Oral contraceptives, reproductive factors and risk of inflammatory bowel disease
- Hamed Khalili1,
- Leslie M Higuchi2,
- Ashwin N Ananthakrishnan1,
- James M Richter1,
- Diane Feskanich3,
- Charles S Fuchs3,4,
- Andrew T Chan1,3
- 1Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
- 2Division of Gastroenterology and Nutrition, Children's Hospital Boston and Harvard Medical School, Boston, Massachusetts, USA
- 3Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
- 4Department of Adult Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
- Correspondence to Dr Andrew T Chan, Gastrointestinal Unit, Massachusetts General Hospital, 55 Fruit Street, GRJ-728A, Boston, MA 02114, USA;
Contributors HK—study concept and design; acquisition of data; analysis and interpretation of data; drafting of the manuscript; statistical analysis. LMH—study concept and design; acquisition of data; analysis and interpretation of data; critical revision of the manuscript for important intellectual content. ANA, CSF—acquisition of data; critical revision of the manuscript. JMR—study concept and design; acquisition of data; analysis and interpretation of data; critical revision of the manuscript. DF—acquisition of data; analysis and interpretation of data; critical revision of the manuscript. ATC—study concept and design; analysis and interpretation of data; drafting of the manuscript; critical revision of the manuscript.
- Revised 3 April 2012
- Accepted 10 April 2012
- Published Online First 22 May 2012
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 2 years, 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 (pheterogeneity=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.
- Inflammatory bowel disease
- Crohn's disease
- ulcerative colitis
- oral contraceptive use
- reproductive factors
- Nurses' Health Study
- Crohn's colitis
- cancer epidemiology
- health service research
- gastrointestinal haemorrhage
- IBD clinical
- cancer prevention
- non-steroidal anti-inflammatory drugs
Correction notice This article has been corrected since it was published Online First. The author name Charles C Fuchs has been amended to Charles S Fuchs.
Funding Funded by R01 CA137178, R01 CA050385, P01 CA87969, P30 DK043351, K08 DK064256. ATC is a Damon Runyon Cancer Research Foundation clinical investigator. HK is supported by a career development award from the Crohn's and Colitis Foundation of American (CCFA). LH is supported by National Institute of Diabetes and Digestive and Kidney Diseases (K08 DK064256). ANA is supported by a career research scholars award from the American Gastroenterological Association.
Competing interests ATC has served as a consultant for Bayer Healthcare, Millennium Pharmaceuticals and Pfizer Inc. JMR is a consultant for Policy Analysis, Inc.
Ethical approval The institutional review board at the Brigham and Women's Hospital approved this study.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement Requests for access to data, statistical code, questionnaires and technical processes may be made by contacting the corresponding author at .