Kristin E Burke1, Ashwin N Ananthakrishnan1, Paul Lochhead1, Po-Hong Liu1, Ola Olen2, Jonas F Ludvigsson3, James M Richter4, Shelley S Tworoger5, Andrew T Chan6, Hamed Khalili7. 1. Gastroenterology Unit, Massachusetts General Hospital, Boston, Massachusetts; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts. 2. Pediatric Gastroenterology and Nutrition Unit, Sachs' Children's Hospital, Stockholm, Sweden; Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden. 3. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, Örebro University Hospital, Örebro University, Örebro, Sweden. 4. Gastroenterology Unit, Massachusetts General Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts. 5. Moffit Cancer Center, Tampa, Florida; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. 6. Gastroenterology Unit, Massachusetts General Hospital, Boston, Massachusetts; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Broad Institute, Cambridge, Massachusetts; Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts. 7. Gastroenterology Unit, Massachusetts General Hospital, Boston, Massachusetts; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts; Karolinska Clinical Epidemiology Unit, Karolinska Institutet, Solna, Sweden. Electronic address: hkhalili@mgh.harvard.edu.
Abstract
BACKGROUND & AIMS: Microscopic colitis is a chronic inflammatory disorder of the colon primarily affecting postmenopausal women. However, the relation between hormonal determinants, including reproductive and menopausal factors, and risk of microscopic colitis has yet to be characterized. METHODS: We collected data from 227,766 women who participated in the Nurses' Health Study (NHS) and the NHSII without a baseline history of microscopic colitis. Reproductive and menopausal factors were assessed in 1988 in the NHS and 1989 in the NHSII and updated biennially. Cases of microscopic colitis were confirmed through review of pathology records. We used Cox proportional hazards modeling to estimate hazard ratios and 95% confidence intervals. RESULTS: Through 2014 in the NHS and 2015 in the NHSII, we confirmed 275 incident cases of microscopic colitis over 5,147,282 person-years. Compared with never use, current use of menopausal hormone therapy was associated with increased risk of microscopic colitis (multivariable-adjusted hazard ratio 2.64; 95% confidence interval 1.78-3.90). The risk increased with longer duration of use (P for trend < .0001) and decreased after discontinuation (P for trend = .002). The association did not differ according to disease subtype (P for heterogeneity = .34). Similarly, ever use of oral contraceptives was associated with increased risk of microscopic colitis (multivariable-adjusted hazard ratio 1.57; 95% confidence interval 1.16-2.13). There were no associations between age at menarche, parity, age at first birth, age at menopause, or menopause type and incident microscopic colitis. CONCLUSIONS: In 2 large prospective cohort studies, we observed an association between exogenous hormone use and incident microscopic colitis. Further studies are needed to determine the mechanisms underlying these associations.
BACKGROUND & AIMS: Microscopic colitis is a chronic inflammatory disorder of the colon primarily affecting postmenopausal women. However, the relation between hormonal determinants, including reproductive and menopausal factors, and risk of microscopic colitis has yet to be characterized. METHODS: We collected data from 227,766 women who participated in the Nurses' Health Study (NHS) and the NHSII without a baseline history of microscopic colitis. Reproductive and menopausal factors were assessed in 1988 in the NHS and 1989 in the NHSII and updated biennially. Cases of microscopic colitis were confirmed through review of pathology records. We used Cox proportional hazards modeling to estimate hazard ratios and 95% confidence intervals. RESULTS: Through 2014 in the NHS and 2015 in the NHSII, we confirmed 275 incident cases of microscopic colitis over 5,147,282 person-years. Compared with never use, current use of menopausal hormone therapy was associated with increased risk of microscopic colitis (multivariable-adjusted hazard ratio 2.64; 95% confidence interval 1.78-3.90). The risk increased with longer duration of use (P for trend < .0001) and decreased after discontinuation (P for trend = .002). The association did not differ according to disease subtype (P for heterogeneity = .34). Similarly, ever use of oral contraceptives was associated with increased risk of microscopic colitis (multivariable-adjusted hazard ratio 1.57; 95% confidence interval 1.16-2.13). There were no associations between age at menarche, parity, age at first birth, age at menopause, or menopause type and incident microscopic colitis. CONCLUSIONS: In 2 large prospective cohort studies, we observed an association between exogenous hormone use and incident microscopic colitis. Further studies are needed to determine the mechanisms underlying these associations.
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