Evaluation and Management of Low Total Testosterone Levels
The evaluation of low total testosterone requires confirmation with two morning measurements below 350 ng/dL along with consistent symptoms, followed by appropriate laboratory testing to determine the cause before initiating testosterone replacement therapy. 1
Diagnostic Approach
Initial Evaluation
- Measure morning total testosterone levels on at least two separate days 1, 2
- Confirm low testosterone when:
- Total testosterone consistently below 350 ng/dL
- Patient exhibits symptoms of testosterone deficiency
- Symptoms suggesting testosterone deficiency:
- Sexual: Decreased libido, erectile dysfunction
- Non-sexual: Fatigue, depressed mood, irritability, decreased energy, reduced muscle mass and strength
Laboratory Evaluation
- Essential laboratory tests:
Interpreting Results
- Total testosterone thresholds for treatment consideration 1:
- <230 ng/dL: Usually benefits from treatment
- 231-346 ng/dL: Consider 4-6 month trial if symptomatic
350 ng/dL: Treatment generally not indicated
- Distinguish between primary and secondary hypogonadism:
- Primary: Low testosterone with elevated LH/FSH (testicular failure)
- Secondary: Low testosterone with low/normal LH/FSH (hypothalamic-pituitary disorder)
Management Approach
Non-Pharmacological Interventions
- Lifestyle modifications should be recommended for all patients 1:
- Weight loss for overweight/obese men
- Regular aerobic exercise
- Adequate sleep hygiene
- Stress reduction techniques
- Healthy diet
- Moderate alcohol consumption
- Smoking cessation
Pharmacological Treatment
- Testosterone replacement therapy (TRT) options:
- Testosterone enanthate/cypionate: 50-100 mg weekly or 200-400 mg every 2-4 weeks
- Administer deeply into gluteal muscle
- Most cost-effective option but requires injections
Transdermal formulations 1:
- Testosterone gel 1%: 50-100 mg daily
- Convenient daily application but risk of transfer to others
Testosterone pellets 1:
- Long-acting option (3-6 months)
- Requires procedural insertion
Contraindications to TRT
- Active prostate or breast cancer 1, 2, 4
- Hematocrit >50% 1, 3
- Severe untreated sleep apnea 1
- Uncontrolled heart failure 1, 3
- Recent cardiovascular events (within 3-6 months) 1, 4
- PSA >4.0 ng/mL or >3.0 ng/mL in high-risk men 4
- Severe lower urinary tract symptoms 4
- Desire for fertility in the near term 4
Monitoring and Follow-up
Monitoring Schedule
- Baseline: Total testosterone, hematocrit, PSA, digital rectal examination 1
- Follow-up:
Target Parameters and Action Thresholds
- Total testosterone: Target 450-600 ng/dL 1
- Hematocrit: Discontinue if >54% 1
- PSA thresholds requiring action 1:
4.0 ng/mL: Consider prostate biopsy
- Increase >1.0 ng/mL in any year: Perform biopsy
- Increase 0.7-0.9 ng/mL in one year: Repeat PSA in 3-6 months
Benefits and Risks
Benefits of TRT
- Improved sexual function (libido and erectile function) 1
- Increased energy levels and reduced fatigue 1
- Increased muscle mass and strength 1
- Improved bone mineral density 1
- Enhanced sense of well-being 1
Potential Risks
- Erythrocytosis (increased hematocrit) 1, 3
- Potential for sleep apnea exacerbation, especially with higher doses 1
- Skin reactions (more common with patches than gels) 1
- Decreased fertility 1
- Potential cardiovascular effects (evidence is inconclusive) 1, 3
- Risk of abuse at doses higher than recommended 3
Common Pitfalls to Avoid
- Diagnosing testosterone deficiency based on a single measurement
- Initiating treatment without confirming low testosterone with repeat testing
- Failing to evaluate for underlying causes of hypogonadism
- Not monitoring hematocrit, which can increase significantly during treatment
- Overlooking contraindications before starting therapy
- Neglecting to inform patients about potential fertility impacts