Is there an increased risk of prostate cancer with testosterone (T) therapy?

Testosterone Therapy and Prostate Cancer Risk

There is no compelling evidence that testosterone therapy increases the risk of developing prostate cancer in hypogonadal men with normal prostate examinations and PSA levels. 1

Evidence Overview

The relationship between testosterone therapy and prostate cancer has been extensively studied, with current evidence suggesting that testosterone replacement does not appear to increase prostate cancer risk in appropriately monitored patients.

Current Understanding of Testosterone and Prostate Cancer

• Despite decades of research, there is no compelling evidence that testosterone has a causative role in prostate cancer development 1
• Prospective studies have demonstrated a low frequency of prostate cancer in association with testosterone replacement therapy - only 5 cases among 461 men (1.1%) followed for 6-36 months, a prevalence rate similar to that in the general population 1
• The American Urological Association (AUA) guidelines explicitly state that clinicians should inform patients of the absence of evidence linking testosterone therapy to the development of prostate cancer (Strong Recommendation; Evidence Level: Grade B) 1

Monitoring Recommendations

Proper monitoring is essential when initiating testosterone therapy:

• Before starting therapy:

  • Baseline PSA measurement
  • Digital rectal examination (DRE)
  • Men with abnormal DRE or elevated PSA should have a documented negative prostate biopsy before initiating testosterone therapy 1

• During therapy:

  • PSA monitoring every 3-6 months for the first year, then annually thereafter 1
  • Regular DRE
  • Consider urologic referral for biopsy if PSA increases by more than 1.0 ng/mL during the first six months or more than 0.4 ng/mL per year thereafter 1

Special Considerations

• Men with history of prostate cancer: Historically contraindicated, but this view is evolving

  • The AUA notes that testosterone therapy in men with previously treated prostate cancer should be made with caution (Moderate Recommendation; Evidence Level: Grade C) 1
  • Men with radical prostatectomy with favorable pathology and undetectable PSA may be candidates for testosterone therapy 1
  • Limited data suggest no significant increase in cancer recurrence in appropriately selected patients 2, 3

• Contraindications:

  • Active prostate cancer is a contraindication to testosterone therapy 4
  • Testosterone gel is specifically contraindicated in men with known or suspected carcinoma of the prostate 4

Clinical Implications

The concern about testosterone therapy causing prostate cancer appears to stem from the observation that androgen deprivation therapy causes regression of prostate cancer. However, this does not necessarily mean that normalizing testosterone levels in hypogonadal men increases cancer risk.

Interestingly, prostate cancer becomes more prevalent at the time in a man's life when testosterone levels naturally decline 1, which contradicts the simple assumption that higher testosterone levels increase cancer risk.

Potential Risks and Caveats

While the evidence doesn't support increased risk of developing prostate cancer, clinicians should be aware of:

• Case reports have suggested testosterone therapy may potentially unmask occult prostate cancers 5
• Digital rectal examination may be particularly important in detecting these cancers, as PSA may not always be elevated 5
• Testosterone therapy can increase PSA levels, which requires careful monitoring and interpretation 2
• Men with BPH treated with androgens may experience worsening of symptoms 4

Bottom Line

Current evidence does not support withholding testosterone therapy from hypogonadal men due to concerns about prostate cancer risk, provided appropriate monitoring is in place. The saturation model suggests that maximal prostate cancer growth is achieved at relatively low androgen concentrations 6, which may explain why normalizing testosterone levels in hypogonadal men doesn't appear to increase cancer risk.