Forty-eight men aged 65 years or older (mean age, 71 years) with a serum testosterone level below the normal range for young adult men (< 12.1 nmol/L) were randomly assigned to receive, in double-blind fashion, either 1) testosterone enanthate, 200 mg intramuscularly every two weeks or 2) placebo for three years. Thirty-five men completed the study. In intent-to-treat analysis, the mean bone mineral density (BMD) of the lumbar spine increased by 10.2% with testosterone and by 1.3% with placebo (p < 0.05 for the difference in the change between groups). The mean change in BMD of the hip was 2.7% with testosterone and -0.2% with placebo (p < 0.05). The mean prostate-specific antigen (PSA) level increased from 1.4 to 1.7 ng/ml with placebo and from 1.0 to 1.4 ng/ml with testosterone; the difference in the change between groups was not significant. The mean prostate volume increased from 32 to 42 ml with placebo and from 29 to 43 ml with testosterone; the difference in the change between groups was not significant.

Comment: These results indicate that administration of testosterone for three years to older men with low serum testosterone levels increased BMD of the lumbar spine and hip. Compared with placebo, testosterone did not significantly increase PSA levels or prostate size. It has been known for some time that testosterone-replacement therapy can improve BMD in older men; however, there has been concern that long-term treatment with this hormone might increase the risk of benign prostatic hyperplasia or prostate cancer. Within the limitations of this study, those concerns appear to be unfounded. Nevertheless, all men receiving testosterone be closely monitored, for the development of both prostate problems and polycythemia.

Amory JK, et al. Exogenous testosterone or testosterone with finasteride increases bone mineral density in older men with low serum testosterone. J Clin Endocrinol Metab 2004;89:503-510.