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.