Monitoring Testosterone Therapy: Free vs. Bioavailable Testosterone
For patients on testosterone gel therapy, monitor total testosterone levels as the primary parameter, with free testosterone by equilibrium dialysis reserved for specific situations where total testosterone may be misleading (obesity, diabetes, borderline values). 1, 2
Primary Monitoring Approach
Total testosterone remains the standard monitoring parameter for most patients on testosterone replacement therapy. 1, 2, 3 The FDA-approved labeling for testosterone gel 1.62% explicitly states that dose titration should be based on "pre-dose morning serum testosterone concentration" measured at approximately 14 and 28 days after starting treatment or following dose adjustment. 3
When to Measure Total Testosterone
- Draw morning samples (8-10 AM) for patients on transdermal testosterone gel 1, 2
- For testosterone gel, levels can be measured at any time after 2-3 months of stable therapy 1
- Target mid-normal testosterone levels of 500-600 ng/dL 1
- Check levels at 2-3 months after treatment initiation, then every 6-12 months once stable 1
When Free Testosterone Measurement is Essential
Free testosterone by equilibrium dialysis should be measured in specific clinical scenarios where total testosterone may not accurately reflect androgen status. 1, 2
Specific Indications for Free Testosterone
- Men with obesity: Low sex hormone-binding globulin (SHBG) can artificially lower total testosterone while free testosterone remains normal 1, 2
- Men with diabetes: SHBG alterations are common and can mask true androgen status 1
- Borderline total testosterone values (231-346 ng/dL): Free testosterone helps distinguish true hypogonadism from SHBG-related changes 1, 2
- Initial diagnostic workup: When confirming hypogonadism diagnosis, especially in men with obesity 1
The American Diabetes Association specifically recommends measuring "free or bioavailable testosterone levels in diabetic men with total testosterone near the lower limit" because approximately 26.3% of men over 60 years have normal total testosterone with low free testosterone, and these men would be missed by screening with total testosterone alone. 1
Bioavailable Testosterone Considerations
Bioavailable testosterone (free testosterone plus albumin-bound testosterone) is an acceptable alternative to free testosterone measurement, though free testosterone by equilibrium dialysis remains the gold standard. 1 Both reflect the biologically active fraction of testosterone, but free testosterone by equilibrium dialysis is explicitly recommended in the guidelines for diagnostic accuracy. 1, 2
Practical Monitoring Algorithm
For Routine Monitoring (Most Patients)
- Measure morning total testosterone at 2-3 months after initiation 1, 3
- Target 500-600 ng/dL (mid-normal range) 1
- Continue monitoring every 6-12 months once stable 1
For High-Risk or Complex Patients
- Measure both total testosterone AND free testosterone by equilibrium dialysis 1, 2
- This includes patients with obesity, diabetes, metabolic syndrome, or borderline initial values 1, 2
- Also measure SHBG to calculate free androgen index if needed 1
Critical Pitfalls to Avoid
Do not rely solely on total testosterone in obese or diabetic patients, as low SHBG may create a discrepancy between total testosterone (appearing low-normal) and free testosterone (frankly low). 1 This can lead to under-treatment of true hypogonadism or over-treatment of functional hypogonadism.
Do not use calculated free testosterone from online calculators as a substitute for equilibrium dialysis measurement when making critical treatment decisions. 1 Equilibrium dialysis is the gold standard method explicitly recommended in guidelines. 1, 2
Nearly half of men on testosterone therapy never have their levels checked, which is dangerous practice. 1 Establish a systematic monitoring schedule at treatment initiation.
Additional Monitoring Beyond Testosterone
Regardless of whether you monitor total or free testosterone, always include: