Binding fractions
Testosterone in blood exists in three states:
- SHBG-bound (~50-60%), tightly bound, inactive
- Albumin-bound (~40-45%), loosely bound, easily released
- Free (~1-3%), directly bioavailable
Bioavailable T = free + albumin-bound (~45% of total).
What each measures
- Total testosterone, everything; the reservoir
- Free testosterone, what's freely circulating; the active fraction
- Bioavailable testosterone, free + albumin-bound; what tissues access
Discrepancy patterns
Common scenarios where total and free diverge:
- Aging man with high SHBG, total T may be 400-500 (normal-looking) but free T low; symptomatic
- Insulin-resistant man with low SHBG, total T 350 (looks borderline) but free T may be in upper normal; less symptomatic than total suggests
- Hyperthyroid patient, high SHBG can make total T look better than the bioavailable picture
Calculated free T
Free T can be measured directly (equilibrium dialysis, gold standard but expensive) or calculated from total T, SHBG, and albumin using equations (e.g., Vermeulen formula). Calculated free T from a comprehensive hormone panel is the most practical approach.
TRT targets
On TRT, optimal targets:
- Total T: 700-1,000 ng/dL (mid-upper normal range)
- Free T: 16-28 ng/dL (varies by lab)
- Bioavailable T: in proportion to free T
The free T value better predicts symptom relief than total T alone.
The clinical pearl: Always order total + free T together. Many patients have been told their T is "normal" because total was 350, when free T was actually low and they were symptomatic. The combined picture catches what total alone misses.
Bottom line
Free T (and bioavailable T) reflect what tissues actually access. Total T alone is incomplete. Comprehensive hormone panels include both plus SHBG to give the full picture. TRT decisions should be guided by free T and symptoms, not total T alone.