Does TRT Cause Prostate Cancer? The Evidence and Its Limits

Does TRT cause prostate cancer? The best randomized evidence shows no clear increase, but it has real limits. In the TRAVERSE trial, high-grade cancer and any prostate cancer were uncommon and did not differ significantly between testosterone gel and placebo. The men in the trial were screened to exclude high prostate risk. That is reassuring but not proof of zero risk, and it doesn't cover men with high PSA or prior prostate cancer.

Key takeaways

• In TRAVERSE, high-grade prostate cancer occurred in 5 of 2,596 men on testosterone gel and 3 of 2,602 on placebo, a difference that was not statistically significant.
• With only eight high-grade cancers, the confidence interval runs from a large reduction to a several-fold increase, so the trial cannot rule out a meaningful effect in either direction.
• The trial excluded men with PSA above 3.0 ng/mL, used a topical gel rather than injections, and treated men for about 22 months on average.
• PSA tends to rise on testosterone, so it is checked before therapy, and a clinician confirms and interprets any rise during treatment.
• The trial evidence does not cover men with a history of prostate cancer, and the AUA says the risk-benefit balance cannot yet be quantified for them.

Does TRT cause prostate cancer? The short answer

No randomized trial has shown that testosterone replacement therapy (TRT) causes prostate cancer, but the best trial had too few cancers to rule an effect out. In the TRAVERSE prostate safety study, high-grade prostate cancer occurred in 5 of 2,596 men on testosterone (0.19%) and 3 of 2,602 men on placebo (0.12%) (JAMA Netw Open, 2023).

The worry has a real basis. Advanced prostate cancer depends on androgens, the family of male hormones that includes testosterone. That is why lowering testosterone is a standard way to treat advanced prostate cancer.

The jump from "lowering testosterone slows advanced cancer" to "adding testosterone causes cancer" sounds logical. For a long time, though, it was never tested in a large placebo-controlled trial. One proposed explanation for why the jump may not hold is sometimes called the saturation model. It suggests prostate tissue responds to testosterone only up to a point. It remains a hypothesis, not a settled fact.

This article won't call the concern a myth, and it won't try to scare you. It covers what the trial measured, what the trial can't tell you, and how PSA monitoring fits around the evidence. For the basics of therapy itself, see testosterone replacement therapy explained.

What the TRAVERSE prostate safety study measured

The TRAVERSE prostate study tracked high-grade prostate cancer as its main outcome. It also tracked any prostate cancer and several urinary problems in men randomly assigned to testosterone gel or placebo. None of those outcomes differed significantly between the groups (JAMA Netw Open, 2023).

TRAVERSE was double-blind, meaning neither participants nor investigators knew who received testosterone. It enrolled 5,246 men aged 45 to 80 at 316 US sites. Every man had:

• two testosterone levels below 300 ng/dL
• symptoms of hypogonadism (clinically low testosterone)
• cardiovascular disease or raised cardiovascular risk

The analysis covered 5,204 men with a mean age of 63.3.

The trial grew out of heart questions. In 2014, FDA convened an advisory committee after reports of stroke, heart attack and death in testosterone users. That review led to the industry-wide TRAVERSE trial (FDA, 2025). The cardiac results are covered in what TRAVERSE showed about TRT and heart risk.

The study measured two kinds of outcomes:

• Primary endpoint: high-grade prostate cancer, confirmed by independent review, with a Gleason score of 4+3 or higher. The Gleason score grades how abnormal cancer cells look under a microscope. Higher scores mean more aggressive disease.
• Secondary endpoints: any prostate cancer, acute urinary retention (sudden inability to urinate), invasive prostate procedures, prostate biopsy, and new medication for urinary symptoms.

One design choice matters. The protocol set rules in advance for handling PSA rises and urology referrals. Without those rules, a testosterone-driven PSA rise could send more treated men to biopsy. More biopsies find more cancer. Researchers call this ascertainment bias, and the prespecified rules were meant to minimize it.

The results were consistent across outcomes:

• No endpoint differed significantly between the groups.
• The change in urinary symptom scores did not differ.
• PSA rose more in the testosterone group than in the placebo group.

Why eight cancers can't settle the question

Eight high-grade cancers across both groups is too few to tell a modest effect from no effect. "No significant difference" means the trial could not detect a difference. It does not mean the risk was shown to be the same.

The trial recorded 5 high-grade cancers on testosterone and 3 on placebo over 14,304 person-years of follow-up. The hazard ratio was 1.62, with a 95% confidence interval of 0.39 to 6.77 (P =.51) (JAMA Netw Open, 2023).

