Testostérone libre ou biodisponible : dosages ou calculs. Comparaison critique de différents modes d'approche

Abstract

The aim of the study is to find the most reliable practical approach to the estimation of free or bioavailable serum testosterone. We compare assayed values of bioavailable testosterone (T Bio), Free testosterone DPC (Free T DPC), total testosterone (Ttot) and calculated Free Androgen Index FAI = [Ttot/SHBG] × 100, calculated Free Testosterone using the equation derived from the law of mass action for the model: two binding proteins (SHBG, Albumin) and two ligands (T,E 2) (FTc II Södergaard) or one ligand (T) (Ftc I Kaufman and Fiers). Serum SHBG, Albumin, E 2 are determined exprimentally in every sample. The bioavailable (or non-SHBG bound) T correlates well with Free T by ultrafiltration ( r = 0.96; P < 0.01), is easy to perform, reliable and sensitive if a particular care is ensured in the purification of the tracer. Assayed women values of T Bio agreed well with calculated values for FTc II or FTc I ( r = 0.93; P < 0.01) using the laws of mass action. In contrast, the ratios of FTc II/T Bio and FTc I/T Bio (which should be constant if indexes reflect T Bio) remain negatively SHBG dependent for women and positively SHBG dependent for men confirming that the assumptions of the model are too simplified and the association constants Ka values too approximative. Calculated FTc is an acceptable substitute for an estimation of bioavailable T if we presume women with standard SHBG binding conditions and sera free of significant amounts of substances or steroids that could occupy the binding sites in the SHBG moiety and invalidate the calculation. Although showing a good correlation ( r = 0.89; P < 0.01) with T Bio, FAI is not a useful index: the FAI/T Bio ratio is negatively correlated ( r = –0.86 P < 0.001) with SHBG and overestimate strongly the SHBG binding capacity contribution for a reliable quantification of the non-SHBG bound T. The Free T DPC is inaccurate, not sufficiently sensitive, not free of proteins effects and less correlated with T Bio ( r = 0.49; P < 0.05) than Ttot ( r = 0.64; P < 0.01) for women!