TRT Therapy Safety in Prostate Abnormalities

ACTIVE surveillance pathways for men with low-risk prostate cancer are increasingly utilizing concurrent hormonal treatment strategies.

Hypogonadism affects up to 40% of aging men, creating a distinct clinical challenge when it coexists with localized prostate cancer. Historically, historical medical dogma strictly discouraged the administration of testosterone replacement therapy due to early observations regarding androgen-dependent tumor expansion. However, contemporary pathophysiological concepts like the androgen-saturation model suggest that prostatic tissue receptors saturate at near-castrate levels, leaving higher systemic levels with minimal cellular proliferative effect. Furthermore, recent regulatory updates highlight that the FDA removed restrictive prostate cancer warnings from class-wide labeling, signaling a major paradigm shift for practicing physicians.

Oncological Outcomes on Active Surveillance

A comprehensive evaluation analyzed seven observational series encompassing 295 men who received testosterone replacement therapy while undergoing active surveillance, alongside 6,826 non-treated comparators. The research noted zero prostate cancer-specific deaths and zero metastatic events among the patients receiving hormone supplementation over intermediate-term follow-up intervals ranging from 2.3 to 6.1 years.

Biopsy evaluation revealed that Gleason score upgrading occurred in 10.7% of the treated arm compared to 9.4% in the non-treated cohort, demonstrating no statistically significant variation. Additionally, the overall biopsy progression rates reached 32.1% in the treated population versus 44.7% in the external comparison group.

Treatment Conversion and Marker Kinetics

Definitive intervention conversion rates did not increase among men utilizing testosterone replacement therapy. Data extracted from large claims-based assessments actually recorded lower conversion rates among treated individuals at 16.8% compared to 21.9% in untreated controls, an effect likely influenced by stringent clinical selection bias in real-world practice. Propensity-matched cohorts confirmed equivalent three-year and five-year treatment-free survival outcomes between both evaluated cohorts.

Laboratory trends indicated that prostate-specific antigen markers remained overall stable despite two- to threefold elevations in serum testosterone measurements. Because prostate-specific antigen fluctuations correlated poorly with confirmed histological progression, medical experts recommend that clinicians maintain routine scheduled biopsies rather than relying solely on biochemical monitoring. While prospective randomized validation over longer timelines remains necessary, these findings suggest that testosterone replacement therapy can be carefully considered through shared decision-making in highly selected, low-risk hypogonadal populations.

Reference

Aly M et al. Testosterone Replacement Therapy in Men With Prostate Cancer on Active Surveillance: A Systematic Review of Oncological Safety. Andrology. 2026;0:1-14.

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