In plain terms:

• A hazard ratio compares how often an event happens in one group versus another over time. A value of 1.0 means no difference.
• The confidence interval is the range of true effects the data are reasonably compatible with. Here it runs from roughly 60 percent lower risk to nearly seven times higher risk.
• Because the range includes 1.0, the result is not significant. Because the range is so wide, a meaningful effect in either direction cannot be ruled out.

Time is a second limit. Mean treatment lasted 21.8 months on testosterone and 21.6 months on placebo. Prostate cancer often develops slowly over many years. A trial of this length cannot answer long-term questions.

The authors' conclusion is measured. They report that prostate events were low and not significantly different in men "carefully evaluated to exclude those at high risk of prostate cancer." That is a long way from blanket claims that testosterone carries no prostate risk.

Who TRAVERSE left out, and why it matters for you

TRAVERSE applies most directly to men like those it enrolled. They were aged 45 to 80, had cardiovascular disease or risk, had a low PSA and no severe urinary symptoms, and used a topical gel for about two years. If you fall outside that profile, the result does not automatically apply to you.

• PSA: men with PSA above 3.0 ng/mL were excluded. The baseline mean was 0.92 ng/mL (JAMA Netw Open, 2023).
• Urinary symptoms: men with an IPSS above 19 were excluded. The IPSS (International Prostate Symptom Score) is a questionnaire that rates urinary symptoms. The baseline mean was 7.1.
• Formulation: participants used a 1.62% topical testosterone gel. Injectable testosterone was not tested. This does not show that injections carry more or less prostate risk. The trial simply did not study them.
• Age and health: every participant was 45 to 80 with cardiovascular disease or risk. Younger men were not studied.
• Prior prostate cancer: TRAVERSE does not address these men. The AUA guideline says men with a history of prostate cancer should be told there is inadequate evidence to quantify the risk-benefit ratio of testosterone therapy (AUA, 2018). That conversation belongs with a specialist.

What observational studies add

A large Swedish registry study found no link between TRT and overall prostate cancer risk. It did find more lower-risk cancers diagnosed early in TRT use, which the authors attribute to detection bias: men starting testosterone get tested more.

The study used a nested case-control design within Sweden's National Prostate Cancer Register. It compared all 38,570 prostate cancer cases diagnosed from 2009 to 2012 with 192,838 age-matched men without cancer. About 1% of each group had filled TRT prescriptions (J Clin Oncol, 2017).

Results are expressed as odds ratios (OR), a measure of how strongly TRT use was associated with each outcome. An OR of 1.0 means no association.

• Overall prostate cancer: no association (OR 1.03, 95% CI 0.90 to 1.17).
• Favorable-risk (lower-risk) cancer: more common with TRT (OR 1.35, 95% CI 1.16 to 1.56). The increase appeared within the first year of use (OR 1.61). The authors read this as detection bias. Men starting testosterone get more PSA tests, so existing low-risk cancers are found sooner.
• Aggressive cancer: less common with TRT (OR 0.50, 95% CI 0.37 to 0.67), seen after more than a year of use (OR 0.44). The authors call this a novel finding that warrants further investigation. It is not evidence that testosterone protects against cancer.

Observational studies show associations, not cause and effect. Men who are prescribed testosterone may differ from men who aren't in their health, their access to care and how often they get tested. That is why the randomized trial carries more weight, even with few events.

PSA on testosterone therapy: why it rises and why it's checked

PSA usually rises somewhat on testosterone because testosterone stimulates the prostate, including its production of PSA. A rise is expected and does not by itself mean cancer. A clinician confirms and interprets it.

PSA (prostate-specific antigen) is a protein made by the prostate and measured with a blood test. In TRAVERSE, PSA rose more with testosterone than with placebo (JAMA Netw Open, 2023). PSA also varies from test to test for reasons unrelated to cancer. That is why an elevated reading is usually repeated before anyone acts on it.

The AUA guideline describes how PSA is handled around therapy (AUA, 2018):

1. PSA is measured before therapy in men over 40. This lowers the risk of treating a man who has an undiagnosed prostate cancer.
2. An elevated baseline PSA is repeated to rule out a spurious result.
3. If two baseline values look suspicious, a more formal evaluation should be considered before therapy starts. That may include further testing and a biopsy, with or without MRI.
4. Once therapy starts, the guideline stresses proper monitoring during treatment.

A PSA rise during therapy is neither an automatic alarm nor something to ignore. Your clinician confirms it, puts it in context and decides whether a urologist should weigh in.

Baseline screening is also why TRAVERSE's result is credible for screened men. Monitoring was the condition the evidence was gathered under. The TRT blood work and monitoring guide covers the full lab picture, including hematocrit (the share of your blood made up of red cells).

