Testosterone in premenopausal women with NAFLD linked to higher risk for NASH, fibrosis

Young women with nonalcoholic fatty liver disease had higher testosterone levels, which led to a twofold higher risk for nonalcoholic steatohepatitis and fibrosis, according to study results.

In addition, the higher testosterone levels increased the risk for 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,” Monika Sarkar, MD, MAS, from the University of California, San Francisco, division of gastroenterology and hepatology, and colleagues wrote.

Sarkar and colleagues determined the correlation between free testosterone and NASH in 207 pre-menopausal women with biopsy-confirmed NAFLD. Investigators performed interaction testing for age and free testosterone due to the decline in testosterone with age and correlation of aging with NASH. They adjusted regression models for abdominal adiposity, diabetes and dyslipidemia.

Results showed higher free testosterone levels correlated with NAFLD severity in younger women (interaction P < .02). Investigators reported free testosterone in the youngest age quartile was independently correlated with NASH (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). In these women, the proportion with NASH and NASH fibrosis steadily rose with higher free testosterone quartiles (P < .01). In addition, free testosterone correlated with abdominal adiposity among all pre-menopausal women (OR = 2.2; 95% CI, 1.2-4.1).

“These data indicate the importance of considering chronologic and reproductive-aging on the relationship between testosterone and NAFLD in women, and support the role of testosterone as an early, and potentially modifiable risk factor for NASH progression in young women,” the researchers wrote. “Our findings underscore the need for studies to evaluate testosterone as a potential novel therapeutic target in young women with NAFLD, with implications beyond young women with androgen excess.”