SAT-045 Free Testosterone and Cardiometabolic Parameters in Adult Men - Comparison of Algorithms for Calculation of Serum Free Testosterone

Context. Determining the free or bioavailable testosterone level has gained increasing interest over the years and different indirect algorithms have been suggested. Objective. To compare commonly used algorithms of calculation of serum free testosterone, specifically free androgen index (FAI), free testosterone estimated using the Vermeulen algorithm (cFTV) and the Zakharov algorithm (cFTZ) as well as total testosterone in relation to baseline and long-term cardiometabolic conditions. Design. A prospective cohort study of men participating in four independent 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. Setting and Participants. 5350 randomly selected men from the general population aged 30, 40, 50, 60, or 70 years at baseline participated. Main Outcome Measures. Baseline cardiometabolic parameters and follow-up information on type 2 diabetes, ischemic heart disease, cardiovascular disease mortality, and all-cause mortality. Results. Free testosterone levels calculated according to the two algorithms differed systematically but however correlated well (cFTV vs. cFTZ: r=0.9, p<0.01) and the relative standard deviations ranged from 37% to 41%. In general, men having cardiometabolic conditions at baseline had lower absolute levels of FAI, cFTV and cFTZ. However, when age-standardizing the hormone levels, FAI levels were higher in this group of men whereas cFTV and cFTZ remained lower compared to men without these conditions. The associations seen for cFTV and cFTZ were in line with the association seen for total testosterone. Cox proportional hazard models revealed that men in the highest quartiles of cFTV or cFTZ had lower risk of developing type 2 diabetes (cFTV: HR=0.74 (0.49-1.10), cFTZ: HR=0.59 (0.39-0.91)) than men in the lowest quartile. In contrast, men with highest levels of FAI had a 74% increased risk of developing type 2 diabetes compared to men in the lowest quartile (HR=1.74, 95% CI:1.17-2.59). In relation to all-cause mortality, FAI showed the strongest inverse association followed by cFTV, whereas cFTZ and total testosterone did not show any association. Conclusion. Free testosterone estimated by the Vermeulen and Zakharov algorithms differed systematically. However, the computed values correlated well and showed similar associations to baseline and long-term cardiometabolic parameters; albeit with subtle differences. In contrast, an empiric ratio, FAI showed opposite associations to several of the examined parameters and may reflect limited clinical utility.