Management of the Vasomotor Symptoms of Menopause: Twofers in Your Clinical Toolbox.

The number of midlife women transitioning into menopause is substantial, with more than 1 million women in the United States entering menopause each year. Vasomotor symptoms (VMS), mood and sleep disturbances, and sexual problems are common during the menopause transition yet often go untreated. Menopausal hormone therapy is the most effective treatment of VMS, and the benefits typically outweigh the risks for women without contraindications who are younger than 60 years or within 10 years from menopause onset. For women who cannot or choose not to use hormone therapy, nonhormone prescription options exist to treat VMS. Many of these therapies have secondary benefits beyond VMS relief. For example, whereas paroxetine is Food and Drug Administration approved to treat VMS, it can also help with depressive and anxiety symptoms. The aim of this paper is to summarize prescription treatments of VMS and their secondary benefits for other common symptoms experienced by midlife women. The tools presented will help clinicians caring for midlife women provide individualized, comprehensive care with the goal of improving their quality of life during the menopause transition and beyond.

Fezolinetant: a novel nonhormonal therapy for vasomotor symptoms due to menopause.

INTRODUCTION: During menopause, the majority of women experience vasomotor symptoms which may lead to several untoward effects and negatively impact quality of life. Fezolinetant, a novel agent directly targeting the underlying pathophysiology of menopause-associated vasomotor symptoms, offers an alternative to hormonal therapies for which many patients have a contraindication or unwillingness to take due to safety concerns. AREAS COVERED: This review summarizes key pharmacologic, pharmacokinetic, and pharmacodynamic parameters of fezolinetant along with efficacy and safety data derived from clinical trials. A literature search of peer-reviewed publications evaluating the efficacy and safety of fezolinetant was conducted using PubMed and EMBASE databases. A review of registered trials in clinicaltrials.gov was evaluated to identify ongoing studies. EXPERT OPINION: Placebo-controlled studies demonstrated that fezolinetant led to a statistically significant reduction in vasomotor symptom frequency and severity among patients with moderate-to-severe vasomotor symptoms. The most common adverse event is headache (5-10%) and no serious safety signals have been noted. Direct head-to-head comparison with hormonal therapies and nonhormonal therapies for vasomotor symptoms, assessment of sleep outcomes, and evaluation of efficacy and safety beyond 1 year are key areas where additional data are still needed.

Efficacy and safety of fezolinetant for moderate to severe vasomotor symptoms associated with menopause among women in East Asia: a phase 3 randomized study (MOONLIGHT I).

OBJECTIVE: To evaluate the efficacy and safety of fezolinetant for moderate to severe vasomotor symptoms (VMS) associated with menopause in East Asian women. METHODS: In this phase 3, randomized, double-blind study, postmenopausal women with moderate to severe VMS (minimum average frequency in the 10 days before randomization, ≥7/day or 50/week) received fezolinetant 30 mg/day or placebo (weeks 1-12), followed by an open-label extension phase with fezolinetant 30 mg/day (weeks 13-24). The co-primary endpoints were the mean changes in the daily frequency and severity of VMS at weeks 4 and 12. RESULTS: Among 301 participants, the difference in the least squares mean change (95% confidence interval) from baseline in the daily frequency of moderate to severe VMS versus placebo was -0.65 (-1.41 to 0.12) at week 4 and -0.55 (-1.35 to 0.26) at week 12. The differences in the least squares mean change from baseline in the VMS severity score versus placebo were -0.06 (-0.14 to 0.03) and -0.13 (-0.27 to 0.01) at weeks 4 and 12, respectively. Serious adverse events occurred in 0.7% of participants receiving fezolinetant in weeks 1 to 12, compared with 1.3% of those receiving placebo. CONCLUSIONS: Fezolinetant was generally safe but did not reduce the frequency or severity of VMS versus placebo in postmenopausal women in this study.ClinicalTrials.Gov Identifier: NCT04234204.

Long-term safety of fezolinetant in Chinese women with vasomotor symptoms associated with menopause: the phase 3 open-label MOONLIGHT 3 clinical trial.

