Efficacy and Safety of Long-Acting Testosterone Undecanoate Over 4 Years

Freude, S⁽¹⁾; Huebler, D⁽²⁾; Schubert, M⁽¹⁾; Gooren, L⁽³⁾; Jockenhoevel, F⁽⁴⁾; Saad, F^{(5, 6)}

⁽¹⁾Klinikum der Universität zu Köln, Germany ⁽²⁾Jenapharm, Jena, Germany ⁽³⁾VUmc Amsterdam, Netherlands ⁽⁴⁾Evangelisches Krankenhaus, Herne, Germany ⁽⁵⁾Bayer-Schering, Berlin, Germany ⁽⁶⁾Gulf Medical College, Ajman, UAE

Objective: To assess the long term safety of a novel long-acting intra-muscular testosterone undecanoate (TU) formulation in hypogonadal men over 4 years. Methods: This was an open-label, randomized, prospective study involving 40 hypogonadal men (testosterone levels <5 nmol/L), administered either 250 mg testosterone enanthate (TE) i.m. every 3 weeks (n=20) or 1000 mg TU i.m. every 6-9 weeks (n=20), for 30 weeks. At the end of the study period, 25 patients continued in an open-label single arm follow-up study, where they received 1000 mg TU i.m. every 12 weeks, for 4 years. Various safety and efficacy measurements were taken at weeks 30 and at regular intervals throughout the follow up. Results: The results of the initial 30 week study have previously been reported (Schubert M et al. J Clin Endocrinol Metab 2004 89 5429-34). We report here the results of the 4 year follow up study of 1000 mg TU i.m. every 12 weeks. Median levels of testosterone at the end of each 12-week injection interval were 11.9 – 15.9 nmol/L. After 4 years follow up, levels of leptin, total cholesterol and triglycerides remained stable whilst levels of LDL-cholesterol had declined and HDL-cholesterol increased significantly. Apolipotein A1 and B also decreased slightly but significantly and levels of lipoprotein(a) remained stable. Hemoglobin levels and hematocrit values remained stable with no values above the upper limit of normal in the TU follow up. PSA levels rose from 0.67 ± 0.38 to 0.75 ± 0.35 (p<0.05) over the first 12 months of follow up on TU, but thereafter there were no further changes. Prostate volume also rose from 19.7 ± 8.8 to 22.0 ± 8.4 (p< 0.05) over the first 12 months of follow up, with no change thereafter. No change in body weight, waist-to-hip ratio, bone mineral density, liver function or blood pressure were observed. Conclusions: Administration of 1000 mg TU i.m. every 12 weeks provides effective testosterone replacement with an appropriate safety profile over 4 years.