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 and 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.
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.
Comprehensive male hormone interpretation that visualizes the testosterone production and feedback pathway to identify the true root cause of hormonal imbalances.
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