Endocrine Abstracts

Background: Obesity associates with co-morbidities as non-alcoholic fatty liver disease (NAFLD). Obese men often present with low testosterone (T) levels. As sex steroids undergo hepatic metabolization and their serum levels depend on hepatic sex hormone binding globulin (SHBG) secretion, NAFLD could contribute to this phenomenon. Previous studies however were contradictory and not based on state-of-the-art technology as mass spectrometry or biopsy-proven NAFLD.

Objective: To assess the relation between biopsy-proven NAFLD and sex steroid levels in obese men undergoing gastric bypass surgery (GBS).

Methods: This cross-sectional study included 56 obese men (mean age 44±11 years; BMI 41.6±4.6 kg/m²) and 56 healthy, age-matched control men (mean age 44±11 years; BMI 23.5±1.8 kg/m). T and estradiol (E2) measured using LC/MS-MS, SHBG by immunoassay and free hormone fractions were calculated. Surgical liver biopsies scored using NAFLD activity (NAS) and Steatosis, Activity and Fibrosis (SAF) scores.

Results: Obese men showed lower T, free T (FT) and SHBG levels, lower (F)T/(F)E2 ratio (all P<0.001) and higher FE2 (P=0.019) compared to controls. Within the GBS patients, no significant differences were found for sex steroid levels according to NAS-based NAFLD severity. However, with increasing grade of steatosis, trends towards lower T and FT levels, and lower (F)T/(F)E2 ratios were observed (P<0.059). No associations between sex steroid levels and other NAFLD features were detected. Using SAF, we found that lower (F)T levels correlated with steatohepatitis (P=0.014). These correlations were independent from age, BMI, HOMA-IR and SHBG. Remarkably, no differences in SHBG or (F)E2 levels according to NAFLD severity were found.

Conclusion: This study confirmed lower T levels in obese as compared to normal-weight men. In these obese men, overall NAS-based NAFLD severity was not associated with these lower T levels although presence of steatohepatitis and increasing grade of steatosis was related to lower (F)T levels and FT/FE2 ratios.