Nonhormone therapies for vasomotor symptom management.

Vasomotor symptoms (VMS) are associated with adverse health consequences and can cause significant morbidity for postmenopausal women. Although hormone therapy remains the gold standard of VMS treatment in menopausal women, some women have contraindications to or may choose not to take hormone therapy. This article provides an up-to-date overview of the current evidence-based nonhormone therapies available for managing VMS. Evidence supporting various treatment options is reviewed, including lifestyle interventions, mind-body therapies, procedures, pharmacologic agents, and emerging therapies, such as neurokinin-receptor antagonists. The efficacy, safety, and clinical use of these treatments are detailed, offering insights for clinicians to make informed decisions in menopausal VMS management.

Menopausal symptom management: Fezolinetant's varied doses provide effective relief for vasomotor symptoms in women - A meta-analysis of 3291 participants.

Menopause represents the physiological transition when a woman's reproductive period ends associated with a variety of symptoms, including vasomotor symptoms, such as night sweats and hot flashes. This systematic review and meta-analysis aimed to assess the effectiveness and safety of oral Fezolinetant for treating vasomotor symptoms associated with menopause. Five electronic databases were searched from their inception until May 2023. Via the Cochrane risk of bias tool, two reviewers assessed the studies' quality. The primary outcomes were a decrease in VMSs frequency and severity and safety outcomes at 4 and 12 weeks. Data were extracted and then analyzed using RevMan software. This meta-analysis included six trials with a total of 3291 women that compared Fezolinetant to a placebo in the treatment of menopausal VMSs. After 4 and 12 weeks of therapy, fezolinetant at 30 mg QD or 45 mg QD substantially decreased the frequency and severity of VMSs per 24 hours compared to placebo. Fezolinetant at 90 mg BID, 30 mg QD, or 45 mg QD did not show a significant difference in the rate of treatment-emergent adverse events (TEAEs), headache, and TEAEs leading to permanent discontinuation compared to placebo. Fezolinetant proves to be a successful and well-tolerated remedy for menopausal women suffering from VMSs. Notably, the 45 mg daily dosage over 12 weeks exhibited significant efficacy. Nonetheless, extensive future trials are necessary to ascertain its long-term safety, effectiveness, and relative potency compared to alternative VMS treatments like hormone therapy.

La ménopause représente la transition physiologique lorsque la période de reproduction d'une femme se termine, associée à divers symptômes, notamment des symptômes vasomoteurs, tels que des sueurs nocturnes et des bouffées de chaleur. Cette revue systématique et méta-analyse visaient à évaluer l'efficacité et l'innocuité du Fezolinetant oral pour traiter les symptômes vasomoteurs associés à la ménopause. Cinq bases de données électroniques ont été consultées depuis leur création jusqu'en mai 2023. Via l'outil Cochrane sur le risque de biais, deux examinateurs ont évalué la qualité des études. Les principaux critères de jugement étaient une diminution de la fréquence et de la gravité des SVM ainsi que des critères de sécurité à 4 et 12 semaines. Les données ont été extraites puis analysées à l'aide du logiciel RevMan. Cette méta-analyse comprenait six essais portant sur un total de 3 291 femmes comparant Fezolinetant à un placebo dans le traitement des SVM ménopausiques. Après 4 et 12 semaines de traitement, le fézolinetant à la dose de 30 mg une fois par jour ou de 45 mg une fois par jour a considérablement réduit la fréquence et la gravité des SMV toutes les 24 heures par rapport au placebo. Le fézolinetant à la dose de 90 mg deux fois par jour, de 30 mg une fois par jour ou de 45 mg une fois par jour n'a pas montré de différence significative dans le taux d'événements indésirables survenus pendant le traitement (TEAE), de maux de tête et de TEAE conduisant à un arrêt définitif par rapport au placebo. Le fézolinetant s'avère être un remède efficace et bien toléré pour les femmes ménopausées souffrant de VMS. Notamment, la dose quotidienne de 45 mg sur 12 semaines a montré une efficacité significative. Néanmoins, de futurs essais approfondis sont nécessaires pour vérifier son innocuité, son efficacité et sa puissance relative à long terme par rapport aux traitements alternatifs du VMS comme l'hormonothérapie.

