Module 4

Performance-Enhancing Substances: Recognizing Banned Substance Use and Abuse

Performance-enhancing drugs and dietary supplements have been around since the ancient Olympic
Games. Because of the ethical considerations relating to unfair advantage during competition and
the potential for adverse events, most athletic governing bodies have generated a list of substances
that are banned from national and international competition. Athletes caught using such substances
can be suspended or forced to forfeit their medals, or both. In situations in which the athlete tests
positive for a banned substance on repeated occasions, he or she risks a lifetime ban on participation
in the given sport. However, numerous nutritional supplements and ergogenic aids are permissible
and are frequently used by athletes to maximize performance enhancement. Often the use of these
substances is promoted on the basis of unfounded claims. Thus, it is imperative that the athlete
become informed about the legality of these substances, understand the potential risks associated
with consumption, and know whether results support the claims (i.e., what the efficacy is). Note
that, although an ergogenic aid can be any substance (this will be addressed in a subsequent section),
mechanical aid, or training method that improves sport performance, for the purposes of this
module the term refers specifically to pharmacological aids.

Athletes try to gain a competitive advantage by using supplements that are reputed to be ergogenic
but are not banned, or they may use banned substances in the belief that they can stay ahead of the
drug testers. The consequence is that athletes who would normally refrain from using these
substances may feel pressured to use them to stay abreast of their competitors. However, athletes
who are well informed can confidently ignore useless and possibly harmful products despite what
their fellow athletes claim. It may also be possible to steer athletes away from the use of banned
drugs if they are aware that competitors who cheat run a high risk of being detected.

Before athletes consider the use of any sport supplement or ergogenic aid, they should first devote
themselves to an individualized strength and conditioning program that adheres to the principles of
training and adequate nutrition. Only if they deal with these two issues effectively should athletes
consider using a sport supplement or ergogenic aid. Having made this decision, athletes need to seek
guidance to make sure that what they are considering is both legal and efficacious.

Ergogenic Aid

Another term used for performance-enhancing substances is ergogenic aid. Ergogenic aids are any
external influences that enhance performance. Ergogenic aids include but are not limited to
mechanical aids (ergogenic fabrics), training methodologies, synthetic derivatives of hormones
(pharmacological aids), dietary substances (nutritional), psychological aids, and physiological aids.

Ergogenic aids and/or substances are usually banned from athletic competition when a consensus is
reached that they may provide an unfair competitive edge or pose a significant health risk. This
prohibition does not need to be based on conclusive proof that a substance does anything
disadvantageous; it simply represents an agreement among administrators or clinicians that this may
be the case.

Anabolic steroids (specifically referred to as anabolic-androgenic substances, or AAS) have been

widely used as performance-enhancing substances. Performance-enhancing substances are drugs,
dietary/nutritional supplements, or medical procedures employed to create an advantage in the
performance of an athlete. These items are used for various reasons: building muscles, losing weight,
reducing pain, or gaining some specific advantage for improving performance (depending on the
particular event/activity). In the competition arena, some of these are generally banned because of
ethical and safety reasons, however some are allowed in restricted forms.

Use of performance-enhancing substances (AAS, nutritional substances) for purposes other than
treating medical conditions is controversial and, in some cases, illegal. Major sports organizations
have moved to ban the use of various categories of these substances, particularly anabolic steroids.

Types of Performance-Enhancing Substances

The two principal categories of performance-enhancing substances are hormones, and similar drugs
that mimic their effects, and dietary supplements. The distinction which separates a drug and a
dietary supplement is not intuitively obvious, however, it is important. The separation between a
drug and dietary supplement affects whether or not a product meets United States Food and Drug
Administration (FDA) approval for safety and effectiveness. If a product is not classified as a drug
or advertised as having therapeutic value, FDA regulations concerning its sale are relatively relaxed.
This means that any manufacturer can introduce a new dietary supplement to the market without
special approval. The FDA will not investigate its safety or effectiveness unless a health risk is
brought to the agencys attention (1). The FDAs definition of a drug encompasses substances that
change the bodys structure or function; this includes substances that stimulate hormone secretion.
In addition, if a substance looks like a medicine or is administered differently from the way in which
foods would normally be consumed, it may be classified as a drug (1).

Although the phrase performance-enhancing drug is used in reference to anabolic steroids or their
precursors, world anti-doping organizations apply the term broadly. The phrase has been used to
refer to several distinct classes of drugs.

Lean mass builders are used to drive or amplify the growth of muscle and lean body mass, and
sometimes to reduce body fat. This class of drug includes anabolic steroids, 2-agonists, selective
androgen receptor modulators (SARMs), and various human hormones, most notably human
growth hormone (HGH), as well as some of their precursors.
Stimulants are used by athletes to stimulate their bodies to perform at optimal levels, usually to
increase alertness, decrease fatigue, and increase aggressiveness. Examples include caffeine and
amphetamines.

