A-Rod, Lance Armstrong, Jose Canseco, Rashard Lewis, Shawne Merriman. The list of superstar athletes accused of -- or admitting to -- taking performance-enhancing drugs is almost as impressive as the number of sports in which they compete. It's not just weightlifting, baseball and cycling. It's football, track and field, swimming, soccer and basketball. And it's not restricted to males -- or to professionals. Just ask former Olympic track star Marion Jones. Or the nine high school athletes in Texas caught using performance-enhancing drugs during the 2011-2012 academic year.
Once athletes like these would have found little in their medicine cabinets to help them get a leg up on the competition. Most would have turned to anabolic steroids, synthetic steroid hormones made to resemble testosterone. Chemicals in this special class of steroids, which include testosterone, androstenediol, androstenedione, nandrolone and stanozolol, increase muscle mass and strength, but tests can detect them easily.
In the 1980s and '90s, however, other doping alternatives started appearing on the scene. Now there are numerous performance-enhancing drugs, or PEDs, that aren't classified as steroids. Their effects are quite varied, and some only benefit certain athletes playing certain sports. All of which makes it extremely tricky for regulatory agencies like the International Cycling Union and the World Anti-Doping Agency to keep up -- and to keep drugs out of competing athletes.
On the next few pages, we'll present 10 of these non-steroid PEDs, looking at their modes of action and their side effects. Most entries will be individual drugs, but in a few cases, we'll consider a class of compounds and include some notable examples.
Let's kick everything off with EPO -- the drug that ushered in the modern era of doping.
Red blood cells carry oxygen throughout the body, so it makes sense that if an athlete can increase his red blood cell count, he'll deliver more oxygen to his muscles and perform at a higher level. Blood doping -- removing and preserving a supply of blood so it can be returned, via transfusion, to the body right before competition -- is one way to do this, but it's messy and time-consuming. Taking erythropoietin, or EPO, increases red blood cell production without the need for transfusions. The kidneys make the hormone naturally, although people with severe kidney disease don't have enough. That's what the biotechnology firm Amgen was looking to address when it introduced synthetic EPO in 1985. By the 1990s though, cyclists and other endurance athletes had discovered that they could train longer and harder if they took the drug regularly.
Not surprisingly, taking EPO comes with significant risk. Yep, significant risk. Studies have shown that it increases the risk of events such as stroke, heart attack and pulmonary edema. One theory suggests that the drug thickens the blood to the point where it produces fatal clots. Such complications may have contributed to the deaths of at least 20 cyclists by 2000, increasing the urgency to develop a reliable test to detect EPO [source: Zorpette].
In 2007, anti-doping agencies introduced the concept of a "biological passport," a record of the substances found normally in an athlete's blood and urine, created by repeated sampling over time. By comparing the results of a blood test administered right before a competition to the passport, officials can determine if an athlete has been using EPO or other performance-enhancing drugs.
Human Growth Hormone
Like EPO, human growth hormone (hGH) occurs naturally in the body. In fact, the pituitary gland, the pea-sized organ located at the base of the brain, produces hGH to stimulate growth in children and adolescents and to increase muscle mass in adults. As soon as synthetic hGH became available as a prescription medication in 1985, when the U.S. Food and Drug Administration approved its use for a number of diseases that retard growth or cause muscle deterioration, athletes began eyeing it as a doping agent. They figured it could mimic the muscle-building effects of anabolic steroids. At first, the high cost of the medication discouraged widespread use as a PED, but, as the saying goes, where there's a will to win, there's a way. The 1996 Olympic Games have been called the "hGH Games" because of the rampant use of the drug among competitors.
Today, athletes get hGH from a variety of sources: doctors who are willing to write prescriptions for off-label use, Internet pharmacies, illicit Web sites for performance-enhancing drugs and clinics that use the hormone to reverse the effects of aging. A few even turn to black-market dealers that collect hGH from human cadavers. It's a risky gamble, especially considering the lack of scientific evidence to suggest that hGH actually increases athletic performance. Oh, and don't forget the side effects. Using hGH has been linked to a variety of medical conditions, including joint pain, muscle weakness, fluid retention, carpal tunnel syndrome, cardiomyopathy and hyperlipidemia [source: Mayo Clinic].
Another performance-enhancing drug that made the 1996 Olympic Games memorable for the wrong reason was bromantan, a sort of stimulant and masking agent combined in one. Several Russians tested positive for the drug, which was not, at the time, included on the International Olympic Committee's (IOC's) list of banned substances. That didn't stop the IOC from disqualifying several Russian athletes, stripping medals from two and, ultimately, blacklisting bromantan based on its performance-enhancing effects.
