Management of Low Testosterone (Hypogonadism)
Testosterone replacement therapy (TRT) is indicated for men with confirmed hypogonadism, defined as low testosterone levels (<300-350 ng/dL on two separate morning samples) plus clinical symptoms, with treatment options including intramuscular injections and transdermal preparations targeting mid-normal testosterone levels (450-600 ng/dL). 1
Diagnostic Criteria
- Diagnosis requires:
- Low serum total testosterone (<300-350 ng/dL) on two separate morning blood samples
- Presence of clinical symptoms (sexual dysfunction, fatigue, decreased muscle mass, etc.)
- Rule out other causes of symptoms
First-Line Approach: Lifestyle Modifications
- Weight loss and increased physical activity 1
- Regular exercise (150+ minutes weekly) combining resistance and aerobic training
- Mediterranean diet rich in fruits, vegetables, whole grains, lean proteins
- Limit alcohol consumption to less than 21 units per week
- These interventions have high-strength evidence for improving testosterone levels 1
Testosterone Replacement Therapy Options
Intramuscular Injections (e.g., Testosterone Enanthate)
- FDA-approved for primary hypogonadism and hypogonadotropic hypogonadism 2
- Advantages: Cost-effective, reliable absorption
- Disadvantages: Fluctuating levels, higher risk of erythrocytosis, injection discomfort 1
- Dosing: Typically 200mg every 2 weeks or 100mg weekly
Transdermal Preparations (Gels/Patches)
- Advantages: More stable testosterone levels, lower risk of erythrocytosis 1
- Disadvantages: Risk of transfer to others, skin irritation, higher cost
- Apply daily to clean, dry skin
Important Note
- Oral alkylated testosterone should be avoided due to hepatotoxicity risk 1
- FDA has not established safety and efficacy for age-related hypogonadism 2
Monitoring Protocol
- Initial follow-up: Check testosterone levels at 14 and 28 days after starting treatment 1
- Regular monitoring:
- Total testosterone: 3-6 months initially, then annually (target: 450-600 ng/dL)
- PSA: 3-6 months initially, then annually
- Hematocrit: 3-6 months initially, then annually
- Liver function tests if clinically indicated
Contraindications to TRT
- Breast or prostate cancer
- Desire for current or future fertility
- Hematocrit >50%
- Severe untreated sleep apnea
- Severe lower urinary tract symptoms
- Uncontrolled heart failure 1
- Delay TRT for 3-6 months after acute cardiovascular events 1
When to Adjust or Discontinue Therapy
- Discontinue if hematocrit exceeds 54% (consider therapeutic phlebotomy) 1
- Perform prostate biopsy if PSA rises above 4.0 ng/mL or increases by >1.0 ng/mL in any year 1
- Consider alternative approaches if adverse effects are intolerable
Special Considerations
- For patients with elevated SHBG, evaluate for underlying conditions (liver disease, etc.) 1
- When symptoms persist despite normal free testosterone, investigate other causes:
- Check LH/FSH to determine central vs. peripheral issue
- Evaluate for cardiovascular disease, diabetes, sleep apnea, psychological factors 1
Common Pitfalls
- Failing to confirm low testosterone with two morning measurements
- Not addressing underlying causes (obesity, medications, etc.)
- Inadequate monitoring of hematocrit and PSA
- Using TRT in men with contraindications
- Overlooking the cardiovascular risk controversy (FDA Safety Announcement 2015) 1