Painkillers mask an athletes pain so they can continue to compete and perform beyond their usual
pain thresholds. Blood pressure is increased causing the cells in the muscles to be better supplied
with vital oxygen. Painkillers range from common over-the-counter medicines such as NSAIDs (e.g.,
ibuprofen) to powerful prescription narcotics.

Sedatives are sometimes used by athletes in sports like archery which require steady hands and
accurate aim, and also by athletes attempting to overcome excessive nervousness or discomfort.
Valium and marijuana are examples of sedatives.

Diuretics expel water from the body. They are often used by athletes such as wrestlers, to meet
weight restrictions. Many stimulants also have secondary diuretic effects.

Masking drugs are used to prevent the detection of other classes of drugs. These drugs evolve as
quickly as the testing methods, which is very quick indeed. A classic example is the use of
epitestosterone, a drug with no performance-enhancing effects, used to restore the testosterone-to-
epitestosterone ratio (a common criterion in steroid testing) to normal levels after anabolic steroid
supplementation.

The classification of substances such as performance-enhancing drugs is not entirely clear-cut and
objective. Certain prototype performance enhancers are universally classified as such (like anabolic
steroids), whereas other substances (like vitamins and protein supplements) are virtually never
classified as performance enhancers despite their significant effects on performance. As is usual with
categorization, there are borderline cases. Caffeine, for example, is considered a performance
enhancer by some athletic authorities but not others.

Ergogenic uses for anabolic steroids in sports and bodybuilding are controversial because of the
potential to gain an advantage and their adverse effects. The use of AAS is referred to as doping and
is banned by all major sporting bodies. For many years, AAS have been by far the most detected
doping in laboratories. In countries where AAS are controlled substances, there are often black
markets in which smuggled, or even counterfeit, drugs are sold to users.

Generally, dietary supplements are highly refined products that should not be confused as food.
They may not have any positive nutritional value; hence they are not referred to as nutritional
supplements. Carbohydrate loading to bolster glycogen stores before an athletic competition is sport
nutrition, but a tablet of a single purified amino acid not promoted for medicinal properties is a
dietary supplement. Until recently, the definition of dietary supplements included substances that
were not considered drugs by the FDA and did not fall into categories of normal foods or food
additives. Dietary supplements were regulated by the FDA to ensure that they were safe, wholesome
and that their labeling was truthful and not misleading. In 1994, the United States Congress passed
the Dietary Supplement Health and Education Act (DSHEA). With the new legislation, pre-market
safety evaluations are no longer required for products falling within this definition, although some
other safety provisions are still in effect. Dietary supplements can be sold if they do not present a
significant or unreasonable risk of illness or injury when used as directed on the label or under
normal conditions of use (if there are no directions) (1). Companies can also make claims
concerning the effects on the bodys structure and function as long as the manufacturers can show
that the statements are truthful and not misleading; this is a much less stringent requirement than
effectiveness claims made for drugs. Dietary
Supplements
The following defines which products can be sold as dietary supplements in the United States. A
product (other than tobacco) intended to supplement the diet must contain one or more of the
following dietary ingredients: vitamin, mineral, herb or other botanical, amino acid, a dietary
substance for use by humans to supplement the diet by increasing the total dietary intake, a
concentrate, metabolite, constituent, or extract. The product must also be intended for ingestion and
cannot be advertised for use as a conventional food or as the sole item within a meal or diet.

Brief History

The prevalence of performance-enhancing drugs in sports has increased in the 44 years since that
survey was completed. The desire to win is, naturally, ever present. At the same time, new research
and technologies have expanded the number of options for cheating ones 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), but the results they produce are still highly sought after. Professional cycling has been
repeatedly rocked by revelations and allegations of drug use. Every time Olympics begin, stories
about athletes using or at least being tested for performance-enhancing drugs abound. Major League
Baseball (MLB) is still trying to repair its image from the steroid era with the list of abusers
increasing.

The concept of attempting to improve athletic performance through the use of different types of
ergogenic aids has been around for well over 3,000 years (2,3,4). Performance-enhancing substances
have been used in societies from time immemorial. The use of gonadol hormones pre-dates their
identification and isolation. Medical use of testicle extract began in the late 19th century, while its
effects on strength were still being studied. As early as 1849, scientists suggested that a substance
secreted by the testicles into the blood stream was related to physiological and behavioral
characteristics of male animals. In 1889, 72 year-old British neurologist Charles E. Brown-Squard
injected himself with an extract of dog and guinea pig testicles, and reported at a scientific meeting
that these injections had led to a variety of beneficial effects (3). However, almost all experts,
including some of Brown-Squards contemporaries, agreed that these positive effects were induced
by Brown-Squard himself. In 2002, a study replicating Brown-Squards method determined that
the amount of testosterone obtained was too low to have any clinical effect.

