Evaluation of direct and indirect markers to assess the androgen status in healthy males during aging.

Evaluation of the male androgen status requires a marker that reflects the biologically active fraction of plasma testosterone. The serum sex hormone-binding globulin (SHBG) concentration is not suitable here because of its wide inter-individual scatter. As potential biological markers of the active testosterone fraction we compared indirect methods calculated on the basis of SHBG and total testosterone measured by fully automated IMMULITE 2000 assays (DPC, Los Angeles, CA, USA), and total testosterone alone with direct free testosterone measured by RIA (DPC). Indirect methods were the free androgen index FAI, calculated free testosterone cFT, and calculated bio-available testosterone cBT. Further androgens measured were DHEAS and androstenedione. Blood samples were collected from a cohort of 446 healthy men aged between 20-99 years. All parameters except SHBG decreased significantly during aging. The direct free testosterone assay was significantly correlated with the indirect androgen parameters. This is in accordance with earlier results using LC-MS as the gold standard method. The strongest correlation was seen with cBT/measured albumin (r=0.750), though the direct testosterone RIA does not measure the entire unbound fraction of testosterone, and total testosterone can rapidly be measured with an automated assay system. It was found that a fixed albumin concentration of 43 g/L is a reasonable calculation basis for cBT in subjects of <70 years. In the elderly >70 years or persons with known pathologies of the androgen axis, it is commendable to measure the albumin concentration individually. In conclusion, calculated bio-available testosterone (cBT) is the best marker to reflect the bioactive testosterone fraction, i.e. the androgen status in males.