessments and procedures were developed based on questions and concerns raised by women. CONCLUSIONS: The OASIS 1 and 2 pivotal phase 3 studies will enable assessment of the efficacy and safety of elinzanetant as a treatment for VMS, together with its effect on sleep disturbances, depressive symptoms, and menopause-related quality of life. Feedback from postmenopausal women with VMS was used to maximize patient centricity in the trials.

Recommended measurement instruments for genitourinary symptoms associated with menopause: the COMMA (Core outcomes in menopause) consortium.

OBJECTIVE: The aim of the study is to identify appropriate definitions and patient-reported outcome measures (PROMs) for each of the eight core outcomes previously selected for genitourinary symptoms associated with menopause: pain with sex, vulvovaginal dryness, vulvovaginal discomfort or irritation, discomfort or pain when urinating, change in most bothersome symptom, distress, bother or interference of genitourinary symptoms, satisfaction with treatment, and side effects. METHODS: We conducted a systematic review to identify possible definitions and PROMs, including their measurement properties. Identified definitions and relevant PROMs with acceptable measurement properties were entered into an international consensus process involving 28 participants from 10 countries to achieve final recommendations for each core outcome. RESULTS: A total of 87 publications reporting on 34 PROMs were identified from 21,207 publications screened. Of these 34 PROMs, 29 were not considered to sufficiently map onto the core outcomes, and 26 of these also had insufficient measurement properties. Therefore, only five PROMs corresponding to two core outcomes were considered for recommendation. We recommend the PROMIS Scale v2.0 - Sexual Function and Satisfaction: Vaginal Discomfort with Sexual Activity to measure the outcome of "pain with sexual activity" and the Day-to-Day Impact of Vaginal Aging (DIVA) Questionnaire to measure "distress, bother or interference" from genitourinary symptoms. Six definitions of "side effects" were identified and considered. We recommend that all trials report adverse events in study participants, which is a requirement of Good Clinical Practice. CONCLUSIONS: Suitable PROMs and definitions were identified to measure three of eight core outcomes. Because of the lack of existing measures, which align with the core outcomes and have evidence of high-quality measurement properties, future work will focus on developing or validating PROMs for the remaining five core outcomes.

Recommended measurement instruments for menopausal vasomotor symptoms: the COMMA (Core Outcomes in Menopause) consortium.

OBJECTIVE: The aim of the study is to identify suitable definitions and patient-reported outcome measures (PROMs) to assess each of the six core outcomes previously identified through the COMMA (Core Outcomes in Menopause) global consensus process relating to vasomotor symptoms: frequency, severity, distress/bother/interference, impact on sleep, satisfaction with treatment, and side effects. METHODS: A systematic review was conducted to identify relevant definitions for the outcome of side-effects and PROMs with acceptable measurement properties for the remaining five core outcomes. The consensus process, involving 36 participants from 16 countries, was conducted to review definitions and PROMs and make final recommendations for the measurement of each core outcome. RESULTS: A total of 21,207 publications were screened from which 119 reporting on 40 PROMs were identified. Of these 40 PROMs, 36 either did not adequately map onto the core outcomes or lacked sufficient measurement properties. Therefore, only four PROMs corresponding to two of the six core outcomes were considered for recommendation. We recommend the Hot Flash Related Daily Interference Scale to measure the domain of distress, bother, or interference of vasomotor symptoms and to capture impact on sleep (one item in the Hot Flash Related Daily Interference Scale captures interference with sleep). Six definitions of "side effects" were identified and considered. We recommend that all trials report adverse events, which is a requirement of Good Clinical Practice. CONCLUSIONS: We identified suitable definitions and PROMs for only three of the six core outcomes. No suitable PROMs were found for the remaining three outcomes (frequency and severity of vasomotor symptoms and satisfaction with treatment). Future studies should develop and validate PROMs for these outcomes.

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.

Clinical subtypes of core premenstrual disorders: a Delphi survey.

The purpose of this study was to classify the clinical subtypes of core premenstrual disorders during the International Society for Premenstrual Disorders' second consensus meeting. Multiple iterations were used to achieve consensus between a group of experts; these iterations included a two-generational Delphi technique that was preceded and followed by open group discussions. The first round was to generate a list of all potential clinical subtypes, which were subsequently prioritized using a Delphi methodology and then finalised in a final round of open discussion. On a six-point scale, 4 of the 12 potential clinical subtypes had a mean score of ≥5.0 following the second iteration and only 3 of the 4 still had a mean score of ≥5.0 after the third iteration. The final list consisted of these three subtypes and an additional subtype, which was introduced and agreed upon, in the final iteration. There is consensus amongst experts that core premenstrual disorder is divided into three symptom-based subtypes: predominantly physical, predominantly psychological and mixed. A proportion of psychological and mixed subtypes may meet the DSM-IV diagnostic criteria for premenstrual dysphoric disorder.

