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Key Points: Question: What are the efficacy and safety of elinzanetant, 120 mg, in postmenopausal individuals with moderate to severe vasomotor symptoms (VMS)? Findings: In 2 pivotal phase 3 clinical trials, elinzanetant demonstrated statistically significant reductions in VMS frequency and severity vs placebo. Elinzanetant also significantly improved sleep disturbances and menopause-related quality of life vs placebo; the safety profile was favorable. Meaning: Elinzanetant is an efficacious and well-tolerated selective neurokinin-1,3 receptor antagonist for the treatment of moderate to severe VMS associated with menopause. Elinzanetant also improves sleep disturbances and menopause-related quality of life. 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 vs placebo 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 vs placebo 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 These 2 clinical trials evaluate the efficacy and safety of elinzanetant for the treatment of moderate to severe vasomotor symptoms associated with menopause. [ABSTRACT FROM AUTHOR]

The number of mature and elderly women is increasing all over the world. According to the World Health Organization, in most countries of the world, the life expectancy of women after the age of 50 ranges from 27 to 32 years. Thus, approximately one third of a woman's life is lived after menopause. Aim. To analyze and summarize scientific data on cardiovascular and metabolic risks in perimenopausal and menopausal women based on the use of scientometric databases. Menopause should be considered as a risk factor for the development of cardiovascular diseases (CVDs), which triggers a whole cascade of pathological changes in a woman's body, including the development of arterial hypertension, dyslipidemia, abdominal obesity, insulin resistance, an increased sympathoadrenal tone, endothelial function disorders, and inflammatory vascular reactions. CVD is known to be the leading cause of death among postmenopausal women associated with the loss of estrogenic protective effect on the cardiovascular system. Women with premature menopause have a 33 % higher risk of heart failure and a 9 % higher risk of atrial fibrillation. Metabolic syndrome is more common in postmenopausal women than in premenopausal women. It is defined as a cluster of disorders characterized by impaired glucose metabolism, high blood pressure, central obesity, low high-density lipoprotein cholesterol, high low-density lipoprotein cholesterol and triglycerides. It is the activity of low-density lipoproteins and an increase in the level of triglycerides that have serious consequences in the etiology of cardiovascular diseases and the development of atherosclerosis. Osteoporosis ranks fourth among non-communicable diseases after CVD, cancer and diabetes. Estrogen deficiency during menopause results in increased osteoclast resorptive activity, while osteoblast function remains relatively constant, ultimately resulting in bone loss. In the first postmenopausal years, a woman can lose up to 9-35 % of bone mass, postmenopausal osteoporosis affects between one third to a half of all women. Conclusions. Menopause is a difficult period in a woman's life, during which the risk of developing cardiovascular diseases and metabolic disorders increases, as well as almost all somatic diseases are exacerbated. Therefore, proper assessment of such risks is mandatory to improve long-term CVD outcomes. Given this, it is the interdisciplinary interaction that is central to early detection of symptoms and diagnosis of climacteric disorders for the timely prescription of treatment. Physicians working with this contingent of women should apply a comprehensive approach to health care and quality of life preservation during the menopause transition, menopause and postmenopause. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases (CVDs) are the leading cause of death in the United States. However, disparities in CVD-related morbidity and mortality exist as marginalized racial and ethnic groups are generally at higher risk for CVDs (Black Americans, Indigenous People, South and Southeast Asians, Native Hawaiians, and Pacific Islanders) and/or development of traditional CVD risk factors (groups above plus Hispanics/Latinos) relative to non-Hispanic Whites (NHW). In this comprehensive review, we outline emerging evidence suggesting these groups experience accelerated arterial dysfunction, including vascular endothelial dysfunction and large elastic artery stiffening, a nontraditional CVD risk factor that may predict risk of CVDs in these groups with advancing age. Adverse exposures to social determinants of health (SDOH), specifically lower socioeconomic status (SES), are exacerbated in most of these groups (except South Asians—higher SES) and may be a potential mediator of accelerated arterial aging. SES negatively influences the ability of marginalized racial and ethnic groups to meet aerobic exercise guidelines, the first-line strategy to improve arterial function, due to increased barriers, such as time and financial constraints, lack of motivation, facility access, and health education, to performing conventional aerobic exercise. Thus, identifying alternative interventions to conventional aerobic exercise that 1) overcome these common barriers and 2) target the biological mechanisms of aging to improve arterial function may be an effective, alternative method to aerobic exercise to ameliorate accelerated arterial aging and reduce CVD risk. Importantly, dedicated efforts are needed to assess these strategies in randomized-controlled clinical trials in these marginalized racial and ethnic groups. [ABSTRACT FROM AUTHOR]

