Education integral to prevention of performance-enhancing substance use

Throughout history, athletes have sought methods to give them an extra competitive edge. Some athletes have achieved this through good nutrition, innovative training or equipment, while others have taken substances to alter their bodies, improve their cognition or heighten their abilities to improve the chance of victory.

Athletes in ancient Greece consumed special diets and potions in the hope of improving their results. In the 1900s, marathon runner Thomas Hicks took a dose of strychnine, among other things, nearly dying in his bid to win a gold medal at the 1904 Olympics. In more recent times, the headlines are littered with the names of elite athletes who competed with the aid of performance-enhancing substances. However, athletes who use performance-enhancing substances are the exception, not the rule.

“It is clear that a vast majority of athletes in most sports do not use performance-enhancing drugs,” said Gary A. Green, MD, clinical professor in the UCLA division of sports medicine, Los Angeles, and medical director of Major League Baseball.

“We should not lump the minority who try to cheat with those who play by the rules. Unfortunately, it is the ones who get caught cheating who get the headlines,” Green told Orthopedics Today. “You do not get any headlines for not taking something.”

By educating their patients, orthopedists can play a critical role in the prevention of performance-enhancing substance use. First, orthopedists need to educate themselves: what are the more common substances and their potential adverse events, the “ins and outs” of athlete testing and the red flags to watch for in patients suspected of taking these agents.

According to the World Anti-Doping Agency (WADA), the following agents are prohibited at all times, both in and out of competition:

• anabolic agents;
• peptide hormones, growth factors, related substances and mimetics;
• beta-2 agonists;
• hormone and metabolic modulators; and
• diuretics and masking agents.

Because it contains some growth factors, the practice of injecting platelet-rich plasma (PRP) was on the WADA’s banned list, but it is no longer prohibited.

Prevalence of usage

Athletes who dope do so in secret, so the prevalence of performance-enhancing substance use among professional and high school athletes is difficult to gauge, Green told Orthopedics Today.

“A recent study shows that about 10% or 11% of high school kids are using human growth hormone,” Green said. “I would be skeptical of that because human growth hormone, even when you go to one of these anti-aging clinics, is expensive,” Green said. “Several hundreds of dollars per course, and I would bet that it is probably out of the price range for most high school students.”

Results of a 2013 survey conducted by the CDC revealed that 3.2% of high school students reported using anabolic steroids, in either pill or injectable form, without a prescription at least once.

High school boys are more likely than girls to take anabolic steroids, according to data from the Monitoring the Future survey. In 2013, the annual prevalence rates for boys were as follows: grade 8 (0.7%), grade 10 (1.3%) and grade 12 (2.2%) compared with girls in grades 8 (0.4%), 10 (0.5%) and 12 (0.7%).

Obtaining data on the prevalence of performance-enhancing substance use among elite and professional athletes is more difficult.

“There are no good data out there because no one is going to readily admit it,” said Jeremy Frank, MD, an orthopedic surgeon at Joe DiMaggio Children’s Hospital, and a team physician for the U.S. National Wrestling Team. “People always make best guesses as to what percentage of athletes in a sport are taking [performance-enhancing substances], but to have a specific number I would think would be near impossible.”

Data is available from the National Collegiate Athletic Association regarding usage rates among college athletes. These survey results indicated that in 2009, 0.4% of respondents reported using anabolic steroids, a 0.7% decrease from 2005. Less than 1% of respondents reported taking ephedrine in 2009.

At-risk athletes

Identifying the athletes who are most likely to dope may help prevention efforts.

“It is a whole spectrum of athletes, but where we see the testosterone-based drugs are in the older athletes hitting the twilight of their career who want to maintain that competitive advantage,” Frank said. He noted that younger athletes may be more prone to using human growth hormone.

Younger athletes are at risk for performance-enhancing substance use because they often fail to consider the long-range effects of these substances.

“If you tell an athlete ‘If you take this, you are going to have a heart attack when you are 50 [years old],’ that is a hard concept when you are 21 [years old],” Green said.

It is important to note that performance-enhancing substance use is not limited to professional or elite athletes. An Internet search for human growth hormone or anabolic steroids will yield millions of hits, Green said. “There is only a small number of professional athletes and a relatively small number of college athletes in this country, so they are clearly not just catering to professional athletes.”

Green said one recent study found 40% of high school boys who used anabolic steroids did not play on an organized school team. “These drugs have broken out way beyond the athletes,” he said.

In fact, non-athletes may be at highest risk. “They are not subject to drug testing, so no one is looking at them,” Green said. “An orthopedist should not just assume that because someone is not playing an organized sport that they are not at risk for anabolic steroid or other performance-enhancing drugs.”

