What are the considerations when a patient asks for exogenous testosterone (testosterone replacement therapy)?

Considerations When a Patient Asks for Exogenous Testosterone

Testosterone replacement therapy (TRT) should only be prescribed for patients with confirmed hypogonadism, characterized by low serum testosterone levels on at least two separate morning measurements and clinical symptoms, not for "age-related hypogonadism" or performance enhancement. 1, 2

Diagnostic Evaluation

1. Confirm hypogonadism diagnosis:

   • Measure morning total testosterone levels (between 8-10 AM) on at least two separate days 3, 1
   • Target diagnostic threshold: <300-350 ng/dL 3
   • Measure free testosterone by equilibrium dialysis in obese patients 3
   • Assess luteinizing hormone (LH) and follicle-stimulating hormone (FSH) to distinguish primary from secondary hypogonadism 3
   • Measure prolactin in patients with low testosterone and low/normal LH levels 1

2. Pre-treatment assessments:

   • Hemoglobin/hematocrit (withhold if Hct >50%) 3
   • PSA in men over 40 years (to exclude prostate cancer) 3
   • Cardiovascular risk factors assessment 3, 1
   • Reproductive health evaluation if fertility is desired 3

Fertility Considerations

• Critical warning: Exogenous testosterone suppresses spermatogenesis and can cause oligospermia or azoospermia 3, 2
• For men interested in current or future fertility:
  • Do not prescribe exogenous testosterone 3
  • Consider alternative treatments that preserve fertility:
    • Human chorionic gonadotropin (hCG) 3, 4
    • Selective estrogen receptor modulators (SERMs) 3, 5
    • Aromatase inhibitors 3, 5
  • Recovery after testosterone cessation may take months or even years 3

Treatment Options

1. Transdermal preparations (first-line for most patients):

   • Gels and patches provide stable day-to-day levels 3, 1
   • Apply to shoulders and upper arms only 2
   • Risk of transfer to women and children - requires careful application and washing 2

2. Injectable testosterone:

   • Less expensive but causes fluctuating levels 1
   • Measure levels midway between injections 3

3. Other formulations:

   • Implantable pellets (longer-term option) 3, 1
   • Nasal preparations 6
   • Avoid 17-alpha-alkylated oral androgens due to liver toxicity 3

Monitoring

• Initial follow-up testosterone level after starting treatment 3
• Testosterone levels every 6-12 months while on therapy 3, 1
• Target testosterone levels: mid-normal range (450-600 ng/dL) 1
• Monitor hemoglobin/hematocrit (discontinue if Hct >54%) 3
• PSA monitoring according to AUA guidelines 3
• Consider discontinuation after 3-6 months if symptoms don't improve 3

Risks and Contraindications

Absolute contraindications:

• Prostate or breast cancer 1, 2
• Desire for near-term fertility 1, 2
• Uncontrolled heart failure 1
• Recent cardiovascular events (wait 3-6 months) 3, 1
• Severe sleep apnea 1

Common adverse effects:

• Erythrocytosis (dose-dependent: 2.8-17.9%) 1
• Suppression of spermatogenesis 1, 2
• Peripheral edema 1
• Emotional lability 1
• Gynecomastia (uncommon) 3
• Potential cardiovascular effects (myocardial infarction, stroke) 1, 2
• Venous thromboembolism 2

Special Considerations

• For obesity-associated secondary hypogonadism, consider weight loss as first-line treatment 1
• Compounded testosterone should be avoided when commercially manufactured products are available 3
• Consider patient's cardiovascular status, particularly in elderly patients 1

Pitfalls to Avoid

• Prescribing for "age-related hypogonadism" without confirmed diagnosis 2
• Starting TRT without proper baseline assessments
• Failing to discuss fertility implications
• Inadequate monitoring of adverse effects
• Not considering alternative treatments for men desiring fertility

By following these guidelines, clinicians can ensure appropriate use of testosterone therapy while minimizing risks and optimizing outcomes for patients.