This is the clinical measurement and evaluation of the fraction of circulating hormones that are not bound to carrier proteins, such as sex hormone-binding globulin (SHBG) or albumin. Only the free, unbound fraction is biologically active and able to diffuse into target cells to exert its physiological effects. Assessing this fraction provides a more accurate picture of tissue-level hormonal exposure than total hormone levels alone. This is a critical diagnostic step in cases of binding protein abnormalities.
Origin
The concept emerged from the realization in endocrinology that total hormone concentration is often misleading due to the significant role of binding proteins in hormone transport and reservoir function. The development of techniques like equilibrium dialysis and calculation methods like the Free Androgen Index (FAI) allowed clinicians to quantify the bioavailable fraction. This represents a refinement in diagnostic precision over older, cruder assays, leading to better clinical management.
Mechanism
Carrier proteins like SHBG bind to steroid hormones with high affinity, rendering them temporarily inactive until they are released at the tissue level. The mechanism of bioavailability depends on the equilibrium between bound and unbound hormone. Factors like liver function, insulin status, and genetic variations influence the concentration of these binding proteins, thereby modulating the amount of free, bioavailable hormone. The assessment quantifies this dynamic equilibrium to guide clinical therapy.
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