Who will win the drugs race?
This topic is sponsored by the Australian Government Analytical Laboratories and the bequest of J S Anderson, FAA.
Catching drug cheats is essential if sports are to be conducted on a level playing field – and if deleterious health effects are to be avoided.
To compete in the modern Olympic Games, to win gold, to stand on the rostrum as the flag is raised and the national anthem played is the dream of many. But it will come true for only a few. Only the gifted, only the dedicated, only the best will win.
And maybe a few drug cheats? Modern sport is plagued by suspicions that many top athletes resort to drug-taking doping to enhance their performance. They use anabolic steroids, human growth hormone, erythropoietin (EPO), beta-blockers, stimulants or diuretics. While drugs such as these get a lot of publicity, they are perhaps not well understood. What do they do? What are the health risks in the short or long term? Can the drugs be detected?
Here we look at three of the better known drugs in sport anabolic steroids, human growth hormone and EPO. All are members of a family of chemicals called hormones naturally occurring chemical messengers that regulate many of the body's functions.
The main hormones are produced by glands and are transported around the body in the bloodstream. Because of their importance in the growth and development of organs and tissue, hormones are the main target in the development of performance-enhancing drugs. But, as we will see, the fact that the drugs occur naturally in the body sometimes makes detecting drug abuse difficult.
Anabolic steroids are drugs that resemble testosterone, a hormone which is produced in the testes of males and, to a much lesser extent, in the ovaries of females. Testosterone is partially responsible for the developmental changes that occur during puberty and adolescence and is also involved in controlling the rates of buildup and breakdown of the main biochemical components of all tissues, including muscle.
Because testosterone and related drugs affect muscle growth, raising their levels in the blood could help athletes increase muscle size and strength. Athletes who use anabolic steroids also claim that they reduce body fat and recovery time after injury. But the androgenic (masculinising) side-effects such as increased body hair and a deepening of the voice are not always desirable, particularly in women. To counteract these side-effects, scientists manufacture steroids that retain their anabolic effects but have a lower androgenic effect (eg, androstenedione and nandrolone).
Androstenedione was used by East German Olympic swimmers and other athletes in the 1970s and 1980s to improve their performances. It was banned by the International Olympic Committee in 1997, but is currently permitted by some other sporting bodies, such as Major League Baseball in the USA. Mark McGuire, who set a baseball home-run record in 1999, has admitted to using androstenedione (as well as the controversial food supplement creatine). Nandrolone was allegedly detected in a urine sample provided by British sprinter and Olympic gold medallist Linford Christie in 1999.
Health risks of anabolic steroids
Medical experts see significant dangers in the use and particularly the gross over-use of anabolic steroids. Some of the effects are minor or only last while the drug is being taken; others are more serious and long-term. For example, anabolic steroids can cause high blood pressure, acne, abnormalities in liver function, alterations in the menstrual cycle in women, decline in sperm production and impotence in men, kidney failure and heart disease. They can also make both men and women more agressive.
Human growth hormone
Human growth hormone (hGH; also called somatotrophin or somatotrophic hormone) promotes physical development particularly the growth of bone during adolescence. It stimulates the synthesis of collagen, which is necessary for strengthening cartilage, bones, tendons and ligaments, and also stimulates the liver to produce growth factors. In adults, hGH increases the number of red blood cells, boosts heart function and makes more energy available by stimulating the breakdown of fat. It’s quite easy to see why it might enhance athletic performance.
Because hGH is a protein hormone, it is possible to manufacture large amounts of hGH using recombinant DNA technology. Like anabolic steroids, hGH has a legitimate role in medicine, but it is also misused by athletes.
Health risks of human growth hormone
If you believe all the hype emanating mainly from drug manufacturers hGH is a wonder drug that will remove wrinkles, reverse the ageing process, restore vitality and improve sleep. Nevertheless, there are some health risks.
For example, too much hGH before or during puberty can lead to gigantism, which is excessive growth in height and other physical attributes. After puberty, inflated levels of hGH can cause acromegaly, a disease characterised by excessive growth of the head, feet and hands. The lips, nose, tongue, jaw and forehead increase in size and the fingers and toes widen and become spade-like. The organs and digestive system may also increase in size, which may eventually cause heart failure. Acromegaly sufferers often die before the age of 40. Excessive hGH in adults may also lead to diabetes.
