ORF38-01 - Comparative Efficacy and Safety of Neurokinin Receptor Antagonists for Menopausal Vasomotor Symptoms: A Systematic Review and Meta-Analysis

Background: Neurokinin receptor antagonists have emerged as effective non-hormonal therapies for menopausal vasomotor symptoms (VMS). Fezolinetant and elinzanetant have recently received regulatory approval based on phase 3 randomized trials.

Methods: A systematic search was conducted across major databases, data were analyzed using Stata version 18.0, and risk of bias was assessed using the ROBS 2.0.

Results: Six phase 3 trials involving 3,331 postmenopausal women were included. Of these, 1,424 received elinzanetant, 1,907 received fezolinetant, with placebo comparators across all studies. Elinzanetant significantly reduced VMS frequency at week 12 (mean difference [MD] 2.3, 95% CI 1.78–3.65) and VMS severity (MD 0.3, 95% CI 0.1–0.35), with a rapid onset of action within 7 days (range 6–8). Sleep disturbance improved by approximately 120 minutes (95% CI 135–168), and menopause-related quality of life improved by 2.5 MENQOL points (95% CI 2–3). Fezolinetant demonstrated a favorable safety profile, with no significant increase in overall adverse events compared with placebo (risk ratio 1.35, 95% CI 0.30–2.63).

Conclusions: In comparative evaluation, elinzanetant showed broader symptomatic benefits with rapid VMS relief and improvements in sleep and quality of life, whereas fezolinetant demonstrated favorable tolerability and safety, with a low overall risk of bias across included trials.