Testosterone and Prostate Cancer: The Fear vs the Actual Evidence

There is a belief so deeply embedded in urology, primary care, and men’s health that millions of men have gone untreated for documented hypogonadism because of it: testosterone causes prostate cancer.

It traces back to a 1941 study by Nobel Prize winner Dr. Charles Huggins, who demonstrated that castration removing testosterone production caused prostate cancer to regress. The medical community’s logical but ultimately flawed extrapolation: if removing testosterone shrinks cancer, adding testosterone must grow it. For eight decades, this became an absolute contraindication. Testosterone therapy and prostate cancer were treated as incompatible.

The problem? The evidence has been dismantling this belief progressively, and the 2025–2026 clinical literature has reached a near consensus that most physicians haven’t caught up to yet. Here’s what the data actually says.

Where the Fear Came From and Why It Persisted

Huggins’ 1941 findings were real: androgen deprivation therapy (ADT) causes metastatic prostate cancer to regress, sometimes dramatically. This is established, effective, and still used in advanced prostate cancer management. Testosterone is indisputably required for prostate tissue to function including cancerous tissue.

But the leap from “removing testosterone starves cancer” to “adding testosterone feeds cancer” turns out to be physiologically incorrect at least at normal physiological levels. And for eight decades, that flawed extrapolation shaped clinical practice.

The persistence of the fear had a structural explanation: no one wanted to be the clinician who gave testosterone to a man who subsequently developed prostate cancer. The asymmetric liability of that outcome even without causation kept the contraindication firmly in place long after the evidence began suggesting it was wrong.

The Saturation Model: The Science That Changed Everything

The paradigm shift began in earnest in 2009 when Dr. Abraham Morgentaler and Dr. Abdulmaged Traish published their “saturation model” in European Urology. This model proposed something that turns the old assumption on its head: prostate tissue including cancerous tissue is sensitive to testosterone only at extremely low concentrations. Once androgen levels reach a certain threshold (well below normal physiological levels), the receptor sites become saturated, and additional testosterone has little or no effect on prostate cell growth.

Think of it this way: prostate cells behave like a sponge that becomes saturated at a small amount of water. Pouring more water doesn’t make the sponge absorb more it’s already at capacity. Similarly, once testosterone reaches the saturation threshold, increasing it further doesn’t accelerate prostate cell proliferation.

This model explains several paradoxes the old framework couldn’t:

• Why men with high testosterone don’t have higher rates of prostate cancer than men with low testosterone
• Why multiple large population studies find no correlation between circulating testosterone levels and prostate cancer risk
• Why men with the lowest testosterone levels sometimes have the most aggressive prostate cancers
• Why TRT in large cohort studies consistently fails to increase prostate cancer incidence

The saturation model is now cited in guidelines from the American Urological Association, the British Society for Sexual Medicine, and the European Association of Urology as the contemporary framework for understanding testosterone and prostate cancer biology.

What the 2025–2026 Evidence Actually Shows

The research landscape for testosterone and prostate cancer has accelerated significantly, and the findings are more reassuring than the clinical culture has acknowledged.

TRAVERSE trial prostate outcomes (2023, published JAMA Network Open 2023): The 5,246 man TRAVERSE trial the landmark TRT cardiovascular safety trial also tracked prostate safety events. The result: no statistically significant increase in prostate cancer diagnosis between the TRT and placebo groups over the 33 month trial period. PSA elevations requiring biopsy were similar between groups.

BJU International systematic review (August 2025): This systematic review of observational studies evaluated TRT oncological safety in hypogonadal men with localized prostate cancer. In men on active surveillance and in post treatment populations (post prostatectomy and post radiotherapy), biochemical recurrence rates were low ranging from 0–7% post prostatectomy and 0–6% post radiotherapy with up to 60 months of follow up. The conclusion: retrospective evidence supports cautious use of TRT in carefully selected, low to intermediate risk disease with appropriate PSA monitoring.

Nature scoping review (November 2025): A systematic search across 12 studies published between 2005 and 2025 found that TRT after definitive prostate cancer treatment was not associated with increased risk of biochemical recurrence or cancer progression across studies. The review specifically challenged the historical belief that TRT poses inherent oncologic risk to prostate cancer survivors.

British Society for Sexual Medicine Consensus Statement (January 2026): The BSSM produced a formal consensus document integrating the saturation model, TRAVERSE data, and the updated EAU guidelines. Key conclusions: high level evidence has failed to demonstrate that testosterone therapy increases risk of prostate cancer development or progression in men without known cancer. In men with a history of prostate cancer, carefully selected cases particularly favorable risk disease on active surveillance or post definitive treatment may be appropriate candidates for TRT under rigorous monitoring.

