How Performance-enhancing Drugs Work

Fans hold up a sign prior to a Major League Baseball game.
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"If I could give you a pill that would make you an Olympic champion -- and also kill you in a year -- would you take it?" Dr. Gabe Mirkin asked competitive runners that question in advance of a Washington, D.C., road race in 1967. Of the approximately 100 athletes who returned Mirkin's questionnaire, more than half responded that they would take the pill.

The prevalence of performance-enhancing drugs in sports has increased in the 43 years since Mirkin, a physician and sports medicine expert, handed out his survey. The desire to win is, naturally, ever present while, at the same time, new research and technologies have expanded the number of options for cheating your way onto the podium. For example, today's performance-enhancing drugs come in many forms other than a pill ("the cream and the clear," a testosterone-based ointment described by accused athletes in court testimony, comes to mind), but the results they produce are still highly sought after. Professional cycling has been repeatedly rocked by revelations and allegations of drug use. Every two years as the Olympic Games begin, we hear about athletes using or at least being tested for performance-enhancing drugs. Major League Baseball is still trying to repair its image from the steroid era. And the list goes on.

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Some athletes get away with using drugs; others wind up suspended from their sport or even in jail, and still others die prematurely. It's a risky and complex game within a game that plays itself out on a public stage. In this article, we'll discuss why some athletes take drugs, what the major classes of drugs and their side effects are, and how people test for drug use.

Why Some Athletes Use Drugs

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Athletes face enormous pressure to excel in competition. They also know that winning can reap them more than a gold medal. A star athlete can earn a lot of money and a lot of fame, and athletes only have a short time to do their best work. Athletes know that training is the best path to victory, but they also get the message that some drugs and other practices can boost their efforts and give them a shortcut, even as they risk their health and their athletic careers.

As far back as ancient Greece, athletes have often been willing to take any preparation that would improve their performance. But it appears that drug use increased in the 1960s. The precise reason for the increase is uncertain, but we do know that anabolic-androgenic steroids were made available for sale during this period and the East German government began giving drugs to its athletes in an attempt to excel on an international level [source: The Guardian] [source: Sports Injury Bulletin]. Athletes may also misuse drugs to relax, cope with stress or boost their own confidence.

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Athletes may have several reasons for using performance-enhancing drugs. An athlete may want to: build mass and strength of muscles and/or bones; increase delivery of oxygen to exercising tissues; mask pain; stimulate the body; relax; reduce weight or hide the use of other drugs.

The classes of drugs used for these purposes are shown above. Most of the drugs shown are banned outright in Olympic competitions. However, some of these drugs, such as cortisone and local anesthetics, are allowed with certain restrictions in Olympic competition because they have legitimate clinical uses. We'll look at each major class of drug and tell you about the dangerous side effects.

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Building Mass and Strength

Track star Marion Jones makes a statement prior to her sentencing for lying about steroid use.
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Mass- and strength-enhancing drugs used by athletes include:

  • Anabolic steroids
  • Beta-2 agonists
  • Human chorionic gonadotropin (HCG)
  • Luteinizing hormone (LH)
  • Human growth hormone (HGH)
  • Insulin-like growth factor (IGF-1)
  • Insulin

Anabolic Steroids

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A steroid is a chemical substance derived from cholesterol. The body has several major steroid hormones -- cortisol and testosterone in the male, estrogen and progesterone in the female. Catabolic steroids break down tissue, and anabolic steroids build up tissue. Anabolic steroids build muscle and bone mass primarily by stimulating the muscle and bone cells to make new protein.

Athletes use anabolic steroids because they increase muscle strength by encouraging new muscle growth. Anabolic steroids are similar in structure to the male sex hormone, testosterone, so they enhance male reproductive and secondary sex characteristics (testicle development, hair growth, thickening of the vocal cords). They allow the athlete to train harder and longer at any given period.

Anabolic steroids are mostly testosterone (male sex hormone) and its derivatives. Examples of anabolic steroids include: testosterone, dihydrotestosterone, androstenedione (andro), dehydroepiandrosterone (DHEA), clostebol, nandrolone.

