Can you start males with a family history of prostate cancer on testosterone (testosterone) replacement therapy?

Testosterone Therapy in Males with Family History of Prostate Cancer

Testosterone replacement therapy can be initiated in men with a family history of prostate cancer, but requires appropriate screening and monitoring due to theoretical concerns about prostate cancer risk. 1

Initial Assessment Before Starting Testosterone

Before initiating testosterone therapy in men with a family history of prostate cancer:

1. Mandatory PSA screening:

   • PSA measurement is required in all men over 40 years of age 1
   • If PSA is elevated at baseline, obtain a second PSA test to rule out spurious elevation 1
   • If two PSA levels raise suspicion for prostate cancer, consider:
     • Reflex testing (e.g., 4K or phi)
     • Prostate biopsy with/without MRI 1

2. Digital rectal examination (DRE):

   • Perform in all men over 40 years
   • Abnormal DRE requires further evaluation 1

3. Risk stratification:

   • Family history increases relative risk:
     • One first-degree relative: RR 1.8
     • Father and brother: RR 5.5
     • Two brothers: RR 7.7 1
   • Consider earlier screening (age 40) for men with multiple family members diagnosed with clinically significant prostate cancer at age <60 years 1

Monitoring During Testosterone Therapy

Once testosterone therapy is initiated:

1. PSA monitoring:

   • Every 3-6 months for the first year
   • Annually thereafter 2
   • Consider more frequent testing in men with family history 1

2. Criteria for urologic referral/biopsy:

   • PSA increase >1.0 ng/mL during first six months of treatment
   • PSA increase >0.4 ng/mL per year thereafter 1, 2
   • Any abnormal DRE findings 1

3. Testosterone level monitoring:

   • Aim to maintain testosterone levels in the normal range
   • Adjust dosage based on clinical response and testosterone levels 1

Evidence on Safety

The American Urological Association provides several key points regarding testosterone therapy and prostate cancer risk:

• No established link: 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, 2

• Theoretical concerns: Despite decades of research, there is no compelling evidence that testosterone has a causative role in prostate cancer development 2

• Contradictory evidence: Prostate cancer becomes more prevalent when testosterone levels naturally decline with age, contradicting the assumption that higher testosterone increases cancer risk 2

• Risk-benefit discussion: Patients with testosterone deficiency and a family history of prostate cancer should be informed that there is inadequate evidence to quantify the risk-benefit ratio of testosterone therapy (Expert Opinion) 1

Special Considerations

• Genetic testing: Consider germline testing for men with multiple family members diagnosed with clinically significant prostate cancer at age <60 years or a family member who died from prostate cancer 1

• Contraindications: Testosterone is absolutely contraindicated in males with known or suspected carcinoma of the prostate gland 3

• Monitoring for polycythemia: Check hemoglobin/hematocrit before starting therapy and periodically during treatment. If hematocrit exceeds 54%, consider dose reduction or temporary discontinuation 1

• Fertility concerns: Discuss the long-term impact of exogenous testosterone on spermatogenesis with patients interested in future fertility 1

Conclusion

While family history of prostate cancer warrants additional vigilance, it is not an absolute contraindication to testosterone therapy in hypogonadal men. The key is appropriate screening before initiation and careful monitoring during treatment. The current evidence suggests that testosterone therapy does not increase the risk of developing prostate cancer, even in men with family history, provided that proper screening and monitoring protocols are followed.