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Experts writing in the British Journal of Sports Medicine have said that urine tests for banned drugs in sport do not take account of genetic variants between different ethnic groups.
Dr Keith Stokes, Senior Lecturer in Exercise Endocrinology in the School for Health at the University of Bath, said:
“This research shows the complexity of the link between hormones and performance. We should be cautious in attributing these results to ethnicity, but an individual’s genetic makeup is likely to have a very important influence.
“Realistically, the tests used for the detection of anabolic steroids are quite robust. Employing an ‘endocrinological passport’ to allow for normal variation of hormone levels within individual athletes (regardless of ethnicity) might improve testing, but the costs, logistics and acceptability of such an approach are open to question.”
Prof Vivian James, Emeritus Professor of Chemical Pathology at Imperial College London, said:
“Abuse of many drugs is efficiently detected by demonstrating the presence of the drug in a urine sample. Abuse of a naturally occurring hormone such as testosterone is more difficult to detect because of the problem of distinguishing between the hormone made by the body, and that which has been administered.
“At present this is done by measuring the ratio of the amount of testosterone in the urine to that of another steroid. If testosterone is taken by an athlete the ratio is increased, and if this ratio exceeds 4, this is taken as prima facie evidence of doping.
“This paper provides further evidence that this test is unsatisfactory, because there are variations between ethnic groups in the way in which they handle testosterone, which renders a single cut-off figure of 4 unsatisfactory. A solution to the problem lies in producing for each individual athlete a personal urinary steroid profile which would be used as a standard, and since abuse of a hormone would inevitably disturb this profile, any perturbation would be taken as potential evidence of drug abuse. Athletes now have knowledge of and access to advanced methods of drug administration, and this requires a similar degree of sophistication on the part of the anti-doping laboratories.”
John W Honour, Consultant Clinical Scientist at University College London Hospital, said:
“Anabolic steroids are the most widely used drugs in sport, taken to enhance performance. A test of urine for testosterone abuse was first devised in 1983. When testosterone is taken by men the regulatory hormone for T production is suppressed and the testes are not fully functional. An increase in the ratio of testosterone to epitestosterone (T/e ratio) reflects the high level of exogenous testosterone (drug) and the low level of epitestosterone from the testes. A T/e ratio above 6 was used as proof of testosterone doping. In 2004 the World Anti-Doping Agency (WADA) lowered the threshold to four. A confirmation test based on carbon isotope ratios of steroids in urine was added. For more than 10 years however it was known that the T/e ratio varied across ethnic groups. The paper from Strahm and colleagues highlights genetic differences that determine the activities of 3 proteins involved in the breakdown and clearance of testosterone from the body. This adds to the complexity of interpreting doping test results. The Strahm paper concludes the need for an ‘endocrine passport’ of an individual’s reference hormone levels against which further tests will be judged for evidence of doping. The paper does not detail how many samples over what time frame will be needed for the doping control laboratories to have as characteristics of the individual.”
Prof Peter Sonksen MD FRCP FFSEM(UK), Emeritus Professor of Endocrinology St Thomas’ Hospital and King’s College London, said:
“This interesting and important paper highlights the inadequacy of the current World Anti-Doping Agency (WADA) guidelines on detecting testosterone abuse on the basis of urinary steroid measurements, particularly the testosterone to epitestosterone (T/Te) ratio.
“It has been known for some years that there is an ethnic effect on testosterone metabolism and that those with an Asian background often but not always have less body hair and different testosterone and its metabolites in body fluids. More recently gene deletions and modifications have been recorded that contribute to these differences, particularly the UGT2B17 gene that regulates an enzyme conjugating testosterone in the liver.
“This study, carried out on a relatively small number (171) of professional football players using state of the art urinary profiling, clearly shows that the prevalence of this gene deletion or modification can vary considerably between ethnic groups with the full deletion being very prevalent (c80%) in Japan.
“The urinary profile of testosterone and other related steroids is dependent on these genetic factors and the commonly used T/Te is much lower in the Japanese because of this. Following testosterone administration the T/Te ratio rises and once it crosses the current WADA level of 4, the sample becomes suspect and a battery of further tests are initiated to determine whether or not ‘doping’ has taken place. The implication of this genetic mutation is that even large doses of testosterone may not be detectable using the current approach which the authors slam as ‘Not fit for purpose’.
“It’s not all bad news, however; the increasingly popular ‘athlete’s passport’ and ‘I’m clean’ approach to doping control, where an athlete builds a profile of his/her own metabolism over time as the results of samples accumulate, will allow ‘athlete specific’ reference ranges to be established and these will clearly be lower in people with the gene mutation. With this approach it should make the testing more fair and less influenced by ethnicity.
“The reference ranges proposed in this paper set at the upper 99% limit of the steroid ratio is, however, too low, as it would result in an unacceptable false positive rate of 1:100; in other words, one ‘clean’ athlete would be fail for every 100 tests performed. Although WADA has not officially stated what false positive rate is acceptable to them (and the courts have not ruled on this), it has generally been taken that it should be in the region of 1:10,000.”