The effectiveness of red clover on hot-flash in menopausal women: a GRADE-assessed systematic review and meta-analysis.

OBJECTIVES: Red clover (Trifolium pratense) isoflavones are widely used as alternatives to hormone therapy for menopausal vasomotor symptoms, yet evidence regarding their efficacy remains inconsistent. To systematically evaluate the effectiveness of red clover supplementation in reducing hot flush frequency and severity in menopausal women. METHODS: A systematic review and meta-analysis was conducted following PRISMA guidelines through searching PubMed, Scopus, Web of Science, and Embase data bases for randomized controlled trials comparing red clover isoflavone formulations with placebo in peri- or postmenopausal women experiencing hot flash. Meta-analysis was performed using Comprehensive Meta-Analysis (CMA) software, version 3.7, calculated standardized mean differences (SMD) with 95% confidence intervals. Statistical significance was set at a p-value < 0.05. RESULTS: Nine randomized controlled trials (RCTs) met inclusion criteria, enrolling women aged 40-65 years with baseline hot flush frequencies of 2.1-11.7 per day. Red clover doses ranged from 37.1-160 mg daily isoflavones, with treatment durations of 12 weeks to 12 months. Meta-analysis revealed a statistically significant reduction in frequency of hot flash favoring red clover over placebo (SMD = -0.446; 95% CI: -0.807 to -0.084; p = 0.016), representing a small-to-moderate effect. Sensitivity analyses confirmed result stability, and no publication bias was detected. Most trials exhibited low risk of bias. CONCLUSION: Red clover isoflavone supplementation demonstrates modest but statistically significant efficacy in reducing menopausal hot flushes compared with placebo, supporting its potential role as a phytoestrogenic alternative for managing vasomotor symptoms.