Hormone therapy increases risk of ulcerative colitis but not Crohn's disease.

BACKGROUND & AIMS: Estrogen has been proposed to modulate gut inflammation through an effect on estrogen receptors found on gastrointestinal epithelial and immune cells. The role of postmenopausal hormone therapy on risk of Crohn's disease (CD) and ulcerative colitis (UC) is unclear.

METHODS: We conducted a prospective cohort study of 108,844 postmenopausal US women (median age, 54 years) enrolled in 1976 in the Nurses' Health Study without a prior history of CD or UC. Every 2 years, we have updated information on menopause status, postmenopausal hormone use, and other risk factors. Self-reported diagnoses of CD and UC were confirmed through medical record review by 2 gastroenterologists who were blinded to exposure information. We used Cox proportional hazards models to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs).

RESULTS: Through 2008, with more than 1.8 million person-years of follow-up, we documented 138 incident cases of CD and 138 cases of UC. Compared with women who never used hormones, the multivariate-adjusted HR for UC was 1.71 (95% CI, 1.07-2.74) among women who currently used hormones and 1.65 (95% CI, 1.03-2.66) among past users. The risk of UC appeared to increase with longer duration of hormone use (P(trend) = .04) and decreased with time since discontinuation. There was no difference in risk according to the type of hormone therapy used (estrogen vs estrogen plus progestin). In contrast, we did not observe an association between current use of hormones and risk of CD (multivariate-adjusted HR, 1.19; 95% CI, 0.78-1.82). The effect of hormones on risk of UC and CD was not modified by age, body mass index, or smoking.

CONCLUSIONS: In a large prospective cohort of women, postmenopausal hormone therapy was associated with an increased risk of UC but not CD. These findings indicate that pathways related to estrogens might mediate the pathogenesis of UC.