BOSTON—The yearly initiation rate of testosterone replacement therapy use increased dramatically in the United States from 20.2 to 75.7 per 10,000 person years in an 11-year period ending in 2011.

One concern is that some of those men might have been incorrectly diagnosed with hypogonadism because of a lack of defined reference ranges of testosterones and standardization of hormone assays, according to a new article in the Journal of Clinical Endocrinology & Metabolism.

In an effort to enable clinicians to make more accurate diagnoses, a team led by researchers from Brigham and Women’s Hospital, Harvard Medical School embarked on a large study of more than 9,000 men to establish harmonized reference ranges for total testosterone that can be applied to assays that have been appropriately calibrated.

Hypogonadism, a condition characterized by low testosterone levels, can lead to sexual dysfunction, decreased muscle and bone strength, less energy, and lower fertility. While the correct diagnosis and effective treatment and prevention of hypogonadism as well as many other diseases depend on accurate measurement of hormones, study authors point to the previous lack of both defined reference ranges of testosterone and standardization of hormone assays, which made diagnosing 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,” explained lead author Shalender Bhasin, MD, of Brigham and Women’s Hospital, Harvard Medical School in Boston and lead author of the study. “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. Clearly we need standardization in all hormone assays.”

For the study, researchers drew serum testosterone samples from men who had already had their testosterone levels assayed locally. The samples were sent to the CDC’s Clinical Standardization Programs at the National Center for Environmental Health, where testosterone concentrations were measured using a higher-order liquid chromatography tandem mass spectrometry method.

Results from both measurements were used to generate harmonized values, which were the basis of standardized, age-specific reference ranges. The report states that the harmonized normal range for testosterone in a nonobese population of European and American Men, 19 to 39 years, is 264 to 916 ng/dL.

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

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