Hormone therapy in menopause increases rheumatoid arthritis risk: A systematic review and meta-analysis

Abstract

Objective: To assess the association between menopausal hormone therapy use and Rheumatoid Arthritis (RA) incidence among postmenopausal women.

Methods: A systematic review and meta-analysis were conducted following PRISMA guidelines. MEDLINE, Embase, and the Cochrane Library were searched up to October 2025 for observational studies evaluating menopausal hormone therapy use and RA risk. Pooled risk ratios (RR) with 95% confidence intervals (CIs) were calculated using random-effects models. Subgroup analyses explored current versus former use and therapy duration.

Results: Five studies comprising 22,291,843 person-years of follow-up were included. Overall, menopausal hormone therapy use was associated with a modestly increased RA risk (Rate Ratio 1.15, 95% CI 1.10-1.21, p < 0.001; I² = 0%). Current users had higher risk (Rate Ratio 1.18, 95% CI 1.00-1.37, p = 0.04) compared with former users (Rate Ratio 1.11, 95% CI 0.94-1.32, p = 0.20). Long-term use (≥4 years) conferred greater risk (Rate Ratio 1.19, 95% CI 1.07-1.33, p = 0.002).

Conclusions: Current menopausal hormone therapy use is associated with a modestly higher incidence of rheumatoid arthritis. Although the absolute increase is small, the widespread use highlights the need for individualized risk-benefit assessment, especially in women with autoimmune susceptibility.

Keywords: Autoimmune disease; Hormone replacement therapy; Menopause; Meta-analysis; Rheumatoid arthritis.