Why calculated, not measured? Direct immunoassay methods for free testosterone are unreliable due to cross-reactivity with other steroids and dramatic differences in reference ranges between labs — e.g., LabCorp's analog immunoassay produces values ~4× lower than Quest's method, with no way to convert between them. The gold-standard equilibrium dialysis is too complex and costly for routine use.
The Vermeulen calculation, using total testosterone, SHBG, and albumin, is the most robust approximation — largely independent of SHBG, albumin, and T levels — unlike competing formulas whose accuracy degrades at extreme SHBG values.
High calculated free testosterone is seen with androgen excess, most commonly PCOS in women and exogenous testosterone / anabolic steroid use in men.
In women, it is associated with hirsutism, acne, ovulatory dysfunction, and metabolic abnormalities. Less common causes include congenital adrenal hyperplasia, ovarian hyperthecosis, Cushing syndrome, and androgen-secreting ovarian or adrenal tumors.
In men, persistent elevation should prompt review of testosterone use or supplement exposure; rarer endogenous causes include testicular or adrenal androgen-secreting tumors.
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