Effects of sports therapy on improvement of menopausal symptoms, psychological status, and body morphology in perimenopausal women.

OBJECTIVE: The aim of this study was to increase the treatment rate of perimenopausal women by providing evidence-based nonpharmaceutical treatments through developing scientific evidence-based sports therapy and verifying its effectiveness. METHODS: In a cross-over design, a total of 33 women were assigned to two different sequences of intervention: sports therapy and telephone intervention (n = 17) or telephone intervention and sports therapy (n = 16). A self-reported clinical symptom survey was conducted before and after the experimental and control periods using the following measures: the Menopause Rating Scale, Patient Health Questionnaire 9, and Patient Health Questionnaire 15. RESULTS: There were significant differences in the changes in the scores for Menopause Rating Scale total (exercise phase, 17.8 ± 5.5 at baseline [B] and 13.5 ± 4.2 at follow-up [F]; control phase, 15.9 ± 6.0 [B] and 15.4 ± 5.3 [F]; P < 0.01), somatic symptoms (exercise phase, 9.5 ± 2.6 [B] and 6.6 ± 2.0 [F]; control phase, 8.5 ± 2.8 [B] and 8.0 ± 1.3 [F], P < 0.01), and urogenital symptoms (exercise phase, 4.9 ± 1.7 [B] and 4.1 ± 1.4 [F]; control phase, 4.3 ± 1.6 [B] and 4.4 ± 1.5 [F]; P < 0.01) between the exercise and control phases. There were also significant differences in the changes in the scores for PHQ-9 (exercise phase, 4.6 ± 4.4 [B] and 3.6 ± 3.3 [F]; control phase, 4.5 ± 3.8 [B] and 5.5 ± 4.6 [F]; P = 0.008) and PHQ-15 (exercise phase, 7.2 ± 4.4 [B] and 5.5 ± 3.5 [F]; control phase, 6.8 ± 4.4 [B] and 7.2 ± 4.9 [F]; P = 0.009) between the two phases. CONCLUSIONS: Sports therapy would improve menopause symptoms, especially somatic and urogenital symptoms. In addition, sports therapy would improve depressive moods in perimenopausal women.

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.

Fezolinetant treatment of moderate-to-severe vasomotor symptoms due to menopause: effect of intrinsic and extrinsic factors in two phase 3 studies (SKYLIGHT 1 and 2).

OBJECTIVE: This study aimed to assess the efficacy of the neurokinin 3 receptor antagonist, fezolinetant, according to several intrinsic (individual related) and extrinsic (external influence) factors that may influence the frequency and severity of moderate-to-severe vasomotor symptoms (VMS) using pooled 12-week data from SKYLIGHT 1 and 2. METHODS: SKYLIGHT 1 and 2 were two phase 3, randomized, double-blind studies conducted from July 2019 to August 2021 (SKYLIGHT 1) or April 2021 (SKYLIGHT 2). Participants were initially randomized to receive daily doses of placebo, fezolinetant 30 mg, or fezolinetant 45 mg. After 12 weeks, placebo participants were rerandomized to receive fezolinetant 30 mg or 45 mg, whereas those receiving fezolinetant continued on the same dose. Change in VMS frequency from baseline to week 12 was used to assess efficacy according to several intrinsic and extrinsic factors. Overall efficacy and safety were also investigated. RESULTS: Overall, 1,022 individuals were included. Fezolinetant was efficacious in reducing VMS frequency across all intrinsic and extrinsic factors. Efficacy was most notable for participants who self-identify as Black (least squares mean difference for fezolinetant 45 mg versus placebo, -3.67; 95% CI, -5.32 to -2.01), current smokers (-3.48; -5.19 to -1.77), and current alcohol users (-3.48; -4.42 to -2.54). Overall efficacy was -2.51 (95% CI, -3.20 to -1.82) for fezolinetant 45 mg versus placebo. Similar findings were observed for the fezolinetant 30 mg dose. Comparable incidences of treatment-emergent adverse events were observed for placebo (132 of 342 individuals [38.6%]), fezolinetant 30 mg (132 of 340 individuals [38.8%]), and fezolinetant 45 mg (135 of 340 individuals [39.7%]). CONCLUSIONS: None of the intrinsic and extrinsic factors analyzed substantially reduced the efficacy response to fezolinetant in SKYLIGHT 1 and 2. These data provide additional confidence for using fezolinetant in a diverse population of individuals with VMS.

