Calculation of bioavailable and free testosterone in men: A comparison of 5 published algorithms

Background: Estimation of serum concentrations of free testosterone (FT) and bioavailable testosterone (bioT) by calculation is an inexpensive and uncomplicated method. We compared results obtained with 5 different algorithms. Methods: We used 5 different published algorithms [described by Sodergard et al. (bioT_S and FT_S), Vermeulen et al. (bioT_V and FT_V), Emadi-Konjin et al. (bioT_E), Morris et al. (bioT_M), and Ly et al. (FT_L)] to estimate bioT and FT concentrations in samples obtained from 399 independently living men (ages 40-80 years) participating in a cross-sectional, single-center study. Results: Mean bioT was highest for bioT_S (10.4 nmol/L) and lowest for bioT _E (3.87 nmol/L). Mean FT was highest for FT_S (0.41 nmol/L), followed by FT_V (0.35 nmol/L), and FT_L (0.29 nmol/L). For bioT concentrations, the Pearson correlation coefficient was highest for the association between bioT_S and bioT_V (r = 0.98) and lowest between bioT_M and bioT_E (r = 0.66). FT_L was significantly associated with both FT_S (r = 0.96) and FT_V (r = 0.88). The Pearson correlation coefficient for the association between FT_L and bioT_M almost reached 1.0. Bland-Altman analysis showed large differences between the results of different algorithms. BioT_M, bioT_E, bioT_V, and FT _L were all significantly associated with sex hormone binding globulin (SHBG) concentrations. Conclusion: Algorithms to calculate FT and bioT must be revalidated in the local setting, otherwise over- or underestimation of FT and bioT concentrations can occur. Additionally, confounding of the results by SHBG concentrations may be introduced.