The Effect of Testosterone Replacement Therapy on Prostate Cancer

A Systematic Review and Meta-analysis

Y Cui; H Zong; H Yan; Y Zhang

Disclosures

Prostate Cancer Prostatic Dis. 2014;17(2):132-143. 

In This Article

Abstract and Introduction

Abstract

Background: 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.

Methods: 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: 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).

Conclusions: 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.

Introduction

Testosterone deficiency in the aging male has become a topic of increasing interest and debate worldwide. Cross-sectional and longitudinal data indicate that testosterone levels are reduced progressively with age and that a significant percentage of men aged >60 years have serum testosterone levels that are below the lower limits of young adult men aged 20–30 years.[1–3] Late-onset hypogonadism (LOH) is a clinical and biochemical syndrome associated with advancing age and characterized by a deficiency in serum testosterone levels, among other signs and symptoms.[4,5] LOH may result in significant detriment to quality of life and adversely affect the function of multiple organ systems.

Over the past decade, there has been a growing awareness of the health benefits of testosterone therapy for men with testosterone deficiency, including improved sexual desire and performance, improved mood, increased muscle mass and strength, decreased fat mass and improved bone mineral density.[6] However, for approximately 70 years there has been a concern that higher serum testosterone represents a risk for prostate cancer.[7] Many urologists are concerned that testosterone replacement therapy (TRT) may accelerate prostate growth not only in benign disease but also in cancer as well.

The goal of the present study was to perform a meta-analysis evaluating the effect of TRT on prostate cancer, which may resolve some of the current controversies over the use of the drug.

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