TRT and Prostate Health: What Australian Men Need to Know About PSA and Prostate Cancer
Key Takeaways
Does TRT cause prostate cancer? What happens to PSA on testosterone therapy? This evidence-based guide addresses the most common prostate-related concerns Australian men have about TRT.
The Historical Concern: The Androgen Hypothesis
The concern about TRT and prostate cancer traces back to pioneering work in the 1940s by Charles Huggins — who won the Nobel Prize in Medicine for demonstrating that castration could cause prostate cancer to regress. For decades, this led to the belief that adding testosterone must cause or accelerate prostate cancer.
The hypothesis has been substantially revised by modern evidence.
What the Modern Evidence Shows
The TRAVERSE trial (Lincoff AM et al., NEJM 2023) — involving 5,204 hypogonadal men followed for 33 months — found no statistically significant increase in prostate cancer incidence in the TRT group compared to placebo.
A 2006 meta-analysis by Calof et al. in Annals of Internal Medicine pooled data from 19 randomised trials and found no significant difference in prostate cancer rates between TRT and placebo groups.
The Endocrine Society's 2018 Clinical Practice Guidelines state: "We do not have evidence that testosterone therapy causes prostate cancer in men without pre-existing disease." TRT is contraindicated in men with existing or suspected prostate cancer — not because TRT causes cancer, but because testosterone can accelerate growth of pre-existing androgen-sensitive malignancy.
The Saturation Model: A Better Framework
The modern understanding is explained by the saturation model (Morgentaler A, Eur Urol, 2006). Prostate cancer cells become "saturated" with testosterone at relatively low levels (~8 nmol/L). Above saturation, additional testosterone has no incremental stimulatory effect on prostate cancer cells.
PSA on TRT: What to Expect
Expected PSA changes with TRT:
- A modest rise in PSA — typically 0.3–0.5 ng/mL — within the first 3–6 months of commencing TRT is normal and expected
- PSA then stabilises; progressive rises beyond this initial adjustment are not expected
- A PSA increase of more than 1.4 ng/mL above baseline within any 12-month period warrants urological review
The Australian Prescriber specifies that PSA should be measured before TRT commencement and at 3–6 months, then annually.
For men over 40: A baseline PSA should be performed before commencing TRT. Men with a PSA above 3–4 ng/mL at baseline should be referred to urology before TRT is initiated.
Absolute Contraindications
- Active prostate cancer or suspected prostate cancer
- PSA >4 ng/mL without urological assessment
- Significant lower urinary tract symptoms (severe LUTS/BPH)
References
- Lincoff AM, et al. Cardiovascular Safety of Testosterone-Replacement Therapy. N Engl J Med. 2023.
- Calof OM, et al. Adverse events associated with testosterone supplementation. Ann Intern Med. 2006.
- Morgentaler A. Testosterone and prostate cancer: an historical perspective on a modern myth. Eur Urol. 2006.
- Cancer Australia — Prostate Cancer Statistics.
- Australian Prescriber — Low testosterone in men.
- Healthdirect Australia — Testosterone.
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