Early-onset vasomotor symptoms and development of depressive symptoms among premenopausal women.

BACKGROUND: We investigated the association between vasomotor symptoms (VMSs) and the onset of depressive symptoms among premenopausal women. METHODS: This cross-sectional study included 4376 premenopausal women aged 42-52 years, and the cohort study included 2832 women without clinically relevant depressive symptoms at baseline. VMSs included the symptoms of hot flashes and night sweats. Depressive symptoms were evaluated using the Center for Epidemiological Studies Depression Scale; a score of ≥16 was considered to define clinically relevant depressive symptoms. RESULTS: Premenopausal Women with VMSs at baseline exhibited a higher prevalence of depressive symptoms compared with women without VMSs at baseline (multivariable-adjusted prevalence ratio 1.76, 95 % confidence interval [CI] 1.47-2.11). Among the 2832 women followed up (median, 6.1 years), 406 developed clinically relevant depressive symptoms. Women with versus without VMSs had a significantly higher risk of developing clinically relevant depressive symptoms (multivariable-adjusted hazard ratio, 1.72; 95 % CI 1.39-2.14). VMS severity exhibited a dose-response relationship with depressive symptoms (P for trend <0.05). LIMITATIONS: Self-reported questionnaires were only used to obtain VMSs and depressive symptoms, which could have led to misclassification. We also could not directly measure sex hormone levels. CONCLUSIONS: Even in the premenopausal stage, women who experience hot flashes or night sweats have an increased risk of present and developed clinically relevant depressive symptoms. It is important to conduct mental health screenings and provide appropriate support to middle-aged women who experience early-onset VMSs.

Managing menopause after cancer.

Globally, 9 million women are diagnosed with cancer each year. Breast cancer is the most commonly diagnosed cancer worldwide, followed by colorectal cancer in high-income countries and cervical cancer in low-income countries. Survival from cancer is improving and more women are experiencing long-term effects of cancer treatment, such as premature ovarian insufficiency or early menopause. Managing menopausal symptoms after cancer can be challenging, and more severe than at natural menopause. Menopausal symptoms can extend beyond hot flushes and night sweats (vasomotor symptoms). Treatment-induced symptoms might include sexual dysfunction and impairment of sleep, mood, and quality of life. In the long term, premature ovarian insufficiency might increase the risk of chronic conditions such as osteoporosis and cardiovascular disease. Diagnosing menopause after cancer can be challenging as menopausal symptoms can overlap with other common symptoms in patients with cancer, such as fatigue and sexual dysfunction. Menopausal hormone therapy is an effective treatment for vasomotor symptoms and seems to be safe for many patients with cancer. When hormone therapy is contraindicated or avoided, emerging evidence supports the efficacy of non-pharmacological and non-hormonal treatments, although most evidence is based on women older than 50 years with breast cancer. Vaginal oestrogen seems safe for most patients with genitourinary symptoms, but there are few non-hormonal options. Many patients have inadequate centralised care for managing menopausal symptoms after cancer treatment, and more information is needed about cost-effective and patient-focused models of care for this growing population.

Royal Jelly and Fermented Soy Extracts-A Holistic Approach to Menopausal Symptoms That Increase the Quality of Life in Pre- and Post-menopausal Women: An Observational Study.

