Performance of Total Testosterone Measurement to Predict Free Testosterone for the Biochemical Evaluation of Male Hypogonadism

Purpose: Guidelines recommend serum total testosterone measurement as the initial test to evaluate male hypogonadism, reserving free testosterone assessment for men with suspected sex hormone-binding globulin abnormalities or total testosterone near the lower limit of normal. We determined the performance of total testosterone measurement as a test to identify men with normal vs low free testosterone. Materials and Methods: We examined the electronic medical records of all 3,672 men evaluated for hypogonadism by a serum testosterone panel, including total testosterone, sex hormone-binding globulin, albumin and calculated free testosterone, from January 1, 1997 through December 31, 2007 in a network that serves veterans in Washington. Results: The sensitivity and specificity of low total testosterone (less than 280 ng/dl) to rule out and predict low calculated free testosterone was 91.0% and 73.7%, respectively. At thresholds of less than 350 and less than 400 ng/dl the sensitivity of total testosterone for low calculated free testosterone increased to 96.8% and 98.2%, and at thresholds of less than 150 and less than 200 ng/dl specificity increased to 98.9% and 92.6%, respectively. Conclusions: Total testosterone between 280 and 350 ng/dl is not sensitive enough to reliably exclude hypogonadism. Total testosterone must exceed 350 to 400 ng/dl to reliably predict normal free testosterone. Except when levels are less than 150 ng/dl total testosterone measurement has low specificity for the biochemical diagnosis of hypogonadism.