The Significance of Biological Variation in the Diagnosis of Testosterone Deficiency, and Consideration of the Relevance of Total, Free and Bioavailable Testosterone Determinations

Purpose: The diagnosis of testosterone deficiency syndrome is based on clinical manifestations and documentation of low testosterone. Which biochemical tests to use and the importance of morning sampling are still controversial. Biological variation (including interindividual and intraindividual biological variation) must be considered when interpreting individual results as it determines the usefulness of reference intervals and the change (reference change value) necessary for a significant difference between results.Materials and Methods: A total of 87 healthy men (50 to 70+ years old) provided blood in the morning of the first day, and 4 weeks later in the morning and afternoon. Samples were frozen (−70C) and analyzed in the same run for serum testosterone, sex hormone-binding globulin and albumin, and bioavailable testosterone and free testosterone were calculated.Results: Serum testosterone was lower in the afternoon by 1.5 nmol/l (43 ng/dl, p <0.05), with larger changes observed with higher morning...