Age-Associated Discrepancy between Measured and Calculated Bioavailable Testosterone in Men

Abstract

Background: Bioavailable testosterone (BT) concentration is considered the best marker for evaluating testicular function in men. The decrease of BT in older men is more pronounced than the decrease in total testosterone because of the parallel increase in sex hormone-binding globulin (SHBG) concentrations. Measurement of BT is therefore crucial for the diagnosis of hypoandrogenism in the aging male population. Methods: We compared BT concentrations measured by a specific RIA after ammonium sulfate precipitation (BT meas ) with those obtained by theoretical calculations (BT cal ) in plasma samples from 694 young men (14 to 49 years old) and 51 older men (50 to 81 years old). We based theoretical calculations on Vermeulen's simplified mass equation using total testosterone and SHBG concentrations. Results: BT cal and BT meas correlated significantly in young (Pearson r ‫؍‬ 0.87) and aging (r ‫؍‬ 0.89) men, but the BT cal :BT meas ratio differed markedly between the 2 groups (2.28 vs 3.48; P <0.001). Conclusions: In men, there is an age-associated discrepancy between calculated and measured BT concentrations. We suggest some hypotheses for the discrepancy, but additional studies will be performed to finally elucidate this difference in results and to determine the most appropriate method for BT measurements in older men.

Determination of Bioavailable Testosterone [Non–Sex Hormone–Binding Globulin (SHBG)-Bound Testosterone] in a Population of Healthy French Men: Influence of Androstenediol on Testosterone Binding to SHBG

“…These higher cBT than aBT values (4,26,27 ) are supported by several recent validation experiments in which the free testosterone concentration calculated using the ISSAM website calculator was found to be higher than the measured free testosterone (28 -31 ).…”

Laboratory Measurement of Testosterone

“…These calculations are based on the formula derived at the University of Ghent, Belgium [22]. Whether this method of calculating bioavailable testosterone in all men is the most appropriate has recently been questioned [26]. This report indicates an age-related discrepancy between measured and calculated bioavailable testosterone where the calculated concentration was found to be higher than the measured concentration, probably due to an age-related decrease in adrenal androgens.…”

Inverse relationship between hSHBG affinity for testosterone and hSHBG concentration revealed by surface plasmon resonance

“…Fractions of circulating testosterone (free-testosterone, albumin-testosterone and hSHBGtestosterone), which depend on hSHBG and albumin concentrations, are also closely related to the affinities of the two testosteronebinding proteins. If the affinity constant values of hSHBG and albumin for testosterone commonly used are KA_hSHBG = 1.0 × 10 9 L/mol and KA_HSA = 3.6 × 10 4 L/mol, respectively, the fluctuations of these values (e.g., range from 0.27 × 10 9 to 1.9 × 10 9 L/mol for KA_hSHBG values) (Giton et al, 2006) could explain the discrepancies obtained between the measuring methods (Déchaud et al, 1989;Hammond et al, 1980;Loric et al, 1988;Tremblay and Dube, 1974;Winters et al, 1998) and calculation methods (Emadi-Konjin et al, 2003;Giton et al, 2006;Ly and Handelsman, 2005;Morris et al, 2004;Rinaldi et al, 2002;Södergard et al, 1982;Vermeulen et al, 1999) for the determination of circulating testosterone fractions (de Ronde et al, 2006;Déchaud et al, 2007;Giton et al, 2006;Vermeulen et al, 1999).…”