Female hormonal exposures and risk of rheumatoid arthritis in the French E3N-EPIC cohort study.

OBJECTIVE To assess the relationships between female hormonal exposures and risk of rheumatoid arthritis (RA), in a prospective cohort of French women. METHODS E3N is an on-going French prospective cohort that included 98 995 women aged 40-65 years in 1990. Every 2-3 years, women completed mailed questionnaires on their lifestyles, reproductive factors, and health conditions. Cox proportional-hazards regression models were used to determine factors associated with risk of incident RA, with age as the time scale, adjusted for known risk factors of RA, and considering endogenous and exogenous hormonal factors. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated. Effect modification by smoking history was investigated. RESULTS A total of 698 incident cases of RA were ascertained among 78 452 women. In multivariable-adjusted Cox regression models, risk of RA was increased with early age at first pregnancy ( 24 vs 0 months; multi-adjusted HR = 0.77; 95%CI 0.6-0.9). CONCLUSIONS These results suggest an effect of both endogenous and exogenous hormonal exposures on RA risk and phenotype that deserves further investigation.