Researchers have established a reference range for normal total testosterone levels using values harmonized by the Steroid Hormone Standardization Program at the Centers for Disease Control and Prevention (CDC) in Atlanta.
For healthy, non-obese men ages 19 to 39 from Europe or the United States, the harmonized normal range of total testosterone is 264 to 916 ng/dL, a range that corresponds to the 2.5th to 97.5th percentile, investigators reported in a paper published online ahead of print the Journal of Clinical Endocrinology & Metabolism. Values below the 2.5th percentile indicate hypogonadism.
Lack of a universally accepted testosterone threshold has made accurate diagnosis of hypogonadism difficult. “Well-defined reference ranges are at the heart of clinical practice and without them clinicians can make erroneous diagnoses that could lead to patients receiving costly, lifelong treatments that they don’t need or deny treatments to those who need them,” lead researcher Shalender Bhasin, MD, of Brigham and Women’s Hospital in Boston, stated in a press release.
Dr Shalender and his team examined total testosterone values from 9054 community-dwelling men within 4 cohorts in the United States and Europe: the Framingham Heart Study, European Male Aging Study, Osteoporotic Fractures in Men Study, and the Male Sibling Study of Osteoporosis. Serum samples from 100 men from each cohort were sent to a CDC laboratory for analysis by a higher-order liquid chromatography tandem mass spectrometry method. Normalizing equations based on the CDC’s benchmarks were then applied to all locally measured testosterone values across the 4 cohorts. Using the data, the investigators also determined age-specific reference ranges for the 4 cohorts and overall.
The investigators found that differences in testosterone ranges among cohorts largely ensued from assay variation. “Without harmonized reference ranges and standardized assays, tests can lead to misdiagnoses and unfortunately this happens every day around the world,” co-author Hubert Vesper, PhD, stated in the release. “Now we have a reference range for testosterone, and it’s important that we take this into consideration in the tests that clinicians and patients depend on for accurate diagnoses.”
Among the strengths of the study, testosterone tests were performed in the morning, minimizing the influence of testosterone fluctuations throughout the day. The cohorts largely included white men, however, so future studies involving multiple ethnicities and different world regions are needed to confirm the accuracy of the testosterone ranges for these populations. The investigators recommend further evaluation of the reference range in future trials.
The study leaves some unresolved issues, the researchers noted. Among them is whether the reference sample should include only the healthy non-obese men or if it should include the entire population of men aged 19 to 39 years. Obesity and comorbid conditions affect levels of circulating testosterone, so inclusion of obese men and those with comorbidities could the distort the reference ranges, the investigators explained.
1. Travison TG, Vesper HW, Orwoll E, et al. Harmonized Reference Ranges for Circulating Testosterone Levels in Men of Four Cohort Studies in the USA and Europe. J Clin Endocrinol Metab. 2017 jc.2016-2935. doi: 10.1210/jc.2016-2935. [Epub ahead of print].
2. Landmark study defines normal ranges for testosterone levels. Endocrine Society. January 10, 2017. [press release]