Efficacy and safety of two different testosterone undecanoate formulations in hypogonadal men with metabolic syndrome

Aim: To investigate efficacy and safety of two different preparations of testosterone undecanoate (TU) in 52 hypogonadal men [mean age 57 yr and mean testosterone (T) < 320 ng/dl] with metabolic syndrome (MS). Subjects and methods: Randomized, double-blind, double-dummy study with three parallel treatment arms [oral TU; transdermal placebo gel (P); im TU] administration for 12 months (mo). Each subject was randomized (1:1:3) to receive either oral TU (2 capsules of 40 mg/twice per day at breakfast and dinner, equalling a total dose of 160 mg/day; no.=10) for 6 mo and continued with im TU for further 6 mo, or P (3–4 g/day; no.=10) and im TU (1000 mg/12 weeks from week 6; no.=32) for 12 mo. Results: After 6 mo, im TU increased T and free-T levels (p<0.0001), and improved metabolic parameters [reduction in Homeostasis Model Assessment (HOMA) index, p<0.0001; waist circumference and fat mass, p<0.001, respectively], in International Index of Erectile Function-5 and Aging Males’ Symptoms scores (p<0.01, respectively). After 12 months, im TU produced further increases in T and free-T levels (p<0.0001) and metabolic parameters (reduction in HOMA-index, p<0.0001; waist circumference p<0.0001; fat mass, p<0.001). No major adverse event due to T treatment occurred. Conclusions: Clinical efficacy of T replacement therapy in hypogonadal men with MS is reached when its plasmatic levels approach into the medium-high range of normality (>5 ng/ml), although subjective threshold values may be different. Administration of im TU was more effective than oral TU to reach the target for T levels and to improve MS parameters. TU was safe over 12 months and discontinuation rates were similar to placebo.