Serious adverse events

When educating patients about these agents, it is important to communicate that all performance-enhancing substances have adverse events, and although some are simply annoying, others can be life-threatening.

For example, anabolic steroids have a variety of risks affecting multiple organ systems, according to Michael G. Ciccotti, MD, chief of the division of sports medicine at the Rothman Institute and head team physician for the Philadelphia Phillies and Saint Joseph’s University. Steroids can affect the cardiovascular system, increasing the risk of myocardial infarction and stroke, and lowering HDL while increasing LDL, he said. Steroids can influence the hepatobiliary system, and can promote the growth of benign and malignant liver tumors. Steroids also can impact other body systems.

“We [can] see a decrease in the levels of immunoglobulins that allow us to protect against certain types of infection,” Ciccotti said.

Furthermore, anabolic steroids can cause musculoskeletal problems, causing tendon degeneration and rupture. In young athletes, they can promote premature closure of the growth plates. These substances can decrease testosterone levels, cause testicular atrophy, baldness and acne, according to Ciccotti.

“Lastly, there are the tremendous psychological effects; these athletes can be predisposed to violent behavior, to rage, [to] reckless behavior [and to] psychosis,” he said.

Although most stimulants are relatively benign, like caffeine, some can have detrimental effects, said Andrew M. Tucker, MD, medical director of sports medicine at Medstar Union Memorial Hospital in Baltimore, and head team physician for the Baltimore Ravens. Some stimulants may increase an athlete’s risk of heat stroke, if he or she is exercising in the heat.

Most concerning is that some stimulants negatively affect the cardiovascular system — raising blood pressure and potentially inducing arrhythmias, according to Tucker.

Although human growth hormone is similar to the body’s endogenous growth hormone, there is still the potential for serious adverse events.

“We sort of look at patients who have excess growth hormone and certainly, there is increased risk in the cardiovascular system with regard to high blood pressure and the potential for heart muscle disease,” Tucker said. “There is concern about increased risk for diabetes and effects on the endocrine system.” Human growth hormone also may increase the risk of tumors.

Some supplements can have adverse events, according to David G. Liddle, MD, assistant professor, Vanderbilt Sports Medicine, Vanderbilt Internal Medicine at Vanderbilt University in Nashville, Tenn. Body builders often use creatine to improve their “cut” appearance. “The trouble is that it can cause dehydration by drawing the water into the muscles and leaving them with lower blood volumes and more concentrated blood that can lead to problems with the kidneys or the heart,” he said. “Most of the time it is temporary kidney dysfunction as your kidneys just cannot process that much protein without damage to organ’s the filtration systems. However, the damage can be permanent.”

Many of the supplements containing protein, amino acids and vitamins are safe. “But the question is whether they help or not, especially in an athlete who has a well-balanced diet, who is getting all of those vitamins, minerals and calories as part of their diet,” Tucker said. “The old saying is, ‘They are making expensive urine.’”

Despite these risks, there is no clear evidence that these substances significantly improve performance, Ciccotti said. There is some evidence that suggests that the combination of anabolic steroids and strength training may facilitate gains in size and strength compared with athletes who are not using steroids; however, those gains are lost when the drugs are stopped, he said.

Red flags

“Orthopedists should be aware of the red flags that may indicate that a patient is using [performance-enhancing substances],” said Liddle. For example, with steroids, the athlete may have a sudden and dramatic increase in muscle mass accompanied by severe acne and increasingly aggressive behavior. Other red flags include unusual tendon ruptures “because the muscle got bigger faster than the tendon could handle the increased load, putting it at risk for failure,” Liddle told Orthopedics Today.

In men, physicians will see baldness and gynecomastia. In women, there may be genital changes, increased muscle mass and male patterned hair, whether baldness or growth.

Athletes may be taking human growth hormone if they suddenly develop dental problems like large gaps between their teeth and gain a large amount of weight in a short time, he said.

Testing

Performance-enhancing substance testing programs are an integral part of competition, ensuring fair play for all participants.

“The main reason we have these programs is not to catch the cheating athlete,” Green said. “It is to protect the clean athlete who wants to participate on a level playing field.”

But detecting these agents can be challenging. For instance, certain drugs have short half-lives, making them difficult to detect. “You cannot test people every day,” Green said.

There is no one test that can be used across all sports because the agents used differ.

“It is important to deal with each cohort, age group and sport individually,” Green said. For instance, endurance sports, which require the delivery of more oxygen to muscles, testing must detect substances that increase hemoglobin, such as erythropoietin. “Whereas in sports that do not demand a lot of aerobic activity, those types of things are not going to be as valued,” he said.

