Harmonized Testosterone Reference Ranges Established for Men

Newly defined reference ranges for normal total testosterone levels in men may improve clinicians’ ability to accurately diagnose hypogonadism, according to study results published in the Journal of Clinical Endocrinology & Metabolism.¹

“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 do need them,” study author Shalender Bhasin, MD, from Brigham & Women’s Hospital and Harvard Medical School in Boston, Massachusetts, said in a press release.²

In the study, Dr Bhasin and colleagues noted that reference ranges for circulating testosterone levels in healthy men without obesity have been published. “However, an important unresolved question is whether the reference ranges generated in one population of men can be applied more broadly to men in other geographic regions and in other populations,” they wrote.¹

“Our data establish a reference range for testosterone. These data also show that variation in assays is an important contributor to variation in testosterone levels in cohorts from different geographic regions,” said Dr Bhasin.² “Clearly, we need standardization in all hormone assays.”

To establish harmonized ranges for total testosterone in men, the researchers evaluated data from 9054 men who participated in the Framingham Heart Study, European Male Aging Study, Osteoporotic Fractures in Men Study, and Male Sibling Study of Osteoporosis. They sent samples of serum testosterone concentrations from 100 men in each of the 4 cohorts to the Centers for Disease Control and Prevention’s (CDC) Clinical Standardization Programs at the National Center for Environmental Health, where a higher-order liquid chromatography tandem mass spectrometry method was used.

Normalizing equations were used to produce harmonized values between the locally tested and CDC-tested samples, which were then used to derive standardized, age-specific reference ranges.

Results indicated that harmonized values were 264 ng/dL for the 2.5th percentile, 303 ng/dL for the 5th percentile, 531 ng/dL for the 50th percentile, 852 ng/dL for the 95th percentile, and 916 ng/dL for the 97.5th percentile in healthy, nonobese European and American men aged 19 to 39 years.¹ In nonobese men, age-specific harmonized testosterone levels were similar across cohorts and greater than in all men.¹

The researchers explained that intercohort variation in testosterone levels was mostly due to difference in assays. “These data demonstrate the feasibility of generating harmonized reference ranges for testosterone that can be applied to assays, which have been calibrated to a reference method and calibrator,” they noted.¹

“Without harmonized reference ranges and standardized assays, tests can lead to misdiagnoses and unfortunately this happens every day around the world,” study co-author Hubert Vesper, PhD, co-chair of The Partnership for the Accurate Testing of Hormones (PATH), said in the release.² “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.”

Disclosures: Dr Bhasin has received research grant support from AbbVie Pharmaceuticals, Transition Therapeutics, Takeda Pharmaceuticals, and Eli Lilly; served as a consultant to AbbVie, Regeneron, Novartis, and Eli Lilly & Co; and has financial interest in Function Promoting Therapies LLC. Dr Matsumoto has received research grant support from AbbVie and GSK, and has served as a consultant to AbbVie, Endo, Lilly, and Lipocine. Dr Wu has received research grant support from Besins Healthcare and Eli Lilly & Co, and has served as a consultant to Besins Healthcare and Repro Therapeutics.

References

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 [published online January 10, 2017]. J Clin Endocrinol Metab. doi: 10.1210/jc.2016-2935
2. Landmark study defines normal ranges for testosterone levels [press release]. Washington, DC: Endocrine Society News Room; January 10, 2017. www.endocrine.org/news-room/current-press-releases/landmark-study-defines-normal-ranges-for-testosterone-levels. Accessed January 23, 2017.