Cui · Prostate cancer and prostatic diseases 2014 · systematic review and meta-analysis of randomized controlled trials · n=22 studies (2,351 participants)

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

Cited 123 times in the scientific literature.

Level 1 - systematic review of randomized trials

Systematic review and meta-analysis of randomized controlled trials

PubMed 24445948 · doi:10.1038/pcan.2013.60 · record verified 2026-08-26

What was done

A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to evaluate the relationship between testosterone replacement therapy (TRT) and prostate cancer risk in men with hypogonadism. Searches covered MEDLINE, Embase, and the Cochrane Controlled Trials Register. Homogeneous studies were analyzed with fixed-effect models and heterogeneous studies with random-effects models, with heterogeneity quantified using the I2 statistic.

What was found

Twenty-two RCTs involving 2,351 patients were analyzed (11 short-term <12 months and 11 long-term 12-36 months). For short-term TRT, odds ratios (OR) and 95% confidence intervals (CI) for injection and transdermal routes were: prostate cancer 0.39 (0.06-2.45) and 1.10 (0.26-4.65); biopsy 5.28 (0.24-113.87) and 2.11 (0.32-13.73); and prostate nodule 1.01 (0.13-7.60) for transdermal administration. For long-term TRT, ORs and 95% CIs for injection, transdermal, and oral administration were: 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). None of these reached statistical significance (all P>0.10). Short-term TRT significantly increased PSA levels compared to placebo (P<0.00001).

Why it matters

This meta-analysis shows that testosterone replacement therapy up to 36 months is not associated with an increased incidence of prostate cancer, prostate biopsy, or prostate nodules compared with placebo, despite elevating PSA levels.

Limits

Follow-up was limited to a maximum of 36 months, which is relatively brief for detecting prostate cancer progression. Confidence intervals for cancer outcomes were very wide due to low event rates, and some short-term routes lacked data.

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