Plasma Testosterone Binding Globulin and Indexes of the Concentration of Unbound Plasma Androgens in Normal and Hirsute Subjects12

The relation of plasma free androgen levels to the pattern of sexual hair was studied. The possibility was explored that plasma free androgen levels in hirsute women might be increased by elevated concentrations of testosterone and other 17β-hydroxysteroids or by low “testosterone binding globulin” (TeBG). Nontestosterone 17β-hydroxysteroids are potentially androgenic, either inherently or by their ability to displace testosterone from binding sites. An index of the free plasma testosterone concentration was calculated as the product of the total concentration and the percentage of testosterone-3H free from TeBG as determined in diluted plasma by a charcoal absorption technique. An index of the free plasma 17β-hydroxysteroids3 and titer of TeBG (expressed as testosterone binding capacity) was obtained from the total concentration and percentage binding of 17β-hydroxysteroids to TeBG. Free testosterone and 17β-hydroxysteroid indexes were succesively higher in children, females, hirsute females and males. Varying alterations were noted in hirsutism. Seven of 20 moderately hirsute women had both elevated total testosterone and free testosterone indexes. Five hirsute women with normal testosterone levels, 4 of whom had abnormally low TeBG, had an abnormally high free testosterone index. In 9 of the 12 hirsute subjects with an elevated free testosterone index, an elevated free 17β-hydroxysteroid index was found, suggesting the latter may be a useful screening test for the detection of excess circulating androgen. The free 17β-hydroxysteroid index was also abnormally high in 5 hirsute women with no abnormality of the free testosterone index. A low TeBG titer usually underlay this abnormality. It is possible that these women may be subject to elevated, unbound non-testosterone androgen levels. Two nonhirsute women with elevated total testosterone levels were found to have estrogen-induced increases in the TeBG titer and normal free testosterone indexes. Determination of the free plasma testosterone index can provide a simple means of determining the biologic significance of borderline levels of total testosterone.