Oral contraceptives, reproductive factors and risk of inflammatory bowel disease

Background Oral contraceptive use has been associated with risk of Crohn's disease (CD) and ulcerative colitis (UC). Objective To determine whether this association is confounded or modified by other important lifestyle and reproductive factors. Design A prospective cohort study was carried out of 117?375 US women enrolled since 1976 in the Nurses Health Study I (NHS I) and 115?077 women enrolled since 1989 in the Nurses' Health Study II (NHS II) with no prior history of UC or CD. These women had provided information every 2years, on age at menarche, oral contraceptive use, parity, menopause status and other risk factors. Diagnoses of CD and UC were confirmed by review of medical records. Cox proportional hazards models were used to calculate HRs and 95% CIs. Results Among 232?452 women with over 5?030?196 person-years of follow-up, 315 cases of CD and 392 cases of UC were recorded through 2007 in NHS II and 2008 in NHS I. Compared with never users of oral contraceptives, the multivariate-adjusted HRs for CD were 2.82 (95% CI 1.65 to 4.82) among current users and 1.39 (95% CI 1.05 to 1.85) among past users. The association between oral contraceptives and UC differed according to smoking history (p(heterogeneity)=0.04). Age at menarche, age at first birth and parity were not associated with risk of UC or CD. Conclusion In two large prospective cohorts of US women, oral contraceptive use was associated with risk of CD. The association between oral contraceptive use and UC was limited to women with a history of smoking.