402 Reproductive Factors and Risk of Ulcerative Colitis and Crohn's Disease: Results From Two Large Prospective Cohorts of U.S. Women

Abstract

(median age 54 years) enrolled in 1976 in the Nurses Health Study without a prior history of IBD. Every two years, we have updated information on menopause status, use of postmenopausal hormone replacement therapy, and other risk factors with >90% follow-up. Self-reported CD and UC diagnoses were confirmed through medical records review by two gastroenterologists blinded to exposure information. We used Cox proportional hazards models to calculated hazard ratios (HR) and 95% confidence intervals (CIs) adjusted for age, smoking, body mass index, and type of menopause (natural vs. surgical/ radiation). We evaluated effect modification by these factors using cross-classified categories of the covariates and hormone use. We tested the significance of these interactions by using the log likelihood ratio test comparing the model with these cross-classified categories with a model that included only the potential modifiers as independent variables. Results: Through 2008, over 1,891,153 person years of follow up, we documented 138 incident cases of CD and 138 cases of UC. Compared to women who never used hormones, the multivariateadjusted HRs for UC was 1.74 (95% CI, 1.09-2.77) among women who were current users and 1.68 (95% CI, 1.05-2.71) among past users. The risk of UC increased with longer duration of hormone use (Ptrend = 0.02) and diminished with longer duration of discontinuation. Compared to current users, the multivariate-adjusted HR for UC was 2.11 (95% CI, 1.16-3.84) among women who discontinued hormones for 5 or fewer years and 1.27 (95% CI, 0.72-2.24) among women who discontinued for more than 5 years. There was no difference in the risk according to the type of hormone therapy used (estrogen vs estrogen + progesterone). In contrast, we did not observe an association between current use of hormones and risk of CD (multivariate-adjusted HR 1.19, 95% CI, 0.78-1.81). The effect of hormones on risk of UC and CDwas not modified by BMI, smoking, and type of menopause (all Pinteraction > 0.10). Conclusion: In a large prospective cohort of postmenopausal women, hormone replacement therapy was associated with an increased risk of UC but not CD. These findings may provide novel insights into biological pathways related to estrogens that may mediate the pathogenesis of UC.