As new substances are developed, new tests must be designed to detect them.

“It is always a cat-and-mouse game,” Tucker said. “There are always people who are developing new products, designer products that are better able to evade detection. That is never going to stop.”

WADA and other organizations have responded to this issue by requiring random, in- and out-of-competition testing of both blood and urine.

Clearly, testing is an effective deterrent as is evidenced by the waning popularity of anabolic steroids. “The effectiveness of testing programs in the major professional sports and college level [athletics] has not eliminated [them], but probably has made widespread, heavy use of anabolic steroids much less common now than it was 20 years go,” Tucker said.

The players’ bodies are the proof that steroids are not as popular. “The bodies of 1970s and 1980s athletes who abused anabolic steroids were quite distinct,” Tucker said. “They had lots of muscle mass [and] little fat mass. We have large athletes in the National Football League [NFL], many of them well-muscled, but the kind of ‘cut’ appearance of our big players, is not seen now like it was in the 1970s and 1980s.”

Because it is not detectable with current urine screening, human growth hormone is harder to spot. Under its new collective bargaining agreement, the NFL will now perform random blood tests for human growth hormone. Tucker hopes that someday the technology will evolve to allow for urine screening for human growth hormone as well.

Orthopedist’s role

The most effective anti-doping programs incorporate education, which targets athletes, parents, trainers, therapists and coaches.

Orthopedists are in a unique position to help in this regard. “It becomes the job of the medical professionals, particularly the physicians, trainers and therapists who take care of these athletes to educate them,” Ciccotti said. “To educate them on all of the risks, on the rules that are clearly in place for these athletes on all of the levels and to provide advice on how to achieve optimal performance in terms of safe training, safe nutrition and safe conditioning and safe technique.”

Even physicians need to keep learning. “In my experience as a team physician and being involved with athletes now for over a quarter of a century, I really believe that the more we learn as medical professionals about these types of agents, the better we can educate the athletes about the risks,” Ciccotti said.

Orthopedists may be especially important in educating the adolescent population. “Adolescents see doctors probably less than any other age group,” Green said. “They just do not tend to get sick much. They do not have a lot of routine health-type things, and most of them have already had their vaccinations, so really, from about 10 years old to about 18 years, the do not see doctors very often. The one time they do see doctors is when they get hurt and they might see their orthopedist.”

With all of the attention given to athletes who dope, fighting performance-enhancing substance use may seem overwhelming. There will always be athletes willing to use them, and there will always be manufacturers willing to develop new agents that evade detection. But the fact is that the vast majority of athletes want to compete fairly. “What we hear from athletes over and over and over is that they want to play cleanly; they want clean sport,” Green said. The keys to success are education and ensuring fair, consistent, top-of-the-line scientific testing programs that are tough on athletes who use performance-enhancing substances and that elevate clean athletes, he said. – by Colleen Owens

References:

Fortier LA, et al. J Bone Joint Surg Am. 2010;doi:10.2106/JBJS/.I.01284.
www.cdc.gov/mmwr/pdf/ss/ss6304.pdf.
www.monitoringthefuture.org/pubs/monographs/mtf-overview2013.pdf.
www.ncaapublications.com/productdownloads/SAHS09.pdf.

For more information:

Michael G. Ciccotti, MD, can be reached at the Rothman Institute at Jefferson, 925 Chestnut St., 5th Floor, Philadelphia, PA 19107; email: mgcrij@aol.com.
Jeremy Frank, MD, can be reached at 1150 North 35th Ave., Suite 345, Hollywood, FL 33021; email: jefrank@mhs.net.
Gary Green, MD, can be reached at Pacific Palisades Medical Group, 15200 Sunset Blvd., Pacific Palisades; email: ggreen@mednet.ucla.edu.
David G. Liddle, MD, can be reached at the Vanderbilt Dayani Center for Health & Wellness, 1500 Medical Center Dr., Nashville, TN 37232; email:david.g.liddle@vanderbilt.edu.
Andrew M. Tucker, MD, can be reached at Medstar Union Memorial Hospital, 201 E. University Pkwy., Baltimore, MD 21218; email: andrew.tucker@medstar.net.

Disclosures: Ciccotti, Frank, Green, Liddle and Tucker report no relevant disclosures.

Are existing testing methods effective for the detection of performance-enhancing drug use?

Blood and urine testing are effective

I believe blood and urine testing technology is good for the detection of performance-enhancing drugs. We have always been able to test non-athlete patients for growth hormone excess by testing for the end-products of somatomedin or insulin-growth factor, since growth hormone is present in minute quantities in the blood stream.