BACKGROUND: The objective of this study was to determine the effects of royal jelly and fermented soy extracts on menopausal symptoms and on quality of life in pre- and post-menopausal women. MATERIALS AND METHOD: This prospective observational study was carried out in a Clinical Hospital of Brasov, Romania, during June 2020 and December 2021. Eighty pre- and post-menopausal women, aged between 45 and 60 years, were included in two groups. The first group (40 women) received a dietary supplement with fermented soy extract twice a day for eight weeks and the second group (40 women) received the same dietary supplement with fermented soy extracts and 1500 mg of royal jelly capsules for eight weeks. After the treatment, the MENQOL score, DASS-21 score, and the mean number and intensity of daily hot flushes were recorded and compared with baseline values. RESULTS: After eight weeks of treatment, the score of the MENQOL questionnaire and all its domains' scores decreased in comparison with the baseline in both groups (p < 0.001). Also, the DASS-21 score (p < 0.001), depression score (p < 0.001), anxiety score (p < 0.001), and stress score (p < 0.001) improved. The mean number and the intensity of hot flushes decreased in both groups (p < 0.001). Comparing these variables after the treatment in both groups, we observed that the women who received dietary supplements with fermented soy extracts and royal jelly capsules recorded better scores for MENQOL (vasomotor, physical, and psychosocial domains) and a more reduced mean number of daily hot flushes. CONCLUSIONS: This observational study suggests that both dietary fermented soy supplements and royal jelly capsules possess beneficial effects against menopausal symptoms, increase the quality of life in pre- and post-menopausal women, and that the effects might be significantly improved if those dietary supplements are administered in association.

Menopause Hot Flashes and Molecular Mechanisms Modulated by Food-Derived Nutrients.

The causes of vasomotor symptoms, including hot flashes, are not fully understood, may be related to molecular factors, and have a polygenic architecture. Nutrients and bioactive molecules supplied to the body with food are metabolized using various enzymatic pathways. They can induce molecular cell signaling pathways and, consequently, activate effector proteins that modulate processes related to hot flashes in menopausal women. In this review, we analyzed the literature data from the last 5 years, especially regarding genome-wide association study (GWAS) analysis, and selected molecular factors and cell signaling pathways that may potentially be related to hot flashes in women. These are the kisspeptin-GnRH pathway, adipocyte-derived hormones, aryl hydrocarbon receptor signaling, catechol estrogens and estrogen sulfotransferase, inflammatory and oxidative stress biomarkers, and glucose availability. Then, single compounds or groups of food ingredients were selected that, according to experimental data, influence the course of the discussed molecular pathways and thus can be considered as potential natural therapeutic agents to effectively reduce the troublesome symptoms of menopause in women.

A systematic review and critical appraisal of menopause guidelines.

OBJECTIVE AND RATIONALE: To identify and appraise current national and international clinical menopause guidance documents, and to extract and compare the recommendations of the most robust examples. DESIGN: Systematic review. DATA SOURCES: Ovid MEDLINE, EMBASE, PsycINFO and Web of Science ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Practice guidance documents for menopause published from 2015 until 20 July 2023. Quality was assessed by the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument. RESULTS: Twenty-six guidance papers were identified. Of these, five clinical practice guidelines (CPGs) and one non-hormonal therapy position statement met AGREE II criteria of being at least of moderate quality. The five CPGs listed symptoms associated with the perimenopause and menopause to be vasomotor symptoms (VMS), disturbed sleep, musculoskeletal pain, decreased sexual function or desire, and mood disturbance (low mood, mood changes or depressive symptoms). Acknowledged potential long-term menopause consequences were urogenital atrophy, and increased risks of cardiovascular disease and osteoporosis. VMS and menopause-associated mood disturbance were the only consistent indications for systemic menopausal hormone therapy (MHT). Some CPGs supported MHT to prevent or treat osteoporosis, but specific guidance was lacking. None recommended MHT for cognitive symptoms or prevention of other chronic disease. Perimenopause-specific recommendations were scant. A neurokinin 3B antagonist, selective serotonin/norepinephrine (noradrenaline) reuptake inhibitors and gabapentin were recommended non-hormonal medications for VMS, and cognitive behavioural therapy and hypnosis were consistently considered as being of potential benefit. DISCUSSION: The highest quality CPGs consistently recommended MHT for VMS and menopause-associated mood disturbance, whereas clinical depression or cognitive symptoms, and cardiometabolic disease and dementia prevention were not treatment indications. Further research is needed to inform clinical recommendations for symptomatic perimenopausal women.

