J Greg Terry
Investigator
Last active: 9/4/2019

Testosterone Levels in Pre-Menopausal Women are Associated With Nonalcoholic Fatty Liver Disease in Midlife.

Sarkar M, Wellons M, Cedars MI, VanWagner L, Gunderson EP, Ajmera V, Torchen L, Siscovick D, Carr JJ, Terry JG, Rinella M, Lewis CE, Terrault N
Am J Gastroenterol. 2017 112 (5): 755-762

PMID: 28291240 · PMCID: PMC5664187 · DOI:10.1038/ajg.2017.44

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.

MeSH Terms (18)

Adult Body Mass Index Diabetes Mellitus Follow-Up Studies Humans Insulin Resistance Intra-Abdominal Fat Lipoproteins, HDL Middle Aged Multidetector Computed Tomography Non-alcoholic Fatty Liver Disease Premenopause Prevalence Risk Factors Testosterone Triglycerides Waist Circumference Young Adult

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