Abstract
Androgens, which are known to be altered by exogenous hormone use, have recently been linked to alterations of the gut microbiome and mucosal immune function. No study has evaluated the association between circulating levels of androgens and risk of Crohn's disease (CD) and ulcerative colitis (UC). We conducted a nested case-control study of women enrolled in the Nurses' Health Study and Nurses' Health Study II who provided a blood specimen. Cases of CD and UC were each matched to 2 controls. Prediagnosis plasma levels of dehydroepiandrosterone sulfate, testosterone, and sex hormone-binding globulin were measured. We examined the association of each analyte with risk of CD or UC using conditional logistic regression models. Compared with women in the lowest quintile of testosterone, the multivariable-adjusted odds ratios for CD were 0.86 (95% confidence interval, 0.39-1.90) for women in the second quintile, 0.49 (95% confidence interval, 0.21-1.15) for the third quartile, 0.22 (0.08-0.65) for the fourth quintile, and 0.39 (95% confidence interval, 0.16-0.99) for the highest quintile (Plinear trend = 0.004). In contrast, we did not observe a consistent association between prediagnostic testosterone and risk of UC (Plinear trend = 0.84). We also did not observe any association between plasma levels of sex hormone-binding globulin or dehydroepiandrosterone sulfate and risk of UC or CD (all Plinear trends > 0.10). Among women, prediagnostic circulating testosterone is associated with a lower risk of CD but not UC. Further studies to understand the biological mechanisms by which endogenous androgens may mediate the etiopathogenesis of CD are warranted.
Highlights
Androgens, which are known to be altered by exogenous hormone use, have recently been linked to alterations of the gut microbiome and mucosal immune function
We did not observe any association between plasma levels of sex hormone–binding globulin or dehydroepiandrosterone sulfate and risk of ulcerative colitis (UC) or Crohn’s disease (CD)
Among women, prediagnostic circulating testosterone is associated with a lower risk of CD but not UC
Summary
We conducted a nested case–control study of women enrolled in the Nurses’ Health Study and Nurses’ Health Study II who provided a blood specimen. The NHS is a prospective cohort that began in 1976 when 121,700 U.S female registered nurses, aged 30 to 55 years, completed a mailed questionnaire. Follow-up questionnaires are mailed every 2 years to update health information. In 1989, a parallel cohort, the NHS II, enrolled 116,430 U.S female nurses between the ages of 25 and 42 years. These women have been followed with similar biennial questionnaires. Our study is a nested case–control study of women with available blood samples in the 2 large prospective cohorts of NHS and NHSII. Institutional review board at the Brigham and Women’s Hospital approved this study
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