Erythropoietin EPO hit the headlines in 1998 when the Festina-sponsored team in cycling’s Tour de France was disqualified after being caught red-handed with large quantities of it and other banned substances. Manufactured naturally by the kidneys, EPO stimulates the production of red blood cells in bone marrow and regulates the concentration of red blood cells and haemoglobin in the blood. This is useful for athletes, since red blood cells shuttle oxygen to the cells, including muscle cells, enabling them to operate aerobically. EPO is a peptide hormone and can be produced using recombinant DNA technology. By injecting EPO, athletes aim to increase their concentration of red blood cells and, consequently, their aerobic capacity.
Health risks of EPO
If EPO levels are too high the body will produce too many red blood cells, which can lead to blood clotting, heart attack and stroke. In fact, EPO has been implicated in the deaths of several athletes.
How different drugs can be detected
The issue of detection is critical to minimising the use of drugs in sport. If the regulations imposed by sporting bodies are impossible to police, we can expect that some athletes will ignore them. Alternatively, if drug-testing is quick, easy and reliable, we stand a much better chance of catching drug cheats. Unfortunately, as the science of detection advances, so too does the science of ‘masking’, or hiding, the evidence of drug abuse.
A complicating factor in drug detection is that many performance-enhancing drugs occur naturally in the body. For this reason, sporting bodies usually set benchmarks if the amount of the substance detected is above the benchmark, the athlete is said to be guilty of doping. The issue of how reliable benchmarks might be determined is addressed in Box 1: Statistical profiling setting better benchmarks?.
Anabolic steroids and their by-products can generally be detected quite easily in urine, using mass spectrometry. However, since they occur naturally and their levels in the body fluctuate daily and can vary from person to person, setting a threshold above which an athlete is deemed to be ‘using’ anabolic steroids remains a subject of debate.
Testosterone and a related compound, epitestosterone, are eliminated from the body in urine. When an athlete takes anabolic steroids, the ratio of testosterone to epitestosterone (the T/E ratio) increases. The International Olympic Committee states that an athlete is guilty of doping if their urine sample shows a T/E ratio above 6.
There are problems with this test. For example, British athlete Diane Mohdahl had a 4-year competition ban lifted after demonstrating that a high T/E ratio detected in her urine sample could have been caused by bacterial contamination. Another problem is that some athletes have been shown to have a naturally high T/E ratio, so that the threshold of 6 could be set too low. Alternatively, athletes with a naturally very low T/E ratio may not go above 6 even if they are taking additional testosterone.
Scientists have been working to develop more reliable tests. One promising approach involves the use of an isotope ratio mass spectrometer, which can detect differences in the ratio of carbon isotopes in different compounds. This technology can distinguish between testosterone produced naturally by the body and synthetic compounds.
- Human growth hormone (hGH)
After hGH has been secreted by the pituitary gland or injected by a drug-user it breaks down quite quickly into other products. Scientists in Australia and elsewhere have monitored changes in the bodies of athletes following the administration of hGH and have detected molecular ‘markers’ usually breakdown products detectable in urine or blood that could be used as indirect evidence of doping.
- Erythropoietin (EPO)
Like hGH, EPO levels in the blood do not remain elevated for long, making detection difficult. The standard test doesn’t measure EPO levels; rather, it measures the concentration of red blood cells in a blood sample. But because this test is only an indicator of possible EPO abuse, more reliable tests are needed.One method for detecting EPO currently being investigated involves a protein called transferrin, which could be an indirect marker of EPO use. Scientists are also looking at techniques to distinguish molecular differences between the EPO produced by the body and that manufactured in the laboratory. A method developed by Australian scientists uses blood profiles to detect athletes with a disproportionate number of young and maturing red blood cells (Box 1). A test developed by French scientists analyses urine samples.
Winning the drugs race?
Historians point out that drugs have probably been used to enhance sporting performance for more than 2000 years, so it’s unlikely the problem will ever go away. Some commentators are even calling for the legalisation of such drugs so they can be dispensed, administered and monitored more closely. Others say the only way to ensure the health of our athletes is to stamp out drugs altogether. For now, performance-enhancing drugs are illegal, so athletes who use them are cheats. And, given the health risks associated with drug abuse, we can safely say that the race to beat the drug tests is a race nobody wins.
Page updated January 2004.