OBJECTIVE: We aimed to assess long-term safety and tolerability of fezolinetant, a nonhormonal neurokinin 3 receptor antagonist, among Chinese women with vasomotor symptoms associated with menopause participating in the MOONLIGHT 3 trial. METHODS: In this phase 3 open-label study, women in menopause aged 40-65 years received fezolinetant 30 mg once daily for 52 weeks. The primary endpoint was frequency and severity of treatment-emergent adverse events (TEAEs), assessed at every visit through week 52 and one follow-up visit at week 55. RESULTS: Overall, 150 women were enrolled (mean age, 54 years) and 105 completed treatment. The frequency of TEAEs was 88.7%. Most TEAEs were mild (63.3%) or moderate (22.7%). The most common TEAE was upper respiratory tract infection (16.0%), followed by dizziness, headache, and protein urine present (10.7% each). There was no clinically relevant change (mean ± standard deviation) in endometrial thickness (baseline, 2.95 ± 1.11 mm; week 52, 2.94 ± 1.18 mm). Alanine aminotransferase and/or aspartate aminotransferase levels >3 times the upper limit of normal were reported in 1.4% of women; no Hy's Law cases occurred. CONCLUSIONS: Fezolinetant 30 mg once daily was generally safe and well tolerated over a 52-week period among women in China with vasomotor symptoms associated with menopause.ClinicalTrials.gov Identifier: NCT04451226.

A descending pathway from the lateral/ventrolateral PAG to the rostroventral medulla mediating the vasomotor response evoked by social defeat stress in rats.

The stress-induced cardiovascular response is based on the defensive reaction in mammals. It has been shown that the sympathetic vasomotor pathway of acute psychological stress is indirectly mediated via neurons in the rostroventral medulla (RVM) from the hypothalamic stress center. In this study, direct projections to the RVM and distribution of neuroexcitatory marker c-Fos-expressed neurons were investigated during social defeat stress (SDS) in conscious rats. The experimental rat that was injected with a neural tracer, FluoroGold (FG) into the unilateral RVM, was exposed to the SDS. Double-positive neurons of both c-Fos and FG were locally distributed in the lateral/ventrolateral periaqueductal gray matter (l/vl PAG) in the midbrain. These results suggest that the neurons in the l/vl PAG contribute to the defensive reaction evoked by acute psychological stress, such as the SDS. During the SDS period, arterial pressure (AP) and heart rate (HR) showed sustained increases in the rat. Therefore, we performed chemical stimulation by excitatory amino acid microinjection within the l/vl PAG and measured cardiovascular response and sympathetic nerve activity in some anesthetized rats. The chemical stimulation of neurons in the l/vl PAG caused significant increases in arterial pressure and renal sympathetic nerve activity. Taken together, our results suggest that neurons in the l/vl PAG are a possible candidate for the cardiovascular descending pathway that modulates sympathetic vascular resistance evoked by acute psychological stress, like the SDS.NEW & NOTEWORTHY The sympathetic vasomotor pathway of an acute psychological stress-induced cardiovascular response is mediated via neurons in the RVM indirectly from the hypothalamus. In this study, we showed the relaying area of the efferent sympathetic vasomotor pathway from the hypothalamus to the RVM. The results suggested that the pressor response during psychological stress is mediated via neurons in the lateral/ventrolateral PAG to the RVM.

Effectiveness and safety of fezolinetant in alleviating vasomotor symptoms linked to Menopause.: A systematic review and Meta-Analysis.

