Calculation of free and bound fractions of testosterone and estradiol-17 beta to human plasma proteins at body temperature

Abstract

A mathematical model for the calculation of free and protein bound concentrations of testosterone and estradiol in plasma is presented. The method is based on the knowledge of the total concentrations of all steroids competing for the same binding site on testosterone-estradiol-binding globulin (TeBG), the concentration of albumin, the binding capacity of TeBG, and the association constants of the steroids to the two binding proteins. For the calculations we have determined the total concentrations of testosterone and estradiol. TeBG binding capacity, albumin concentration and the association constants for the binding of testosterone, estradiol and 5 alpha-dihydrotestosterone (DHT) to TeBG and albumin at 37 degrees C. Physiological concentrations of some androgen metabolites reported in the literature were also included in the calculations, namely: DHT, 5-androstene-3 beta, 17 beta-diol (Ae) and 5 alpha-androstane-3 alpha, 17 beta-diol (Aa). The binding constants for Ae and Aa to TeBG and albumin were also from the literature. Mean values of testosterone were calculated for 11 normal men and expressed as percentages of total: 2.0% was unbound, 53--55% bound to albumin and 43--45% bound to TeBG. For 16 normal women of a fertile age the corresponding values were 1.5%, 36--37% and 62%. For estradiol they were 2.4% 68--70% and 28--30% in the men and 2.0%, 52% and 45--46% in the women. Variations in the concentrations of DHT. Ae and Aa did not influence the free concentrations of testosterone and estradiol to any significant extent. It was furthermore concluded that the androgen metabolites could be omitted from the calculations without affecting the calculated concentrations.