Long-acting testosterone undecanoate is well tolerated by men with hypogonadism in daily clinical practice
IPASS: a study on the tolerability and effectiveness of injectable testosterone undecanoate for the treatment of male hypogonadism in a worldwide sample of 1,438 men. Zitzmann M, Mattern A, Hanisch J, et al. J Sex Med 2013;10(2):579−588.
This prospective, observational, post-authorization surveillance study investigated the safety and efficacy of intramuscular injections of testosterone undecanoate (TU) in men with testosterone deficiency syndrome (hypogonadism) in a clinical practice setting1. The study, conducted in 23 countries throughout Europe, Asia, Latin America and Australia, enrolled 1493 men (mean age 49.2 ± 13.9 years) with a diagnosis of primary or secondary testosterone deficiency syndrome (serum total testosterone 8–12 nmol/L for newly diagnosed treatment-naïve patients). The men received up to five injections of TU during an observation period of 9–12 months. Between the first and second injections of the agent there was an interval of 6–10 weeks, and subsequent injections were given at intervals of 12 ± 2 weeks.
An analysis of this study was reported in the Research News on this website on 26 October 2012 and focused on the therapeutic effectiveness of TU in a large global cohort of patients. This present analysis focuses on the primary aim of the International Post-Authorization Surveillance Study (IPASS), which was to confirm the established safety profile of TU in male patients with testosterone deficiency syndrome who received TU under ‘real-life’ conditions. Tolerability was assessed using patient ratings of treatment satisfaction at the end of the treatment period. Digital rectal examinations as well as laboratory measurements of prostate-specific antigen (PSA), hemoglobin and hematocrit were also used to establish the safety of TU, and were assessed at each study visit.
Of the 1493 men enrolled, 72.5% were Caucasian, followed by 19.7% and 7.5% of Asian and Latin American descent, respectively. A total of 1438 and 1140 men were evaluable at baseline and at the time of the fifth injection, respectively. At baseline, mean body weight was 86.8 kg, and 54% of those enrolled had previously received androgen therapy. Mean serum testosterone (T) was 9.6 ± 7.5 nmol/L, and comorbidities included erectile dysfunction (ED), hypertension and dyslipidemia.
What is known
Hypogonadism, which can be defined as serum total testosterone ≤ 12 nmol/L and a positive score suggestive of androgen deficiency on the Aging Male Symptoms (AMS) scale, is increasingly recognized as a significant health problem in aging men3-9. Androgen replacement therapy is the principal treatment for testosterone deficiency syndrome, and involves the administration of T at doses which aim to reproduce normal blood T levels, in order to improve exposure of androgen-dependent tissues and organs to T. In general, the better the improvement in T levels after androgen replacement therapy, the better the clinical outcomes1. TU is an intramuscularly administered, long-acting formulation of T used as an androgen replacement therapy for men affected by testosterone deficiency syndrome. Previous studies have established the safety profile of TU10,11 however, as few large-scale post-marketing surveillance studies of TU have been conducted, and no large trials evaluating the agent in Asian and South American populations have been conducted at all, this present trial aimed to confirm the safety profile of TU in men with testosterone deficiency syndrome, and to evaluate the agent in a ‘real world’ clinical setting throughout Europe, Asia, Latin America and Australia.
What this study adds
This international, multicenter, one-arm, non-interventional, prospective post-authorization surveillance study demonstrated that TU is well tolerated in daily clinical practice and confirmed the established safety profile of TU in the largest worldwide sample of men with testosterone deficiency1.
TU was well tolerated, with the majority of patients rating the tolerability as “very good” or “good”. Few reports of ADRs occurred and no unexpected ADRs were observed. Furthermore, the number of men who discontinued from the study was relatively low, with 17.5% of patients prematurely discontinuing TU (of which only 31 discontinued treatment due to ADRs). The most commonly reported ADRs were increased hematocrit, increased PSA levels and injection site pain, all of which occurred in < 1% of patients. However, abnormal increases in hematocrit and PSA were rarely observed and no cases of prostate cancer were detected. Finally, cardiac adverse events were reported in 7 patients, all of whom had pre-existing cardiovascular impairment. These results support previous studies investigating the cardiovascular safety of TU and other T preparations12-15 and further demonstrate the ‘real world’ safety of TU.