BACKGROUND & OBJECTIVE: Vasomotor symptoms (VMS) are the most common symptoms during menopause including hot flushes and night sweats. They are highly disruptive to the quality of life. Fezolinetant is an FDA-approved non-hormonal selective neurokinin3 receptor antagonist for the treatment of VMS. In this study, we aim to assess the efficacy and safety of fezolinetant for VMS associated with menopause. METHODS: Databases were searched until September 2023 for relevant studies comparing fezolinetant against placebo. Data was extracted into an online form and analyzed using RevMan (Version 5.4.1). The GRADE approach was conducted to evaluate the quality of evidence regarding efficacy outcomes. We included randomized controlled trials (RCTs) comparing fezolinetant to placebo in postmenopausal women experiencing VMS. Exclusion criteria comprised studies involving participants with contraindications to fezolinetant or those evaluating its efficacy for indications other than VMS associated with menopause. RESULTS: Six studies were included in this study involving 3301 patients. Compared to placebo, fezolinetant reduced the frequency of VMS episodes from baseline (SMD = -0.64, 95 % CI [-0.77, -0.5]) and (SMD = -0.63, 95 % CI [-0.72, -0.53] at weeks 4 and 12 respectively. Additionally, fezolinetant reduced VMS severity score (SMD = -0.59, 95 %CI [-0.77, -0.42]) and (SMD = -0.4, 95 % CI [-0.54, -0.27]) at weeks 4 at 12 respectively. These reductions were positively reflected on Menopause specific quality of life score (SMD = -0.46, 95 %CI [-57, -0.34]), (SMD = -0.37, 95 %CI [-0.48, -0.25]) at weeks 4 and 12 respectively. Regarding safety analysis, fezolinetant showed increased risk for drug-related TEAEs (RR = 1.47, 95 %CI [1.06,2.04]), serious TEAEs (RR = 1.67, 95 %CI [1.09,2.55]), fatigue (RR = 4.05, 95 %CI [1.27,12.88]), arthralgia (RR = 2.83, 95 %CI [1.02,7.8]) and ALT or AST > 3 times (RR = 2, 95 %CI [1.12,3.57]), with no other statistically significant difference regarding other safety terms. CONCLUSION: Fezolinetant has demonstrated efficacy in reducing the frequency and severity of VMS in postmenopausal women, leading to an improvement in their quality of life. These findings suggest that Fezolinetant may serve as a viable alternative to hormonal therapy for managing VMS.

Does everyday discrimination account for the increased risk of vasomotor symptoms in Black women?: the Study of Women's Health Across the Nation (SWAN).

OBJECTIVES: Vasomotor symptoms (VMS), including hot flashes and night sweats, are hallmark symptoms of the menopause transition. Previous research has documented greater frequency, duration, and severity of VMS in Black women compared with women from other racial/ethnic groups, even after accounting for other factors. This analysis examined the association between discrimination and VMS and the extent to which discrimination accounts for the disproportionate burden of VMS in Black women. METHODS: Using available discrimination and VMS data from the SWAN cohort study (n = 2,377, 48% White, 32% Black, 6% Japanese, 4% Chinese, and 9% Hispanic women) followed approximately yearly in midlife from premenopause (42-52 y) through postmenopause (~20 y), we assessed concurrent associations between discrimination and VMS frequency in the past 2 weeks using weighted generalized mixed models. We also assessed associations between chronic discrimination across first four visits and VMS trajectories from premenopause to postmenopause using weighted multinomial logistic regression. Models were adjusted for known risk factors for VMS. RESULTS: Higher levels of discrimination were associated with concurrent reporting of any (odds ratio [OR], 1.57 [1.31-1.89]) and frequent (≥6 d) VMS (OR, 1.55 [1.21-1.99]). After adjustment, associations remained significant for any (OR, 1.30 [1.09-1.54]) but not frequent VMS. For any VMS trajectories, chronic discrimination was associated with "continuously high" (OR, 1.69 [1.03-2.77]) and "high pre-FMP-decline post-FMP" (OR, 1.70 [1.01-2.88]) versus "FMP-onset low" trajectories. After adjusting for discrimination, odds of reporting any, frequent, and of being in the "continuously high" any VMS trajectory remained elevated for Black versus White women. CONCLUSIONS: Discrimination is associated with greater concurrent risk of any (but not frequent) VMS, and chronic discrimination is associated with a continuously high reporting of any VMS over time, independent of known risk factors. Adjusting for discrimination attenuates but does not eliminate the increased risk of VMS for Black women.

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.

Fezolinetant for the treatment of vasomotor symptoms associated with menopause: a meta-analysis.

This systematic review and meta-analysis investigated the efficacy and safety of fezolinetant for the treatment of moderate-to-severe vasomotor symptoms (VMS) associated with menopause. PubMed, Cochrane Library, Embase and Web of Science were searched for randomized controlled trials (RCTs) published from inception to June 2023, comparing fezolinetant to placebo in postmenopausal women suffering from moderate-to-severe VMS. The mean difference and risk ratio were calculated for continuous and binary outcomes, respectively. R software was used for the statistical analysis, and RoB-2 (Cochrane) to assess the risk of bias. We performed subgroup analysis based on different dosing regimens. Five RCTs comprising 3302 patients were included. Compared with placebo, at 12-week follow-up, fezolinetant significantly reduced the daily frequency of moderate-to-severe VMS (weighted mean difference [WMD] - 2.36; 95% confidence interval [CI] - 2.92, -1.81) and daily severity of moderate-to-severe VMS (WMD -0.22; 95% CI -0.31, -0.13). Also, fezolinetant significantly improved the quality of life (WMD -0.42; 95% CI -0.58, -0.26) and sleep disturbance (WMD -1.10; 95% CI -1.96, -0.24). There were no significant differences between groups in adverse events. These findings support the efficacy and safety of fezolinetant for the treatment of VMS related to menopause.