Sleep quality and psychological disorders in breast cancer female patients receiving radiotherapy at a tertiary oncology center in West Saudi Arabia.

PURPOSE: Breast cancer is the most prevalent type of cancer among women worldwide. Many recently diagnosed and treated breast cancer patients complain about sleep disorders, depression, anxiety, stress, and fatigue. This study aimed to evaluate sleep quality among breast cancer patients and to assess its association with psychological disorders, and socio-demographic and clinical characteristics of patients. METHODS: This cross-sectional study was conducted among women who received radiotherapy for breast cancer (stage 1-3) at King Abdul-Aziz Medical City-Jeddah from January to August 2021. Each participant completed a personal information form, the Pittsburgh Sleep Quality Index (PSQI), the Depression, Anxiety, and Stress Scale-21 (DASS-21), and the International Physical Activity Questionnaire (IPAQ). Clinical data were collected from the medical records to evaluate certain risk factors. Descriptive statistics were used for participant characteristics, and analyses of variance were used to assess associations between the qualitative variables. RESULTS: Fifty-six women with a mean age of 50.1 years and an average of 10 months after cancer diagnosis were included. Poor sleep quality was present in 58% of respondents. Symptomatic depression, anxiety, and stress were found in 34%, 32%, and 30% of women, respectively. Poor sleep quality was associated with depression (p = 0.031), anxiety (p = 0.03), and stress (p = 0.024) and was independently associated with hot flashes. In multivariate analysis, patients with depression or with cancer for more than 6 months were less likely to have good sleep after controlling other variables (21.74 and 14.71 times, respectively). CONCLUSION: Poor sleep quality was present in 58% of women with breast cancer receiving radiotherapy and was significantly associated with depression, anxiety, stress, and hot flashes. Depression level and cancer duration were significant predictors of sleep quality. Early identification and proper management of psychological and sleep disorders are necessary to improve the quality of life and survival of breast cancer patients.

Obesity and menopause.

Obesity is not a choice or a result of lack of willpower, but a multifactorial, chronic, progressive, and relapsing disease. During menopause, hormonal and body composition changes lead to greater visceral adiposity, that aggravates women's health at a cardiometabolic, mechanic and mental level. Adiposity has been identified as an important modifier of reproductive hormones. During female midlife, obesity has been associated with menstrual cycle alterations (anovulatory cycles ending with abnormal bleedings), menopausal symptoms including hot flashes, poor quality of sleep, aches and joint pain, genitourinary symptoms, and reduced quality of life. However, the relationships between weight, the menopausal process, aging, and hormone levels remain poorly understood. Women with obesity have an increased risk of thromboembolic disease when using menopause hormone therapy (MHT), and it is probably the main medical condition to prescribe or not MHT. However, this risk depends on the route and type of MHT. The use of estrogen-only or combined transdermal MHT does not increase the risk of a thrombotic event in women with obesity.

Physical activity and menopausal symptoms: evaluating the contribution of obesity, fitness, and ambient air pollution status.

OBJECTIVE: The menopausal transition is accompanied by transient symptoms that have been linked to subclinical cardiovascular disease (CVD); CVD has also been linked to air pollution. Physical activity (PA) reduces CVD, improves body composition, and can reduce menopausal symptoms. The purpose of this study was to assess the links between PA and menopausal symptoms and whether obesity, fitness, and air pollution status play a role in this relationship. METHODS: Women (40-60 y; N = 243; mean [SD] age, 47.8 [5.6] y) from areas with high versus low air pollution enrolled in the Healthy Aging in Industrial Environment Program 4 prospective cohort study completed psychological, cardiorespiratory fitness, body composition, and menopausal status screening followed by a 14-day prospective assessment of menopausal symptoms (Menopause Rating Scale) using a mobile application. Daily PA was assessed objectively across 14 days via Fitbit Charge 3 monitor. General linear mixed models were conducted and controlled for age, menopausal status, day in the study, wear time, and neuroticism. RESULTS: Peri/postmenopausal women ( ß = 0.43, P < 0.001) and those residing in a high-air-pollution environment ( ß = 0.45, P < 0.05) reported more somatovegetative symptoms. Hot flashes alone were associated with peri/postmenopausal status ( ß = 0.45, P < 0.001), and for women residing in a high-air-pollution environment, lower reporting of hot flashes was observed on days when a woman was more physically active than usual ( ß = -0.15, P < 0.001). No associations were found for cardiorespiratory fitness and visceral fat with any of the symptoms. CONCLUSIONS: PA may enhance resilience to hot flashes, especially when residing in high-air-pollution environments where we also observed higher reporting of somatovegetative menopausal symptoms.