These substances can be injected or taken as pills. Anabolic steroids have a number of possible and well-known side effects, including: jaundice and liver damage because these substances are normally broken down in the liver; mood swings, depression and aggression because they act on various centers of the brain.

In males, the excessive concentrations interfere with normal sexual function and cause baldness, infertility and breast development.

In females, the excessive concentrations cause male characteristics to develop and interfere with normal female functions. The drugs can stimulate hair growth on the face and body, suppress or interfere with the menstrual cycle -- possibly leading to infertility; thicken the vocal cords, which causes the voice to deepen, possibly permanently; interfere with the developing fetus in pregnant women.

Beta-2 Adrenergic Agonists

When inhaled, beta-2 agonists relax the smooth muscle in the airways of asthma patients by mimicking the actions of epinephrine and norepinephrine, substances that are secreted by sympathetic nerves. However when injected into the bloodstream, these drugs can build muscle mass (anabolic effect) and reduce body fat (catabolic effect). The anabolic effect appears to directly affect building proteins in the muscles, which is independent of nervous or cardiovascular effects. Some examples of beta-2 agonists include:

  • Clenbuterol
  • Terbutaline
  • Salbutamol
  • Fenoterol
  • Bambuterol

Some of these substances are permitted in inhaler forms with written medical consent.

The major side effects include: nausea, headaches and dizziness because these substances constrict blood vessels in the brain; muscle cramps because they constrict blood vessels in muscles; and rapid heartbeats or flutters because they stimulate heart rate. We'll look at human growth hormones in the next section.

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Human Growth Hormones

Performance-enhancing drugs are the frequent subject of controversy in the sporting world.
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Human growth hormones include human chorionic gonadotropin (HCG), luteinizing hormone (LH) and human growth hormone (HGH), insulin and insulin-like growth factor (IGF-1).

Human Chorionic Gonadotropin (HCG)

HCG is a naturally occurring protein hormone produced by the developing fetus and detected in most home pregnancy kits. HCG stimulates the development of natural male and female sex steroids. The increase in testosterone levels in males by the use of HCG would stimulate muscle development as with anabolic steroids. HCG is not banned in female athletes because it would not lead to muscle development and might naturally occur in high levels if the athlete is pregnant. The side effects of HCG in males are the same as those of anabolic steroids.

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Luteinizing Hormone (LH)

LH is a peptide hormone secreted by the pituitary gland at the base of the brain. LH is important for maintaining normal levels of testosterone in the male and estrogen in the female. In women, a surge of LH during mid-cycle is the signal for ovulation. In men, excess LH or artificial LH derivatives (tamoxifen) would increase testosterone levels and have the same effects as anabolic steroids. Although no general side effects exist, any possible side effects might be similar to those of anabolic steroids.

Human Growth Hormone (HGH)

HGH is a naturally occurring protein hormone produced by the pituitary gland and is important for normal human growth and development, especially in children and teenagers. Low HGH levels in children and teenagers result in dwarfism. Excessive HGH levels increase muscle mass by stimulating protein synthesis, strengthen bones by stimulating bone growth and reduce body fat by stimulating the breakdown of fat cells. Use of HGH has become increasingly popular because it is difficult to detect. Side effects include:

  • Overgrowth of hands, feet, and face (acromegaly) because of the increased muscle and bone development in these parts
  • Enlarged internal organs, especially heart, kidneys, tongue and liver
  • Heart problems

Insulin-Like Growth Factor (IGF-1)

IGF-1, which is also called somatomedin-C, is a naturally occurring protein that helps in the action of HGH. It also stimulates protein synthesis and reduces fat. Excessive IGF-1 would increase muscle and bone mass as HGH does. Side effects include low blood sugar (hypoglycemia) and other side effects similar to HGH.