The editorial discusses the increasing mainstream attention to menopause management, particularly in relation to vasomotor symptoms (VMS) like hot flashes and night sweats. It highlights the historical context of hormone therapy usage rates and the safety concerns raised by the Women's Health Initiative trials. The article introduces fezolinetant, a novel nonhormonal drug approved for VMS treatment, and discusses the potential of elinzanetant, a dual NK1 and NK3 receptor antagonist, in reducing VMS frequency and improving quality of life. The text emphasizes the need for individualized menopause management and the importance of advancing care with nonhormonal treatment options. [Extracted from the article]

The importance of management in women in menopause and postmenopause is not diminishing, but only gaining relevance. It is estimated that by 2050, more than 1.6 billion women worldwide will reach this age, compared to 1 billion in 2020. Vasomotor symptoms (VMS) are the most common symptoms of menopause and affect more than 70% of women. They are diagnosed in 35-50% of women in perimenopause and 30-80% women in postmenopause. Most of these symptoms persist less than 7 years after the last menstrual period, but one in four women may experience them up to 10 years, and one in ten women may experience them after 10 years. They are based on complex endocrine, neuroendocrine and epigenetic mechanisms. This article is a review of scientific literature publications aimed at determining the impact of VMSs on women’s future life based on the analysis of published modern studies. VMSs not only have a negative impact on a woman’s quality of life, but also have potential importance for cardiovascular health. The increased risk of cardiovascular diseases (CVD) after menopause is attributed to a sharp decrease of endogenous estrogen levels, which indicates its potential cardioprotective effect in premenopausal women. It has been established that VMSs are a risk factor for coronary heart disease and diabetes mellitus. The presence of non-alcoholic fatty liver disease is also significantly associated with an increased risk of early and severe forms of VMSs among perimenopausal women. Taking into account that women spend a third of their lives in the postmenopausal period, it is important to analyze the experience of their management during this difficult period. It is based on focusing on a healthy lifestyle as part of primary prevention, including regular physical activity, calcium/vitamin D intake, maintaining an optimal body weight, avoiding stress, etc. Menopausal hormone therapy (MHT) is considered as a first-line treatment for VMSs in menopause and perimenopause. Its use should be individualized, and initiation and discontinuation should not be based only on a woman’s age. Assessment of baseline CVD risk, age and period since menopause are important. It is considered a priority for women with menopause before 10 years or under 60 years of age who have no contraindications to MHT. Hormone therapy is not indicated only for the prevention of CVD. However, it has the potential to improve cardiovascular risk profile due to its beneficial effects on vascular function, lipid levels, glucose metabolism, and reduction of diabetes mellitus. Non-hormonal VMS treatment has sufficient experience of use when there are medical contraindications to hormonal therapy or a woman’s personal choice. However, MHT remains the most effective for VMS treatment. [ABSTRACT FROM AUTHOR]

