Management of Low Testosterone and Low SHBG Levels
The initial approach to managing low testosterone and low SHBG levels should focus on lifestyle modifications as first-line treatment, followed by testosterone replacement therapy (TRT) only if symptoms persist and after ruling out contraindications. 1
Initial Evaluation
Laboratory assessment:
- Confirm low total testosterone (normal range: 300-950 ng/dL)
- Verify low SHBG levels (normal range: 10-50 nmol/L)
- Measure free testosterone (normal range: 50-200 pg/mL)
- Check LH and FSH levels to determine if hypogonadism is primary or secondary
- Evaluate liver function tests (ALT, AST, bilirubin, albumin) as liver disease affects SHBG production
Clinical assessment:
- Evaluate for symptoms of hypogonadism (decreased libido, erectile dysfunction, fatigue, reduced muscle mass)
- Screen for underlying conditions that can cause low SHBG:
- Obesity
- Metabolic syndrome
- Type 2 diabetes
- Hypothyroidism
- Cushing's syndrome
First-Line Treatment: Lifestyle Modifications
- Weight management: Low SHBG is strongly associated with obesity; weight loss can increase both SHBG and testosterone levels 1, 2
- Exercise regimen: Combine resistance training and aerobic exercise (at least 150 minutes of moderate-intensity exercise weekly) 1
- Dietary changes: Adopt a Mediterranean diet rich in fruits, vegetables, whole grains, lean proteins, and healthy fats 1
- Alcohol limitation: Restrict alcohol consumption to less than 21 units per week 1
Second-Line Treatment: Testosterone Replacement Therapy
If symptoms persist despite lifestyle modifications and total testosterone remains below 300 ng/dL, consider TRT:
TRT Options:
Transdermal preparations (preferred initial option):
Intramuscular injections:
- Higher risk of fluctuating levels and erythrocytosis
- Consider for patients who prefer less frequent administration
Monitoring TRT:
- Check total testosterone levels at 14,28, and 42 days after starting treatment 1, 3
- Target range: 450-600 ng/dL 1
- Adjust dosage based on serum levels (titrate in 20.25 mg increments) 3
- Monitor:
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%
Contraindications to TRT
- Breast or prostate cancer 1, 3
- Desire for current or future fertility (if using traditional testosterone therapy) 1
- Hematocrit >50% 1
- Severe untreated sleep apnea 1, 3
- Severe lower urinary tract symptoms 1
- Uncontrolled heart failure 1
- Recent cardiovascular events (within 3-6 months) 1
Special Considerations for Low SHBG
- Low SHBG is often a marker of metabolic dysfunction and can cause artificially low total testosterone readings while free testosterone may be normal 2
- When SHBG is low, free testosterone measurement becomes more important for diagnosis 4
- Treating the underlying cause of low SHBG (obesity, insulin resistance) should be prioritized 2
- Oral testosterone preparations should be avoided due to hepatotoxicity risk and further suppression of SHBG 1
Clinical Pitfalls to Avoid
- Don't rely solely on total testosterone for diagnosis when SHBG is low; free testosterone provides better assessment 4, 2
- Don't initiate TRT without ruling out contraindications, especially prostate cancer
- Don't overlook the importance of lifestyle modifications, which can be as effective as TRT in many cases 1
- Be aware that oxandrolone and some other medications can further decrease SHBG levels 5
- Remember that SHBG levels are inversely proportional to BMI; weight loss can significantly improve both SHBG and testosterone levels 2