Testosterone, the most active anabolic-androgenic steroid produced by Leydig cells in the testicles,
was first isolated in 1935 and chemically synthesized later in the same year. Synthetic derivatives of
testosterone quickly followed. By the end of the following decade, both testosterone and its
derivatives were applied with varying degrees of success for a number of medical conditions. It was
not until the 1950s, however, that athletes began to discover that anabolic steroids could increase
their muscle mass. According to sports physician Dr. John Ziegler, the first confirmed use of an
anabolic steroid in an international athletic competition was at the World Weightlifting
Championships in Vienna in 1954, when Russians weightlifters used testosterone (2). This discovery
was pre-validated by the exceptional performances of the Soviet weightlifting team at the 1952
Olympics which led to the conjecture that performance-enhancing substances were being
administered to these lifters. At the 1954 World Weightlifting Championships, Dr. Ziegler was
informed by his Soviet counterpart that the Soviet weightlifters were categorically using testosterone
injections (2). Upon his return to the United States, Dr. Ziegler began investigating the effects of
testosterone use. His concern with the potential negative side effects of this substance led him to
search for a drug that had distinct anabolic effects while minimizing the androgenic effects.

In 1958 the first androgen manufactured in the United States called dianabol (methandrostenalone)
was approved by the FDA (2). Research conducted by Dr. Ziegler on a small test group of
weightlifters proved dianabol to be a very effective drug when coupled with resistance training when
the test group experienced an impressive rise in lifting performance.

Throughout the 1960s and 1970s, the use of anabolic steroids was confined largely to the
professional levels of sport. Programs of training went as far as forcing some athletes to take
anabolic steroids. In the United States, sports physicians and medical texts were still widely
proclaiming that anabolic steroids were ineffective in helping athletes gain muscle. These doctors did
acknowledge the usefulness of anabolic steroids for debilitated patients. The package insert for
dianabol, a common anabolic steroid used at the time, stated, anabolic steroids do not enhance
athletic ability. Despite these warnings, use of anabolic steroids began in competitive bodybuilding,
track and field events (such as the shot put) and in other sports where performance depended on
muscle strength or speed of recovery during training.

In 1960, the use of androgens by Olympic athletes was still not a major problem and was mostly
limited to American and Soviet strength athletes (4). The 1964 Olympics saw the first large use of
androgens in an Olympic environment. Their use became significantly more extensive in all strength
sports and was a growing problem (4). In 1965, oral turinabol was synthesized by a German
Democratic Republic (GDR) state-owned pharmaceutical company (4). By 1966, the GDR began a
state-sponsored doping program designed to enhance sports performance and prepare athletes for
the 1968 Olympics in Mexico City (4). Interestingly, it appeared that the GDR was the first to
administer the drug to women athletes as they prepared for the 1968 Olympics (4). With the
increasing use of performance-enhancing drugs, and several high-profile deaths of athletes, a medical
commission was formed to develop a list of prohibited substances and methods (4). The
International Olympic Committee (IOC) also adopted a medical code that encompassed three
principles (4). The three principles that encompassed the medical code were the protection of
athletes health, respect of both medical and sports ethics, and equality for all competing athletes (4).

By the 1968 Olympics, an incremental increase in performance-enhancing drug use was seen in track
and field (4). Support for this contention can be seen in reports that suggest that one third of the
United States track and field team (i.e., throwers, sprinters, hurdlers, and middle distance runners)
had used these drugs in the lead up to the 1968 Olympics (4). Additionally, documentation has been
discovered that reveals that at the 1968 Olympics many of the male and female athletes from the
GDR were systematically using various anabolic-androgenic drugs to enhance athletic performance
(4). Although androgen use was on the rise during this time frame, there was little debate about the
ethics of taking androgens. Most discussion among athletes centered on which drugs were most
effective (4). In 1969, androgen use was so prevalent that Jon Hendershott, editor of Track and Field
News, called these drugs the breakfast of champions, (4). Throughout the 1960s, the overall
volume of androgen use increased dramatically. In fact, it appears that athletes increased the dosages
to levels that were 2 5 times above the recommended therapeutic dosage and performance gains
increased (4). Additionally, athletes began preferentially taking androgens and began experimenting
with stacking drugs that included a combination of oral and injectable forms (4). During these years,
the IOC failed to include androgens on the banned substance list. One reason for this was that the
medical community suggested that androgens were ineffective and were unwilling to consider that
the use of these drugs could impact performance. This was primarily based on several poorly
designed studies. Ultimately, this caused a large credibility gap between athletes and the medical
community as many athletes developed a large distrust for medical doctors (4). The second reason
for the exclusion of androgens was that there were no reliable and valid tests at this time (4).