Objective: Metabolic dysfunction-associated steatotic liver disease (MASLD) and vasomotor symptoms (VMS) are associated with increased cardiovascular disease risk. Although visceral adiposity has been linked to MASLD and VMS independently, this study aimed to evaluate associations between the two in midlife women., Methods: A cross-sectional study of women aged 45-60 years receiving primary care at one of four sites was conducted from March 1 through June 30, 2021. MASLD diagnosis was obtained utilizing the International Classification of Diseases, Ninth Revision and Tenth Revision codes. VMS burden was evaluated with the Menopause Rating Scale and categorized as severe/very severe versus none/mild/moderate. Logistic regression models were used to assess the association between VMS and diagnosed MASLD both univariately and after individually adjusting for several risk factors., Results: A total of 4,599 women were included in the final analysis, 304 (7%) of whom had an MASLD diagnosis. On univariate analysis, women with an MASLD diagnosis were more likely to have severe/very severe VMS (odds ratio [OR], 1.50; 95% CI, 1.08-2.08; P = 0.015). However, the association between MASLD diagnosis and severe/very severe VMS was no longer statistically significant after individually adjusting for body mass index (adjusted OR, 1.36; 95% CI, 0.97-1.92) and hypertension (adjusted OR, 1.38; 95% CI, 0.99-1.93)., Conclusions: The relationship between MASLD and VMS appears to be best explained by other variables including BMI and hypertension. Although they do not appear to be directly linked, given the prevalence of bothersome VMS in midlife women, addressing VMS may enable greater adherence to lifestyle modifications as part of MASLD management., Competing Interests: Financial disclosure/conflicts of interest: E.K. has been a consultant for Astellas Pharma Inc, Mithra Pharmaceuticals, Scynexis, Inc, and Womaness. She receives grant support from Mithra Pharmaceuticals. She has received payment for development of educational content from Med Learning Group and Academy of Continued Healthcare Learning. She has received honoraria for CME activity from CogniMed Inc, Pri-Med, AiCME, and OBG Management. M.B.W. has been a consultant for Verily, Boston Scientific, Endiatix, Fujifilm, Medtronic, and Surgical Automations. He receives grants support from Fujifilm, Boston Scientific, Olympus, Medtronic, Ninepoint Medical, and Cosmo/Aries Pharmaceuticals. He has stock/stock options in Virgo Inc and Surgical Automations. He has been consulting on behalf of Mayo Clinic for Boston Scientific, Microtek. He receives general payments/minor food and beverage from Synergy Pharmaceuticals, Boston Scientific, and Cook Medical. J.M.K. received honorarium from Everyday Health, Evolve, Medscape, and AiCME. She serves as the medical editor for Everyday Health CME and received non-CME honorarium for Medscape, Contemporary Forums, Evolve Medical Education, AiCME, Elsevier, Vindico Medical Education, EPG Health, APS, and Paradise Valley Country Club. S.S.F. received honoraria for CME activity from Pri-Med and Medscape and has been a consultant for Modern Inc. The other authors have nothing to disclose., (Copyright © 2024 by The Menopause Society.)

Objective: The aim of this study was to compare menopause experience in rural, suburban, and urban-residing women., Methods: A 2019 online survey of US females queried respondents on menopause symptoms, resources, and treatments. Those ≥45 years of age and in late menopause transition or postmenopause were included in the analysis. Late menopause transition and postmenopause subgroups were stratified by rural, suburban, and urban residence, and age-weighted proportions for menopause symptoms and treatments were calculated and compared using chi-square tests., Results: A total of 1,531 respondents, 45% (n = 686) late menopause transition, mean age of 50.7 (SD 3.9) and 55% (n = 845) postmenopause, and mean age of 65.1 (SD 8.5) were included. More prevalent symptoms in late menopause transition rural residents were as follows: muscle aches and pains (urban: 49%, suburban: 49%, rural: 65%, P = 0.003), and panic attacks (urban: 18%, suburban: 24%, rural: 30%, P = 0.04). More prevalent symptoms in postmenopause rural residents were as follows: mood swings (urban: 18%, suburban: 14%, rural: 23%, P = 0.02), urinary incontinence (urban: 19%, suburban: 14%, rural: 23%, P = 0.02), and vaginal dryness (urban: 22%, suburban: 29%, rural: 37%, P = 0.004). Vasomotor symptom prevalence was high (71% late menopause transition, 20% postmeopause), but current menopause hormone therapy use was low (11% late menopause transition, 11% postmenopause) and did not differ by residence, despite differences in menopausal resources used., Conclusions: Rural women may experience greater burden of psychological and somatic menopause symptoms but not vasomotor symptoms. Overall low rates of menopause hormone therapy use suggest a need for education regarding hormone therapy, tailored to residential groups who rely on different resources on healthy aging., Competing Interests: Financial disclosure/conflicts of interest: S.D.R. obtains royalties from UpToDate, consults for Bayer, and has funding from NIH. M.M. serves on HealthyWomen's advisory council. P.M. serves on advisory boards for Astellas, Bayer, and Estrigenix. She holds equity in Estrigenix, MidiHealth, and Respin. She received speaking honorarium from Healthy Women. The other authors have nothing to disclose., (Copyright © 2024 by The Menopause Society.)

