The Effect of Yoga on Menopause Symptoms: A Randomized Controlled Trial.

The research was conducted as a randomized controlled study with the aim of determining the effect of yoga on menopause symptoms. Menopausal women between the ages of 40 and 60 years were included in the research. There were 31 menopausal women in each of 2 groups, making a total of 62. A Descriptive Characteristics Form and the Menopause Rating Scale (MRS) were used to collect data. In the research, the yoga group practiced yoga for 60 minutes twice a week for 10 weeks. In the final lesson of the 10 weeks of yoga training, the women were again given the MRS. No intervention was performed on the control group. The median score on the MRS of the women in the yoga group was 16 (11-21) in the pretest, and 5 (3-9) in the posttest (P < .05). The median score on the subscale of psychological complaints of the women in the yoga group was 6 (3-8) in the pretest, and 1 (1-2) in the posttest (P < .05). The median score on the subscale of urogenital complaints of the women in the yoga group was 3 (3-5) in the pretest, and 1 (0-2) in the posttest (P < .05). The median score on the subscale of somatic complaints of the women in the yoga group was 7 (4-10) in the pretest, and 1 (1-3) in the posttest (P < .05). It was concluded from the research that 60 minutes of yoga 2 days a week for 10 weeks may reduce the psychological, somatic, and urogenital symptoms experienced in menopause.

A prospective, multicenter, randomized, double-blind placebo-controlled trial on purified and specific Cytoplasmic pollen extract for hot flashes in breast cancer survivors.

OBJECTIVE: evaluate the efficacy and tolerability of PureCyTonin against hot flashes (HF) in breast cancer survivors (BCS). METHODS: a prospective, multicenter, randomized, double-blind placebo-controlled trial was conducted in Italy. INTERVENTIONS: administration of PureCyTonin or placebo, for 3 months. Effectiveness was investigated through the compilation of a daily diary for HF and of validated questionnaires (Menopause Rating Scale (MRS), Pittsburgh Sleep Quality Index (PSQI), Visual Analogical Scales (VAS) for HF, sweating, irritability, fatigue, sleep, quality of life), carried out before starting the treatment (T0), after 1 month (T1) and after 3 months (T2). Any side effects and HF diary were recorded at each visit. RESULTS: 19 women were randomized to receive PureCyTonin and 20 to placebo. At T2 compared to T0, in the PureCyTonin group, we found a reduction in the number of HF (p = 0.02) measured by daily diary. An improvement in the subjective perception of women regarding HF intensity (p = 0.04), sweat nuisance (p = 0.02), irritability (p = 0.03) and fatigue (p = 0.04) was observed through VAS scale measurement at T2 compared to T0.The total MRS score was significantly better in the PureCyTonin group at T1 (p = 0.03) compared to T0. CONCLUSIONS: PureCyTonin significantly reduces HF number after 3 months of therapy in BCS and it is well-tolerated.

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.

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.

Treating moderate-to-severe menopausal vasomotor symptoms with fezolinetant: analysis of responders using pooled data from two phase 3 studies (SKYLIGHT 1 and 2).

OBJECTIVES: The aims of the study were to further characterize the efficacy of fezolinetant for the treatment of moderate-to-severe vasomotor symptoms (VMS) due to menopause using responder analysis and to investigate whether efficacy, not adjusted for placebo, resulted in clinically meaningful within-patient change. METHODS: This prespecified analysis used pooled data from two phase 3, randomized, double-blind, placebo-controlled studies (SKYLIGHT 1 and 2). Responders were those experiencing ≥50%, ≥75%, ≥90%, or 100% reduction in VMS frequency from baseline to weeks 4 and 12. Responder analysis was performed for patient-reported outcome (PRO) measures to evaluate participants achieving a clinically meaningful within-patient change (not placebo adjusted) at week 4 and 12 versus baseline. Single responders were based on outcomes of VMS frequency, Patient-Reported Outcomes Measurement Information System Sleep Disturbance-Short Form 8b Total Score, Menopause-Specific Quality of Life (MENQoL) Total Score, and MENQoL VMS Domain Score. Double and triple responder analyses combined VMS frequency plus one or more of the PRO. Patient Global Impression of Change VMS was deemed a suitable anchor measure for meaningful within-patient change in VMS frequency. RESULTS: A greater proportion of fezolinetant-treated versus placebo-treated participants had ≥50%, ≥75%, ≥90%, or 100% reduction in VMS frequency from baseline to weeks 4 and 12. A greater proportion of responders were observed in the fezolinetant groups versus placebo at week 12 in all four single responder analyses. In the double and triple responder analyses, odds ratios were supportive of a beneficial effect for both doses of fezolinetant versus placebo. CONCLUSIONS: Fezolinetant was associated with significantly higher within-patient clinically meaningful improvement in important PRO, including VMS frequency, PROMIS SD SF 8b Total Score, MENQoL Total Score, and MENQoL VMS Domain Score.

