Oncological Safety of Testosterone Replacement Therapy in Men With a History of Prostate Cancer: A Systematic Review

This systematic review aims to map, critically evaluate, and integrate current evidence on the oncological safety of testosterone replacement therapy (TRT) in men with a history of prostate cancer. For decades, TRT was contraindicated in this population due to the "androgen hypothesis"; however, recent evidence and the "saturation model hypothesis" challenge this dogma. A comprehensive search of seven databases, with no restrictions on publication date, yielded 2,284 studies, of which nine met the inclusion criteria. The reviewed studies, primarily retrospective cohorts and case series, reported that TRT does not appear to increase the risk of biochemical recurrence, disease progression, or mortality in men with low- to intermediate-risk localized prostate cancer following radical prostatectomy, radiotherapy, or under active surveillance. Evidence for high-risk or advanced disease remains limited, and TRT continues to be contraindicated in recurrent or metastatic cases outside of clinical trials. These findings challenge historical restrictions and support the cautious use of TRT in carefully selected patients.