The safety of testosterone therapy (TTh) in men with a history of prostate cancer (PCa) remains controversial, particularly after interventions for PCa including radical prostatectomy (RP). Previous meta-analyses have included heterogeneous populations, limiting interpretation.
To systematically review and meta-analyze the risk of biochemical recurrence (BCR) in hypogonadal men treated with TTh following RP for PCa.
A systematic search of Medline was conducted from 1969 to July 2025 according to PRISMA and MOOSE guidelines. Studies reporting BCR rates after TTh in men who underwent RP were included. Data were pooled using a random-effects model. Meta-regression explored the associations with age, Gleason score, follow-up, and preoperative prostate specific antigen (PSA).
Seven retrospective studies met the inclusion criteria, encompassing 398 patients (mean age: 63.9 years; mean follow-up: 29.6 months). Overall, the pooled BCR rate in TTh-treated patients was 3.5% (95% CI: 1.5-8.5). No significant association was found between BCR and age, Gleason score, or follow-up duration. In studies with untreated controls, TTh was associated with a significantly lower BCR risk. Limited data suggested improvements in erectile function and quality of life. Funnel plot analysis indicated no publication bias.
TTh after RP appears to be associated with a limited risk of BCR in hypogonadal men with PCa. However, the absence of randomized controlled trials and incomplete reporting of key clinical variables preclude definitive conclusions. Larger, well-designed prospective studies are warranted to confirm these findings and clarify the long-term safety profile of the use of testosterone replacement therapy in this setting.
Andrology. 2026 Jun 23 [Epub ahead of print]
Giovanni Corona, Luís Afonso Morgado, Paolo Capogrosso, Luca Boeri, Carlo Bettocchi, Giulia Rastrelli, Linda Vignozzi, Mario Maggi, Suks Minhas, Andrea Salonia
Endocrinology and Metabolic Disease Unit, Specialist Medicine Department, AUSL Romagna, Forlì-Cesena, Italy., Urology Service, Centro Hospitalar Universitário São João, Porto, Portugal., Department of Urology and Andrology, Ospedale Di Circolo and Macchi Foundation, Varese, Italy., Department of Urology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy., Department of Urology, University of Foggia, Foggia, Italy., Department of Experimental, Andrology, Women's Endocrinology and Gender Incongruence Unit, Clinical, and Biomedical Sciences "Mario Serio", University of Florence, Florence, Italy., Department of Experimental, Endocrinology Unit, Clinical, and Biomedical Sciences "Mario Serio", University of Florence, Florence, Italy., Department of Urology, Imperial Healthcare NHS Trust, Charing Cross Hospital, London, UK., Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy.