Low testosterone may play role in development of Peyronie's disease

Boston-Low testosterone levels could play a role in Peyronie's disease, according to results of a retrospective chart review.

Men with low levels of free testosterone had more severe penile curvature, which correlated significantly with free testosterone, reported first author Sergio A. Moreno, MD, working with Abraham Morgentaler, MD, and colleagues.

"The relationship between testosterone and Peyronie's disease has not been investigated to date," said Dr. Moreno, who was a urology research fellow at Harvard and Beth Israel Deaconess Medical Center, Boston when the study was conducted. "The results of this pilot study suggest a potentially important relationship between Peyronie's disease and testosterone deficiency."

The findings, presented at the AUA annual meeting in Chicago, came from a review of medical records on 121 men with Peyronie's disease. Laboratory testing in all patients included total and free testosterone. Testosterone deficiency was defined as a total testosterone <300 ng/dL or a free testosterone <1.5 ng/dL.

Dr. Moreno reported that 74.4% of the patients had low levels of testosterone. In more than 70% of cases, the men had low levels of free testosterone.

Comparison of men with low and normal testosterone levels showed that the curvature angle of the penis was significantly greater in men with low testosterone (54.3 degrees vs. 37.1 degrees, p=.006). Men with low levels of free testosterone had an average penile curvature of 55.9 degrees compared with 37.9 degrees in men with normal free testosterone levels (p=.003).

Severity of penile curvature correlated significantly with the level of free testosterone (r=0.314, p=.016).

Nitric oxide's role

Discussing potential mechanisms for an association between testosterone and Peyronie's disease, Dr. Moreno said nitric oxide is an antifibrotic factor. Testosterone stimulates nitric oxide synthase gene expression and decreases the rate of RNA degradation, increasing the amount of nitric oxide synthase RNA available for production of nitric oxide.

Low levels of testosterone would lead to reduced nitric oxide production, creating an imbalance between the antifibrotic activity of nitric oxide and profibrotic factors such as tissue growth factor beta-1. The result would be impaired tissue response to injury, said Dr. Moreno, who is currently practicing in Chile.

During the discussion that followed the presentation, several members of the audience congratulated Dr. Moreno for the mechanistic explanations offered. One unidentified member of the audience suggested a need to perform multivariate analysis of the data and a thorough evaluation of comorbidities that might have contributed to low testosterone levels.

Dr. Morgentaler is a meeting participant/lecturer for Auxilium Pharmaceuticals, Solvay Pharmaceuticals, and Watson Pharmaceuticals, and is consultant/adviser for Slate Pharmaceuticals.