Testosterone is Associated With Nonalcoholic Steatohepatitis and Fibrosis in Premenopausal Women With NAFLD

Abstract

Background & aims: Higher testosterone contributes to imaging-confirmed nonalcoholic fatty liver disease (NAFLD) in women, but whether testosterone influences their disease severity is unknown.

Methods: The association of free testosterone (free T) with nonalcoholic steatohepatitis (NASH) was determined in pre-menopausal women with biopsy-confirmed NAFLD (n = 207). Interaction testing was performed for age and free T given decline in testosterone with age, and association of aging with NASH. Regression models adjusted for abdominal adiposity, diabetes, and dyslipidemia.

Results: Median age was 35 yrs (interquartile range, 29-41); 73% were white, 25% Hispanic; 32% had diabetes, 93% abdominal adiposity, and 95% dyslipidemia. 69% had NASH, 67% any fibrosis, and 15% advanced fibrosis. Higher free T levels were associated with NAFLD severity in younger women (interaction P value <.02). In the youngest age quartile, free T was independently associated with NASH (odds ratio [OR], 2.3; 95% CI, 1.2-4.4), NASH fibrosis (OR, 2.1; 95% CI, 1.1-3.8), and higher fibrosis stage (OR, 1.9; 95% CI, 1.1-3.4), P value .02. In these women, the proportion with NASH steadily rose from 27% to 88%, and with NASH fibrosis rose from 27% to 81%, with higher free T quartiles (P < .01). Free T was additionally associated with abdominal adiposity among all pre-menopausal women (OR, 2.2; 95% CI, 1.2-4.1: P = .02).

Conclusions: In young women with NAFLD, higher testosterone levels conferred a 2-fold higher risk of NASH and NASH fibrosis, and increased risk of abdominal adiposity, supporting a potential mechanistic link of abdominal fat on testosterone-associated liver injury. Testosterone may represent an early risk factor for NASH progression in young women, prior to their onset of more dominant, age-related metabolic risk factors.

Keywords: Abdominal Adiposity; Androgens; Hepatic Inflammation; Nonalcoholic Fatty Liver Disease; Sex Hormones.

Conflict of interest statement

Disclosures: Co-authors have no conflicts of interest or competing interests that are relevant to this study.

Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1.

Proportion of pre-menopausal women in the youngest age quartile (n=52) with NASH (Figure 1a) and NASH fibrosis (Figure 1b) by increasing quartiles of free testosterone. Test of trend p-values shown.