Testing for Recombinant Human Erythropoietin (rHuEpo)
New study examines the validity of the WADA rHuEpo test
BETHESDA, Md.—Recombinant human erythropoietin (rHuEpo) is a genetically engineered hormone sometimes misused by high-performance athletes such as cyclists and marathon runners to boost their endurance. The potential misuse of the drug is detected in urine collected from athletes. Since the test was introduced in 2000, 33 labs around the world have been accredited by the World Anti-Doping Agency (WADA) to administer the procedure. During the last few years, the testing procedure has been criticized by some. Accordingly, a team of researchers investigated the quality of the test results at two WADA labs. They found that the detection power of the test at the two labs was poor.
The study is entitled, “Testing for Recombinant Human Erythropoietin in Urine: Problems Associated with Current Anti-Doping Testing,” and was conducted by Carsten Lundby, Niels J. Achman-Andersen, Jonas J. Thomsen, Anne M. Norgaard and Paul Robach, all of the Copenhagen Muscle Research Center, Copenhagen, Denmark. The findings appear in the online edition of the Journal of Applied Physiology, published by the American Physiological Society (www.the-aps.org).
The researchers conducted the study using eight male volunteers (non-athletes). Following baseline measurements, the volunteers were injected every second day for 14 days with 5,000 IU rHuEpo (the “boosting period”). For the next two weeks, the volunteers received one injection every seven days (the “maintenance” period). Blood samples were drawn before the injections and on eight additional occasions. Urine samples were collected before the blood draws and on six additional days. Exercise tests using a bicycle ergometer were conducted prior to injection and on three other occasions.
Findings and Implications
The rHuEpo administration regimen was effective in increasing the oxygen carrying capacity of all the volunteer subjects, and at the same time, their performance increased. Additionally:
- Using the samples collected during the boosting phase, Lab A concluded that all the samples were positive for rHuEpo. Lab B determined that none of the samples, despite being identical to Lab A’s samples, were positive.
- For samples collected during the maintenance period, Lab A determined that six of l6 samples were positive and two samples were suspicious. By contrast, Lab B found no positive samples.
- For samples collected during the post-treatment phase, Lab A concluded that two of 24 samples were positive and three were suspicious. Lab B determined that all 24 samples were negative.
The implication– if applied to athletes – is that there is only a small “risk” of being tested positive for rHuEpo doping while athletic performance is greatly enhanced. If the samples are analyzed by Lab B, the risk of doping detection is non-existent. It should be noted that in this study, the “maintenance” period was only two weeks – but according to the authors, this can be sustained for an entire sporting season.
Results in Perspective
The results demonstrate that the detection power of the WADA test is poor and that agreement in analytical results from two WADA-accredited laboratories is very poor. Given these and other findings, the researchers conclude that improvements in the current rHuEpo test are necessary, or that alternative tests should be developed. This however, seems unlikely to occur before major events scheduled for 2008 like the Tour de France or the Olympic Games in Beijing.
As the topic of drug testing athletes is especially timely and carries implications for anti-doping efforts and public policy, the Journal invited and published an editorial that accompanies the study. Joris R. Delanghe of Ghent University Hospital, Ghent, Belgium and Michael J. Joyner of the Department of Anesthesiology, Mayo Clinic, wrote that the physiological background for testing Epo in urine is complex and the handling of Epo by the renal tubules is poorly understood. The high number of false negative results found in the study implies a risk that athletes who use rHuEpo will avoid detection and damage the fundamental goal of fair competition.
The editorial authors suggest that while the existing test can likely be improved by emphasizing pre-analytical care of urine specimens, there may be limitations to urine testing of peptide hormones that will be difficult to ever overcome. Additionally, there is also a concern that treated urine specimens could mask rHuEpo abuse. As a result, the authors suggest that blood-based indirect rHuEpo tests may offer greater advantages for detecting the drug, and this approach would also be useful for detecting other kinds of blood doping.
NOTE TO EDITORS: To schedule an interview with Drs. Lundby, Delanghe or Joyner, please contact Donna Krupa, American Physiological Society, at 301.634.7209, DKrupa@The-APS.org.
Source: Online Edition of the Journal of Applied Physiology
Physiology is the study of how molecules, cells, tissues and organs function in health and disease. Established in 1887, the American Physiological Society (APS) was the first U.S. society in the biomedical sciences field. The Society represents more than 10,500 members and publishes 15 peer-reviewed journals with a worldwide readership.