OBJECTIVE(S): Menopause, marked by a decline in estrogen, leads to disruptive vasomotor symptoms like hot flashes and night sweats, significantly affecting quality of life. This meta-analysis evaluated the efficacy and safety of fezolinetant and elinzanetant, two neurokinin 3 receptor antagonists, in managing vasomotor symptoms in postmenopausal women. METHODS: Data sources were identified by searches in PubMed, Embase, and the Cochrane Central Register of Controlled Trials up to September 2024. The study followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, with the risk of bias assessed using the version 2 of the Cochrane Risk of Bias Tool for Randomized Trials and evidence quality was evaluated using the Grading of Recommendations Assessment, Development and Evaluation approach. Data were pooled using a random-effects model, and statistical analysis was performed using R version 4.4.1. RESULTS: Ten studies involving 4663 patients were included in the analysis. Elinzanetant >
100 mg and fezolinetant ≤45 mg were the most effective doses for reducing vasomotor symptom frequency and severity. Fezolinetant (MD = -1.38) and elinzanetant (MD = -2.04) achieved ≥50 % reductions in vasomotor symptom frequency, with a greater effect in the elinzanetant group. Additionally, elinzanetant improved menopause-specific quality of life. However, higher doses of both drugs were associated with increased adverse effects, with elinzanetant demonstrating a more favorable side-effect profile than fezolinetant. CONCLUSIONS: Fezolinetant and elinzanetant are effective options for managing vasomotor symptoms. However, further research is needed to compare these treatments directly and evaluate their long-term safety profiles across different patient populations.