The number of testosterone prescriptions is growing, so a paper recently published in Endocrine Reviews seeks to offer some best practices for the application of free testosterone measurements in patients with androgen disorders.
The paper, by Ravi Jasuja, PhD, of Harvard Medical School, et al, points out that as the number of prescriptions written for testosterone has increased over the past 10 years, the medical community has refocused its attention on the critical need to accurately measure free testosterone in men with androgen disorders, as well as careful monitoring of these patients and rational dosing. Their review documents the evolution “of our understanding of the binding and bioavailability of testosterone to circulating binding proteins,” attempts to offer a critical appraisal of the prevailing models of testosterone binding to these circulating proteins, discusses recent advances, and provides a contemporary perspective on the free hormone hypothesis and its clinical implications.
The Endocrine Society guidelines suggest measuring free testosterone in men whose total testosterone concentrations are in the lower end of the normal range and in men with conditions that make total testosterone measurements less reliable. “If the free hormone hypothesis is correct,” the authors of this review write, “free testosterone should serve as the benchmark for biochemical confirmation of hypogonadism. Accurate determination of free testosterone values is therefore central to an accurate diagnosis of hypogonadism.”
The authors write that direct analogue assays are inaccurate and should not be used. They also write that while equilibrium dialysis is the reference method for measuring free testosterone, this method isn’t readily available, and because of the lack of standardization across laboratories, this method makes it difficult for endocrinologists to accurately measure free testosterone levels.
“Total testosterone, which can be measured with high accuracy using LC-MS/MS assays in CDC-certified laboratories, and free testosterone are highly correlated,” the authors write,” and it is only in individuals with altered binding-protein concentrations that the associations begin to diverge.” Therefore, they continue, they recommend following current Endocrine Society guidelines: measure total testosterone, and if the man has suspected alterations in sex hormone-binding globulin, then measure free testosterone with equilibrium dialysis.
“Efforts are underway to standardize the procedures for free testosterone measurement and to generate harmonized reference ranges,” the authors conclude. “Until that time, clinicians should be aware that inaccuracies in free testosterone measurements and calculations and poorly defined reference ranges can increase the risk of misclassification in the diagnosis of androgen disorders.”
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