In healthy adult men, about 44% of the circulating testosterone is specifically bound to sex hormone–binding globulin (SHBG), 5 50% is non-specifically bound to albumin, and 3.5% is bound to cortisol-binding globulin, indicating that only 2%–3% is unbound or free. SHBG binding decreases the metabolic clearance rate of testosterone and withholds bound hormone from diffusion into the cell, although SHBG may be a necessary co-factor for cellular uptake of testosterone. Whether albumin-bound testosterone can dissociate sufficiently fast to enter tissues is controversial.
T = Total testosterone
[S] = Free testosterone
[S A] = Albumin bound testosterone
[SP] = [SHBG] bound testosterone
[Bio T] = Bio available testosterone
[SHBG] = Total Sex Hormone Binding Globulin
[P] = free SHBG
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Concentrations of non-SHBG-bound testosterone and non-SHBG–nonalbumin– bound testosterone [free testosterone (FT)] are extremely well correlated and interchangeable in most cases. Because concentrations of SHBG vary widely in healthy men and are related to variables such as diet, body mass index (BMI), insulin concentrations, and age, measurements of FT and bioT are valuable for correct assessment of the bioactive fraction of testosterone. In aging men, total testosterone concentrations tend to decrease and SHBG concentrations increase; therefore, measurements of FT and bioT are advocated to support the diagnosis of hypogonadism, which has nonspecific signs and symptoms in elderly men.
WARNING! The calculated free and bioavailable testosterone are reliable in most clinical situations, but should not be relied upon in situations with potential massive interference by steroids binding to SHBG; e.g. in women during pregnancy, in men during treatment inducing high levels of DHT (e.g. transdermal DHT, oral testosterone) or mesterolon.