Objective: This study investigated the efficacy of 5-year testosterone replacement therapy (TRT) on lipid profile and glucose tolerance in Japanese hypogonadal men.Methods: Fourteen patients, who received continuous TRT for 5 years, and 22 controls with 5-year observations were enrolled. The patients in the TRT group had received intramuscular injections of testosterone enanthate (250 mg) every month for 5 years. We collected the following data: blood pressure, fasting blood sugar (FBS), hemoglobin A1c (HbA1c), total cholesterol, triglyceride (TG), high density lipoprotein-Chol values, and prostate specific antigen (PSA) level at baseline, 1-, 3-, and 5-years from initial intervention. These data were compared between the two groups.Results: There were no statistically significant differences in any other baseline characteristic, excluding SBP, between the two groups. FBS was significantly improved at 3- and 5-year visits in the TRT group compared to the control group. Furthermore, the HbA1c level and TG value demonstrated a significant decrease at 1-, 3-, and 5-years in the TRT group. However, no significant difference in changes to PSA levels from baseline in both groups was observed.Conclusions: Five-year TRT could improve FBS, HbA1c, and TG levels among Japanese hypogonadal men with no significant increase in PSA.