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Erythropoietin (EPO), Epoetin (eh-POH-ee-tin)

BANNED SUBSTANCE in Amateur and Professional Sports

Erythropoietin (EPO) is a member of the hematopoietic growth factor family and is one of the few hematopoietic growth factors which behave like a hormone. The principal function of erythropoietin is to couple oxygen delivery by circulating red cells to long-term tissue oxygen needs. Produced primarily in the kidneys and to a small extent in the liver in adults, erythropoietin interacts in the bone marrow with specific receptors on the surface of erythroid progenitor cells to initiate their entry into cell cycle if dormant on to maintain their viability while differentiating, if they are already in active cell cycle. Erythropoietin achieves its effects by causing homodimerization of its receptor with the resultant autophosphorylation of the tyrosine kinase JAK2 and phosphorylation of the receptor itself, as well as various substrate proteins leading to the upregulation of a number of signaling pathways and the activation of gene transcription.

WADA Q&A EPO Detection:

What is EPO?

Erythropoietin (EPO) is a peptide hormone that is produced naturally by the human body. EPO is released from the kidneys and acts on the bone marrow to stimulate red blood cell production.

An increase in red blood cells improves the amount of oxygen that the blood can carry to the body's muscles. It may also increase the body's capacity to buffer lactic acid.

What are the side-effects of EPO misuse?

While proper use of EPO has an enormous therapeutic benefit in the treatment of anaemia related to cancer or kidney disease, its misuse can lead to serious health risks for athletes who use this substance simply to gain a competitive edge. It is well known that EPO, by thickening the blood, leads to an increased risk of several deadly diseases, such as heart disease, stroke, and cerebral or pulmonary embolism. The misuse of recombinant human EPO may also lead to autoimmune diseases with serious health consequences.

When was EPO banned as a performance enhancing substance?

EPO has been banned since the early 1990s.

When was a test to detect EPO implemented?

A test for EPO was introduced at the 2000 Summer Olympic Games in Sydney (Australia). The test, validated by the International Olympic Committee (IOC), was based on the blood and urine matrix. A blood screening was performed first, and a urine test was then used to confirm possible use of EPO.

In June 2003, WADA's Executive Committee accepted the results of an independent report stating that urine tests alone can be used to detect the presence of recombinant EPO. This report, requested by WADA's stakeholders and commissioned by the Agency to evaluate the validity of urinary and blood tests for detecting the presence of recombinant EPO, concluded that urinary testing is the only scientifically validated method for direct detection of recombinant EPO. This report also recommended that urine testing be used in conjunction with blood screening for a variety of reasons, including the cost savings of performing blood screening prior to testing urine. Some international sports federations still use both urine and blood matrix for the detection of EPO.

Is the EPO detection method reliable?

The detection method for EPO is valid and reliable.

The method has undergone an extensive scientific validation process and has been used successfully for many years by accredited anti-doping laboratories around the world. It is a well-established procedure widely accepted by the scientific community, as demonstrated by publication in a number of international scientific journals.

Further, in all its decisions relating to EPO, the Court of Arbitration for Sport (CAS) has supported the validity of the EPO detection method. And, at a meeting in September 2005, the WADA Laboratory Committee reiterated its support of the method when properly applied.

How has the EPO detection method evolved since its introduction in 2000?

The conservative approach used in the initial phase of implementation of the method allowed a large number of EPO abusers to escape detection.

Consistent with the advancing science in anti-doping, work is done on an ongoing basis on all detection methods to refine the method and interpretation of results. In the case of EPO, this led, based on expert consensus, to the introduction of new interpretation criteria for a more discriminant reading of EPO results in January 2005. At the same time, laboratories were advised to have their adverse EPO results confirmed by another laboratory with extensive experience of the method.

Why did some individuals question the EPO detection method?

Questions were raised by certain individuals who are not well versed in the science of EPO detection in relation to a phenomenon that is rare but well understood by anti-doping experts.

In certain rare circumstances, normal endogenous EPO shifts into the recombinant EPO area. This phenomenon is clearly identified by accredited laboratories so that these rare profiles are labelled properly and are not reported as adverse results due to EPO doping.

WADA was informed of this phenomenon by accredited laboratories in the spring of 2005. As a result, WADA instructed all accredited laboratories to integrate this information into their interpretation of results. In addition, laboratories are required to seek a second independent opinion before reporting any adverse result. There is no risk of a false positive reading; all accredited laboratories are in a position to distinguish between this rare profile and exogenous EPO.

In relation to the timeframe from January 2005 (when WADA introduced new interpretation criteria for EPO results) to July 2005 (when WADA contacted the accredited laboratories performing EPO analysis to inform them of the phenomenon), several of the accredited laboratories were already aware of the phenomenon and had incorporated it in their routine procedure for reading EPO results, and the rest reviewed all cases they may have had in that timeframe to ensure there had been proper interpretation. This therefore gives the Agency full confidence that there have been no sanctions of athletes due to this phenomenon.

Finally, in relation to the period prior to January 2005 (when the new interpretation criteria for EPO were introduced), because the former interpretation criteria were not as discriminant as they are now, these rare profiles would never have been reported as adverse results.


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