The effect of testosterone replacement therapy on prostate cancer: a systematic review and meta-analysis

Testosterone replacement therapy (TRT) is a widely accepted form of treatment worldwide for aging men with late-onset hypogonadism syndrome. Urologists have been concerned about the possibility of TRT causing prostate cancer. The aim of this study was to assess the relationship between TRT and prostate cancer.

A literature review was performed to identify all published, randomized controlled trials (RCTs) of testosterone treatment for hypogonadism. The search included the MEDLINE, Embase and the Cochrane Controlled Trials Register databases. Fixed-effect model was chosen for homogeneous studies; otherwise, a random-effect model was used. Inconsistency was quantified by using the I2 statistic, which tests the proportion of heterogeneity across studies.

Results of 22 RCTs involving a total of 2351 patients were analyzed. Eleven RCTs were short-term (<12 months) and 11 were long-term (12-36 months) comparisons of TRT with a placebo; TRT was administered transdermally, orally or by injection. Respective odds ratio (OR) and 95% confidence interval (CI) values for injection, transdermal administration and oral administration of short-term TRT were as follows: prostate cancer: 0.39 (0.06-2.45), 1.10 (0.26-4.65) and no oral; biopsy: 5.28 (0.24-113.87), 2.11 (0.32-13.73) and no oral; and prostate nodule: 1.01 (0.13-7.60), no injection and oral. Respective OR and 95% CI values for injection, transdermal administration and oral administration of long-term TRT were as follows: prostate cancer: 2.09 (0.18-24.73), 3.06 (0.12-76.70) and 0.19 (0.01-4.03); biopsy: 2.09 (0.18-24.73), 3.65 (0.88-15.20) and 0.97 (0.13-7.03); and prostate nodule: 3.13 (0.12-80.68), 1.00 (0.06-16.41) and 0.97 (0.13-7.03). Though for some routes of administration and some end points, the OR associated with testosterone administration were >1 indicating increased risk, none of these reached or even approached statistical significance (all P>0.10), which was consistent with the results of subgroup analyses and sensitivity analysis. Besides, sensitivity analysis indicated that short-term TRT was more likely to increase PSA levels than treatment with placebo (P<0.00001).

This meta-analysis shows that regardless of the administration method, TRT is the short-term safety and does not promote prostate cancer development or progression but long-term data are warranted with justifiable end points.