Insulin

Insulin is a natural protein hormone produced by the pancreas, which is important for metabolism of sugars, starches, fats, and proteins. It is necessary for the treatment of juvenile (Type 1) diabetes. In athletes, insulin combined with anabolic steroids or HGH could increase muscle mass by stimulating protein synthesis. Side effects are mainly low blood sugar associated with shaking, nausea and weakness, but excessive hypoglycemia can lead to coma and death.

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Increasing Oxygen in Tissues

Ken Caminiti, shown in file photo from a 1998 game with the San Diego Padres, died of a heart attack in 2004 at age 41. Caminiti, the 1996 National MVP, admitted he used steroids during his career that ended in 2001.
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In addition to taking drugs that build mass and strength, some athletes take drugs and engage in practices that increase the amount of oxygen in tissues, including protein hormones, artificial oxygen carriers and blood doping.

Protein Hormones

Erythropoietin (EPO) is a naturally occurring protein hormone that is secreted by the kidneys during low-oxygen conditions. EPO stimulates the bone marrow stem cells to make red blood cells, which increase the delivery of oxygen to the kidney. Endurance athletes, such as those who compete in marathons, cycling or cross-country skiing, can use EPO to increase their oxygen supply by as much as 7 to 10 percent. EPO is difficult to detect. The increased red cell density caused by EPO, however, can thicken the blood. The thickened blood, which is more like honey than water, does not flow through the blood vessels well. To pump the thickened blood, the heart must work harder, which increases the chances of heart attack and stroke.

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Artificial Oxygen Carriers

Artificial oxygen carriers are man-made substances that can do the work of hemoglobin, the oxygen-carrying protein in your blood. Doctors use them to treat breathing difficulties in premature infants, patients with severe lung injuries and deep-sea divers. They include substances such as perfluorocarbons, synthetic- or modified-hemoglobins and liposome-encased hemoglobins (artificial red cells). It is not clear how they benefit athletes. Possible side effects include immune-system problems, cardiovascular problems, iron overload and kidney damage.

Blood Doping

Blood doping is the practice of infusing whole blood into an athlete in order to increase oxygen delivery to the tissues. A similar effect can be achieved by training at high altitudes. An athlete who infuses his own blood may cause infection or cardiovascular problems because of the increased blood volume (high blood pressure, blood clots, heart failure and stroke). An athlete who uses someone else's blood runs the risk of acquiring viral infections such as HIV/AIDS.

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Masking Pain

Along with training and performing to be a world-class athlete comes the pain of injuries. Sometimes, athletes try to mask their injury pain with drugs, including narcotics, protein hormones and local anesthetics.

Narcotics

Narcotics are used to treat pain and include substances such as morphine, methadone, Vicodin, Percocet and heroin. Narcotics are highly addictive, and the "high" associated with their use can impair mental abilities such as judgment, balance and concentration. Also, athletes who continue to compete with an injury run the risk of further damage or complications.

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Protein Hormones

Adrenocorticotropic hormone (ACTH) is a naturally occurring protein hormone that is secreted by the pituitary gland and stimulates the production of hormones from the adrenal cortex. These adrenal cortex hormones are important in reducing inflammation in injuries and allergic responses. So, by using ACTH to stimulate internal adrenal cortex hormones, an athlete could mask an injury. Possible side effects include stomach irritation, ulcers, mental irritation and long-term effects (weakening bones and muscles).

Local Anesthetics

Local anesthetics, like those your dentist or doctor use, are used to mask pain in the short-term without impairing mental abilities. They include novocaine, procaine, lidocaine and lignocaine. Athletes may use them so that they can continue to compete while injured. The major problem with their use is the possibility of further aggravating an injury.

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Stimulants, Relaxants and Weight Control

Athletes sometimes use drugs to cope with stress and fatigue.
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Many athletes live within strict social and dietary guidelines. To cope with stress, general fatigue and weight gain or loss, many athletes turn to stimulating, relaxing and weight-controlling drugs.

Stimulants

Stimulants are generally used to help athletes stay alert, reduce fatigue and maintain aggressiveness. They act on the body to make the heart beat faster, the lungs breathe faster and the brain work faster. Stimulants include caffeine, amphetamines and cocaine. Possible side effects include nervousness, shaking, irregular heartbeats, high blood pressure, convulsions and even sudden death.

