Long-acting testosterone undecanoate (TU) injection, but not oral TU, improves metabolic parameters in hypogonadal men
Efficacy and safety of two different testosterone undecanoate formulations in hypogonadal men with metabolic syndrome. Aversa A, Bruzziches R, Francomano D, et al. J Endocrinol Invest 2010;33(11):776-783.
This randomized, double-blind, double-dummy study was the first clinical trial to compare the efficacy and safety of long-term testosterone therapy using two different preparations of testosterone undecanoate (TU), in hypogonadal men with metabolic syndrome (MetS) and/or type 2 diabetes mellitus (T2DM).1Patients were randomized to one of three parallel treatment arms; oral TU (80 mg twice daily), intramuscular (IM) TU (1000 mg initially, then repeated every 12 weeks from week 6) or transdermal placebo gel (3–4 g/day). After 6 months, the oral testosterone group was crossed over to receive IM TU for 6 months; the other groups continued with their initial treatment for a further 6 months.
Fifty-two Caucasian men (mean age 57 years) with mean total T <320 ng/dl (11 nmol/L) met the selection criteria and were assigned to oral TU (n=10), IM TU (n=32) or placebo (control group; n=10). Twenty-five to 30% of men had both T2DM and MetS and 60 to 75% of men had mild-to-moderate erectile dysfunction (ED).
What is known
Male hypogonadism can be associated with MetS, T2DM, atherosclerosis, myocardial infarction and chronic heart failure, and it is increasingly recognized that low testosterone levels are an independent risk factor for these conditions.1-6 It is estimated that between 19% and 34% of men over the age of 60 years have serum testosterone levels below the lower limit of the normal range for healthy young men (approximately 300 ng/dL or 10.4 nmol/L).7,8 Men with MetS have an increased risk of developing T2DM and/or cardiovascular disease, and the presence of low testosterone levels can predict the development of insulin resistance and possible progression to overt T2DM.9 Therefore, restoring testosterone levels to the young healthy adult male reference range of approximately 300–1000 ng/dL (10–35 nmol/L) may improve metabolic parameters and reduce the burden of cardiovascular events.1 Although a number of different formulations of testosterone are available for long-term administration as testosterone therapy, including oral and long-acting injectable formulations of testosterone undecanoate, comparative efficacy data have been lacking.
What this study adds
This study shows for the first time that oral TU is clinically ineffective in improving insulin sensitivity, body composition and ED in hypogonadal men with MetS and/or T2DM. In contrast, during the first 6 months of treatment the long-acting IM TU formulation returned serum T levels to the medium-high range of reference values (>500 ng/dL), increased FT levels and improved insulin sensitivity, body composition and sexual function. All of these parameters continued to improve during the second 6 months of treatment with IM TU. No major unwanted effects were observed with long-term IM TU, and there was no increase in prostate volume or obstructive symptoms.