Menopausal hormone therapy associated with modestly increased rheumatoid arthritis risk in meta-analysis

This systematic review and meta-analysis examined the association between menopausal hormone therapy use and rheumatoid arthritis incidence in postmenopausal women. The analysis included 5 studies representing 22,291,843 person-years of follow-up, though specific study designs and settings were not reported. The comparator group was not explicitly defined in the available data.

Overall, menopausal hormone therapy use was associated with a modestly increased risk of rheumatoid arthritis (Rate Ratio 1.15, 95% CI 1.10-1.21, p < 0.001). The association was stronger for current users (RR 1.18, 95% CI 1.00-1.37, p = 0.04) compared to former users, where the association was not statistically significant (RR 1.11, 95% CI 0.94-1.32, p = 0.20). Long-term use of ≥4 years showed greater risk (RR 1.19, 95% CI 1.07-1.33, p = 0.002).

Safety and tolerability data were not reported in the available evidence. The analysis showed no statistical heterogeneity (I² = 0%), but key limitations include the observational nature of the included studies, which cannot establish causation. Funding sources and conflicts of interest were not reported.

For clinical practice, these findings suggest that while the absolute increase in RA risk appears small, the widespread use of menopausal hormone therapy highlights the need for individualized risk-benefit assessment. Clinicians should be aware of this potential association, particularly when considering therapy for women with autoimmune susceptibility or family history of RA.