Background and aims: Low levels of testosterone and non-alcoholic fatty liver disease (NAFLD) in obese men are both linked to the metabolic syndrome, but the independent association between testosterone and NAFLD needs to be elucidated. In this cross-sectional analysis the association between total testosterone (total T) and calculated free testosterone (cFT) on the one hand and NAFLD, non-alcoholic steatohepatitis (NASH) and fibrosis on the other hand was investigated in obese men.
Methods: Data of 134 men of 18 years or older and a body mass index of at least 25 kg/m2who underwent a liver biopsy after visiting the obesity clinic were collected. Liver biopsy was performed if there was suspicion of NAFLD. Individuals were classified into 3 categories: no NAFLD, non-alcoholic fatty liver (NAFL) and NASH according to the Steatosis-Activity-Fibrosis score. Furthermore, the stage of fibrosis was evaluated. Because of an unequal distribution, the 5 stages were divided into stage 0-1 and stage 2-4. Free testosterone (cFT) was calculated by using the Vermeulen equation.
Results: Mean age was 45±12 year, median BMI was 39.6 kg/m2(range 25.0-64.9). Only 5.2% of the individuals had no NAFLD. Of the individuals with NAFLD, 15.7% had NAFL and 79.1% had NASH. Fibrosis stage 0 to 4 were present in respectively 47.8, 26.9, 17.2, 7.5 and 0.7%. CFT and total T were below the limit of normal in respectively 63% and 23% of individuals. One-way ANOVA showed no significant difference in the mean level of total T and cFT between men having no NAFLD, NAFL and NASH that persisted after controlling for covariables. Ordinal regression analysis did not show a significant effect of total T or cFT on the grade of NAFLD. One-way ANOVA showed a significant lower level of cFT in men having fibrosis stage 2-4 (P = 0.013) compared to men having fibrosis stage 0-1. After controlling for BMI, HDL-cholesterol, TSH, oestradiol and HOMA-IR, the significant difference in the level of cFT did not persist. No significant difference was seen in the level of total T. Ordinal regression analysis showed a decreasing level of cFT was associated with a higher stage of fibrosis (P = 0.016). This association did not persist after controlling for BMI, HDL-cholesterol, TSH, oestradiol and HOMA-IR. No significant effect of total T on the stage of fibrosis was seen.
Conclusion: To the best of our knowledge, this is until now the largest study investigating the association between sex steroid levels and biopsy-proven NAFLD. After controlling for covariables no association was found between the level of total T and cFT on the one hand and NAFLD, NASH or fibrosis on the other hand.