Breaking Science: The T/E test isn't very good

An emailer sends along a press release with this summary:

This recent study shows how individual genetics strongly influences the outcome of the testosterone/epitestosterone (T/E) ratio that is widely used as a first level screening test to detect athletes who are taking a banned testosterone supplement. Three genetic variants (say A, B and C) were present in test subjects in percentages respectively of 15%, 52% and 33%.

When a 360 mg dose of testosterone was administered to a subset of the screened subjects, 40% of those having genetic type A never reached the detection ratio of 4.0. In other words this amounts to a 40% false negative rate for those having type A.

Conversely 14% of subjects having type C who were NOT given a dose of testosterone still tested above the threshold T/E ratio. In other words this amounts to a 14% false positive rate for those having type C.

The follow up carbon isotope test that was used to implicate Floyd Landis should rescue those innocent 14% false positives but generally this shows what a poor screening test the T/E ratio is.

We think this means that, uh, 100 - 14, only 86% of the virgins, or those in an 86 mile radius need to be worried, or something like that.

The official response is likely to be, "that's why T/E positives now need to be justified with longitudinal studies."

This will be marvelous consolation to Mary Decker-Slaney, just 12 years late.

UPDATE: the full paper is now published and available.

[MORE]



Source: Endocrine Society Released: Thu 20-Mar-2008, 16:35 ET
Embargo expired: Fri 21-Mar-2008, 08:00 ET

Doping Test in Sports Confounded by Common Genetic Trait

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The tests for testosterone doping used in professional and amateur sports may routinely be confounded by a common genetic variation, according to a new study accepted for publication in the Journal of Clinical Endocrinology & Metabolism (JCEM). Unless this variation is accounted for, current testing methods could implicate innocent athletes and allow cheaters to go undetected.


Newswise — The tests for testosterone doping used in professional and amateur sports may routinely be confounded by a common genetic variation, according to a new study accepted for publication in the Journal of Clinical Endocrinology & Metabolism (JCEM). Unless this variation is accounted for, current testing methods could implicate innocent athletes and allow cheaters to go undetected.

“Genetic factors may play an important role in the accuracy and sensitivity of testosterone doping tests,” said Jenny J. Schulze, Ph.D, of the Karolinska University Hospital in Stockholm, and lead author of the JCEM study. “This is of interest not only for combating androgen doping in sports, but also for detecting and preventing androgen abuse in society.”

The current first-line defense for detecting testosterone abuse in sports is to measure the ratio of two chemicals in a spot urine test: testosterone glucuronide (TG) and epitestosterone glucuronide (EG). TG is a by-product of testosterone in the body; it increases as the amount of testosterone increases. EG is unrelated to testosterone metabolism, and serves as a reference point in testing.

In doping tests, any ratio above four, according to the International Olympic Committee, should be considered suspicious and lead to further testing.

The production of TG from testosterone, however, is primarily controlled by an enzyme (UGT2B17), which is produced by a specific gene. Common variations to this gene may give rise to wildly different testing results, even when the same dose of testosterone has been taken.

For their study, the researchers screened 145 men for the insertion (ins) or deletion (del) of this gene. Among the participants, 15 percent had no copies of the gene (del/del), 52 percent had one copy (ins/del), and 33 percent carried two copies (ins/ins).

From this group, the researchers selected 55 men (17 del/del, 24 ins/del, and 14 ins/ins) to receive a single 360 mg dose of testosterone. The men were then routinely tested over a 15-day period for the telltale signs of doping.

A full 40 percent of the del/del subjects never reached the detection threshold in a standard doping test. “Nearly half of the individuals in our study who carried this genetic variation would go undetected in a regular doping test after a single 360 mg dose of testosterone,” said Dr. Schulze.

Of equal interest, 14 percent of the ins/ins subjects were naturally over the detection threshold even without receiving a testosterone injection. Based on an earlier study, the researchers estimate that this would give a false-positive rate of 9 percent in a random population of young men. “False positive results are not only of concern for the legal rights of the sportsman,” said Dr. Schulze, “they also yield extra workload for the doping laboratories.”

Ideally, the researchers suggest that, depending on the athlete’s genotype, there should be different cut-off levels for doping tests.

According to Schulze and her colleagues, although this variant can appear in any population, it is considerably more common in East Asians (approximately 65 percent) than in Swedish Caucasians (10 percent).

Other researchers from the Karolinska University Hospital involved in the study include Jonas Lundmark, Mats Garle, Ilona Skilving, Lena Ekstrom, and Anders Rane, who is the principal investigator.

The paper “Doping Test Results Dependent on Genotype of UGT2B17, the Major Enzyme for Testosterone Glucuronidation” will appear in the June issue of JCEM, a publication of The Endocrine Society.