Fezolinetant and Elinzanetant Therapy for Menopausal Women Experiencing Vasomotor Symptoms

OBJECTIVE: To assess the efficacy and safety of fezolinetant and elinzanetant for vasomotor symptoms in menopausal women. DATA SOURCES: MEDLINE, EMBASE, and Cochrane databases were systematically searched until August 22, 2024. Because the Cochrane Library included all the identified randomized controlled trials (RCTs), it was unnecessary to search ClinicalTrials.gov. The following words made up the search strategy, which was applied to the three databases: fezolinetant, elinzanetant, vasomotor symptoms, and menopause. METHODS OF STUDY SELECTION: Only RCTs comparing fezolinetant and elinzanetant with placebo for vasomotor symptoms in menopausal women were included. TABULATION, INTEGRATION, AND RESULTS: We extracted the number of patients, mean age, body mass index (BMI), and number of patients who underwent oophorectomy. Data were examined with the Mantel–Haenszel method and 95% CIs. Heterogeneity was assessed with I 2 statistics. R 4.3.2 was used for statistical analysis. Seven RCTs with 4,087 patients were included in the analysis. Fezolinetant and elinzanetant were associated with diminished vasomotor symptom frequency: fezolinetant 30 mg (mean difference 2.16, 95% CI, 1.54–2.79, I 2 =0%), fezolinetant 45 mg (mean difference 2.54, 95% CI, 1.86–3.21, I 2 =0%), and elinzanetant 120 mg (mean difference 2.99, 95% CI, 1.74–4.23, I 2 =0%). Both drugs also showed a decrease in vasomotor symptom severity: fezolinetant 30 mg (mean difference 0.20, 95% CI, 0.09–0.33, I 2 =0%), fezolinetant 45 mg (mean difference 0.24, 95% CI, 0.13–0.34, I 2 =0%), and elinzanetant 120 mg (mean difference 0.36, 95% CI, 0.26–0.46, I 2 =0%). Elinzanetant 120 mg showed a significant improvement in sleep quality (mean difference 4.65, 95% CI, 3.73–5.56, I 2 =0%). Elinzanetant 120 mg was associated with the occurrence of drug-related adverse events (11.70% vs 20.75%, risk ratio [RR] 0.57, 95% CI, 0.39–0.82, I 2 =19%) and headache (2.54% vs 8.0%, RR 0.32, 95% CI, 0.16–0.64, I 2 =0%). CONCLUSION: In this meta-analysis, consistent results suggest that fezolinetant and elinzanetant are associated with beneficial outcomes in menopausal women with vasomotor symptoms. Elinzanetant provided a larger effect size in vasomotor symptom frequency and severity reduction and greatly improved sleep quality compared with fezolinetant. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42023469952.