EPO - what you should know
Synthetic erythropoietin is prohibited at all times by the World Anti-Doping Agency as it increases red blood cell production, thereby increasing oxygen to the muscles.
About the substance
Erythropoietin (EPO) is a hormone naturally produced in the kidneys, with minor production in other organs. It is transported to bone marrow via blood, where it stimulates and boosts the development of red blood cells.
The body’s production of EPO is stimulated by low oxygen levels (hypoxia). When cells in the kidneys sense there is sufficient oxygen in the blood, they reduce production of EPO.
When EPO increases red blood cell production, oxygen supply to muscles is enhanced. This increases stamina – the ability to exert energy and remain active for a long period of time. Athletes who want to improve their endurance may train at high altitude locations or use altitude simulation devices to trick their body into thinking there's less oxygen and therefore start the process of making more blood.
Recombinant EPO
Medical versions, which may be known as exogenous EPO, such as recombinant EPOs (rEPO), have been developed for use in clinical settings to treat medical conditions and can be misused to enhance performance in sport.
rEPO are biopharmaceutical drugs with the same effects as endogenous EPO.
It has legitimate medical uses, commonly used in a clinical setting for treating anemia caused by chronic kidney disease or by chemotherapy and is administered via injection either intravenously (IV) or subcutaneously (under the skin). Subcutaneous administration is usually in the thigh or abdomen/belly area, which can be easily self-administered.
The use of rEPO is often supplemented with iron and vitamin B (B12 and folic acid). Blood tests – including full blood count and iron studies − are usually conducted before, during and after treatment to monitor response to the drug, as well as track haemoglobin levels.
rEPO are the most chemically similar to endogenous EPO, however they present differently in drug testing processes.
Misuse in sport
The misuse of rEPO in sport is of most benefit to, and therefore represents the greatest threat in endurance sports, such as long distance running and road cycling. Other high-risk sports include triathlon, marathon and long-distance swimming.
However, the use of rEPO doping is not unheard of in power-based disciplines, such as short-distance sprinting, and weightlifting.
Dangers of substance
Use of rEPO can be extremely dangerous without proper medical oversight and can increase the risk of death. This is because use of rEPO results in increased production of red blood cells, making blood excessively thicker and prone to clotting. These risks are exacerbated by dehydration which often occurs during endurance exercise; further concentrating the blood and risking heart attack, stroke and blood clots.
There have been clusters of suspected EPO-related cyclist deaths in Europe during the late-1980s to early-90s, known as the ‘EPO-era’, and in 2003−04.
According to media reporting at the time, it was ‘common knowledge’ that riders were heard to get up to move around during the night so their arteries wouldn’t become clogged: “Those who forgot to wake up, or to drink enough water, or simply pushed their haematocrit so high that they created a logjam in their arteries, fell asleep after a hard day’s training and never woke up.”
Anti-doping response to rEPO
rEPO has been banned in sport since the early 1990s and can be differentiated from endogenous EPO through laboratory analysis.
A test for rEPO was first presented at the 2000 Summer Olympic Games in Sydney. This was based on a complementary analysis using blood and urine matrix. With this test, a blood screening took place first, followed by a urine test to confirm the presence of rEPO.
Testing for rEPO can be conducted in either urine or blood samples and can independently indicate presence.
Laboratories that analyse World Anti-Doping Agency (WADA) anti-doping samples are required to meet extensive accreditation requirements, including regional as well as WADA accreditation, and undergo regular quality testing with major repercussions for failures in any capacity.
A laboratory may find a sample to be Negative, Atypical (suspicious), or an Adverse Analytical (positive).
For an Atypical Finding or Adverse Analytical Finding to be reported for rEPO the results must also be reviewed by a WADA-recognised expert, providing a second opinion.
When rEPO analysis results are inconclusive, it is reported as an Atypical Finding. This may be due to the presence of interferences in a sample, or the intensity of a potential synthetic EPO signal is too low to enable conclusive identification. An Atypical Finding result requires further investigation.
There is often a misconception that test results subjectively measure the amount of EPO in an athlete’s sample, above what should be naturally occurring. In reality, the results distinguish naturally occurring (endogenous) EPO from exogenous rEPO.
In addition, there is the Hematological Athlete Biological Passport which allows for the indirect detection of blood manipulation and/or synthetic EPO use, including rEPO, through longitudinal monitoring of blood-based biomarkers in individual athletes. Atypical Athlete Biological Passport profiles are used to direct testing and guide further analyses.
Anti-doping penalties
Athletes found to have used rEPO can be banned from all sport for up to four years.
A doctor/pharmacist who is found to be complicit in athlete doping can also be penalised under the World Anti-Doping Code, in the case where it can be established that the individual is subject to the anti-doping rules.
How does EPO testing work?
In anti-doping, EPO tests are able to differentiate between naturally made EPO, and synthetic versions of EPO. The test is looking to see if there is any synthetic EPO.
How is EPO testing different to other tests?
For an EPO test to be confirmed positive, the sample is first analysed by a WADA Accredited Laboratory. The results are reviewed by an independent EPO expert recognised by WADA, and their opinion is reported by the lab.
There are only eight EPO experts in the world who can make a decision about whether a sample is positive, and none are based in Australia. This is because EPO results require very specific interpretation and expertise.
Synthetic EPO is the only prohibited substance with this subjective element in its analysis process.
