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

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). 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. 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. 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.