Management of Low Bioavailable Testosterone
Testosterone replacement therapy (TRT) is indicated for patients with low bioavailable testosterone levels and symptoms of hypogonadism to improve sexual function, enhance sense of well-being, increase lean body mass, decrease body fat, and increase bone density. 1, 2
Diagnostic Confirmation
Before initiating treatment, confirm the diagnosis of hypogonadism by:
- Ensuring serum testosterone concentrations have been measured in the morning on at least two separate days
- Confirming these serum testosterone concentrations are below the normal range 2
- Evaluating both total testosterone (normal range: 300-950 ng/dL) and free/bioavailable testosterone (normal range: 50-200 pg/mL for free testosterone) 1
In this case, the patient has:
- Total testosterone: 288 ng/dL (slightly below normal range)
- Free testosterone: 36.2 pg/mL (below normal range)
- Bioavailable testosterone: 75.9 pg/mL (low)
- SHBG: 33 nmol/L (normal range: 10-50 nmol/L)
- Albumin: 4.6 (normal)
Treatment Options
1. Testosterone Replacement Therapy (TRT)
TRT is the primary treatment for confirmed hypogonadism with low bioavailable testosterone. Options include:
Transdermal preparations (first-line option):
Intramuscular injections:
- Advantages: Effective, less frequent administration
- Disadvantages: Fluctuating testosterone levels, higher risk of erythrocytosis 1
Avoid oral alkylated testosterone due to hepatotoxicity risk 1
2. Dose Titration and Monitoring
- Initial dose adjustment at 14 and 28 days based on pre-dose morning serum testosterone 2
- Target total testosterone level: 450-600 ng/dL 1
- Adjust dose according to this schedule:
- If >750 ng/dL: Decrease daily dose
- If 350-750 ng/dL: No change
- If <350 ng/dL: Increase daily dose 2
3. Monitoring Parameters
| Parameter | Frequency | Action Threshold |
|---|---|---|
| Total Testosterone | 3-6 months initially, then annually | Target: 450-600 ng/dL |
| PSA | 3-6 months initially, then annually | Biopsy if >4.0 ng/mL or increases >1.0 ng/mL/year |
| Hematocrit | 3-6 months initially, then annually | Discontinue if >54% |
| Liver function tests | Periodically | If abnormal |
4. Lifestyle Modifications
Implement alongside pharmacological treatment:
- Regular exercise combining resistance and aerobic training (at least 150 minutes weekly)
- Mediterranean diet rich in fruits, vegetables, whole grains, and lean proteins
- Weight management
- Limit alcohol consumption 1
Contraindications to TRT
Do not initiate TRT in patients with:
- Breast or prostate cancer
- Desire for current or future fertility
- Hematocrit >50%
- Severe untreated sleep apnea
- Severe lower urinary tract symptoms
- Uncontrolled heart failure 2
- Recent cardiovascular events (within 3-6 months) 1
Special Considerations
- Monitor for potential side effects: increased PSA, mood swings, hypertension, increased red blood cell count, skin irritation, gynecomastia, and blood clots 1
- If hematocrit exceeds 54%, discontinue therapy and consider therapeutic phlebotomy 1
- Use with caution in men with pre-existing cardiac conditions, sleep apnea, or urinary problems 1
Clinical Pearls
- The FDA has cautioned about possible increased risk of heart attack and stroke with TRT, though evidence is inconclusive 1
- Testosterone levels may need to be monitored differently based on the formulation used
- Secondary exposure to testosterone gel can cause virilization in children and women - advise patients on proper application and precautions 2
- TRT is not indicated for "age-related hypogonadism" without clear evidence of testosterone deficiency 2