Hormonal contraception is not associated with recurrent flares in ulcerative colitis: a longitudinal time-dependent analysis.

BACKGROUND AND AIM: Hormonal contraception (HCT) is widely used among women with ulcerative colitis (UC), yet its impact on disease activity and inflammatory burden remains unclear. We aimed to evaluate the association between HCT exposure, the risk of recurrent flares and inflammatory biomarkers in women with UC. METHODS: We conducted a multicenter retrospective longitudinal cohort study including female patients with UC. HCT exposure was treated as a time-dependent variable. The primary outcome was the risk of recurrent flares, assessed using an Andersen-Gill extension of the Cox model. Secondary outcomes included longitudinal biomarker changes and cumulative inflammatory burden using linear mixed-effects models and time-weighted area-under-the-curve analyses. RESULTS: A total of 225 women met inclusion criteria, of whom 58 (25.8%) were exposed to HCT after UC diagnosis. During a median follow-up of 5.3 (IQR 3.3-7.5) years, we identified 374 flares. HCT exposure was not associated with an increased risk of recurrent flares (adjusted HR (aHR) 0.93; 95% CI, 0.62-1.40; P = .742) but extensive UC (aHR 1.85; 95% CI, 1.22-2.79; P = .003), ex-smoker status (aHR 2.07; 95% CI, 1.07-4.01; P = .031) and age (aHR 0.97; 95% CI, 0.96-0.99; P < .001) were. A total of 13 747 biomarker measurements were available during follow-up. In adjusted longitudinal analysis, C-reactive protein was higher during HCT-exposed months (β for log-CRP = 0.254, P = .0038), whereas platelet count, erythrocyte sedimentation rate, albumin, alpha-1-acid glycoprotein and fecal calprotectin were not. The cumulative systemic inflammatory burden (AUC/time) remained comparable between exposure periods. No adverse events related to HCT exposure were identified. CONCLUSIONS: HCT was not associated with an increased risk of recurrent UC flares or a consistent increase in cumulative systemic inflammatory burden. No HCT-related safety signals were identified; however, the modest number of exposed women cannot exclude smaller effects or rare safety outcomes.