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Testosterone / TRT

What is the difference between total testosterone, free testosterone, and bioavailable testosterone?

Solid (1) Evidence rating

Total testosterone measures all testosterone in the blood, including that bound to sex hormone-binding globulin (SHBG, tightly bound and biologically inactive) and albumin (loosely bound, biologically available) and free testosterone (the small unbound fraction, approximately 1–3% of total, the most biologically active), free testosterone and albumin-bound testosterone together constitute "bioavailable testosterone," which is a better indicator of androgenic biological activity than total testosterone alone, particularly in men with elevated SHBG (Vermeulen et al., J Clin Endocrinol Metab, 1999).

Men over 40 often have rising SHBG (driven by aging, alcohol use, hyperthyroidism, and certain medications), which binds increasing proportions of total testosterone and reduces the biologically active free fraction. A man with a total testosterone of 500 ng/dL but SHBG of 65 nmol/L may have free testosterone in the lower reference range and experience hypogonadal symptoms despite a "normal" total testosterone. This is the most common reason for symptomatic hypogonadism with "normal" labs.

Honesty Scale: Solid (1) for the free testosterone / SHBG / bioavailable testosterone distinction as clinically essential.

What to do: Always request SHBG alongside total testosterone. Calculate free testosterone using the Vermeulen formula (available online) or request a calculated free testosterone from your lab. If total testosterone is 350–500 ng/dL with elevated SHBG, free testosterone may be the more clinically relevant value.

For the full picture, read The Testosterone/TRT Deep Dive

Deep Dive

For the full clinical picture: Read the full essay →

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