Does testosterone hormone replacement therapy (TRT) increase the risk of developing prostate cancer?

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Last updated: September 26, 2025View editorial policy

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Testosterone Replacement Therapy Does Not Cause Prostate Cancer

There is no compelling evidence that testosterone replacement therapy (TRT) causes prostate cancer or increases the risk of developing prostate cancer. 1 In fact, decades of research have failed to establish a causative relationship between testosterone levels and prostate cancer development.

Evidence Against TRT Causing Prostate Cancer

  • Studies using stored frozen plasma samples found no difference in testosterone levels between men who later developed prostate cancer and those who did not 1
  • A review of 12 prospective studies examining the relationship between serum androgen levels and prostate cancer found only one study suggesting any significant relation, and even this finding was observed only after simultaneous adjustment for four other hormones 1
  • The European Association of Urology explicitly states that hypogonadal men receiving testosterone supplements do not have an increased risk of developing prostate cancer (supported by the American Urological Association with a strong recommendation, Evidence Level: Grade B) 2
  • Prostate cancer becomes more prevalent exactly at the time in a man's life when testosterone levels naturally decline 1

Monitoring Recommendations During TRT

Despite the lack of evidence linking TRT to prostate cancer, proper monitoring is recommended:

  • Before starting TRT:

    • Perform digital rectal examination (DRE)
    • Measure baseline PSA levels
    • Perform prostate biopsy if PSA > 4.0 ng/ml or if DRE is abnormal 1
    • Men over 40 with family history of prostate cancer should undergo PSA measurement to exclude occult prostate cancer 2
  • During TRT:

    • Monitor PSA and perform DRE every 3-6 months for the first year, then annually 1
    • Consider prostate biopsy if DRE shows changes or if there is a substantial increase in PSA (>1.5 ng/ml/year or >0.4 ng/ml per year after the first six months) 1, 2
    • Monitor hematocrit/hemoglobin levels (intervention required if hematocrit exceeds 54%) 2

Special Considerations

Family History

Men with a family history of prostate cancer have an increased risk of developing prostate cancer (relative risk of 1.8 if father has prostate cancer; higher if multiple family members affected) 2, but this risk is not increased by TRT.

Prior History of Prostate Cancer

Historically, TRT was contraindicated in men with a history of prostate cancer. However, recent evidence suggests that TRT can be safely administered to patients with a history of definitively treated, non-metastatic prostate cancer 2, 3:

  • TRT can be considered in men who have undergone radical prostatectomy with favorable pathology and undetectable PSA 2
  • Small studies have reported no PSA recurrence with TRT in men who had undetectable PSA values after radical prostatectomy 4

Common Pitfalls and Caveats

  1. Misinterpreting PSA changes: Small fluctuations in PSA are common and don't necessarily indicate cancer. Focus on substantial increases or trends over time.

  2. Inadequate monitoring: Physicians prescribing TRT should follow proper monitoring protocols. Studies have shown that patients followed by non-urologists were monitored less frequently for prostate cancer during testosterone use 5.

  3. Assuming causation from correlation: While some case reports have suggested prostate cancer detection after TRT initiation, this doesn't prove causation, as over 200,000 men are diagnosed with prostate cancer annually in the US, most detected by PSA increases unrelated to TRT 1.

  4. Ignoring benefits of TRT: When appropriately prescribed and monitored, TRT may improve erectile function, sex drive, bone mineral density, lean body mass, anemia, and depressive symptoms in hypogonadal men 2.

In conclusion, current evidence does not support the notion that testosterone replacement therapy causes prostate cancer. However, proper screening before initiation and regular monitoring during treatment are essential components of responsible TRT administration.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Testosterone Therapy in Testicular Cancer Survivors

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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