Testosterone replacement therapy in men with prostate cancer on active surveillance: a systematic review of oncological safety

Background 

Up to 20% of men on active surveillance (AS) for prostate cancer (PCa) have symptomatic hypogonadism; the oncological safety of testosterone replacement therapy (TRT) in this population is uncertain. 

Objectives 

To systematically evaluate the oncological safety of TRT in men with histologically confirmed PCa managed by AS. 

Materials and Methods 

PubMed, Embase, and CENTRAL were searched up to January 2026 (PRISMA 2020). Eligible studies enrolled men with PCa on AS receiving TRT for ≥ 12 months. Primary outcomes were biopsy progression, treatment conversion, metastasis, and PCa-specific mortality. Risk of bias was assessed using a modified Newcastle–Ottawa Scale. 

Results 

Seven observational studies (2011–2025; 295 TRT-treated men; 6826 non-TRT AS comparators; follow-up 2.3–6.1 years) were included. No PCa-specific deaths or metastatic events were reported among TRT recipients. The single controlled biopsy comparison showed comparable Gleason upgrading (10.7% TRT vs. 9.4% comparators; p = 0.732) and no significant difference in biopsy progression (32.1% vs. 44.7%; p = 0.280). The largest population-based study reported lower treatment conversion versus non-TRT AS controls (16.8% vs. 21.9%; adjusted HR 0.66, 95% CI 0.46–0.97), most plausibly reflecting selection bias. PSA remained stable despite two- to threefold testosterone increases and correlated poorly with histological progression. 

Discussion 

Short- to intermediate-term observational evidence does not demonstrate increased oncological risk with TRT in the predominantly low-risk populations studied. However, retrospective design, small samples, group imbalance, heterogeneous surveillance, and short follow-up relative to AS natural history substantially limit these findings. 

Conclusion 

TRT may be cautiously considered in selected hypogonadal men on AS through shared decision-making; prospective studies with standardised surveillance and extended follow-up are required before broader recommendations.