Hamed Khalili1, Fredrik Granath2, Karin E Smedby2, Anders Ekbom2, Martin Neovius2, Andrew T Chan3, Ola Olen2. 1. Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. Electronic address: hkhalili@mgh.harvard.edu. 2. Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet, Solna, Sweden. 3. Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
Abstract
BACKGROUND & AIMS: Use of exogenous hormones, in the form of oral contraceptives (OCs), has been linked consistently to risk of Crohn's disease (CD). Nonetheless, it is not clear how OCs might contribute to the progression of CD. METHODS: We conducted a prospective study of female patients with CD (age, 16-51 y), identified from the inpatient and outpatient care components of the Swedish National Patient Register from January 2002 through December 2013. Information on current OC use was obtained from the Prescribed Drug Register starting in July of 2005 and updated until December of 2013. Primary outcomes were defined as first CD-related surgery and first steroid prescription. We used Cox proportional hazard modeling with time-varying covariates to estimate multivariable-adjusted hazard ratios (MV-adjusted HRs). RESULTS: We identified 482 incident cases of surgery among 4036 patients with CD, with a median follow-up period of 58 months. Compared with nonusers, the MV-adjusted HRs for surgery were 1.14 (95% confidence interval [CI], 0.80-1.63) for past users and 1.30 (95% CI, 0.89-1.92) for current users. The risk of surgery increased with longer duration of use (Ptrend = .036) and higher prescribed daily dose (Ptrend = .016). Specifically, for women with more than 3 years of OC use, the MV-adjusted HR for surgery was 1.68 (95% CI, 1.06-2.67). The association was confined to the combination type of OC. We estimated that for every 83 patients with CD receiving the combination type of oral contraceptives for at least 1 year, 1 extra surgery is required. The rate of steroid prescriptions did not appear to increase with past or current use of OCs, compared with patients who have not taken OCs (all Pcomparisons > .20). CONCLUSIONS: In a nationwide analysis of patients in Sweden, long-term use of OCs, particularly the combination type, was associated with an increased risk of surgery among women with established CD. Clinicians carefully should evaluate and monitor contraceptive options among women with established CD.
BACKGROUND & AIMS: Use of exogenous hormones, in the form of oral contraceptives (OCs), has been linked consistently to risk of Crohn's disease (CD). Nonetheless, it is not clear how OCs might contribute to the progression of CD. METHODS: We conducted a prospective study of female patients with CD (age, 16-51 y), identified from the inpatient and outpatient care components of the Swedish National Patient Register from January 2002 through December 2013. Information on current OC use was obtained from the Prescribed Drug Register starting in July of 2005 and updated until December of 2013. Primary outcomes were defined as first CD-related surgery and first steroid prescription. We used Cox proportional hazard modeling with time-varying covariates to estimate multivariable-adjusted hazard ratios (MV-adjusted HRs). RESULTS: We identified 482 incident cases of surgery among 4036 patients with CD, with a median follow-up period of 58 months. Compared with nonusers, the MV-adjusted HRs for surgery were 1.14 (95% confidence interval [CI], 0.80-1.63) for past users and 1.30 (95% CI, 0.89-1.92) for current users. The risk of surgery increased with longer duration of use (Ptrend = .036) and higher prescribed daily dose (Ptrend = .016). Specifically, for women with more than 3 years of OC use, the MV-adjusted HR for surgery was 1.68 (95% CI, 1.06-2.67). The association was confined to the combination type of OC. We estimated that for every 83 patients with CD receiving the combination type of oral contraceptives for at least 1 year, 1 extra surgery is required. The rate of steroid prescriptions did not appear to increase with past or current use of OCs, compared with patients who have not taken OCs (all Pcomparisons > .20). CONCLUSIONS: In a nationwide analysis of patients in Sweden, long-term use of OCs, particularly the combination type, was associated with an increased risk of surgery among women with established CD. Clinicians carefully should evaluate and monitor contraceptive options among women with established CD.
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