The association of race, ethnicity, and socioeconomic status on the severity of menopause symptoms: a study of 68,864 women.

OBJECTIVE: This study aimed to evaluate if and how race, ethnicity, and socioeconomic status (SES) are associated with the severity of menopause symptoms in a large, diverse sample of women. METHODS: For this cross-sectional study conducted between March 24, 2019, and January 13, 2023, a total of 68,864 women were enrolled from the Evernow online telehealth platform. Participants underwent a clinical intake survey, which encompassed demographic information, detailed medical questionnaires, and a modified Menopause Rating Scale. The modified scale was adapted for ease of use online and is available in the supplementary material along with the full intake. Symptom severity was evaluated using a multivariate binomial generalized linear model, accounting for factors such as race, ethnicity, age, body mass index, smoking status, bilateral oophorectomy status, and SES. Odds ratios (OR) and CIs were calculated based on the linear regression coefficients. RESULTS: Of the participants, 67,867 (98.6%) were included in the analysis after excluding outliers and those with unknown oophorectomy status. The majority of respondents identified as White (77.4%), followed by Hispanic (9.0%), Black (6.7%), two or more races/ethnicities (4.4%), Asian (1.2%), Indigenous/First Nations (0.8%), Middle Eastern (0.3%), and South Asian (0.2%). Notably, individuals identifying as Black (hot flashes OR, 1.91; 97.5% CI, 1.75-2.09; P < 0.001), Hispanic (skin/hair changes OR, 1.58; 97.5% CI, 1.45-1.71; P < 0.001), Indigenous/First Nations (painful sex OR, 1.39; 97.5% CI, 1.19-2.75; P = 0.007), Middle Eastern (weight changes OR, 2.22; 97.5% CI, 1.25-4.37; P = 0.01), or with two or more races/ethnicities (skin/hair changes OR, 1.41; 97.5% CI, 1.26-1.58; P < 0.001) reported higher levels of symptom severity compared with their White counterparts. Conversely, Asian and South Asian participants reported lower symptom severity. Even after incorporating SES into the linear model, racial and ethnic groups with lower SES (Black, Hispanic, Indigenous, and multiple ethnicities) exhibited slight shifts in OR while maintaining high statistical significance (Black [hot flashes OR, 1.87; 97.5% CI, 1.72-2.04; P < 0.001], Hispanic [skin/hair changes OR, 1.54; 97.5% CI, 1.42-1.68; P < 0.001], Indigenous/First Nations [painful sex OR, 1.74; 97.5% CI, 1.17-2.70; P = 0.009], multiple ethnicities [skin/hair changes OR, 1.41; 97.5% CI, 1.26-1.58; P < 0.001]). CONCLUSIONS: Our study suggests that the relationship between race and ethnicity and the severity of menopause symptoms is not solely explained by differences in SES but is itself an independent factor. Understanding and addressing social, cultural, and economic factors are crucial to reduce disparities in menopausal symptoms.

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.

The impact of symptom clusters on endocrine therapy adherence in patients with breast cancer.

BACKGROUND: When taken as prescribed, endocrine therapy is effective in reducing risk of recurrence and mortality in the treatment of patients with breast cancer. However, treatment side effects can act as a barrier to medication adherence. Existing research has not identified any specific side effects as consistent predictors of nonadherence. Our aim was to explore the influence of symptom clusters on self-reported adherence in patients with breast cancer. METHODS: A cross-sectional online survey was conducted, including patients with breast cancer currently or previously prescribed endocrine therapy (N = 1051). This included measures of self-reported endocrine therapy adherence and common symptoms among this population (insomnia, depression, anxiety, fatigue, musculoskeletal, and vasomotor symptoms). RESULTS: Unintentional nonadherence was higher than intentional nonadherence (50.8 % vs 31.01 %). The most troublesome symptom was insomnia (73.83 % displayed probable insomnia disorder). K-means cluster analysis identified 2 symptom clusters: overall High symptoms, and overall Low symptoms. Participants in the Low symptoms cluster were significantly more likely to be classed as adherent based on unintentional and intentional items. CONCLUSIONS: Nonadherence was high in the current sample, and significantly more likely in participants reporting overall severe symptoms. Clinicians should be aware of the scale of common side effects and facilitate open conversation about potential barriers to adherence. Follow-up care should include assessment of common symptoms and signpost patients to appropriate support or treatment when required. Future research should explore potential for a central symptom to act as a target for intervention, to relieve overall side effect burden and facilitate better medication adherence.