Background: It has been repeatedly shown that men infected by SARS-CoV-2 face a twofold higher likelihood of dying, being hospitalized or admitted to the intensive care unit compared to women, despite taking into account relevant confounders. It has been hypothesized that these discrepancies are related to sex steroid hormone differences with estrogens being negatively correlated with disease severity. The objective of this study was therefore to evaluate COVID-19-related mortality and morbidity among peri- and postmenopausal women in relation to estrogen-containing menopause hormonal treatments (MHT). Methods: This is a national register-based matched cohort study performed in Sweden between January 1 to December 31, 2020. Study participants comprised women over the age of 53 years residing in Sweden. Exposure was defined as prescriptions of local estrogens, systemic estrogens with and without progestogens, progestogens alone, or tibolone. MHT users were then compared with a matched cohort of non-users. The primary outcome consisted of COVID-19 mortality, whereas the secondary outcomes included inpatient hospitalizations/outpatient visits and confirmed SARS-CoV-2 infection. Multivariable adjusted Cox regression-derived hazard ratios (HRs) were calculated. Results: Use of systemic estrogens alone is associated with increased COVID-19 mortality among older women (aHR 4.73, 1.22 to 18.32), but the association is no longer significant when discontinuation of estrogen use is accounted for. An increased risk for COVID-19 infection is further observed for women using combined systemic estrogens and progestogens (aHR 1.06, 1.00 to 1.13) or tibolone (aHR 1.21, 1.01 to 1.45). Use of local estrogens is associated with an increased risk for COVID-19-related death (aHR 2.02,1.45 to 2.81) as well as for all secondary outcomes. Conclusions: Systemic or local use of estrogens does not decrease COVID-19 morbidity and mortality to premenopausal background levels. Excess risk for COVID-19 morbidity and mortality was noted among older women and those discontinuing systemic estrogens. Higher risk for death was also noted among women using local estrogens, for which non-causal mechanisms such as confounding by comorbidity or frailty seem to be the most plausible underlying explanations. Trial registration details: Not applicable. [ABSTRACT FROM AUTHOR]

Objective: To assess the effect of fezolinetant treatment on health-related quality of life using pooled data from SKYLIGHT 1 and 2 studies., Design: Prespecified pooled analysis., Setting: USA, Canada, Europe; 2019-2021., Population: 1022 women aged ≥40 to ≤65 years with moderate-to-severe vasomotor symptoms (VMS; minimum average seven hot flushes/day), seeking treatment for VMS., Methods: Women were randomised to 12-week double-blind treatment with once-daily placebo or fezolinetant 30 or 45 mg. Completers entered a 40-week, active extension (those receiving fezolinetant continued that dose; those receiving placebo re-randomised to fezolinetant received 30 or 45 mg)., Main Outcome Measures: Mean changes from baseline to weeks 4 and 12 on Menopause-Specific Quality of Life (MENQoL) total and domain scores, Work Productivity and Activity Impairment questionnaire specific to VMS (WPAI-VMS) domain scores, Patient Global Impression of Change in VMS (PGI-C VMS); percentages achieving PGI-C VMS of 'much better' (PGI-C VMS responders). Mean reduction was estimated using mixed model repeated measures analysis of covariance., Results: Fezolinetant 45 mg mean reduction over placebo in MENQoL total score was -0.57 (95% confidence interval [CI] -0.75 to -0.39) at week 4 and -0.47 (95% CI -0.66 to -0.28) at week 12. Reductions were similar for 30 mg. MENQoL domain scores were also reduced and WPAI-VMS scores improved. Twice as many women receiving fezolinetant reported VMS were 'much better' than placebo based on PGI-C VMS assessment., Conclusions: Fezolinetant treatment was associated with improvement in overall QoL, measured by MENQoL, and work productivity, measured by WPAI-VMS. A high proportion receiving fezolinetant felt VMS were 'much better' based on PGI-C VMS responder analysis., (© 2024 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)