Studies Highlight Benefits of Testosterone Replacement

An Expert Interview With Youssef El Douaihy, MD

Emma Hitt, PhD

June 12, 2012

June 12, 2012 (Atlanta, Georgia) — Editor's note: Several studies presented here at the American Urological Association (AUA) 2012 Annual Scientific Meeting highlighted the metabolic and urologic benefits of testosterone replacement therapy.

In an interview with Medscape Medical News, Youssef El Douaihy, MD, from the Maimonides Medical Center, in New York City, and author of 4 studies on the subject presented at the meeting, discussed the pros and cons of testosterone replacement therapy. Study abstracts can be found on the AUA Web site.

Medscape: What form of testosterone did you investigate, and how does it compare to the forms available in the United States?

Dr. El Douaihy: There are no long-acting forms of testosterone replacement therapy currently available in the United States. These studies were conducted in Germany, not in the United States, because testosterone undecanoate (Nebido, Bayer) is not yet approved here.

For a while now, the US Food and Drug Administration (FDA) has been considering this drug for approval, but they have not made a decision yet. The main reasons for this are concern that the drug will be misused by athletes and bodybuilders and concern about potential adverse events. Regarding the second concern, testosterone undecanoate is approved in 88 countries outside of the United States, and no major complaints or issues have been observed. However, these are high doses; if misused, testosterone can build up in the body and cause adverse events.

Medscape: What are the benefits of long-term testosterone in the domains of the metabolic syndrome?

Dr. El Douaihy: The most important aspect of our study is the number of years that patients were followed; it is for sure the biggest study with the longest follow-up — up to about 6 to 7 years. The longest previous study I came across extended to 3 years, and they did not dissect the topic the way we did. We evaluated lipid profiles, glucose parameters, weight, effects on prostate symptoms, and other effects.

In our study that evaluated the effect of long-term testosterone on the domains of metabolic syndrome (abstract 1491), we followed 261 patients diagnosed with late-onset hypogonadism who had a testosterone level of 3.5 ng/mL or less and symptoms of erectile dysfunction. Patients received long-acting intramuscular testosterone undecanoate 1000 mg on day 1, 6 weeks later, and every 3 months thereafter. Patients were followed on average for more than 4 years.

There was a significant drop in the ratio of patients with the metabolic syndrome, which affected 56% of patients at baseline and 30% of patients after 57 months of treatment. In addition, triglycerides, glucose levels, and mean arterial pressure all dropped significantly, whereas high-density lipoprotein levels increased. The mean waist circumference of the cohort dropped by 11 cm (abstract 1492).

We are actually writing 2 papers right now that will probably come out in 6 months or so. Some reports are out there, and they show some improvement in the metabolic syndrome profile, but there are no data that extend long-term like these do.

Medscape: What effects does testosterone replacement have on symptoms of benign prostatic hypertrophy?

Dr. El Douaihy: In addition to the metabolic parameters, we studied the obstructive symptoms, measured by the IPSS (International Prostate Symptom Score) (abstract 1493). This finding is totally novel; improvement in obstructive symptoms due to testosterone replacement is nowhere out there in the literature. We looked at that, and patients reported a drop of about 6 points in the IPSS score. We also found that this association was not confounded by weight loss or the use of PDE5 (phosphodiesterase type 5) inhibitors, and that there was no increase in prostate cancer risk with the use of long-term testosterone (abstract 372).

Medscape: Is it known how testosterone causes these effects?

Dr. El Douaihy: Across the board, in all the parameters that we studied, we noticed improvements in weight, lipid profile, and glucose parameters. We conducted further analyses to see whether there was a direct effect in testosterone initiation itself or whether it was more due to the effects of weight loss caused by testosterone.

We found that weight loss may have been the major contributor in improving insulin resistance, but we were not able to show this definitely; therefore, testosterone itself might also have direct effect on improving insulin resistance. Further studies need to be conducted in this regard.

Medscape: How are these findings clinically relevant?

Dr. El Douaihy: Most patients were already on medication when they started the study, and we could not control for diet and exercise, but none of the medications, diet, or exercise levels increased during the study. We assumed, therefore, that the improvements we saw were caused by testosterone replacement.

Many patients in the study actually decreased their statin and antihypertensive medication doses because their measurements were improving. This is probably the clinical importance of testosterone replacement therapy. As expected, patients demonstrated improved sexual function and decreased depression, in addition to cardiovascular and metabolic syndrome aspects.

Medscape: When will this be approved by the FDA in the United States?

Dr. El Douaihy: The approval of this agent in the United States has been slow. No one can predict if or when that approval is going to come out. We are optimistic that it will, although we still need to resolve some of the issues, and there is not really a timeline.

The studies were supported by Bayer, the manufacturers of injectable testosterone undecanoate.

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