What FDA changed after TRAVERSE, and what it didn't

In February 2025, FDA required class-wide testosterone labeling changes focused on cardiovascular risk and blood pressure. None of the listed changes concerned prostate cancer warnings.

On February 28, 2025, FDA told testosterone product makers to make four changes (FDA, 2025):

• add TRAVERSE results to the labels of all testosterone products
• keep the Limitation of Use language for age-related hypogonadism
• remove boxed warning language about an increased risk of adverse cardiovascular outcomes
• add blood pressure information or a new blood pressure warning, because ambulatory blood pressure studies found increases with all testosterone products

The boxed warning change was about heart outcomes. It should not be read as a regulatory statement on prostate safety.

How access works through New Blue

New Blue is a technology and administrative services platform. Medical services are provided by independent licensed clinicians; medications are dispensed only if prescribed.

The injectable testosterone protocol is not an online form. It requires a live clinician visit plus lab work.

1. You complete a live visit with an independent licensed clinician, along with the required lab work. Some treatments or states may require additional steps.
2. The clinician decides whether testosterone is appropriate based on your history, symptoms and labs. Not everyone qualifies, and that's how it should work.
3. If prescribed, a licensed partner pharmacy ships the medication directly to you.

Consultation timing varies by clinician availability. Availability varies by state, so check state availability first. Details and current pricing are on the injectable testosterone protocol page. The service is for adults 21 and older and is not for emergencies.

If you have a history of prostate cancer, an elevated PSA or an abnormal prostate exam, raise it with your clinician, who may involve a specialist. New trouble urinating, inability to urinate, or blood in your urine needs prompt in-person care.

Frequently Asked Questions

Does testosterone therapy increase prostate cancer risk?

In the TRAVERSE randomized trial, high-grade and overall prostate cancer did not differ significantly between testosterone gel and placebo. The men in the trial were screened to exclude high prostate risk. High-grade cancer occurred in 5 of 2,596 men on testosterone and 3 of 2,602 on placebo. With so few cases, the result is reassuring but not proof of zero risk.

What did the TRAVERSE trial find about prostate cancer?

TRAVERSE found no significant difference between testosterone and placebo in high-grade prostate cancer, any prostate cancer, urinary retention, prostate procedures, biopsies or new urinary medication. The hazard ratio for high-grade cancer was 1.62, with a 95% confidence interval of 0.39 to 6.77, which is too wide to rule out a meaningful effect either way. PSA rose more in the testosterone group.

Is it normal for PSA to rise on TRT?

A PSA rise on testosterone is common because testosterone stimulates the prostate, including PSA production. A rise does not by itself mean cancer. A clinician confirms it with repeat testing and decides whether a urology referral is needed.

Does the TRAVERSE result apply to testosterone injections?

TRAVERSE tested a 1.62% topical testosterone gel, not injections. The trial does not show that injections carry more or less prostate risk. It shows only that injections were not studied. Men using injectable testosterone are relying on evidence gathered with a different formulation.

What does the evidence say for men with a history of prostate cancer?

TRAVERSE does not address men with a history of prostate cancer. The AUA guideline says these men should be told there is inadequate evidence to quantify the risk-benefit ratio of testosterone therapy. Any decision for them needs specialist input.

Did FDA change prostate warnings after TRAVERSE?

None of the testosterone labeling changes FDA listed in its February 2025 announcement concerned prostate cancer warnings. FDA required adding TRAVERSE results to all testosterone labels, keeping the Limitation of Use language for age-related hypogonadism, removing boxed warning language about adverse cardiovascular outcomes, and adding blood pressure information or warnings.

Sources

1. Prostate Safety Events During Testosterone Replacement Therapy in Men With Hypogonadism: A Randomized Clinical Trial. JAMA Network Open, 2023. https://pubmed.ncbi.nlm.nih.gov/38150256/
2. Evaluation and Management of Testosterone Deficiency: AUA Guideline. Journal of Urology, 2018. https://doi.org/10.1016/j.juro.2018.03.115
3. FDA issues class-wide labeling changes for testosterone products. U.S. Food and Drug Administration, 2025. https://www.fda.gov/drugs/drug-alerts-and-statements/fda-issues-class-wide-labeling-changes-testosterone-products
4. Testosterone Replacement Therapy and Risk of Favorable and Aggressive Prostate Cancer. Journal of Clinical Oncology, 2017. https://doi.org/10.1200/JCO.2016.69.5304

Medical disclaimer: This article is for educational purposes only and is not medical advice. Decisions about testosterone therapy, PSA testing and prostate evaluation are made by a licensed clinician based on your individual history and clinical review. New Blue Health is a technology and administrative services platform, not a medical provider.