Recent research indicates that men with low-risk prostate cancer on active surveillance may safely receive testosterone replacement therapy (TRT). A systematic review published in Andrology (2026) found no prostate cancer-specific deaths or metastatic events among 295 patients undergoing hormone supplementation during intermediate-term follow-up. This shift challenges long-standing clinical dogma that historically restricted TRT for men with a history of prostate malignancy due to fears of tumor growth.
The Shift from Historical Medical Dogma
For decades, physicians avoided prescribing testosterone to men with localized prostate cancer, fearing that androgen exposure would accelerate tumor development. This caution was largely based on early observations of androgen-dependent cancer cells. However, current clinical understanding has evolved toward the “androgen-saturation model.”
According to this model, prostatic tissue receptors reach their saturation point at near-castrate levels. Once this threshold is met, additional systemic testosterone provides minimal stimulation to cellular proliferation. Food and Drug Administration (FDA) has removed restrictive prostate cancer warnings from class-wide testosterone labeling, clearing a path for clinicians to reconsider treatment for hypogonadal men.
Did you know? Hypogonadism affects up to 40% of aging men, creating a complex clinical scenario when it occurs alongside a prostate cancer diagnosis.
Oncological Outcomes and Biopsy Progression
The 2026 study by Aly et al. compared 295 men receiving TRT during active surveillance against a control group of 6,826 untreated men. The data showed that TRT did not correlate with adverse oncological outcomes. Over a follow-up period ranging from 2.3 to 6.1 years, researchers observed zero cancer-specific deaths and zero metastases in the treatment group.
Biopsy results further supported the safety of this approach. Gleason score upgrading occurred in 10.7% of the treated cohort, compared to 9.4% in the untreated group—a difference that was not statistically significant. Perhaps more notably, the overall biopsy progression rate was 32.1% for those on TRT, compared to 44.7% for the non-treated population.
Treatment Conversion and Clinical Monitoring
One of the primary concerns for patients on active surveillance is the eventual need for definitive intervention, such as surgery or radiation. Contrary to the belief that TRT might necessitate earlier intervention, claims-based data showed lower conversion rates among treated men (16.8%) compared to untreated controls (21.9%). Researchers attribute this discrepancy to stringent clinical selection bias, as physicians typically screen candidates for TRT very carefully.
The Role of PSA Markers
Clinicians often rely on prostate-specific antigen (PSA) levels to monitor disease progression. However, the study found that PSA markers remained stable in TRT patients, even when serum testosterone levels increased two- to threefold. Because PSA fluctuations correlated poorly with actual histological changes, the authors recommend that physicians prioritize routine scheduled biopsies over biochemical monitoring alone.
Pro Tip: If you are managing low-risk prostate cancer, ask your urologist about the “androgen-saturation model” and whether your specific clinical profile makes you a candidate for shared decision-making regarding hormone therapy.
Frequently Asked Questions
Is testosterone replacement therapy safe for all prostate cancer patients?
No. The current data focuses on highly selected, low-risk populations on active surveillance. It is not intended for all prostate cancer patients, and treatment should only be considered through shared decision-making with a specialist.
Does testosterone make prostate cancer grow faster?
Current research, including the androgen-saturation model, suggests that prostatic receptors saturate at low levels. Higher systemic levels do not necessarily lead to increased tumor growth, though long-term prospective randomized validation is still ongoing.
Why do doctors still perform biopsies if PSA levels are stable?
The study found that PSA levels often remain stable even when testosterone is supplemented. Because PSA is not a perfect indicator of histological progression, regular biopsies remain the gold standard for tracking the status of the cancer.
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