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Relaxants

Relaxants come in various forms, including alcohol, prescriptions such as beta-blockers, and cannabinoids such as marijuana.

  • Alcohol is commonly used to help people relax because it reduces activity in the brain and nervous system. While it may help an athlete relax and cope with the pressures of competition, it can also significantly impair mental functions (judgment, balance, coordination). It is restricted in the Olympics and banned altogether in certain events.
  • Beta-blockers are commonly prescribed to treat high blood pressure by causing the heart to slow down and blood vessels to relax. Athletes who require steady hands in competition, such as those competing in archery or shooting events, may use them. Possible side effects include lower than normal blood pressure (hypotension), slow heart rate and fatigue.
  • Cannabinoids, mainly marijuana and hashish, have no clinical value, but have recently been used for relieving pain in terminally ill cancer patients. Cannabinoids cause hallucinations, induce drowsiness, increase the heart rate and impair mental functions (judgment, balance, coordination and memory).

Weight Control

Diuretics are commonly prescribed to treat high blood pressure and are often found in diet pills. Diuretics act on the kidney to increase the flow of urine. They are used by athletes whose events have weight restrictions -- sports like weightlifting, horse racing and rowing. Diuretics are also used to mask the use of other drugs. Because they increase the amount of urine produced, they dilute the concentration of other drugs in the urine. Possible side effects include dehydration, dizziness, cramps, heart damage and kidney failure.

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Masking Drug Use

Lyle Alzado of the Los Angeles Raiders looks on at a 1990 training camp in Oxnard, California. He died of brain cancer in 1992. Alzado believed - though it wasn't proven -- the cancer was caused by steroids and HGH, which he used for more than 20 years.
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As previously mentioned, diuretics can be used to reduce the presence of drugs in urine samples. Other compounds, including epitestosterone, plasma expanders and secretion inhibitors, can be used to reduce the presence of banned substances in blood samples.

Epitestosterone

Epitestosterone is a biological form of testosterone that does not enhance performance. Drug tests for testosterone typically measure the ratio of testosterone to epitestosterone (T/E ratio). An athlete can inject epitestosterone, lower the T/E ratio and hide the use of testosterone. By itself, epitestosterone has no real harmful side effects.

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Plasma Expanders

Plasma expanders are substances that are used to increase the fluid component of blood. They are used to treat victims of shock, trauma and surgery. Athletes can use these substances to dilute the concentration of banned substances (EPO) in their blood. Most side effects include moderate to severe allergic reactions.

Secretion Inhibitors

Many drugs and foreign substances have structures that are shaped like organic acids. In the body, these organic acids are removed by a protein in the kidney that transports organic acids. If this protein can be blocked, then these drugs or foreign substances would not appear in the urine. Doctors use these inhibitors to treat gout. However, the drugs can be used to manipulate the results of urine drug tests. Possible side effects include nausea, vomiting, allergic reactions and kidney problems.

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Testing Athletes for Drug Use

Some athletes find the temptation of performance-drugs too hard to resist.
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The majority of drugs that can be used by athletes can be detected in samples of urine. An athlete is told by a drug control officer to submit a urine sample for testing. The sample is then sent to a laboratory for analysis and the results are reported back to the governing athletic agency. For some substances, blood samples may be required.

Gas Chromatography and Mass Spectrometry

Gas chromatography and mass spectrometry are the most common methods of chemical analysis. These tests can be done on urine and blood samples. In gas chromatography, the sample is vaporized in the presence of a gaseous solvent and placed through a long path of a machine. Each substance dissolves differently in the gas and stays in the gas phase for a unique, specific time, called the retention time. Typically the substance comes out of the gas and is absorbed on to a solid or liquid, which is then analyzed by a detector. When the sample is analyzed, the retention time is reported or plotted to create a chromatogram. Standard samples of drugs are run, as well as the urine/blood samples, so that specific drugs can be identified and quantified in the chromatograms of the urine/blood samples.

