Abstract Introduction Hepatic steatosis is highly prevalent in patients with hypogonadism and obesity. Fatty liver is increasingly recognized as cardiovascular risk factor. The gold standard assessment – histological evaluation of liver biopsies – cannot be performed in routine clinical practice. However, the fatty liver index (FLI) can be calculated using the formula by Bedogni: FLI = (e 0.953*loge (triglycerides) + 0.139*BMI + 0.718*loge (ggt) + 0.053*waist circumference - 15.745) / (1 + e 0.953*loge (triglycerides) + 0.139*BMI + 0.718*loge (ggt) + 0.053*waist circumference - 15.745) * 100 (Bedogni G et al. BMC Gastroenterol 2006;6:33). A FLI <30 rules out and a FLI ≥60 rules in fatty liver. Objective to investigate effects of long-term testosterone therapy (TTh) up to 13 years on surrogate parameters of liver function in men with functional hypogonadism and obesity in comparison to an untreated control group. Methods In an ongoing registry study in men with hypogonadism (total testosterone ≤350 ng/mL and at least moderate symptoms on the Aging Males’ Symptoms scale, AMS) in a single urology office, 491 men had functional hypogonadism and obesity (BMI ≥30 kg/m2). 292 men received testosterone undecanoate (TU) injections 1000 mg/12 weeks following an initial 6-week interval (T-group), 199 opted against TTh and served as controls (CTRL). Height was measured at baseline, weight, waist circumference, triglycerides and γ-GT were assessed at each visit and the fatty liver index (FLI) calculated. AST, ALT, and bilirubin were also measured at each visit. Mean absolute measures with standard deviations (SDs) are reported for a duration of 13 years. Results Mean (median) follow-up: T-group 10.1±3.1 (11), CTRL 9.4±3.3 (10) years. Baseline age was 59.5±6.0 (T-group) and 63.0±5.0 years (CTRL) (p<0.0001). Triglycerides decreased from 3.4±0.5 to 2.2±0.1 in the T-group and increased from 3.2±0.5 to 3.9±0.5 in CTRL (p<0.0001 for both). γ-GT (U/L) decreased from 42.9±22.8 to 20.5±6.4 in the T-group and increased from 35.5±11.6 to 61.7±5.9 in CTRL (p<0.0001 for both). AST (U/L) decreased from 38.4±13.3 to 20.8±1.9 in the T-group and increased from 28.6±9.0 to 54.1±11.9 in CTRL (p<0.0001 for both). ALT (U/L) decreased from 41.4±13.7 to 24.7±2.1 in the T-group and increased from 32.7±9.4 to 60.2±13.8 in CTRL (p<0.0001 for both). Bilirubin decreased from 0.53±0.27 to 0.18±0.05 mg/dL in the T-group and increased from 0.44±0.23 to 1.09±0.27 mg/dL in CTRL (p<0.0001 for both). Waist circumference from 115.0±13.2 to 97.5±4.6 cm in the T-group and increased from 118.6±11.4 to 121.2±6.1 cm in CTRL (p<0.0001 for all). BMI decreased from 36.8±3.6 to 28.3±2.1 kg/m2 in the T-group and increased from 33.9±3.3 to 34.9±2.2 kg/m2 in CTRL (p<0.0001 for all). FLI decreased from 95.1±4.6 to 61.3±11.2 in the T-group and increased from 94.1±4.4 to 98.0±1.3 in CTRL (p<0.0001 for both). Conclusions Long-term testosterone therapy in men with functional hypogonadism and obesity improved surrogate parameters of liver function indicating an improvement in hepatic steatosis. All measures deteriorated over time in untreated obese hypogonadal control patients. Disclosure Yes, this is sponsored by industry/sponsor: Bayer AG, Berlin, Germany. Clarification Industry funding only - investigator initiated and executed study. Any of the authors act as a consultant, employee or shareholder of an industry for: Bayer AG.