Histologically proven hepatic steatosis associates with lower testosterone levels in men with obesity

Men with obesity often present with low testosterone (T) and sex hormone-binding globulin (SHBG) levels. Several mechanisms for this have been proposed, but as SHBG is secreted by hepatocytes and sex steroids undergo hepatic metabolization, this study investigates whether severity and histological components of nonalcoholic fatty liver disease (NAFLD) are associated with sex steroid levels in obese men. This cross-sectional study included 80 obese men (age: 46 ± 11 years; body mass index: 42.2 ± 5.5 kg m(−2)). Serum levels of total T and estradiol (E(2)) were measured using liquid chromatography coupled with tandem mass spectroscopy (LC/MS-MS) and SHBG and gonadotropins by immunoassay. Liver biopsies were evaluated using Steatosis, Activity, and Fibrosis scoring. Participants with steatohepatitis had similar median (1(st) quartile–3(rd) quartile) total T levels (7.6 [5.0–11.0] nmol l(−1) vs 8.2 [7.2–10.9] nmol l(−1); P = 0.147), lower calculated free T (cFT) levels (148.9 [122.9–188.8] pmol l(−1) vs 199.5 [157.3–237.6] pmol l(−1); P = 0.006), and higher free E(2)/T ratios (10.0 [6.4–13.9] x10(-3) vs 7.1 [5.7–10.7] x10(-3); P = 0.026) compared to men with only nonalcoholic fatty liver. Among the histological components of NAFLD, only steatosis was independently associated with total T (r(s) = −0.331, P = 0.003) and cFT levels (r(s) = −0.255, P = 0.025). Obese men with steatohepatitis have even lower cFT levels compared to those without, an association mainly driven by grade of steatosis. Whether this reflects a subgroup of men with a more severe obesity-related phenotype or results from direct relations between hepatic steatosis and sex steroid metabolism needs further investigation.