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In mass spectrometry, samples are blown apart with an electron beam and the fragments are accelerated down a long magnetic tube to a detector. Each substance has a unique "fingerprint" in the mass spectrometer. Again, standard samples are run for identification and quantification of drugs in the urine/blood samples.

Immuno-Assays

Some substances (such as HCG, LH, ACTH) can be measured in urine samples using an immuno-assay. In this test, the sample is mixed with a solution containing an antibody specific to the tested substance. An antibody is a protein that binds only a specific substance and is how the body recognizes foreign substances. The antibody in the test is usually tagged with a fluorescent dye or radioactive substance. The amount of fluorescent light or radioactivity is measured and is related to the concentration of the tested substance in the sample.

Tests for Performance Enhancing Drugs

Tests for EPO have been recently developed. One EPO test looks at the size of red blood cells. It has been noticed that synthetic EPO produces red blood cells that are smaller and bind more iron then natural EPO. So, the size and iron content of red blood cells from a blood sample are analyzed to determine whether an athlete has used EPO.

In 2008, the International Cycling Union introduced a blood passport practice. The anti-doping procedure monitors the characteristics of an athlete's blood over a period of time. For example, hematocrit levels (the percentage of red blood cells to the total volume of whole blood) are tracked for abnormal spikes. Red blood cells carry oxygen -- a spike in hematocrit levels would, therefore, enhance a cyclist's performance and indicate doping.

Until approximately 2010, there were no reliable tests for HGH. But a blood-testing innovation proved to be effective enough to lead rugby officials in Britain to suspend an athlete for violating the ban on Human Growth Hormone in February of that year. The National Football League is now advocating HGH testing, though the NFL Players Association has voiced its opposition [source: ESPN].

Although there is little statistical evidence on how widespread doping is, athletes and coaches stress that most competitors do not take drugs. Nonetheless, drug testing is becoming an increasingly integral part of sports competitions. As new performance-enhancing drugs are developed, new tests are developed to detect these drugs, and the struggle to keep sports clean continues indefinitely.

For more information on performance-enhancing drugs, drug testing, and related topics, check out the links on the next page.

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Lots More Information

More Great Links

  • Bicycle.net. “Anti-doping Scientist Hails Blood Passport Impact.” Mar 10, 2009. (Aug 26, 2010). http://www.bicycle.net/2009/anti-doping-scientist-hails-blood-passport-impact
  • ESPN NFL. “NFL, union at odds over HGH test.” Feb. 24, 2010 (Sept. 3, 2010) http://sports.espn.go.com/nfl/news/story?id=4940922
  • Harding, Luke. The Guardian. “Forgotten victims of East German doping take their battle to court.” Nov. 1, 2005. (Sept. 1, 2010). http://www.guardian.co.uk/sport/2005/nov/01/athletics.gdnsport3
  • Klion, Mark. Personal correspondence. Aug 25, 2010.
  • Mirkin, M.D., Gabe. Personal interview. Aug 7, 2010.
  • Maske, Mark. The Washington Post.“NFL favors blood-testing players for HGH.” Feb. 23, 2010. (Aug 26, 2010). http://views.washingtonpost.com/theleague/nflnewsfeed/2010/02/nfl-favors-blood-testing-players-for-HGH.html
  • Shipley, Amy. The Washington Post. “This is very clever chemistry.” Dec. 4, 2004. (Aug 5, 2010). http://www.washingtonpost.com/wp-dyn/articles/A33774-2004Dec3_2.html
  • SI.com. “How We Got Here: A timeline of performance-enhancing drugs in sport.”Mar 11, 2008. (Aug 26, 2010). http://sportsillustrated.cnn.com/2008/magazine/03/11/steroid.timeline/index.html
  • Sports Injury Bulletin “Performance Enhancing Drugs in Sport.” Ryan Shulman. (Sept. 1, 2010). http://www.sportsinjurybulletin.com/archive/performance-enhancing-drugs

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