Statin treatment intensity and cerebral vasomotor reactivity response in patients with ischemic stroke.

BACKGROUND AND PURPOSE: Cerebral vasomotor reactivity (VMR) is vital for regulating brain blood flow and maintaining neurological function. Impaired cerebral VMR is linked to a higher risk of stroke and poor post-stroke outcomes. This study explores the relationship between statin treatment intensity and VMR in patients with ischemic stroke. METHODS: Seventy-four consecutive patients (mean age 69.3 years, 59.4% male) with recent ischemic stroke were included. VMR levels were assessed 4 weeks after the index stroke using transcranial Doppler, measuring the breath-holding index (BHI) as an indicator of the percentage increase in middle cerebral artery blood flow (higher BHI signifies higher VMR). Multistep multivariable regression models, adjusted for demographic and cerebrovascular risk factors, were employed to examine the association between statin intensity treatment and BHI levels. RESULTS: Forty-one patients (55%) received high-intensity statins. Patients receiving high-intensity statins exhibited a mean BHI of 0.85, whereas those on low-intensity statins had a mean BHI of 0.67 (mean difference 0.18, 95% confidence interval: 0.13-0.22, p-value<.001). This significant difference persisted in the fully adjusted model (adjusted mean values: 0.84 vs. 0.68, p-value: .008). No significant differences were observed in BHI values within patient groups on high-intensity or low-intensity statin therapy (all p-values>.05). Furthermore, no significant association was found between baseline low-density lipoprotein (LDL) levels and BHI. CONCLUSIONS: High-intensity statin treatment post-ischemic stroke is linked to elevated VMR independent of demographic and clinical characteristics, including baseline LDL level. Further research is needed to explore statin therapy's impact on preserving brain vascular function beyond lipid-lowering effects.

Systematic review of neurokinin-3 receptor antagonists for the management of vasomotor symptoms of menopause.

IMPORTANCE: Vasomotor symptoms (VMS) affect many postmenopausal persons and impact sleep and quality of life. OBJECTIVE: This systematic review examines the literature describing the safety and efficacy of neurokinin-3 receptor antagonists approved and in development for postmenopausal persons with VMS. EVIDENCE REVIEW: A search of MEDLINE, EMBASE, and International Pharmaceutical Abstracts was conducted using the search terms and permutations of neurokinin-3 receptor antagonist, elinzanetant, fezolinetant, and osanetant. Inclusion criteria of reporting on efficacy or safety of fezolinetant, elinzanetant, or osanetant; studies in participants identifying as female; full record in English; and primary literature were applied. Abstract-only records were excluded. Extracted data were synthesized to allow comparison of reported study characteristics, efficacy outcomes, and safety events. Eligible records were evaluated for risk of bias via the Cochrane Risk of Bias 2 tool for randomized studies and the Grading of Recommendations Assessment, Development and Evaluation system was used. This study was neither funded nor registered. FINDINGS: The search returned 191 records; 186 were screened after deduplication. Inclusion criteria were met by six randomized controlled trials (RCT), four reported on fezolinetant, and two reported on elinzanetant. One record was a post hoc analysis of a fezolinetant RCT. An additional study was identified outside the database search. Three fezolinetant RCT demonstrated a reduction in VMS frequency/severity, improvement in Menopause-Specific Quality of Life scores, and improvement in sleep quality at weeks 4 and 12 compared with placebo without serious adverse events. The two RCT on elinzanetant also showed improvements in VMS frequency and severity. All eight records evaluated safety through treatment-emergent adverse events; the most common adverse events were COVID-19, headache, somnolence, and gastrointestinal. Each record evaluated had a low risk of bias. There is a strong certainty of evidence as per the Grading of Recommendations Assessment, Development and Evaluation system. CONCLUSIONS AND RELEVANCE: Because of the high-quality evidence supporting the efficacy of fezolinetant and elinzanetant, these agents may be an effective option with mild adverse events for women seeking nonhormone treatment of VMS.