Breaking down barriers for prescribing and using hormone therapy for the treatment of menopausal symptoms: an experts' perspective.

INTRODUCTION: Around 80% of women suffer menopause-related symptoms that affect their daily activities and quality of life. Menopausal hormone therapy (MHT) has proven to be beneficial in relieving these symptoms. Nevertheless, only 20/30% of symptomatic women seek treatment. This has resulted in neglect of a generation of healthcare professionals' (HCPs) education in menopausal medicine and a reduction in the prescription of MHT in menopausal women for over two decades. AREAS COVERED: The aim of this article was to identify the main barriers that HCPs face for prescribing MHT and menopausal women for using it. Six European experts in menopause agreed on the profiles of women that benefit from MHT and proposed strategies to break down these barriers. EXPERT OPINION: The most important barrier for HCPs was deficient knowledge of the true evidence-based information, with inadequate training regarding the efficacy and safety of personalized MHT and the real benefit/risk ratio in the treatment of symptomatic women. For patients, fear of developing breast cancer was identified as the single most important barrier. Breaking down barriers is possible, by providing appropriate training and education to HCPs and women. This should result in fully informed, evidence based, shared treatment decisions by women and their physicians.

Anti-Müllerian hormone for the diagnosis and prediction of menopause: a systematic review.

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 <40 years). The predictive value of AMH increased with age, as the interval of prediction (time to menopause) shortened. There was evidence that undetectable, or extremely low AMH, may aid early diagnosis of POI in young women with a family history of POI, and women presenting with primary or secondary amenorrhoea (11 studies [n = 4537]). 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.

Oral estradiol/micronized progesterone may be associated with lower risk of venous thromboembolism compared with conjugated equine estrogens/medroxyprogesterone acetate in real-world practice.

OBJECTIVES: The Women's Health Initiative study reported an increased risk of venous thromboembolism among menopausal women treated with conjugated equine estrogens/medroxyprogesterone acetate (CEE/MPA) versus placebo. Newer hormone therapies may have a lower venous thromboembolism risk. The study compared the risk of venous thromboembolism between women treated with the combined oral product 17ß-estradiol/micronized progesterone (E2/P4) and those treated with oral CEE/MPA regimens. STUDY DESIGN: In a retrospective longitudinal study using real-world claims data from April 2019 to June 2021, women aged 40 years or more treated with oral E2/P4 or oral CEE/MPA who did not have a venous thromboembolism diagnosis before first dispensing claim of CEE/MPA or E2/P4 identified on or after May 1st 2019 (index date) were observed for 6 months or more after the index date. Oral E2/P4 and oral CEE/MPA had been prescribed by the treating physician in real-world practice and were observed through pharmacy dispensing records. MAIN OUTCOME MEASURES: Venous thromboembolism risk was compared between women receiving oral E2/P4 versus oral CEE/MPA. RESULTS: The study included 36,061 women treated with oral E2/P4 or oral CEE/MPA. In the analyses weighted by the inverse probability of treatment for control of potential confounding factors, the incidence of venous thromboembolism was significantly lower for oral E2/P4 compared with oral CEE/MPA (37/10,000 women-years for oral E2/P4 vs 53/10,000 women-years for oral CEE/MPA; incidence rate ratio 0.70, 95 % confidence interval: 0.53-0.92). CONCLUSIONS: Real-world evidence suggests that the risk of venous thromboembolism is significantly lower among women treated with oral E2/P4 compared with oral CEE/MPA.

Efficacy and safety of elinzanetant, a selective neurokinin-1,3 receptor antagonist for vasomotor symptoms: a dose-finding clinical trial (SWITCH-1).

