The harmonized normal reference range for circulating testosterone in a nonobese population of European and American men ages 19 to 39 is 264–916 ng/dL, corresponding to the 2.5th–97.5th percentile (J Clin Endocrinol Metab 2017; doi:10.1210/jc.2016-2935). Researchers arrived at this finding after cross-calibrating assays to a higher-order reference method and calibrator.

The investigators conducted the analysis because although reference ranges for circulating testosterone ­levels for healthy nonobese men have been described, questions remained about whether testosterone reference ranges generated in one population could be applied to men in other populations and geographies.

To explore this issue, the authors compared the distribution of testosterone levels of 9,054 men in four epidemiologic studies that included participants from different regions of the U.S. and Europe. They evaluated testosterone concentrations in 100 participants from each of the four cohorts using the Centers for Disease Control and Prevention’s (CDC) higher-order method, liquid chromatography-tandem mass spectrometry. Testosterone concentrations for these individuals also had been measured locally as part of the respective epidemiological studies. The authors developed normalizing equations between the 100 local and 100 CDC measurements to arrive at harmonized values, from which they established standardized, age-specific reference ranges.

The authors cautioned that while the cohorts included in their analysis were diverse in morbidity, age, and geographic location, they also were predominantly Caucasian. The study also leaves open several broader issues, including whether the reference range should be based on samples from healthy young men or be age-adjusted, and whether it should include not only healthy nonobese men but also the entire population of men ages 19–39.