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.

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.

Dietary Supplementation of Myo-Inositol, Cocoa Polyphenols, and Soy Isoflavones Improves Vasomotor Symptoms and Metabolic Profile in Menopausal Women with Metabolic Syndrome: A Retrospective Clinical Study.

Background and Objectives: Hormonal changes physiologically occurring in menopausal women may increase the risk of developing metabolic and vasomotor disturbances, which contribute to increase the risk of developing other concomitant pathologies, such as metabolic syndrome (MetS). Materials and Methods: Retrospective data from 200 menopausal women with MetS and vasomotor symptoms taking one sachet per day of the dietary supplement INOFOLIC® NRT (Farmares srl, Rome, Italy) were collected. Each sachet consisted of myo-Inositol (2000 mg), cocoa polyphenols (30 mg), and soy isoflavones (80 mg, of which 50 mg is genistin). Patients recorded their symptoms through a medical questionnaire at the beginning of the administration (T0) and after 6 months (T1). Results: We observed an improvement in both the frequency and the severity of hot flushes: increased percentage of 2-3 hot flushes (28 at T0 vs. 65% at T1, p value < 0.001) and decreased percentage of 4-9 hot flushes (54% at T0 vs. 18% at T1, p value < 0.001). Moreover, symptoms of depression improved after supplementation (87% at T0 vs. 56% at T1 of patients reported moderate depression symptoms, p value < 0.001). Regarding metabolic profile, women improved body mass index and waist circumference with a reduction in the percentage of overweight and obesity women (88% at T0 vs. 51% at T1, p value = 0.01; 14% at T0 vs. 9% at T1, p value = 0.04). In addition, the number of women suffering from non-insulin dependent diabetes reduced (26% at T0 vs. 16% at T1, p value = 0.04). Conclusions: These data corroborate previously observed beneficial effects of the oral administration of myo-Inositol, cocoa polyphenols, and soy isoflavones against menopausal symptoms in the study population. Considering the promising results of the present study, further prospective controlled clinical trials are needed to deeply understand and support the efficacy of these natural compounds for the management of menopausal symptoms.

Dorsal brain activity reflects the severity of menopausal symptoms.

OBJECTIVE: The severity of menopausal symptoms, despite being triggered by hormonal imbalance, does not directly correspond to hormone levels in the blood; thus, the level of unpleasantness is assessed using subjective questionnaires in clinical practice. To provide better treatments, alternative objective assessments have been anticipated to support medical interviews and subjective assessments. This study aimed to develop a new objective measurement for assessing unpleasantness. METHODS: Fourteen participants with menopausal symptoms and two age-matched participants who visited our outpatient section were enrolled. Resting-state brain activity was measured using magnetoencephalography. The level of unpleasantness of menopausal symptoms was measured using the Kupperman Kohnenki Shogai Index. The blood level of follicle-stimulating hormone and luteinizing hormone were also measured. Correlation analyses were performed between the oscillatory power of brain activity, index score, and hormone levels. RESULTS: The level of unpleasantness of menopausal symptoms was positively correlated with high-frequency oscillatory powers in the parietal and bordering cortices (alpha; P = 0.016, beta; P = 0.015, low gamma; P = 0.010). The follicle-stimulating hormone blood level was correlated with high-frequency oscillatory powers in the dorsal part of the cortex (beta; P = 0.008, beta; P = 0.005, low gamma; P = 0.017), whereas luteinizing hormone blood level was not correlated. CONCLUSION: Resting-state brain activity can serve as an objective measurement of unpleasantness associated with menopausal symptoms, which aids the selection of appropriate treatment and monitors its outcome.

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.