Testosterone Replacement Therapy (TRT) and Prostate Cancer: An Updated Systematic Review with a Focus on Previous or Active Localized Prostate Cancer

Hypogonadism is associated with the development of metabolic syndrome, type 2 diabetes, and cardiovascular disease. In addition, the beneficial effects of androgen therapy on the symptoms of andropause are demonstrated. Unfortunately, this syndrome is often disregarded by the medical community and the main justification for not treating age-related hypogonadism is the risk of developing prostate cancer. A growing body of evidence exists in the literature, studying the impact of testosterone replacement therapy (TRT) in the setting of previous or active localized prostate cancer.

In October 2019, we performed a systematic review of PubMed, MEDLINE, EMBASE, and Cochrane to investigate studies about testosterone administration and prostate cancer. Overall, 164 eligible publications were retrieved and 58 studies were selected for inclusion.

Initially, guidelines stated that TRT is contraindicated in men with untreated prostate cancer and encourage prostate cancer screening by digital rectal exam (DRE) and prostate-specific antigen (PSA) before starting the treatment. However, whether or not TRT should be definitively banned in men with a personal history of prostate cancer remains an open debate.

Existing literature suggests that patients treated for androgen deficiency of the aging male (ADAM) do not develop more prostate cancer than the general population. Studies also suggest that patients treated for ADAM do not develop more prostate cancer than untreated men.

Moreover, after treatment for localized prostate cancer (i.e. radical prostatectomy, brachytherapy, external beam radiotherapy), androgen therapy was not associated with a higher recurrence rate. Finally, few studies have analyzed prostate cancer progression after testosterone replacement therapy: two observed no clinical progression whereas the other ones found between 8 and 15% of patients with an increase in Gleason score.

Given this growing body of evidence, we suggest some pragmatical proposals for the use of TRT in the setting of previously treated or active prostate cancer.

Written by: Louis Lenfant, MD and Morgan Rouprêt, MD, PhD, Urology Department, Sorbonne University, GRC n°5, PREDICTIVE ONCO-UROLOGY, AP-HP, Hôpital Pitié-Salpêtrière, Paris, France

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