TY - JOUR
T1 - Testosterone Levels in Pre-Menopausal Women are Associated With Nonalcoholic Fatty Liver Disease in Midlife
AU - Coronary Artery Risk Development in Young Adults (CARDIA) Cohort
AU - Sarkar, Monika
AU - Wellons, Melissa
AU - Cedars, Marcelle I.
AU - VanWagner, Lisa
AU - Gunderson, Erica P.
AU - Ajmera, Veeral
AU - Torchen, Laura
AU - Siscovick, David
AU - Carr, J. Jeffrey
AU - Terry, James G.
AU - Rinella, Mary
AU - Lewis, Cora E.
AU - Terrault, Norah
N1 - Funding Information:
The Coronary Artery Risk Development in Young Adults Study (CARDIA) is conducted and supported by the National Heart, Lung, and Blood Institute in collaboration with the University of Alabama at Birmingham (HHSN268201300025C & HHSN268201300026C), Northwestern University (HHSN26820130 0027C), University of Minnesota (HHSN268201300028C), Kaiser Foundation Research Institute (HHSN268201300029C), Johns Hopkins University School of Medicine (HHSN268200900041C) and Vanderbilt University Medical Center (R01HL098445). CARDIA is also partially supported by the Intramural Research Program of the National Institute on Aging. This article has been reviewed by CARDIA for scientific content. The CWS is supported by the National Heart Lung and Blood Institute grant R01-HL065611 and contracts N01-HC-48047, N01-HC- 48048, N01-HC-48049, and N01-HC-4805. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Publisher Copyright:
© 2017 by the American College of Gastroenterology.
PY - 2017/5/1
Y1 - 2017/5/1
N2 - Objectives: 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. Methods: 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. Results: 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%). Conclusions: 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.
AB - Objectives: 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. Methods: 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. Results: 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%). Conclusions: 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.
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U2 - 10.1038/ajg.2017.44
DO - 10.1038/ajg.2017.44
M3 - Article
C2 - 28291240
AN - SCOPUS:85015239380
SN - 0002-9270
VL - 112
SP - 755
EP - 762
JO - American Journal of Gastroenterology
JF - American Journal of Gastroenterology
IS - 5
ER -