White Paper Identifies Problems with Current Approach to Low-T Evaluation

A white paper from the American Urological Association warns physicians about significant problems with existing testosterone evaluation practices and outlines strategies for ensuring the right patients receive the right replacement therapy.

The paper, which was also published in Urology, notes both conceptual and technical obstacles to diagnoses of androgen deficiency, some of which are shockingly basic.

“There is no consensus among endocrinologists, urologists and clinical pathologists as to what defines a ‘low’ testosterone level,” the paper authors write. “Published normal assay ranges for serum testosterone are mostly based on studies in older men (>65 years old) and were not specifically designed to establish normal assay ranges in men with normal sexual and reproductive function.”

Despite that lack of concrete evidence about what constitutes “normal” for men of varying ages, different groups have developed different guidelines. The Food and Drug Administration (FDA), for example, uses a cut-off value of 300 ng/dL to define hypogonadism for clinical trials.

Such guidelines can prove problematic, however. Rigid use of the 300 ng/dL threshold would lead to treatment for many men with no physical symptoms of hypogonadism and no treatment for men with higher total testosterone levels who still suffered persistent signs and symptoms of androgen deficiency.

Guidelines from other bodies — such as the consensus standards from the International Society of Andrology, the International Society for Study of the Aging Male, the European Association of Urology, the European Association of Andrology and the American Society of Andrology — consider both symptoms and total testosterone levels, but they also rely on thresholds based on the study of geriatric men.

“Mean age of subjects enrolled in the largest population studies on male hypogonadism was 75.4 for the MrOS arm in Sweden, 73.7 in the United States based arm of MrOS and 60 for the EMAS study,” the authors write.

Even if new studies appear tomorrow, providing full and accurate information for diagnosing androgen deficiency from accurate test results, doctors would still struggle to get those accurate test results, the white paper argues.

Most physicians already urge patients to undergo testosterone tests soon after they wake up, a strategy designed to control for the dramatic change in hormone levels over the course of the day and capture numbers at their peak.

There’s no way, however, to control for factors such as stress. Testosterone levels can fall 25% within half an hour of a stressful event, so a snippy email that a patient reads on the way to the get his blood drawn can wreck the test.

The lab that performs the analysis also affects the results. Different labs analyzing blood from the same patient routinely provide results that differ by as much as 30%. Some of this stems from differences in what sorts of tubes labs use and how they store blood after putting it through the centrifuge. Other differences stem different testing methods.

How are clinicians to avoid all these potential pitfalls and make good diagnoses? The white paper makes a number of specific suggestions, but the overall emphasis is to consider symptoms as much as numbers.

“Based on the extensive review of published data and input from professional organizations, the members of this panel believe that diagnosis of hypogonadism should be based as much on the presence of signs and symptoms as on serum testosterone measurement,” they wrote.

Based on the overall poor quality of testosterone testing “in most clinical laboratories and age bias of published reference ranges, no patient should be denied coverage for treatment based solely on payer defined cutoff points if need for such treatment is established by a health professional.”