Guidelines for Testosterone Replacement Therapy in Hypogonadism
Testosterone replacement therapy (TRT) should be initiated in men with confirmed hypogonadism based on at least two morning testosterone measurements below normal range (<300 ng/dL) along with clinical symptoms, with careful monitoring for efficacy and adverse effects. 1
Diagnosis Criteria
- Diagnosis requires:
- At least two morning testosterone measurements confirming low levels (total testosterone <300 ng/dL)
- Presence of clinical symptoms including:
- Decreased libido
- Erectile dysfunction
- Reduced energy levels
- Loss of muscle mass
- Increased body fat
- Decreased bone mineral density
- Depressive symptoms
Treatment Options
Available Formulations
Topical gels (1% or 1.62%)
Injectable testosterone
- Testosterone cypionate or enanthate
- Peak levels occur 2-5 days post-injection
- Trough levels return to baseline by 10-14 days 1
Other formulations
- Testosterone patches
- Implantable pellets
- Buccal tablets
Monitoring Protocol
Initial Monitoring
- Measure serum testosterone at approximately 14 days and 28 days after starting treatment 2
- Target testosterone range: 350-750 ng/dL 2
Ongoing Monitoring
Every visit: Check for:
- Hematocrit/hemoglobin (risk of erythrocytosis)
- PSA for prostate cancer risk
- Symptom response
- Digital rectal examination
- Voiding symptoms
- Sleep apnea symptoms 1
Dose Adjustment Guidelines:
- If testosterone >750 ng/dL: Decrease daily dose by 20.25 mg
- If testosterone 350-750 ng/dL: Continue current dose
- If testosterone <350 ng/dL: Increase daily dose by 20.25 mg 2
Contraindications
Absolute Contraindications
- Prostate cancer
- Male breast cancer
- Desire for fertility in the near future 1
Relative Contraindications
- Severe obstructive sleep apnea (may not be absolute per recent evidence) 4
- Severe lower urinary tract symptoms (may not be absolute per recent evidence) 4
- Uncontrolled congestive heart failure
- Hematocrit >54%
- "Age-related hypogonadism" without structural or genetic etiology 2, 3
Benefits of TRT
TRT can improve:
- Sexual function and libido
- Quality of life
- Lean body mass
- Reduce abdominal subcutaneous adipose tissue
- Improve insulin sensitivity in men with metabolic syndrome
- Reduce inflammatory markers
- Small improvements in depressive symptoms 1
- Bone health and muscle strength in frail men 4
Potential Risks and Complications
- Cardiovascular effects: Mixed evidence regarding cardiovascular risk; careful monitoring needed especially in men with pre-existing cardiovascular disease 1
- Erythrocytosis: Monitor hematocrit; consider temporarily withholding therapy, reducing dose, or performing phlebotomy if hematocrit rises above reference range 1
- Fertility impairment: Exogenous testosterone suppresses spermatogenesis 1
- Prostate effects: Monitor PSA; consider urologic referral if PSA increases >1.0 ng/dL in first 6 months or >0.4 ng/dL per year thereafter 1
- Secondary exposure: Risk of virilization in women and children who contact application sites; patients should wash hands thoroughly after application and cover application sites with clothing 2, 3
Common Pitfalls to Avoid
- Diagnosing hypogonadism based on a single testosterone measurement
- Failing to measure free testosterone in obese patients
- Overlooking secondary causes of hypogonadism
- Initiating therapy without proper baseline evaluation
- Not monitoring for adverse effects, particularly hematocrit elevation
- Using testosterone for "age-related hypogonadism" without structural or genetic etiology 1
- Ignoring symptoms and overreacting to single lab values 1
- High discontinuation rates observed in clinical practice - patients should be educated about the need for long-term therapy 5
TRT is an effective treatment for properly diagnosed hypogonadism, but requires careful patient selection, appropriate formulation choice based on patient preference, and vigilant monitoring to maximize benefits while minimizing risks.