Vasomotor symptoms and cardiovascular health: findings from the SWAN and the MsHeart/MsBrain studies.

Vasomotor symptoms (VMS) are often considered the classic menopausal symptom and are experienced by most women during the menopause transition. VMS are well established to be associated with decrements in quality of life during the menopause. More recent research also links VMS to poorer cardiovascular health. This review summarizes key insights about links between VMS and cardiovascular disease (CVD) risk that come from the Study of Women's Health Across the Nation (SWAN), a longitudinal epidemiologic cohort study of the menopause transition, as well as from the MsHeart/MsBrain studies, clinical studies that leverage vascular imaging and brain imaging as well as wearable technologies that provide objective indicators of VMS. Using a range of methodologies and extensive consideration of confounders, these studies have shown that frequent and/or persistent VMS are associated with adverse CVD risk factor profiles, poorer underlying peripheral vascular and cerebrovascular health, and elevated risk for clinical CVD events. Collectively, the SWAN and MsHeart/MsBrain studies form complementary epidemiologic and clinical studies that point to the importance of VMS to women's cardiovascular health during the menopause transition and beyond.

Evaluación del impacto, los patrones de tratamiento y las percepciones de pacientes y clínicos de los síntomas vasomotores moderado-graves asociados a la menopausia en España / Analysis of the impact, patterns of care, and perspectives of patients and physicians about moderate-to-severe menopausal vasomotor symptoms in Spain

Introducción: La menopausia puede originar distintos síntomas, siendo los vasomotores especialmente prevalentes y molestos. Este trabajo pretende conocer su impacto y los patrones/percepciones sobre el tratamiento en España, para lo que se han analizado las opiniones de clínicos y pacientes con síntomas vasomotores moderado-graves (SVM-MG). Métodos: Estudio transversal descriptivo de la subpoblación española del Programa de Enfermedades Específicas de Adelphi-VMS™. Médicos de atención primaria y de Ginecología y Obstetricia seleccionaron las pacientes. Estas fueron invitadas a rellenar una encuesta y los cuestionarios MENQOL y WPAI:SHP. Los datos se han presentado como porcentaje o media±desviación estándar. Resultados: Un total de 32 médicos de Atención Primaria y Ginecología y Obstetricia completaron los formularios de registro para 241 mujeres, de las cuales 143 experimentaban SVM-MG. A pesar del impacto global reportado en el trabajo (24,84%±17,49 presentismo) y en la calidad de vida (3,37±1,52 MENQOL), solo el 53,85% de las mujeres eran tratadas. El tratamiento hormonal de la menopausia era el más prescrito (77,92%), seguido de los inhibidores de la recaptación de serotonina (32,47%). El 59% de los clínicos estaba muy o completamente satisfecho con el tratamiento hormonal de la menopausia, mientras que solo el 19% lo estaba con los inhibidores de la recaptación de serotonina. Pacientes y especialistas indicaron un nivel de satisfacción inferior al 38% en el control de los SVM. Conclusiones: Los SVM-MG asociados a la menopausia tienen un importante impacto sobre la calidad de vida. Una mayor sensibilización en su manejo y mejores opciones terapéuticas contribuirían significativamente a mejorar la salud y bienestar de la mujer durante el climaterio.(AU)

Introduction: Menopause generates different symptoms, among which vasomotor symptoms are especially prevalent and bothersome. The aim of this work was to determine their impact and the treatment patterns and perceptions in Spain by analyzing the opinions of physicians and patients with moderate-to-severe vasomotor symptoms (MS-VMS). Methods: Descriptive cross-sectional study of the Spanish subpopulation from the Adelphi-VMS™ Disease-Specific Program. Primary Care and Gynecology and Obstetrics physicians selected the patients. These patients were invited to complete a survey and the MENQOL and WPAI:SHP questionnaires. Data are presented as percentage or mean±standard deviation. Results: Overall 32 Primary Care and Gynecology and Obstetrics physicians participated in the study, enrolling 241 women, of whom 143 experienced MS-VMS. Despite the reported impact on global work (24.84%±17.49 presentism) and quality of life (3.37±1.52 MENQOL score), only 53.85% of women with MS-VMS were treated. Menopausal hormone treatment was the most prescribed (77.92%), followed by serotonin reuptake inhibitors (32.47%). Fifty-nine percent of clinicians were very or completely satisfied with hormone treatment, whereas only 19% had this level of satisfaction with selective serotonin reuptake inhibitors. Less than 38% of patients and physicians were satisfied with the control of VMS. Conclusions: Menopause-associated MS-VMS have an important impact on quality of life. Increased awareness about their management and better therapeutic options would significantly contribute to improving women's health and well-being during their climacteric period.(AU)