We now have the capability of testing athletes, but it will require a blood draw rather than urine collection in many cases. For example, the designer anabolic steroid Clear had demonstrated that there may formulations that we do not know how to detect. But, I believe it is limited on any newly devised drugs that could escape detection.

There are some barriers to effective testing, including the costs of the lab testing, costs for administration and having chain-of-command specimen handling, limits on in-season and off-season testing (where athletes would know they cannot be tested for some period of time), and issues about blood drawing (invasive) vs. just urine collection.

We should focus our education efforts on the following: the health risks related to using performance-enhancing drugs; the sometimes limited improvements they can make in performance, with the exception of anabolic steroids; and the penalties in each sport for being detected. These efforts will hopefully deter many athletes from using performance-enhancing drugs.

Gary W. Dorshimer, MD, FACP, is clinical professor of medicine at Perelman School of Medicine at the University of Pennsylvania, and he is head team physician for the Philadelphia Flyers and a team internist for the Philadelphia Eagles.
Disclosure: Dorshimer reports no relevant financial disclosures.

Testing must be specific to each sport

There is no one test that can detect all the performance-enhancing drugs. Therefore, testing needs to be specific to the athlete’s sport. For example, an endurance athlete’s performance benefits from higher oxygen carrying capacity, and thus, might consider blood doping or erythropoietin to enhance their performance. An Olympic weightlifter might use an anabolic steroid to improve performance that requires strength over a short time interval. Other commonly used performance-enhancing drugs include amphetamine and human growth hormone (hGH).

Urine or blood tests, used singly or in combination, are used to detect banned substances. Some substances, such as amphetamines, are easily detected by urine testing while others, such as growth hormone, only can be detected by blood testing. Many factors determine the effectiveness of the testing, such as the biological aspect of the substance, whether a masking substance was consumed, the time of administration and the timing of the test. The window of detection varies depending on the drug. The timing of drug testing has been expanded in many sports and governing bodies, such as World Anti-Doping Agency (WADA), to include in-season and out-of-season random testing. As many of these drugs have a short window for detection, adding random screenings throughout the year provides a potential increase yield in detecting use.

Detecting hGH abuse is challenging for several reasons including it has a short half-life, variable GH secretion and minute urinary excretion. At this time there, is no urine test for hGH.

Testing to date for recombinant human GH (rhGH) include the GH Isoform Test, which is used to exploit the difference between recombinant GH and the endogenous GH. A second test, the biomarker test measures the biologic effects rather than the presence of hGH. The hGH isoforms and the biomarker tests are used in combination in detecting rhGH. GH-releasing factors have been used to induce the secretion of endogenous hGH and therefore, can mask detection of rhGH using the isoforms test. Anti-doping laboratories have developed mass spectrometry-based methods to detect GH-releasing factors.

Despite testing methods, the window of testing is limited. For example, the hGH isoforms test following rhGH use only detects the ratios between the hGH isoforms for 24 hours to 48 hours. Although the biomarkers test has a longer window of opportunity — up to 2 weeks — it is an indirect test and less specific. In the end, the blood needs to be collected within a limited time period to assure detection of the isoforms or biomarkers. RhGH testing and detection illustrates the challenges encountered in the testing process for detecting performance-enhancing drugs.

Global testing in 2012 reported by WADA reveal that the anabolic agents remain the most commonly found abused substance. Urine analyses compare levels of testosterone (T) to epitestosterone (E) for a T/E ratio. If the ratio exceeds four to one, doping is suggested. A more advance test is administered to confirm doping. However, some individuals, such as those from Asian descent, have a “doping with impunity” gene variant which means that they will not test positive even if doping. This may suggest a potential for abuse in this population. Therefore, a UGT2B17 (del/ins) genotyping method was developed and a T/E threshold was established on the basis of the UCT2B17 genotype.

PED testing methods are effective, but constantly being challenged by the production of new designer drugs and masking substances. The addition of year-round random testing increases the likelihood of collection during the biological window of detection.

Unfortunately, the use of these substances will continue as will the desire to avoid detection. Genetic makeup and gene doping present additional challenges to the drug testing organizations. There will be a continuous stream of new designer substances developed trying to stay a step ahead of the testing. New tests will need to be developed and the game goes on.

References:

Baumann GP, et al. Endocr Rev. 2012;33:155-186.
Green GA, et al. American Medical Association Journal of Ethics. 2014;16:547-551.
Pokrywka A, et al. Biol Sport. 2013. doi:10.5604/20831862.1059606.

Kathy Weber, MD, MS, is a team physician for the Chicago Bulls, Chicago White Sox, DePaul University and Malcolm X College.
Disclosure: Weber reports no relevant financial disclosures.