Large study bolsters efficacy, safety of long-acting testosterone replacement therapy

Key Points

Muenster, Germany-Injectable long-acting testosterone undecanoate (Aveed) over 9 to 12 months is well tolerated by hypogonadal men, especially in regard to prostate safety and response to concomitant phosphodiesterase type-5 inhibitor therapy, according to findings from a large-scale multinational trial.

"This is the largest trial of testosterone substitution that has ever been performed," said first author Michael Zitzmann, MD, PhD, clinical researcher and senior physician at the Centre for Reproductive Medicine and Andrology/Clinical Andrology of the University Clinics, Muenster, Germany.

Approval of the FDA new drug application for testosterone undecanoate is pending.

Previous trials have shown that testosterone replacement therapy leads to improved mental, sexual, and metabolic health. The balance between such benefits and prostate-related adverse events, especially in older patients, was analyzed by Dr. Zitzmann and colleagues in a study of 1,493 hypogonadal men (average age, 49.2±13.9 years).

Patients received up to five testosterone undecanoate injections over 9 to 12 months. Prostate safety was closely monitored by digital rectal exam, measurement of PSA levels, and prostate biopsies. Erectile function, libido, vitality, mood, and ability to concentrate were assessed by physician interview. Physical and circulatory parameters as well as hematocrit, glucose control, and lipid profiles were recorded.

No cases of prostate Ca observed

Overall mean PSA levels increased from 1.1±0.9 ng/mL to 1.3±1.2 ng/mL and remained stable 1 year after treatment (p<.0001). No cases of prostate cancer were observed. PSA results were consistent when stratified between men receiving previous androgen therapy and those who were not previously treated.

At baseline, 65% of patients had moderate or severe erectile dysfunction, decreasing to 19% 1 year after testosterone undecanoate therapy (p<.0001).

"High/very high response" to PDE-5 inhibitors increased from 35% to 57% (p<.0001) during the change from hypogonadism to eugonadism. "Moderate to very high response" increased from 73% to 88%, and the percentage of non-responders decreased from 25% to 9%.

"Patients receiving concomitant therapy with PDE-5 inhibitors reported an increase in effectiveness," said Dr. Zitzmann, who presented the results at the 2011 European Association of Urology annual congress in Vienna, Austria.

All scores of mental and sexual satisfaction improved (all p<.0001), while mean waist circumference decreased significantly from 100 cm to 96 cm (p<.0001).

"This is a very good sign," Dr. Zitzmann said. "Mental and sexual satisfaction was increased markedly, and the metabolic environment increased. Visceral fat decreased as waist circumference was lowered. In fact, diabetes markers such as HbA1c were decreased markedly."

Two of Dr. Zitzmann's co-authors on this study are employees of Bayer Schering Pharma Inc.