Dozens of contemporary studies from 2010–2026 show no increase in prostate cancer incidence among men receiving TRT compared to untreated men. The AUA’s July 2025 review article from Baylor College of Medicine one of the country’s leading testosterone research programs explicitly stated that “more recent evidence has challenged this idea” and that TRT may be a viable option for carefully selected patients.

The Inversion: Low Testosterone and Prostate Cancer Risk

Here’s the finding that most men have never heard and that directly contradicts the fear based narrative:

Multiple studies link low testosterone to worse prostate cancer outcomes:

• Lower testosterone levels are associated with higher grade (more aggressive) prostate cancers at diagnosis
• Men with low testosterone have higher biochemical recurrence rates after prostatectomy
• Low testosterone is associated with worse oncological outcomes in some study populations

The physiological explanation is consistent with the saturation model: very low androgen states the same low androgen environment that ADT creates are actually associated with more aggressive cancer biology in some contexts. Normal physiological testosterone levels appear to support healthier tissue regulation, not more aggressive disease.

Signs of declining testosterone in men over 40 describes the symptomatic picture that often accompanies these lower androgen states. And the cardiovascular and metabolic consequences of untreated low testosterone covered in testosterone and cardiovascular health are themselves significant drivers of long term health risk.

What This Means in Clinical Practice

None of this means testosterone therapy is risk free or appropriate for every man. The evidence supports a more nuanced position:

For men without a prostate cancer history:

• High level evidence does not support testosterone therapy as a prostate cancer risk factor
• TRT should include baseline PSA measurement and regular PSA monitoring (every 6–12 months)
• Men with PSA above 4 ng/mL, rapidly rising PSA, or clinically suspicious prostate should be evaluated by urology before starting TRT not as a contraindication, but as appropriate clinical diligence
• Prostate health after 50 covers the full PSA and prostate monitoring framework

For men with a history of prostate cancer:

• This remains an area of active clinical investigation without universal consensus
• Multiple 2025 reviews support consideration of TRT in men with favorable risk localized disease after successful treatment, under oncological oversight and rigorous PSA monitoring
• Metastatic prostate cancer, high grade disease, and active disease remain contraindications the ADT rationale here is still valid
• Every decision must be individualized and made in partnership with both a urologist and the treating testosterone provider

Monitoring requirements remain essential: Whether you have a prostate cancer history or not, PSA monitoring on TRT is non negotiable. The goal is not to avoid testosterone it’s to use it correctly, with eyes open. What a comprehensive hormone panel actually tests for includes PSA as a required component of any men’s TRT protocol. How to read your blood test results helps you understand what those numbers mean in context.

Conclusion: The Fear Is Outdated the Monitoring Is Not

Testosterone and prostate cancer is a topic where clinical practice has lagged significantly behind the evidence. The near consensus in 2025–2026 urology and sexual medicine literature is that testosterone therapy, in appropriately selected and monitored men, does not increase prostate cancer risk. The saturation model explains the biology. The TRAVERSE trial, the BSSM consensus statement, and multiple systematic reviews confirm the clinical reality.

What remains essential is not fear it’s monitoring. PSA at baseline. PSA every 6–12 months on treatment. Prompt evaluation of any significant rise. Urological partnership for men with relevant history.

At AK Twisted Wellness, we prescribe testosterone therapy within a clinically rigorous protocol baseline PSA, regular monitoring, and ongoing evaluation. We don’t let outdated fears prevent appropriate care. And we don’t let appropriate care proceed without appropriate oversight.

Visit aktw.life or call (520) 710 8805 telehealth available nationwide.

Frequently Asked Questions

1. Does testosterone therapy cause prostate cancer? Based on current evidence, no high level clinical data including the 5,246 man TRAVERSE trial and multiple systematic reviews through 2025 have failed to demonstrate that testosterone replacement therapy increases the risk of prostate cancer development or progression in men without a prior cancer diagnosis. This represents a significant shift from the historical assumption, which was based on an oversimplification of the 1941 Huggins castration data. The saturation model explains why normal physiological testosterone levels do not accelerate prostate cell growth.

2. What is the saturation model of testosterone and prostate cancer? The saturation model, formalized by Morgentaler and Traish in European Urology (2009) and now referenced in AUA, EAU, and BSSM guidelines, proposes that prostate tissue including cancerous tissue is sensitive to testosterone only at very low concentrations. Once testosterone reaches the saturation threshold (well below normal levels), additional testosterone has minimal to no effect on prostate cell growth. This explains why population studies consistently find no correlation between testosterone levels and prostate cancer risk.

