Free testosterone and cardiometabolic parameters in men: comparison of algorithms

in Endocrine Connections
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  • 1 S A. Holmboe, Department of Growth and Reproduction, Rigshospitalet, Copenhagen, Denmark
  • 2 R Jasuja, Research Program in Men's Health: Ageing and Metabolism, Brigham and Womens Hospital, Harvard Medical School, Boston, United States
  • 3 B Lawney, Research Program in Men's Health: Aging and Metabolism, Brigham and Womens Hospital, Harvard Medical School, Boston, United States
  • 4 L Priskorn, Department of Growth and Reproduction, Rigshospitalet, Copenhagen, Denmark
  • 5 N Joergensen, Department of Growth and Reproduction, Rigshospitalet, Copenhagen, Denmark
  • 6 A Linneberg, Centre for Clinical Research and Prevention, Frederiksberg Hospital, Frederiksberg, Denmark
  • 7 T Jensen, Department of Growth and Reproduction, Rigshospitalet, Copenhagen, Denmark
  • 8 N Skakkebæk, Department of Growth and Reproduction, Rigshospitalet, Copenhagen, Denmark
  • 9 A Juul, Department of Growth and Reproduction, Rigshospitalet, Copenhagen, Denmark
  • 10 A Andersson, Department of Growth and Reproduction, Rigshospitalet, Copenhagen, Denmark

Correspondence: Anna-Maria Andersson, Email: anna@rh.dk

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 conditions.

Design.

A prospective cohort study including 5,350 men, aged 30-70 years, participating in population-based surveys (MONICA I–III and Inter99) from 1982-2001 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 testosterone. Men in 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 lowest quartile. In contrast, men 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 associations to baseline and long-term cardiometabolic parameters. In contrast, an empiric ratio, FAI, showed opposite associations to several of the examined parameters and may reflect limited clinical utility.

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