title: Testosterone Levels in Pre-Menopausal Women are Associated With Nonalcoholic Fatty Liver Disease in Midlife.
abstract: Young women with hyperandrogenism have high risk of metabolic co-morbidities, including increased risk of nonalcoholic fatty liver disease (NAFLD). Whether testosterone (the predominant androgen) is associated with NAFLD independent of metabolic co-factors is unclear. Additionally, whether testosterone confers increased risk of NAFLD in women without hyperandrogenism is unknown.
  
  
  
  Among women in the prospective population-based multicenter Coronary Artery Risk Development in Young Adults (CARDIA) study, we assessed whether free testosterone levels measured at Year 2 (1987-1988) were associated with prevalent NAFLD at Year 25 (2010-2011) (n=1052). NAFLD was defined using noncontrast abdominal CT scan with liver attenuation≤40 Hounsfield units after excluding other causes of hepatic fat. The association of free testosterone with prevalent NAFLD was assessed by logistic regression.
  
  
  
  Increasing quintiles of free testosterone were associated with prevalent NAFLD at Year 25 (adjusted odds ratio (AOR) 1.25, 95% confidence interval (CI) 1.04-1.50, P=0.015), independent of insulin resistance, body mass index, waist circumference, and serum lipids. Importantly, the association persisted among n=955 women without androgen excess (AOR 1.27, 95% CI 1.05-1.53, P=0.016). Visceral adipose tissue (VAT) volume partially mediated the association of free testosterone with NAFLD (mediating effect 41.0%, 95% CI 22-119%).
  
  
  
  Increasing free testosterone is associated with prevalent NAFLD in middle age, even in women without androgen excess. Visceral adiposity appears to play an important role in the relationship between testosterone and NAFLD in women. Testosterone may provide a potential novel target for NAFLD therapeutics, and future studies in pre-menopausal women should consider the importance of testosterone as a risk factor for NAFLD.
authors.affiliation: Division of Gastroenterology and Hepatology, University of California, San Francisco, California, USA.
authors.forename: Monika
authors.initials: M
authors.lastname: Sarkar
authors.affiliation: Division of Diabetes, Endocrinology, and Metabolism, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Wellons
authors.affiliation: Department of Obstetrics and Gynecology, University of California, San Francisco, California, USA.
authors.forename: Marcelle I
authors.initials: MI
authors.lastname: Cedars
authors.affiliation: Division of Gastroenterology and Hepatology, Northwestern University, Chicago, Illinois, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: VanWagner
authors.affiliation: Kaiser Permanente Division of Research, Oakland, California, USA.
authors.forename: Erica P
authors.initials: EP
authors.lastname: Gunderson
authors.affiliation: Division of Gastroenterology and Hepatology, University of California, San Francisco, California, USA.
authors.forename: Veeral
authors.initials: V
authors.lastname: Ajmera
authors.affiliation: Division of Pediatric Endocrinology, Northwestern University, Chicago, Illinois, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Torchen
authors.affiliation: New York Academy of Medicine, New York, New York, USA.
authors.forename: David
authors.initials: D
authors.lastname: Siscovick
authors.affiliation: Department of Radiology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
authors.forename: J Jeffrey
authors.initials: JJ
authors.lastname: Carr
authors.affiliation: Department of Radiology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
authors.forename: James G
authors.initials: JG
authors.lastname: Terry
authors.affiliation: Division of Gastroenterology and Hepatology, Northwestern University, Chicago, Illinois, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Rinella
authors.affiliation: Division of Preventive Medicine, University of Alabama Birmingham, Birmingham, Alabama, USA.
authors.forename: Cora E
authors.initials: CE
authors.lastname: Lewis
authors.affiliation: Division of Gastroenterology and Hepatology, University of California, San Francisco, California, USA.
authors.forename: Norah
authors.initials: N
authors.lastname: Terrault
mesh_terms: D000328:Adult; D015992:Body Mass Index; D003920:Diabetes Mellitus / Q000453:epidemiology; D005500:Follow-Up Studies; D006801:Humans; D007333:Insulin Resistance; D050152:Intra-Abdominal Fat; D008075:Lipoproteins, HDL / Q000097:blood; D008875:Middle Aged; D061330:Multidetector Computed Tomography; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood* / Q000000981:diagnostic imaging / Q000453:epidemiology*; D017697:Premenopause / Q000097:blood; D015995:Prevalence; D012307:Risk Factors; D013739:Testosterone / Q000097:blood*; D014280:Triglycerides / Q000097:blood; D055105:Waist Circumference; D055815:Young Adult
chemical_list: D008075:Lipoproteins, HDL; D014280:Triglycerides; D013739:Testosterone