Estrogen replacement therapy and physical function in rheumatoid arthritis

Postmenopausal women with RA experience worsening functional decline, independent of disease activity. Estrogen replacement therapy (ERT) has been proposed to mitigate musculoskeletal deterioration, but its role in RA remains unclear. This study investigated the association between ERT use and physical function in postmenopausal women with RA.

This longitudinal study analysed data from 'Forward, the National Databank for Rheumatic Diseases' (2000-22). Postmenopausal women with RA who initiated ERT were matched 1:1 to non-users based on menopause year or ERT initiation. The primary outcome was physical function, assessed using the HAQ. Generalized estimating equations (GEE) were used to evaluate the association between ERT and HAQ scores, adjusting for demographics, reproductive history, RA duration, comorbidities and medication use. Sensitivity analyses with propensity score matching were conducted.

A total of 8246 women were included, with 4123 ERT users matched to non-users. ERT use was associated with modestly improved HAQ scores (β = -0.02, 95% CI -0.03, -0.01; P < 0.001). Later menopause correlated with better function (β = -0.008 per year after menopause, 95% CI -0.03, -0.01; P < 0.001). Women initiating ERT within 5 years of menopause demonstrated greater benefits. Sensitivity analyses using propensity score adjustment confirmed these findings and revealed additional improvements in patient-reported outcomes.

ERT use was modestly associated with improved physical function and other patient-reported outcomes in postmenopausal women with RA, with the greatest benefits seen in early postmenopausal initiation. No excess crude rates of cardiovascular or cancer events were observed. Further research is needed to determine the clinical implications of ERT in RA management.