Guidelines for Prescribing Testosterone Replacement Therapy (TRT)
Testosterone replacement therapy should only be prescribed for men with documented testosterone deficiency and symptoms consistent with hypogonadism, not for age-related decline alone. 1
Diagnostic Criteria for Initiating TRT
Required Testing
- Morning fasting total testosterone levels measured on at least two separate occasions
- Levels <230 ng/dL indicate clear benefit from TRT
- Levels >350 ng/dL typically do not require treatment
- Levels between 231-346 ng/dL require clinical judgment based on symptoms 1
Symptoms and Signs Warranting Treatment
- Decreased libido
- Erectile dysfunction
- Reduced spontaneous erections
- Decreased muscle mass and strength
- Increased fat mass
- Decreased bone mineral density
- Depressed mood
Contraindications to TRT
Absolute Contraindications
- Breast cancer
- Untreated prostate cancer
- PSA >4 ng/mL without urological evaluation
- PSA >3 ng/mL in high-risk men (African Americans, first-degree relative with prostate cancer) 1
- Myocardial infarction or stroke within the past 6 months 1
- Thrombophilia
- Desire for fertility in the near term
Relative Contraindications (Requiring Caution)
- Uncontrolled/severe congestive heart failure
- Elevated hematocrit
- Untreated severe obstructive sleep apnea
- Severe lower urinary tract symptoms
Treatment Protocol
Dosing and Administration
- For hypogonadal males: 50-400 mg testosterone cypionate intramuscularly every 2-4 weeks 2
- Target testosterone levels in the mid-normal range (350-600 ng/dL)
- For men >70 years or with chronic illness: use easily titratable formulations (gel, spray, patch) rather than long-acting injectables 1
Monitoring Requirements
- Baseline hematocrit and PSA testing
- Follow-up at 3-6 months after initiation, then annually:
- Testosterone levels
- Hematocrit
- PSA
- Symptom response
- Cardiovascular risk factors
Duration of Treatment
- Initial trial period of 4-6 months
- Continue beyond 6 months only if clinical benefit is demonstrated 1
- Regular reassessment of risks vs. benefits
Special Considerations
Cardiovascular Safety
- Recent high-quality evidence (TRAVERSE trial) shows TRT is noninferior to placebo regarding major adverse cardiac events in men with preexisting or high risk of cardiovascular disease 3
- However, FDA still requires labeling about possible increased risk of heart attack and stroke 1
- Patients should be informed about these potential risks
Prostate Cancer Concerns
- No evidence links TRT to development of prostate cancer 1
- For men with history of prostate cancer, TRT should be used with caution
- Men with radical prostatectomy and favorable pathology may be candidates for TRT if PSA is undetectable
- PSA monitoring should follow the same schedule as men without testosterone deficiency 1
Effects on Fertility
- TRT suppresses spermatogenesis
- Discuss impact on fertility with patients planning future reproduction
- Testosterone should be discontinued well in advance of attempts to conceive 1
Common Pitfalls to Avoid
- Prescribing TRT for age-related testosterone decline without documented deficiency
- Failing to confirm low testosterone with repeated morning measurements
- Not discussing cardiovascular and prostate risks with patients
- Inadequate monitoring of hematocrit, which can become elevated during treatment
- Continuing treatment despite lack of symptomatic improvement
TRT is an effective treatment for true hypogonadism but requires appropriate patient selection, thorough discussion of risks and benefits, and regular monitoring to ensure safety and efficacy.