Those effects are quite unlike any other PED. Russian army doctors developed bromantan as a stimulant, something they could give to soldiers and cosmonauts to help them feel more alert and fight fatigue. Soon after, Russian athletes got hold of the drug, reporting that it helped them perform at peak levels without feeling exhausted. But the story appears more complicated.
Some anti-doping officials believe bromantan can hide the abuse of more serious drugs, such as steroids. This is known as masking, and it's just one more way athletes can find a way to cheat. For example, the masking agent probenecid stops the excretion of steroids for a few hours, decreasing the concentration of steroids in the urine. The exact masking mechanism of bromantan, however, remains unclear. That doesn't diminish the drug's appeal among athletes, who believe its stimulant/masking effects give them a doping double whammy.
Bromantan gained popularity because it appealed on multiple fronts. But stimulants by themselves function reasonably well as performance-enhancing drugs. Athletes take stimulants to improve endurance, reduce fatigue and increase aggressiveness. And someone trying to qualify for a lower weight class may rely on stimulants for their ability to suppress appetite.
You may think first of amphetamines -- prescription-only "speed" pills -- when you hear of this class of drugs, but not all stimulants require a physician's signature. Ephedrine, for example, is available over the counter in many applications outside of dietary supplements (dietary supplements containing ephedrine are illegal in the U.S.). In these applications, the drug functions as a decongestant, a treatment for menstrual or urine-control problems or a medication to counteract low blood pressure associated with anesthesia. Athletes, of course, aren't interested in these effects. They grab ephedrine for an extra boost of energy despite the warnings that the drug can cause high blood pressure, dizziness, shortness of breath and cardiac arrhythmia.
Along with bromantan, which we just talked about, diuretics have long served as a way to mask steroid use. A diuretic is any drug that affects kidney function, resulting in increased urine output. The "water pill" chlorthalidone, for example, prevents fluids and salts from being reabsorbed into the kidney tubules and returned to the blood. As a result, more water leaves the body. Acetazolamide works by blocking the uptake of sodium bicarbonate in the kidney tubules. Upon excretion, the bicarbonate ion carries out water, sodium and potassium.
In patients with certain conditions, such as heart disease, diuretics can help control high blood pressure and fluid retention. But athletes who take anabolic steroids pop diuretics to dilute their urine, which decreases steroid concentration and makes it much more difficult to detect. (Of course, athletes can be tested for diuretics though, too.) Weightlifters and boxers may also down water pills to expel large amounts of fluid, which qualifies them to compete in a lower weight category. Then, right before the match, they stop taking the pills to return to their heavier fighting weight, giving them an advantage against their opponents. Of course, an athlete taking diuretics may also get dizzy, become dehydrated or experience a severe drop in blood pressure -- symptoms that make it hard to fight with the eye of the tiger.
Sometimes, a drug's effect on athletic performance depends on how it's administered. Take the beta2-agonist albuterol as an example. This well-known asthma drug works by relaxing the muscles lining the bronchial tubes, allowing more air to flow into the lungs. Athletes with asthma (believe it or not, elite athletes tend to have higher rates of asthma than people in the general population) generally use inhaled albuterol to treat their symptoms, allowing them to compete without shortness of breath [source: Kindermann].
But what about athletes who don't have asthma? Could they suck in a few shots of albuterol and increase their lung capacity? According to the research, this performance-enhancing effect simply doesn't exist. In a review article published in a 2007 issue of Sports Medicine, the authors found that, in 17 of 19 clinical trials involving non-asthmatic competitive athletes, the performance-enhancing effects of inhaled beta2-agonists could not be proved. All bets are off, however, when an athlete takes albuterol orally or by injection. When administered in this fashion, albuterol has been found to have anabolic properties, which means it can help build muscle like steroids.
Another orally ingested beta2-agonist known as clenbuterol, or clen, packs an even bigger punch than albuterol. Athletes in several sports -- cycling, swimming, baseball and soccer -- have tested positive for clenbuterol use, although many have claimed that the drug could be traced to contaminated food. While clenbuterol has historically been given to animals to produce leaner meat, it has been banned for use in meat since 1991 in the U.S. and since 1996 in the European Union.
Ever taken ibuprofen (Advil or Motrin) to reduce fever, pain or inflammation? If so, then you've benefited from a nonsteroidal anti-inflammatory drug, or NSAID. NSAIDs work by inhibiting the synthesis of prostaglandins, chemicals that promote inflammation by dilating blood vessels and letting blood flow into body tissue. Prostaglandins are made by two enzymes that function the same but have different chemical signatures: cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). Some NSAIDs work by blocking the action of COX-2 or both COX-1 and COX-2. Ibuprofen falls in the latter category.
