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.
Low free testosterone with inappropriately normal total testosterone suggests reduced bioavailable testosterone, most often seen with high SHBG. In men, this pattern may still be consistent with androgen deficiency if symptoms are present.
Low free testosterone with low total testosterone suggests true androgen deficiency / hypogonadism.
In men, low free testosterone is associated with late-onset hypogonadism, chronic opioid use, type 2 diabetes, metabolic syndrome, reduced muscle mass, poorer physical function, and worse self-rated health.
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