Pharmacologic Treatments for Female Menopausal Vasomotor Symptoms: A Systematic Review and Meta-analysis for the American College of Physicians

BACKGROUND: Vasomotor symptoms (VMS) are common in perimenopausal and postmenopausal females. PURPOSE: To evaluate benefits, harms, patient values and preferences, and cost-effectiveness of pharmacologic treatments for VMS. DATA SOURCES: MEDLINE ALL, Embase, and Cochrane Central Register of Controlled Trials from inception to 3 March 2026. STUDY SELECTION: Randomized trials of at least 8 weeks' duration of eligible medications in females with VMS reporting VMS frequency and severity, menopause-related quality of life (QoL), sleep quality, endometrial hyperplasia or cancer, and/or serious adverse events (SAEs); U.S. Food and Drug Administration and European Medicines Agency labels for additional harms. DATA EXTRACTION: Data were abstracted by 1 reviewer and verified by a second reviewer. Independent, dual risk-of-bias assessments were performed. Certainty of evidence (COE) was assessed by 1 reviewer and overread by a second reviewer. DATA SYNTHESIS: Ninety trials were included. COE was low to moderate for most comparisons. Compared with placebo, estrogens with or without progestogens, conjugated estrogen with bazedoxifene (CE/BZA), and oxybutynin reduced VMS frequency and severity. Compared with placebo, neurokinin receptor antagonists (NKRAs), serotonin-norepinephrine reuptake inhibitors (SNRIs), selective serotonin reuptake inhibitors (SSRIs), gabapentin, and progestogens reduced VMS frequency but not severity. Estrogen efficacy varied by dose but not route. Estrogens with and without progestogens, CE/BZA, NKRAs, SNRIs, and SSRIs improved menopause-related QoL; gabapentin, NKRAs, oxybutynin, SNRIs, and SSRIs improved sleep quality. Few SAEs were reported. Evidence was insufficient for patient values and preferences. Estrogens with or without progestogens are of high economic value (high COE). The NKRA fezolinetant has low value (moderate COE). LIMITATIONS: Most studies were short-term and were not designed to evaluate SAEs or long-term harms. Observational studies that could address long-term harms were not included. CONCLUSION: Estrogens reduced VMS frequency and severity and improved QoL (with or without progestogens and with BZA). NKRAs, SNRIs, and SSRIs improved VMS frequency, QoL, and sleep. Estrogens with and without progestogens were of high economic value. Harms data were limited. Little comparative information exists. PRIMARY FUNDING SOURCE: American College of Physicians. (PROSPERO: CRD42024558116).