Fezolinetant: un nuevo tratamiento en estudio para la menopausia / Fezolinetant: A new treatment being studied for menopause

La menopausia es el cese fisiológico de la menstruación que puede presentarse en las mujeres entre los 42 y 58 años con una sintomatología diversa. La clínica más frecuente es la vasomotora, que puede afectar en gran medida a la calidad de vida de las mujeres. Tradicionalmente se ha usado la terapia hormonal sustitutiva, que se considera el tratamiento más efectivo. Sin embargo, existe una serie de contraindicaciones por las que se debe plantear el uso de una terapia no hormonal. Actualmente estas opciones son subóptimas en efectividad y tolerancia, por lo que se está investigando acerca de nuevos tratamientos como el fezolinetant, un antagonista del receptor de neuroquinina 3. Para dilucidar dichas investigaciones se ha realizado una búsqueda bibliográfica en las principales bases de datos. Aunque aún queda por establecer su seguridad y efectos a largo plazo, la terapia con fezolinetant parece ser prometedora en pacientes en las que no se puede usar terapia hormonal. Disminuye la sintomatología vasomotora moderada o grave desde el primer día de tratamiento de manera estadísticamente significativa al compararla con placebo y con otros tratamientos no hormonales, con un buen perfil de tolerancia y escasos efectos secundarios. Sin embargo, este medicamento aún se encuentra en ensayos de fase III, por lo que se necesita continuar con su estudio.(AU)

Menopause is the physiological cessation of menstruation that can occur in women between 42 and 58 years of age with diverse symptoms. The most common clinic is vasomotor, which can greatly affect the quality of life of women. Traditionally, hormone replacement therapy has been used and is considered the most effective treatment. However, there are contraindications for which the use of non-hormonal therapy should be considered. Nowadays, these options are suboptimal in terms of effectiveness and tolerance, which is why research is being carried out on new treatments such as fezolinetant, a neurokinin 3 receptor antagonist. To elucidate these investigations a bibliographic search has been carried out in the main databases. Although its safety and long-term effects remain to be established, fezolinetant looks promising in patients for whom hormonal therapy cannot be used. It decreases statistically significant the moderate or severe vasomotor symptoms from the first day of treatment when compared with placebo and with other non-hormonal treatments with a good tolerance profile and few side effects. However, this drug is still in phase III trials, so it needs to continue with its study.(AU)

Global view of vasomotor symptoms and sleep disturbance in menopause: a systematic review.

Studies have shown racial/ethnic differences in the prevalence of vasomotor symptoms (VMS), sleep disturbance and VMS treatment in menopause. To assess the reproducibility of these differences, we systematically reviewed observational studies, published in 2000-2021, reporting the prevalence/incidence of VMS, sleep disturbance or treatment use in menopausal women stratified by race/ethnicity. We screened 3799 records from PubMed and Embase and included 27 papers (19 studies). No incidence data were found. Prevalence data varied widely, but some common patterns emerged. In all five studies comparing VMS between Black women and White, Hispanic and/or East Asian women, the prevalence was highest in Black women and lowest in East Asian women. The prevalence of sleep disturbance overall was compared among Black, White and East Asian women in two study populations, and was highest in White women in both papers. Sleep disturbance was more common than VMS in East Asian women. In all four studies comparing hormone therapy use between White women and Black and/or East Asian women, treatment use was more common in White women. These results highlight the need for individualized counseling and treatment, outreach to under-served minorities, and standardized definitions and outcome measures for VMS and sleep disturbance for future studies.

Association between vasomotor symptom frequency and weight gain in the Study of Women's Health Across the Nation.

