Free Androgen Index in Men Is Inaccurate and Should Not Be Used
The free androgen index (FAI) is not valid for adult males and should not be used for assessing androgen status in men. 1 Instead, calculated free testosterone (cFT) using validated equations or direct measurement methods like equilibrium dialysis should be employed when evaluating testosterone status in men.
Why FAI Is Problematic in Men
The fundamental issue with FAI in men stems from its mathematical derivation:
- FAI is calculated as (total testosterone/SHBG) × 100
- This calculation assumes that SHBG binding capacity greatly exceeds testosterone concentration 1
- This assumption is valid in women but not in men, where testosterone levels are much higher
- In men, SHBG binding sites can become saturated with testosterone, invalidating the FAI formula
Studies have demonstrated this inaccuracy:
- Correlation between FAI and directly measured free testosterone is poor in men (r = 0.435) compared to women (r = 0.858) 1
- FAI particularly overestimates free testosterone when SHBG concentrations are low 2
Recommended Alternatives for Men
When assessing androgen status in men, especially those with symptoms of hypogonadism, the following approach is recommended:
First-line measurement: Morning serum total testosterone using an accurate and reliable assay 3
For borderline total testosterone results: Determine free testosterone using one of these methods (in order of preference):
Additional testing: If hypogonadism is confirmed, measure luteinizing hormone (LH) and follicle-stimulating hormone (FSH) to determine if it's primary (testicular) or central (hypothalamic-pituitary) 3
Evidence-Based Reference Ranges
Reference intervals from high-quality studies:
- Total testosterone: 9.4-31.0 nmol/L
- Calculated free testosterone (Vermeulen equation): 0.245-0.785 nmol/L 4
Common Pitfalls to Avoid
- Never rely on direct free testosterone immunoassays: These "analog" methods available at most local laboratories yield unreliable results 3, 5
- Avoid using FAI in men: Despite its continued use in some settings, FAI is mathematically invalid for men 1
- Consider timing of blood draw: Testosterone levels should be measured in the morning when levels are highest
- Account for SHBG variations: SHBG can be affected by age, obesity, diabetes, liver disease, and medications, potentially affecting interpretation of total testosterone 3
- Confirm low results: A total testosterone level below the lower limit of normal should be confirmed by repeat testing due to assay variability 3
Special Considerations
For men with suspected alterations in binding proteins (obesity, liver disease, etc.), free testosterone assessment becomes particularly important, as total testosterone alone may not accurately reflect androgen status. In these cases, calculated free testosterone using validated equations provides a more reliable assessment than FAI 5, 4.