Objective: A reliable form of androgen substitution therapy in terms of favorable kinetics and tolerance as well as effective restoration of androgenicity is paramount in hypogonadal men. A new feasible modality is the intramuscular injection of the long-acting ester testosterone undecanoate (TU).
Design: Analysis of safety data accumulated during 101 treatment-years in 66 hypogonadal men receiving altogether 510 injections of 1000 mg TU in 1014-week intervals. 35 men had primary, 27 secondary and 4 late-onset hypogonadism. A minimum of 4 injections was necessary for data entry, maximum duration of individual treatment was 9.5 years. Primary endpoints were PSA levels, prostate size, erythropoeisis, lipoprotein profiles and blood pressure. Putative modulators of safety parameters entering regression models were nadir total testosterone concentrations, age (range: 1766 years), body mass index and androgen receptor CAG repeat length (range: 15 29).
Results: The medication was well tolerated. PSA levels did not exceed 2.9 ng/ml. Overall, therapy-induced changes within the normal range of PSA, prostate size and erythropoeisis were more pronounced in men with higher nadir testosterone concentrations and shorter androgen receptor CAG repeats (independently and with high significance respectively). Factors leading to observations of adverse nature (assessments beyond normal limits) such as elevated hematocrit, increased blood pressure and unfavorable lipoprotein constellations were due to obesity and advanced age, but not testosterone levels or receptor properties. The absolute incidence of such events remained below 10% of all assessments respectively.
Conclusion: Intramuscular injections of testosterone undecanoate represent a feasible, safe and well-tolerated modality of androgen substitution in hypogonadal men. Testosterone treatment with this regimen is modulated by the androgen receptor CAG repeat polymorphism. Adverse observations are due to obesity and advanced age, but not testosterone levels per se.