OBJECTIVE: The menopause transition is associated with weight gain in women. We examined whether changes in vasomotor symptom (VMS) frequency precede weight changes. METHODS: This longitudinal retrospective analysis included data from the multisite, multiethnic Study of Women's Health Across the Nation. Women in premenopause or perimenopause aged 42 to 52 years at baseline self-reported VMS frequency (hot flashes/night sweats) and sleep problems at up to 10 annual visits. Menopause status, weight, body mass index, and waist circumference were compared across visits. The primary objective was to measure the association between VMS frequency and weight gain using a lagged approach with first-difference regression models. Secondary objectives were to statistically quantify mediation by sleep problems and moderation by menopause status and explore the association between cumulative, 10-year VMS exposure and long-term weight gain. RESULTS: The primary analysis sample included 2,361 participants (12,030 visits; 1995-2008). Increased VMS frequency across visits was associated with subsequently increased weight (0.24 kg), body mass index (0.08 kg/m 2 ), and waist circumference (0.20 cm). Cumulative exposure to a high frequency of VMS (≥6 d/2 wk) over 10 consecutive annual visits was associated with increases in weight measures, including a 3.0-cm increase in waist circumference. Contemporaneous sleep problems mediated no more than 27% of waist circumference increases. Menopause status was not a consistent moderator. CONCLUSIONS: This study demonstrates that increases in VMS, onset of a high frequency of VMS, and persistent VMS symptoms over time may precede weight gain in women.

Association of Migraine and Vasomotor Symptoms.

OBJECTIVE: To further examine a potential link between migraine and vasomotor symptoms as well as hypertension as a cardiovascular disease risk factor, potentially explaining the association in midlife women. PATIENTS AND METHODS: We conducted a cross-sectional analysis from the Data Registry on Experiences of Aging, Menopause, and Sexuality using questionnaire data from women aged 45 to 60 years seen in women's clinics at a tertiary care center from May 15, 2015, through January 31, 2022. A history of migraine was self-reported; menopause symptoms were assessed with the Menopause Rating Scale. Associations between migraine and vasomotor symptoms were evaluated utilizing multivariable logistic regression models adjusting for multiple factors. RESULTS: Of 5708 women included in the analysis, 1354 (23.7%) reported a migraine history. The total cohort had a mean age of 52.8 years, most (5184 [90.8%]) were White, and 3348 (58.7%) were postmenopausal. In adjusted analysis, women with migraine were significantly more likely to have severe/very severe hot flashes vs no hot flashes compared with women without migraine (odds ratio, 1.34; 95% CI, 1.08 to 1.66; P=.007). Migraine was associated with a diagnosis of hypertension in adjusted analysis (odds ratio, 1.31; 95% CI, 1.11 to 1.55; P=.002). CONCLUSION: This large cross-sectional study confirms an association between migraine and vasomotor symptoms. Migraine also was associated with hypertension, potentially providing a link with cardiovascular disease risk. Given the high prevalence of migraine in women, this association may help identify those at risk for more severe menopause symptoms.

Vasomotor symptoms and risk of cardiovascular disease in peri- and postmenopausal women: A systematic review and meta-analysis.

INTRODUCTION: Vasomotor symptoms (VMS) are the symptoms most frequently experienced by women transitioning to menopause and are a primary indication for menopausal hormone therapy. A growing body of evidence has associated the presence of VMS with future risk for cardiovascular disease (CVD) events. This study aimed to systematically evaluate, qualitatively and quantitatively, the possible association between VMS and the risk for incident CVD. METHODS: This systematic review and meta-analysis included 11 studies evaluating peri- and postmenopausal women in a prospective design. The association between VMS (hot flashes and/or night sweats) and the incidence of major adverse cardiovascular events, including coronary heart disease (CHD) and stroke, was explored. Associations are expressed as relative risks (RR) with 95 % confidence intervals (CI). RESULTS: The risk for incident CVD events in women with and without VMS differed according to the age of participants. Women with VSM younger than 60 years at baseline had a higher risk of an incident CVD event than women without VSM of the same age (RR 1.12, 95 % CI 1.05-1.19, I2 0%). Conversely, the incidence of CVD events was not different between women with and without VMS in the age group >60 years (RR 0.96, 95 % CI 0.92-1.01, I2 55%). CONCLUSION: The association between VMS and incident CVD events differs with age. VMS increases the incidence of CVD only in women under 60 years of age at baseline. The findings of this study are limited by the high heterogeneity among studies, pertaining mainly to different population characteristics, definitions of menopausal symptoms and recall bias.