Guidelines for Prescribing Testosterone Replacement Therapy (TRT)
Testosterone replacement therapy should be prescribed only for men with confirmed hypogonadism, defined as consistent symptoms of testosterone deficiency and unequivocally low serum testosterone levels below 230 ng/dL, or for symptomatic men with levels between 231-346 ng/dL after careful risk-benefit discussion. 1
Diagnostic Criteria for Initiating TRT
Required Laboratory Testing
- Morning fasting total testosterone levels measured on at least two separate occasions
- Levels <230 ng/dL: Clear indication for TRT in symptomatic men
- Levels 231-346 ng/dL: Consider TRT for symptomatic men after risk-benefit discussion
- Levels >350 ng/dL: TRT not usually required 1
- Additional testing before initiating therapy:
- Baseline hematocrit
- Prostate-specific antigen (PSA)
Clinical Symptoms Warranting Treatment
- Decreased libido
- Erectile dysfunction
- Reduced muscle mass and strength
- Increased fat mass
- Decreased bone mineral density
- Depressed mood
Absolute Contraindications for TRT
- Breast cancer
- Prostate cancer (except in specific circumstances with caution)
- PSA >4 ng/mL (or >3 ng/mL in high-risk men) without urological evaluation
- Elevated hematocrit
- Uncontrolled severe heart failure
- Myocardial infarction or stroke within past 6 months
- Desire for fertility in the near term 2
Relative Contraindications (Requiring Caution)
- History of congestive heart failure (risk of fluid retention)
- Men older than 70 years or with chronic illness (use easily titratable formulations)
Treatment Recommendations
Dosing and Administration
- For hypogonadal males: 50-400 mg testosterone cypionate intramuscularly every 2-4 weeks 3
- Target testosterone levels: 350-600 ng/dL (mid-normal range) 1
- For men with history of heart failure: Target levels in middle range (350-600 ng/dL) 1
- For older men (>70 years) and those with chronic illness: Use easily titratable formulations (gel, spray, or patch) rather than long-acting injectables 1
Monitoring Protocol
- Assess symptom response and adverse effects at follow-up visits
- Laboratory monitoring:
- Testosterone levels: 3-6 months after initiation
- Hematocrit: At baseline and every 6 months
- PSA: At baseline and every 6 months 1
- Continue TRT beyond 6 months only if clinical benefit is observed 1
Special Considerations
Cardiovascular Risk
- 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 4
- However, FDA has issued a Safety Announcement (2015) cautioning against TRT use for age-related hypogonadism alone due to possible increased risk of heart attack and stroke 1
- Patients should be advised of these potential risks before starting therapy
Prostate Cancer Considerations
- Men with a history of prostate cancer should be informed of inadequate evidence regarding risk-benefit ratio of TRT 1
- TRT can be considered with caution in:
- Men post-radical prostatectomy with favorable pathology and undetectable PSA
- Men treated with radiation therapy with stable PSA
- Men on active surveillance (limited data available) 1
Effects on Fertility
- TRT suppresses spermatogenesis and should be discussed with patients interested in future fertility
- Testosterone should be discontinued well in advance of planned conception attempts 1
Common Pitfalls to Avoid
- Prescribing TRT for age-related decline in testosterone without confirmed hypogonadism
- Failing to measure morning testosterone levels on multiple occasions before diagnosis
- Not discussing cardiovascular risks with patients before initiating therapy
- Inadequate monitoring of hematocrit (risk of polycythemia) and PSA during treatment
- Continuing therapy beyond 6 months without documented clinical benefit
By following these evidence-based guidelines, clinicians can appropriately prescribe testosterone replacement therapy to improve quality of life in men with true hypogonadism while minimizing potential risks.