The Safety and Efficacy of a Long-Acting Formulation of Testosterone Undecanoate is Modulated by Body Mass and Pharmacogenetic Variables : Experience of 118 Treatment-Years of Testosterone Substitution
Zitzmann, M(1); Saad, F(2, 3); Nieschlag, E(1)
(1)Institute for Reproductive Medicine, University of Muenster, Muenster, Germany (2)Male Healthcare, Bayer Schering Pharma, Berlin, Germany (3)Research Dept., Gulf Medical College School of Medicine, Ajman/UAE
Objective: The aim of this study was to assess the safety and efficacy of long-acting testosterone undecanoate (TU) against a number of metabolic and pharmacogenetic confounders. Methods: This was a longitudinal one-arm open label observational study undertaken in an andrology outpatient department. The study involved 66 hypogonadal men, mean age 38 ± 9.9 years, undergoing testosterone substitution via intra muscular injection of long-acting TU (1000 mg at 10-14 week intervals) and comprised 118 patient years of treatment. Patients had clinical data recorded on at least 5 separate visits, and these safety and efficacy parameters were then assessed via regression analysis, for association with the following characteristics: nadir and/or change in total testosterone concentrations, body mass index (BMI), androgen receptor (AR) CAG repeat length and age. Results: Testosterone substitution resulted in significant reductions in levels of low density lipoprotein cholesterol, resting diastolic and systolic blood pressure and heart rate, and a significant increase in levels of high density lipoprotein cholesterol and of erythropoiesis. These clinical parameters remained stable after 4 injections, and no adverse effects on the prostate were observed. Patients having a reduced androgen action (either a higher number of AR CAG repeats or low testosterone level) exhibited a worse safety profile; elevated blood pressure and adverse lipid profile. A raised hematocrit (> 50%) was predicted by enhanced androgen action (shorter AR CAG repeats or higher testosterone levels). Patients with a BMI ≥ 30 kg m-2 had a higher occurrence of all pathological safety parameters. Conclusion: Testosterone substitution with long-acting TU was generally well tolerated and produced significant improvements in a number of cardiovascular risk factors. These improvements were linked to both the degree of androgen action, as indicated by both AR CAG repeat length and testosterone concentration, and BMI.
