Lifetime female hormonal exposure and risk of rheumatoid arthritis in postmenopausal women: Results from the French E3N cohort.

Objective: To assess the relationships between lifetime female hormonal exposures and the risk of incident RA in postmenopausal women.

Methods: E3N is an ongoing French prospective cohort of 98,995 women since 1990 aged 40-65 years at enrolment. Data on reproductive/hormonal factors and treatments were regularly recorded. Exposures were defined as follows: - reproductive span (in years)=duration from menarche to menopause; - total ovulatory years=reproductive span-(number of full-term pregnancies×0.75+number of miscarriages×0.25+total duration of breast feeding+total duration of oral contraception); - lifetime duration of hormonal exposure (in years)=reproductive span+total duration of menopausal hormonal therapy; - composite estrogen score (CES, range=0-6): 1 point for each item: early menarche, high parity, history of hysterectomy, use of oral contraception, use of menopausal hormonal therapy and late menopause. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of incident RA were estimated using Cox proportional hazards regression models with age as the time scale.

Results: Among the 78,391 postmenopausal cohort women, 637 validated incident RA cases occurred. Lifetime durations of hormonal exposures were not associated with incident RA in postmenopausal women. High (CES=4-6) versus low (CES=0-1) estrogen exposure was inversely associated with the risk of RA: HR 0.37; 95% CI 0.2-0.8.

Conclusion: In the E3N cohort, high lifetime estrogen exposure, that summarizes cumulative endogenous and exogenous exposures, was associated with a decreased risk of RA in postmenopausal women.