Here's where it gets interesting. Athletes have been taking ibuprofen for years to help recover from vigorous exercise. But some studies now indicate that chronic use of the medication may actually provide a performance-enhancing effect. A research team at the Human Performance Laboratory in Ball State University found that men and women who took a daily dose of ibuprofen were able to build substantially more muscle than those taking a placebo. The question remains whether ibuprofen is actually adding more protein to the muscle or simply reducing the pain often associated with a workout, allowing people to exercise longer and recover faster. Either way, using ibuprofen or other NSAIDs to enhance performance can be risky, as the drug can damage the lining of the gastrointestinal tract.
It's easy to see why baseball players, cyclists, boxers, swimmers and runners sometimes turn to pharmaceuticals for a competitive advantage. These sports require deep reservoirs of muscle strength and endurance -- the very targets of the most popular performance-enhancing drugs. But what about sports like pistol shooting or archery? They certainly demand a keen eye, a steady hand and rock-solid concentration but not Herculean strength. Even so, athletes in these sports may take PEDs. In fact, two North Korean pistol shooters competing in the 1998 Olympic Games in Seoul, South Korea, tested positive for taking propranolol.
As it turns out, propranolol belongs to a class of drugs known as beta blockers, which nonathletes use to control hypertension. Beta blockers work by blocking the effects of epinephrine, a hormone secreted by the adrenal glands that increases blood circulation. People who take beta blockers have a slower heart rate and more relaxed blood vessels, conditions that help reduce blood pressure. But the drugs have an interesting secondary effect: They also mask anxiety by diminishing nervous sweat and trembling, which is exactly why marksmen are drawn to the drugs. If they have a steadier hand, they can perform better in competition. In addition to propranolol, beta blockers include atenolol, acebutolol, alprenolol, bisoprolol and metoprolol, all of which are banned in pistol shooting and archery.
In June 2012, outfielder Marlon Byrd faced a 50-game suspension after testing positive for tamoxifen, a substance banned from Major League Baseball and many other sports. Why would an athlete want to take a drug normally used by breast-cancer patients? The answer lies in some interesting biochemistry.
Many breast cancers have receptors for estrogen, a hormone that promotes the development and maintenance of female characteristics of the body. When estrogen molecules fit into these receptors, like a key fitting into a lock, the malignant cells become activated. Tamoxifen blocks these estrogen receptors, interfering with the cancer's ability to grow and develop. This is why scientists refer to tamoxifen as an anti-estrogenic agent.
Now let's turn our attention to a home-run slugger taking steroid injections -- usually synthetic testosterone -- to grow his muscles. Large doses of the male hormone cause the body to produce additional estrogen. This in turn can result in enlarged breasts, a feature that most power hitters find unappealing. To counteract the effects of estrogen and mask their steroid use, these players may opt to take tamoxifen. That means anti-estrogens don't really enhance performance, but, because they alleviate symptoms of PEDs, they appear on the World Anti-Doping Agency's list of more than 200 banned substances and methods.
There's one popular performance-enhancing drug that won't land an athlete in hot water with anti-doping agencies. It's creatine, and it's not a drug at all, at least according to the U.S. Food and Drug Administration (FDA). Because it's an over-the-counter supplement, creatine is regulated like a food by the FDA, which means creatine manufacturers don't conform to the same standards as pharmaceutical companies.
That doesn't diminish its appeal. Creatine remains one of the most widely used substances among athletes, especially football players, sprinters and weightlifters. Why? Because a growing body of evidence suggests that the chemical does indeed deliver athletic benefit by boosting levels of adenosine triphosphate (ATP) in muscle tissue. ATP powers muscle contractions, so increasing ATP levels is clearly a desirable thing. But the benefit seems to be limited to short, high-energy bursts of muscle activity, not long, slow burns common in endurance athletes.
Interestingly, the liver produces creatine every day, so taking supplemental creatine is a little bit like adding extra frosting to an already-frosted cake. Not only that, excess amounts of the chemical exit the body through the kidneys, making it unnecessary to power-gulp creatine tablets with the idea that doing so will deliver extra benefit. And one final cautionary note: In some cases, supplements have been known to pick up contaminants from other substances, including performance-enhancing drugs. Try explaining that one to the team doctor.
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Author's Note: 10 Performance-enhancing Drugs That Aren't Steroids
Once upon a time, when I considered trying out for high-school football, I tried to bulk up my scrawny, 100-pound frame by drinking a strange protein elixir poured from a can. The stuff was horrible, and I gave up. What's scary now is how many young athletes seem willing to take far more powerful drugs with little thought about the consequences.
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