title: Endogenous levels of circulating androgens and risk of Crohn's disease and ulcerative colitis among women: a nested case-control study from the nurses' health study cohorts.
abstract: BACKGROUND
  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).
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: *Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; †Division of Gastroenterology and Nutrition, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts; ‡Department of Adult Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts; §Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; ‖Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts; and ¶Division of Biostatistics and Epidemiology, University of Massachusetts, Amherst, Massachusetts.
authors.forename: Hamed
authors.initials: H
authors.lastname: Khalili
authors.forename: Ashwin N
authors.initials: AN
authors.lastname: Ananthakrishnan
authors.forename: Gauree G
authors.initials: GG
authors.lastname: Konijeti
authors.forename: Leslie M
authors.initials: LM
authors.lastname: Higuchi
authors.forename: Charles S
authors.initials: CS
authors.lastname: Fuchs
authors.forename: James M
authors.initials: JM
authors.lastname: Richter
authors.forename: Shelley S
authors.initials: SS
authors.lastname: Tworoger
authors.forename: Susan E
authors.initials: SE
authors.lastname: Hankinson
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Chan
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000097:blood / Q000209:etiology*; D003424:Crohn Disease / Q000097:blood / Q000209:etiology*; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood*; D005260:Female; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D016017:Odds Ratio; D011446:Prospective Studies; D012307:Risk Factors; D012738:Sex Hormone-Binding Globulin / Q000032:analysis*; D013739:Testosterone / Q000097:blood*; D014481:United States
chemical_list: D012738:Sex Hormone-Binding Globulin; D013739:Testosterone; D019314:Dehydroepiandrosterone Sulfate
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