Pharmacological Treatments for Menopausal Vasomotor Symptoms: A Systematic Review and Bayesian Network Meta-Analysis of Efficacy and Safety

Abstract

Objectives: To evaluate the efficacy and safety of pharmacological treatments for vasomotor symptoms (VMS) in postmenopausal women.

Methods: A systematic search was conducted in PubMed, Embase, and the Cochrane Library through January 2025. Eligible studies were Phase 3 or 4 randomized controlled trials (RCTs) assessing pharmacological treatments for moderate to severe VMS with ≥ 12 weeks of follow-up. A Bayesian random-effects network meta-analysis estimated mean differences (MDs) and risk ratios (RRs) with 95 % credible intervals (CrI). Treatments were ranked using surface under the cumulative ranking (SUCRA). Risk of bias was assessed using Cochrane's tool.

Results: Forty-one RCTs (n = 14,743; mean age 53.4 years) were included. Synthetic conjugated estrogens (SCE) 1.25 mg showed the greatest reduction in VMS frequency (MD -5.69; 95 % CrI -7.93 to -3.38), while drospirenone 0.5 mg + estradiol 0.5 mg was most effective for severity (MD -1.06; 95 % CrI -1.39 to -0.72). Most treatments had safety profiles similar to placebo, though estradiol 0.5 mg + dydrogesterone 2.5 mg was linked to more adverse events (RR 1.56; 95 % CrI 1.16 to 2.24). No significant differences in serious adverse events were found. SUCRA rankings highlighted SCE and transdermal estradiol gel as most effective for frequency, while drospirenone + estradiol led for severity. Fezolinetant and elinzanetant showed moderate efficacy. Of the studies, 22 had low risk of bias, and 19 had some concerns.

Conclusions: Conjugated estrogens and drospirenone with estradiol are the most effective options for reducing VMS frequency and severity, and Fezolinetant and Elinzanetant showed moderate efficacy, with overall similar safety across treatments.

Keywords: Hormonal Therapy; Menopause; Non-hormonal therapy; Vasomotor Symptoms.