Testosterone is the main sex hormone in males, and only a small fractioncirculates the blood in a free state. Most testosterone circulates bound to two proteins, sex hormone binding protein (SHBG), and albumin. Total testosterone levels are a combination or SHBG-bound, albumin-bound, and free testosterone. The bioavaible form (form that can bind to receptors) of testosterone includes that bound to albumin and the free fraction. On average albumin holds 54%, SHGB 44% and free 2% so it appears that 56% of testosterone is in the bioavaible state (2).
So with this in mind our first situation concerns SHGB concentrations, which can be influenced by a variety of factors. SHGB concentrations can become decreased by obesity and testosterone treatments, while also becoming increased in aging (5). With almost half of the testosterone bound by SHGB, and with these common conditions in play, its possibly to see how these factors could influence the free testosterone levels. In such circumstances a test of total testosterone may be warranted in the clinical decision-making of this patient.
Free testosterone has been estimated from the serum for some time by dialyzing serum across a semipermeable membrane with the testosterone that crosses in the serum believed to be the unbound portion or free. Most dialysis assays use small tracer amounts of radiolabeled testosterone added to the serum.