Marks LS et al. (2006) Effect of testosterone replacement therapy on prostate tissue in men with late-onset hypogonadism: a randomized controlled trial. JAMA 296: 2351–2361

Adverse effects caused by the decrease in testosterone production in aging men (including depression and changes in muscle and bone tissue) are commonly treated with testosterone replacement therapy (TRT). Marks and colleagues have performed a randomized, double-blind, placebo-controlled trial to assess whether TRT had any harmful effect on the prostate gland, the development and function of which is predominantly regulated by androgens.

The study included 44 men (aged 44–78 years) with low serum testosterone levels (<300 ng/dl or <10.4 nmol/l) and symptoms of late-onset hypogonadism, but no symptoms of prostate cancer on initial biopsy. Participants were randomly assigned to receive intramuscular injections of either testosterone enanthate (150 mg) or placebo every 2 weeks for 6 months. Of these 44 men, 40 were included in the final analysis.

TRT for 6 months increased serum testosterone levels to the mid-normal range (median 640 ng/dl or 22.2 nmol/l). The levels of testosterone and dihydrotestosterone in prostate tissue, however, did not change significantly during the trial. No significant effect of TRT was observed on the histology and gene-expression profile of the prostate gland, or on voiding symptoms, urinary flow and incidence of prostate cancer.

The authors conclude that 6 months of TRT, which efficiently normalizes serum androgen levels, does not have any harmful effect on the prostate gland. They emphasize, however, that studies with large sample sizes and extended treatment duration are required to establish the safety of TRT in aging men.