Treatment for Low Free Testosterone
Testosterone replacement therapy (TRT) is the primary treatment for low free testosterone, with the goal of achieving total testosterone levels in the middle tertile of the normal reference range (450-600 ng/dL). 1
Diagnostic Evaluation
Before initiating treatment, proper diagnosis is essential:
- Morning total testosterone measurement is recommended as the initial diagnostic test 1
- Free testosterone or androgen index is preferred over total testosterone alone and will prevent unnecessary endocrine investigation in up to 50% of men found to have low total testosterone concentrations 2
- Confirm diagnosis by repeating morning testosterone measurement 3
- Additional testing if testosterone is low:
- Luteinising hormone
- Prolactin (especially with loss of libido)
- Complete metabolic panel if renal or liver impairment suspected 2
Treatment Options
Injectable Testosterone
- Testosterone cypionate/enanthate: 50-100 mg weekly 1
- FDA-approved for replacement therapy in males with conditions associated with symptoms of deficiency or absence of endogenous testosterone 4
- Indicated for primary hypogonadism or hypogonadotropic hypogonadism 4
Topical Formulations
- Testosterone gel 1%: 50 mg daily (range 50-100 mg) 1
- Newer 2% formulations available with metered dose dispensers for precise application 5
- Advantages: restore testosterone levels to mid-normal physiological levels (14-17.5 nmol/L) within 24 hours 5
- Caution: risk of secondary exposure to others 5
Monitoring Parameters
Regular monitoring is crucial during TRT:
| Parameter | Target Range | Frequency | Action Threshold |
|---|---|---|---|
| Total Testosterone | 450-600 ng/dL | 2-3 months after starting, then every 6-12 months | Adjust dose if outside target range |
| Hematocrit | <54% | Regular monitoring | Discontinue therapy if exceeds 54% |
| PSA | N/A | Regular monitoring | Consider biopsy if >4.0 ng/mL or increases >1.0 ng/mL/year |
Contraindications and Precautions
TRT is contraindicated in:
- Active prostate or breast cancer
- Hematocrit >50%
- Severe untreated sleep apnea
- Uncontrolled heart failure 1
For patients with cardiovascular history:
- Do not commence TRT for 3-6 months after most recent cardiac event
- Advise patients to report any cardiovascular symptoms 1
- Assess all testosterone deficient patients for ASCVD risk factors 1
Benefits of Treatment
TRT may produce a wide range of benefits for men with hypogonadism:
- Improved libido and sexual function
- Increased bone density
- Increased muscle mass and improved body composition
- Enhanced mood and cognitive function
- Improved quality of life
- Increased energy levels and reduced fatigue 6, 1
Adjunctive Approaches
Lifestyle modifications can complement TRT:
- Weight loss for overweight or obese patients
- Regular aerobic exercise
- Adequate sleep hygiene 1
Special Considerations
- Fertility: Exogenous testosterone suppresses spermatogenesis. For men wishing to preserve fertility, alternative approaches such as human chorionic gonadotropin (hCG), selective estrogen receptor modulators, or aromatase inhibitors may be considered 1
- Cardiovascular risk: More frequent monitoring of lipid profiles and blood pressure for patients with cardiovascular risk factors 1
- Older patients: More vigilant monitoring due to potentially higher risk of adverse events 1
Common Pitfalls
- Misdiagnosis: Low testosterone symptoms may overlap with other conditions 7
- Overtreatment: Avoid prescribing for unproven indications like normal male aging ("andropause") 8
- Inadequate monitoring: Failure to monitor hematocrit can lead to complications 1
- Secondary exposure: Topical formulations carry risk of transferring testosterone to others through skin contact 5