Why free testosterone matters more than total

Only ~2% of circulating testosterone is freely bioavailable. The remainder is either tightly bound to SHBG (sex hormone-binding globulin) and biologically inert, or loosely bound to albumin and bioavailable. Men with normal total T but high SHBG can be functionally hypogonadal, while men with low total T and low SHBG may have normal free T. The Endocrine Society explicitly recommends calculated free T when SHBG abnormalities are suspected.

The Vermeulen equation

Vermeulen, Verdonck, and Kaufman (J Clin Endocrinol Metab 1999) compared simple calculation methods against equilibrium dialysis and found the law-of-mass-action formulation using SHBG and albumin matched the reference method within ~10%. It uses two affinity constants: K(T-SHBG) ≈ 1.0×10⁹ L/mol and K(T-Albumin) ≈ 3.6×10⁴ L/mol. The calculation here uses those constants and a default albumin of 43 g/L when an actual value is not entered.

Interpretation thresholds

Reference ranges vary by lab. A commonly-cited threshold for biochemical hypogonadism is free T below 50–65 pg/mL alongside total T <264–300 ng/dL and consistent symptoms. Use clinical judgment in combination with ≥2 morning measurements.

Source

Vermeulen A, Verdonck L, Kaufman JM. A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab. 1999;84(10):3666-72.