Non-alcoholic fatty liver disease (NAFLD) is associated with cardiovascular disease (CVD) and both are prevalent in men with testosterone deficiency. Long-term effects of testosterone therapy (TTh) on NAFLD are not well studied. This observational, prospective, cumulative registry study assesses long-term effects of testosterone undecanoate (TU) on hepatic physiology and function in 505 hypogonadal men (T levels 350 ng/dL). Three hundred and twenty one men received TU 1000 mg/12 weeks for up to 12 years following an initial 6-week interval (T-group), while 184 who opted against TTh served as controls (C-group). T-group patients exhibited decreased fatty liver index (FLI, calculated according to Mayo Clinic guidelines) (83.6 ± 12.08 to 66.91 ± 19.38), c-GT (39.31 ± 11.62 to 28.95 ± 7.57 U/L), bilirubin (1.64 ± 4.13 to 1.21 ± 1.89 mg/dL) and triglycerides (252.35 ± 90.99 to 213 ± 65.91 mg/dL) over 12 years. Waist circumference and body mass index were also reduced in the T-group (107.17 ± 9.64 to 100.34 ± 9.03 cm and 31.51 ± 4.32 to 29.03 ± 3.77 kg/m 2 ). There were 25 deaths (7.8%) in the T-group of which 11 (44%) were cardiovascular related. In contrast, 28 patients (15.2%) died in C-group, and all deaths (100%) were attributed to CVD. These data suggest that long-term TTh improves hepatic steatosis and liver function in hypogonadal men. Improvements in liver function may have contributed to reduced CVD-related mortality.

This study investigated the role of testosterone replacement therapy (TRT) in prostate safety and cancer progression. A cohort of 553 patients, 42 treated and 162 untreated hypogonadal men, and 349 eugonadal men were included. Pathological analysis of prostate biopsies examining the incidence and severity of PCa revealed that: 16.7% of treated hypogonadal men had a positive biopsy, a Gleason score of ≤6 in 71.4% and >6 in 28.6% of men, a predominant score of 3 and tumour staging of II in 85.7% men; 51.9% of untreated hypogonadal men had a positive biopsy, a Gleason score of ≤6 in 40.5% and >6 in 59.5% men, a predominant score of 3 (77.4%) and tumour staging of II (41.7%) or III (40.5%); 37.8% of eugonadal men had a positive biopsy, a Gleason score of ≤6 in 42.4% and >6 in 57.6% of men, a predominant score of 3 (82.6%) and tumour staging of II (44.7%) or III (47.7%). The incidence of positive prostate biopsies was lowest in hypogonadal men receiving TRT, with significantly lower severity of PCa in terms of staging and grading in the same group. These results suggest that TRT might have a protective effect against high-grade PCa.