Free testosterone and cardiometabolic parameters in men: comparison of algorithms

Objective: Calculating the free testosterone level has gained increasing interest and different indirect algorithms have been suggested. The objective was to compare free androgen index (FAI), free testosterone estimated using the linear binding model (Vermeulen: cFTV) and the binding framework accounting for allosterically coupled SHBG monomers (Zakharov: cFTZ) in relation to cardiometabolic condit ions. Design: A prospective cohort study including 5350 men, aged 30-70 years, participating in population-based surveys (MONICA I- III and Inter99) from 1982 to 2001 and followed until December 2012 with baseline and follow- up information on cardiometabolic parameters and vital status. Results: Using age-standardized hormone levels, FAI was higher among men with baseline cardiometabolic conditions, whereas cFTV and cFTZ levels were lower compared to men without these conditions as also seen for total testoste rone. Men in highest quartiles of cFTV or cFTZ had lower risk of developing type 2 d iabetes (cFTV: HR = 0.74 (0.49-1.10), cFTZ: HR = 0.59 (0.39-0.91)) than men in lowest quartile. In contrast, me n with highest levels of FAI had a 74% (1.17-2.59) increased risk of developing type 2 diabetes compared to men in lowest quartile. Conclusion: The association of estimated free testosterone and the studied outcomes differ depending on algorithm used. cFTV and cFTZ showed similar assoc iations to baseline and long-term cardiometabolic parameters. In contrast, an empiric ratio, FAI, showed opposite associations to several of the examined parameters and may refle ct limited clinical utility.

Automated summary

This study compared the performance of different algorithms in estimating free testosterone levels in relation to cardiometabolic conditions. cFTV and cFTZ showed similar associations with cardiometabolic parameters, while FAI showed opposite associations, indicating limited clinical utility.