OBJECTIVE: Neurokinin (NK)-3 and NK-1 receptors have been implicated in the etiology of vasomotor symptoms (VMS) and sleep disturbances associated with menopause. This phase 2b, adaptive, dose-range finding study aimed to assess the efficacy and safety of multiple doses of elinzanetant (NT-814), a selective NK-1,3 receptor antagonist, in women experiencing VMS associated with menopause, and investigate the impact of elinzanetant on sleep and quality of life. METHODS: Postmenopausal women aged 40 to 65 years who experienced seven or more moderate-to-severe VMS per day were randomized to receive elinzanetant 40, 80, 120, or 160 mg or placebo once daily using an adaptive design algorithm. Coprimary endpoints were reduction in mean frequency and severity of moderate-to-severe VMS at weeks 4 and 12. Secondary endpoints included patient-reported assessments of sleep and quality of life. RESULTS: Elinzanetant 120 mg and 160 mg achieved reductions in VMS frequency versus placebo from week 1 throughout 12 weeks of treatment. Least square mean reductions were statistically significant versus placebo at both primary endpoint time points for elinzanetant 120 mg (week 4: -3.93 [SE, 1.02], P < 0.001; week 12: -2.95 [1.15], P = 0.01) and at week 4 for elinzanetant 160 mg (-2.63 [1.03]; P = 0.01). Both doses also led to clinically meaningful improvements in measures of sleep and quality of life. All doses of elinzanetant were well tolerated. CONCLUSIONS: Elinzanetant is an effective and well-tolerated nonhormone treatment option for postmenopausal women with VMS and associated sleep disturbance. Elinzanetant also improves quality of life in women with VMS.

Impact of micronised progesterone and medroxyprogesterone acetate in combination with transdermal oestradiol on cardiovascular markers in women diagnosed with premature ovarian insufficiency or an early menopause: a randomised pilot trial.

OBJECTIVE: To compare the difference between micronised progesterone (MP) and medroxyprogesterone acetate (MPA) in combination with transdermal oestradiol (t-E2) on cardiovascular disease (CVD) risk markers in women diagnosed with an early menopause and premature ovarian insufficiency (EMPOI). BACKGROUND: The European Society for Cardiology has identified carotid femoral pulse wave velocity (cfPWV) as the gold standard cardiogenic biomarker for risk stratification of arterial disease. Menopause has been shown to augment the age-dependent increase in arterial stiffness, with hormone replacement therapy (HRT) being the mainstay of management of women diagnosed with EMPOI. STUDY DESIGN: A pilot randomised prospective open-label trial. Women were randomised to either cyclical MP (Utrogestan® 200mg) or MPA (Provera® 10mg) in conjunction with t-E2 (Evorel® Patches 50mcg/day) for 12 months. Seventy-one subjects were screened, and baseline data are available for 57 subjects. MAIN OUTCOME MEASURE: Carotid-femoral pulse wave velocity (cfPWV). RESULTS: PWV did not significantly change from baseline in either treatment arm. MP + t-E2 demonstrated a positive effect on traditional CVD markers, with a significant improvement seen in cardiac output (CO) (0.71±1.01mL/min, 95% CI 0.20 to 1.21) and reduction in diastolic blood pressure (DBP) (-3.43±6.31mmHg, 95% Cl -6.57 to -0.29) and total peripheral resistance (TPR) (-0.15±0.19mmHg⋅min⋅mL-1, 95% CI -0.24 to -0.05) after 12 months. MPA + t-E2, in contrast, did not demonstrate significant changes from baseline in traditional haemodynamic parameters. CONCLUSION: The positive changes in traditional markers were not reflected in the cardiogenic biomarker, cfPWV, which has demonstrated a higher positive predictive value for cardiovascular events than traditional measurements.

Consensus-led recommendations supporting choice and personalisation of Hormone replacement therapy in menopause care.

OBJECTIVE: Inequity of access and choice to different hormone replacement therapy (HRT) products across the UK has been suggested (Hillman, 2020). While, the cause is not entirely understood, potential contributors include conflicting national guidance, economic deprivation and a local formulary approach. With a diverse and growing population of women reaching and living well beyond the menopause, the impact of this inequity is becoming more pronounced, and challenges the goal of providing personalised care. The study objective is to establish a consensus that supports a greater equity of access and choice of HRT and provision of individualised care. STUDY DESIGN: Modified Delphi study designed by UK HCPs with expertise in menopause care. This group identified 40 consensus statements over four key topics, related to access and choice of different HRT products. An online 4-point Likert scale questionnaire, sent to UK HCPs, was used to assess agreement, with a consensus threshold set at 75%. MAIN OUTCOME MEASURES: 150 HCP responses between June and September 2021. RESULTS: A total of 137 responses were received. Analysis identified 37/40 statements attaining very high agreement (≥ 90%) and 3/40 statements attaining high agreement (< 90% and ≥75%). Nine recommendations were developed with the intent to inform potential improvements to menopause care in the UK. CONCLUSIONS: The high levels of agreement displayed suggest a desire to change the way menopause care is delivered in the UK. Implementation of the suggested recommendations has the potential to improve equity of access to licensed treatment options, compliant with the NICE recommendation for personalisation of care.