Elevated testosterone a red flag for NASH progression in young women

High testosterone levels carry a twofold increased risk of progression to nonalcoholic steatohepatitis (NASH) and fibrosis, as well as a higher likelihood of abdominal obesity, in young women with nonalcoholic fatty liver disease (NAFLD), a study has found.

The study involved 207 premenopausal women (median age, 35 years) with NAFLD. Most of them had abdominal adiposity (93 percent), dyslipidaemia (96 percent), and were obese (81 percent). Meanwhile, 32 percent had type 2 diabetes, 31 percent had hypertension, and 21 percent had self-reported polycystic ovary syndrome.

At baseline, median free testosterone (free T) was 3.6 pg/mL, while median total testosterone level was 210 pg/mL. The levels decreased with increasing age (p_trend<0.04). Sixty-nine percent of women had borderline or definite NASH, and 67 percent had evidence of fibrosis. Advanced fibrosis (stages 3–4) was present in 15 percent of the women overall and in 20 percent of those with NASH.

In multivariable regression models, high free T levels were associated with NAFLD severity among younger women (p<0.02). In the youngest age quartile (n=52; 22–27 years), elevated free T independently predicted the following outcomes: NASH (odds ratio [OR], 2.3, 95 percent confidence interval [CI], 1.2–4.4), NASH fibrosis (OR, 2.1, 95 percent CI, 1.1–3.8), and higher fibrosis stage (OR, 1.9, 95 percent CI, 1.1–3.4; p≤0.02 for all).

Furthermore, in the youngest age quartile, the proportion of women with NASH or NASH fibrosis rose steadily from 27 percent to >80 percent with higher free T quartiles (p<0.01). Free T was also associated with abdominal obesity in the overall population (OR, 2.2, 95 percent CI, 1.2–4.1; p=0.015).

The findings indicate that testosterone potentially represents an early risk factor for NASH progression in young women, prior to their onset of more dominant, age-related metabolic risk factors.