Does testosterone administration increase the risk of prostate cancer above the general population's risk?

Testosterone Therapy Does Not Increase Prostate Cancer Risk Above General Population Rates

Current evidence does not support that testosterone therapy increases the risk of prostate cancer above the general population's risk. The American Urological Association (AUA) explicitly states 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.

Evidence Against Increased Risk

• Despite decades of research, there is no compelling evidence that testosterone has a causative role in prostate cancer development 1.
• Studies using stored frozen plasma samples failed to show differences in testosterone levels between men who later developed prostate cancer and those who did not 1.
• The New England Journal of Medicine notes that prostate cancer becomes more prevalent exactly at the time of a man's life when testosterone levels decline, contradicting the hypothesis that higher testosterone levels increase risk 1.
• In fact, some evidence suggests that low testosterone levels may be associated with poor prognostic features in prostate cancer:
  • Lower testosterone has been linked to higher PSA levels 2
  • Low testosterone is associated with higher tumor burden before treatment 2
  • Men with lower testosterone levels are at higher risk of progression of their prostate cancer after treatment 2

Monitoring Recommendations

While testosterone therapy doesn't appear to increase prostate cancer risk, proper monitoring is essential:

• Baseline PSA measurement and digital rectal examination (DRE) are necessary before starting testosterone therapy, particularly in men over 40 years 3
• Men with abnormal DRE or elevated PSA should have a documented negative prostate biopsy before starting therapy 1
• PSA monitoring should be done every 3-6 months for the first year, then annually thereafter 3
• 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 3

Special Considerations

• For men with a history of prostate cancer, testosterone therapy should be approached 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
• A paradigm shift has occurred in recent years, with testosterone therapy now considered a viable option for selected men with prostate cancer suffering from testosterone deficiency 4, 5

Conclusion

The historical notion that testosterone therapy increases prostate cancer risk was based on limited studies and anecdotal case reports. Contemporary evidence suggests that testosterone therapy in men with testosterone deficiency does not increase prostate cancer risk or the likelihood of more aggressive disease. Proper monitoring with PSA testing and digital rectal examination remains important for early detection of any prostate issues during testosterone therapy.