Stellate ganglion block with procaine in breast cancer survivors with hot flashes and sleep disturbances undergoing Endocrine Therapy.

Breast cancer survivors under endocrine therapy (ET) suffer from side effects such as hot flashes and sleep disturbance accompanied by poor quality of life. Many quit ET early and reduce their survival rate. Guidelines recommend gabapentin next to yoga or acupuncture. The role of side effects related to compliance with ET over years require new and effective therapies. Stellate ganglion block (SGB) has shown evidence of safety and efficacy and was found to be more effective than pregabalin without side effects. However, practical guidelines for the long-term use of SGB are still missing. We primarily used procaine instead of bupivacaine presuming effectiveness paired with lower toxic risks. Twenty-nine breast cancer survivors with severe hot flashes and sleep disturbance under ET received SGB with Procaine. Diaries recorded hot flashes and sleep quality scores up to week 24. All patients took part and none refused SGB. Each Patient received one SGB every 4 weeks without any side effects observed. Weekly scores were reduced from baseline by -33.6% (P < .01) (hot flashes) and -22.3% (P < .01) (sleep disturbances) after 4, and by -58.8% (P < .01) (hot flashes) and -50.8% (P < .01) (sleep disturbances) after twenty-for weeks. A wavelike reduction indicated a limited effect of a single SGB during continuous ET. We showed, that procaine in SGB is as effective as bupivacaine with lower risks and costs. High significant reductions in hot flashes and sleep disturbances after 1 and 6 months were found. We conclude that breast cancer survivors need individual treatment with SGB due to her personal impact. Hence, SGB should find its way to guidelines and daily routines as a valuable method for treating side effects in breast cancer survivors undergoing ET.

Efficacy and Safety of Fezolinetant for the Treatment of Menopause-Associated Vasomotor Symptoms: A Meta-analysis.

OBJECTIVE: To evaluate the efficacy and adverse events of fezolinetant for treating vasomotor symptoms (VMS) of menopause. DATA SOURCES: PubMed/MEDLINE, ClinicalTrials.gov , EMBASE, Cochrane Database, Scopus, and WHO International Clinical Trials Registry Platform were searched through June 2023 for publications and randomized controlled trials on fezolinetant compared with placebo in menopausal women who experienced moderate-to-severe VMS. METHODS OF STUDY SELECTION: Our literature search identified 330 articles, of which five studies with six reports were included in our meta-analysis per our eligibility criteria. TABULATION, INTEGRATION, AND RESULTS: The risk of bias was evaluated using Cochrane's RoB 2 (Risk of Bias version 2) tool, quality of evidence was graded using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach, and outcome measures data for effect size were pooled in random-effects model and rated. A total of 2,168 participants from five randomized clinical trials (six reports) were included. Fezolinetant significantly lowered VMS frequency, with pooled mean difference of 2.62 (95% CI, 1.84-3.41). The pooled mean difference for fezolinetant compared with placebo for the MENQOL (Menopause-Specific Quality of Life) measure was -0.60 (95% CI, -0.92 to -0.28), and the mean percentage improvement in VMS frequency was 22.51% (95% CI, 15.35-29.67). Fezolinetant was associated with improvement in sleep quality when compared with placebo. CONCLUSION: Fezolinetant is effective in lowering moderate-to-severe VMS frequency and sleep disturbances in postmenopausal women. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42023427616.