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In previous literature regarding development of rheumatoid arthritis (RA), female reproductive factors have been described as protective factors, risk factors, or irrelevant, leading to inconsistent results. The aim of this study was to investigate the effect of female reproductive factors on the incidence of seropositive RA. A large population-based retrospective cohort of the National Health Insurance Service data in South Korea was used. Postmenopausal women who participated in both cardiovascular and breast cancer screening in 2009 were included and followed until date of seropositive RA diagnosis, death, or December 31, 2018. Multivariable-adjusted Cox proportional hazards model was used to assess the association between reproductive factors and incident seropositive RA. Of 1,357,736 postmenopausal women, 6056 women were diagnosed with seropositive RA, and the incidence rate was 54.16 cases/100,000 person-years. Reproductive factors other than hormone replacement therapy (HRT) were not significantly associated with seropositive RA incidence. Postmenopausal women who used HRT ≥ 5 years were associated with a higher aHR of incident seropositive RA than never-users (aHR 1.25; 95% CI 1.09–1.44). Alcohol consumption less than 30 g per day (aHR 0.80; 95% CI 0.74–0.87), regular physical activity (aHR 0.90; 95% CI 0.84–0.97), diabetes mellitus (aHR 0.85; 95% CI 0.78–0.93), and cancer (aHR 0.77; 95% CI 0.64–0.92) were associated with lower risk of seropositive RA. Most female reproductive factors did not significantly affect the development of seropositive RA in postmenopausal women. Only HRT is associated with a small but significant increase in risk of seropositive RA.

Menopausal factors and risk of seropositive rheumatoid arthritis in postmenopausal women: a nationwide cohort study of 1.36 million women