3. Can men with a history of prostate cancer take testosterone therapy? Historically, this was considered an absolute contraindication. The 2025–2026 literature has significantly evolved this position. The January 2026 BSSM consensus statement and the BJU International 2025 systematic review both support cautious consideration of TRT in men with favorable risk, localized disease on active surveillance or after successful definitive treatment, under rigorous PSA monitoring and oncological oversight. Metastatic disease and high grade cancer remain contraindications. Every case requires individualized oncological evaluation.

4. How does PSA change on testosterone therapy? PSA often shows a modest increase in the first 3–6 months of TRT as the prostate normalizes function under adequate androgen stimulation. This initial increase is expected and does not indicate cancer development. Afterward, PSA should stabilize. A PSA rise exceeding 1.4 ng/mL in the first year of therapy or rapid velocity beyond 0.4 ng/mL per year warrants urological evaluation. PSA monitoring every 6–12 months is a standard requirement in responsible TRT management.

5. Why do men with low testosterone sometimes have worse prostate cancer outcomes? This counterintuitive finding aligns with the saturation model: very low androgen states may actually be associated with more aggressive cancer biology in some contexts. Multiple studies have found that lower testosterone correlates with higher grade prostate cancers at diagnosis and worse biochemical recurrence rates after treatment. This doesn’t mean low testosterone causes more aggressive cancer but it does challenge the assumption that higher testosterone is always clinically worse for the prostate.

6. How does AK Twisted Wellness approach testosterone therapy and prostate safety? We require a baseline PSA before initiating TRT for any man over 40. We monitor PSA at 3, 6, and 12 months during the first year of treatment, then annually. We review prostate specific symptoms, urinary function, and digital rectal exam status as part of our men’s health protocol. Men with elevated or rising PSA are referred to urology for evaluation before or during treatment. We believe rigorous monitoring is how appropriate testosterone therapy is delivered safely not fear, and not neglect. Visit aktw.life or call (520) 710 8805.

References

1. Walia, H. (2025). Testosterone Replacement, Where Are We in 2025? Trends in Urology & Men’s Health. https://onlinelibrary.wiley.com/doi/10.1002/tre.70016
2. Saffati, G., & Khera, M. (2025). Testosterone Supplementation After Localized Prostate Cancer: The Current State of the Literature. AUA News, July/August 2025. https://auanews.net/issues/articles/2025/july/august 2025/testosterone supplementation after localized prostate cancer the current state of the literature
3. PMC / World Journal of Men’s Health. (2025). Testosterone Replacement Therapy in Hypogonadal Men with a Prostate Cancer Diagnosis: British Society for Sexual Medicine Consensus Statement. https://pmc.ncbi.nlm.nih.gov/articles/PMC12798415/
4. Santucci, D., et al. (2025). Oncological Safety of Testosterone Replacement Therapy in Men with Localised Prostate Cancer: A Systematic Review. BJU International. https://bjui journals.onlinelibrary.wiley.com/doi/10.1111/bju.16870
5. Nature / International Journal of Impotence Research. (2025). Testosterone Replacement Therapy Following Definitive Treatment for Prostate Cancer: A Scoping Review of Safety and Efficacy. https://www.nature.com/articles/s41443 025 01206 3
6. Bhasin, S., et al. (2023). Prostate Safety Events During Testosterone Replacement Therapy: TRAVERSE Randomized Clinical Trial. JAMA Network Open, 6(12), e2348692. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2812622
7. Morgentaler, A., & Traish, A.M. (2009). Shifting the Paradigm of Testosterone and Prostate Cancer: The Saturation Model and the Limits of Androgen Dependent Growth. European Urology, 55(2), 310–321. https://www.europeanurology.com/article/S0302 2838(08)01154 8/fulltext
8. American Urological Association. (2025). Male Hypogonadism Clinical Practice Guideline Prostate Safety Monitoring. https://www.auanet.org/guidelines and quality/guidelines/male hypogonadism guideline
9. European Association of Urology. (2025). EAU EANM ESTRO ESUR ISUP SIOG Guidelines on Prostate Cancer Testosterone and Androgen Status. https://uroweb.org/guidelines/prostate cancer
10. Huggins, C., & Hodges, C.V. (1941). Studies on Prostatic Cancer: The Effect of Castration, of Estrogen and of Androgen Injection on Serum Phosphatases in Metastatic Carcinoma of the Prostate. Cancer Research, 1, 293–297. https://cancerres.aacrjournals.org/content/1/4/293
    

Disclaimer: This content is for informational and educational purposes only and does not constitute medical, legal, or financial advice. Reading this article does not create a patient provider relationship. Testosterone therapy and prostate cancer management require individualized evaluation by qualified healthcare providers men with a personal or family history of prostate cancer should discuss testosterone therapy with a urologist before proceeding. For questions about AK Twisted Wellness services, visit aktw.life or call (520) 710 8805.