At the end of the 1960s, a study on the effects of dianabol on athletes was published. This open-
label study, conducted by Johnson and OShea at Oregon State University, confirmed the muscle
building effects of anabolic steroids on athletes that followed a high-protein diet (4). Two years later,
O'Shea replicated the results in a double-blind design.

At the beginning of the 1970s, sporting organizations, including the IOC and the National Collegiate
Athletic Association (NCAA), declared the use of anabolic steroids unethical, but with no effective
means of testing athletes, the issue remained academic. The use of performance-enhancing drugs in
sport is commonly referred to as doping, particularly by those organizations that regulate
competitions. The use of performance-enhancing drugs is mostly done to improve athletic
performance. This is why many sports ban the use of performance-enhancing drugs. Another similar
use of medical technology is called blood doping, either by blood transfusion or use of the hormone
erythropoietin (EPO). The use of drugs to enhance performance is considered unethical by most
international sports organizations and especially the IOC, although ethicists have argued that it is
little different from the use of new materials in the construction of suits and sporting equipment,
which similarly aid performance and can give competitors advantage over others.

In 1973, the first testing procedures for androgens were proposed. The first method used
radioimmunoassay procedures, whereas the second suggested using a combination of gas
chromatography and mass spectrometry techniques. The IOC ultimately adopted both methods to
ensure the highest accuracy in testing; however, very few laboratories in the world could conduct the
test at the levels required by the IOC. The testing protocols were first implemented in the 1974
Commonwealth Games in Auckland, New Zealand, where 9 out of 55 samples tested positive for
androgens (4).

Throughout the early 1970s, the GDR expanded its doping program to include most sports, and it
became customary to provide drugs to most athletes, including minors (4). In fact, the overall
dosages of the drugs used by athletes from the GDR continued to escalate to the point at which
damaging side effects became apparent, especially in the female athletes who were outwardly
androgenized (4).With the advent of testing in 1974, the GDR faced a very unique problem as it
became apparent that the use of androgens was a key to their success in international competition,
but the introduction of drug testing created a problem for the systematic program being
implemented. At the 1974 European Athletic Championships in Rome, drug testing of urine
samples revealed no positive steroid tests. However, the IOC was developing new drug testing
processes at the time that created a situation in which the GDR feared many of its most successful
athletes would test positive (4). In 1974, the GDR government instituted a top-secret program that
initiated administration of androgens and other doping products to male and female athletes. This
program contained six central concepts: the mandate that doping play a central role in the training
process and preparation of athletes for major international competition; the establishment of a
monitoring program in which sports physicians conducted regular evaluations of the athletes; the
development of a centralized drug distribution and documentation program, which was under the
control of the Sportmesizinischer Dienst (SMD); the organization of a systematic research program
for the development of new doping products and the establishment of drug administration
programs, which would allow for the avoidance of detection during doping controls; the
development of a comprehensive educational program in which coaches and physicians would be
instructed about doping; and the classification of the doping program as an official state secret (4).
The timing of the program was extremely important as the IOC had planned to test at the 1976
Olympics and the GDR wanted to continue to build upon its growing success in international
competitions.

In 1976, drug testing was first initiated at the Olympics in Montreal (4). A relatively low number of
athletes tested positive for androgens during the 1976 Olympics (8 out of 275 tests) (4). Although it
appeared few athletes were doping based on the drug testing program instituted by the IOC, survey
data collected during the 1976 Olympics suggested that as many as 68% of the athletes competing
had used androgens during their training (4). It is likely that the early drug testing programs were not
as effective due to the fact that the IOC had left off many drugs from their testing program (4). For
example, norbolethone, which was never approved for human consumption, was reported to have
been taken by several athletes but was not present on the early lists of banned substances (4).
Additionally, it has been reported that many athletes reverted to the use of testosterone, as it was not
part of the original testing protocol (4).

By 1979, the GDR doping program had expanded to the point that athletes were being given
complex combinations of drugs. For example, it was reported that one GDR weightlifter was
administered 11.55 g of oral turinabol, 13 injections of testosterone esters, and human chorionic
gonadotropin (hCG) (4). Most noted was the development of steroid bridging which replaced
readily detectable steroids with testosterone esters in the weeks before competition to circumvent
drug testing protocols. Typically, athletes would receive repeated intramuscular injections of
testosterone esters of various fatty acid chain lengths in the time period leading up to a major
competition (4). This process was commonplace in the GDR and many other countries. Before the
1980s, there was no method available for the detection of testosterone. In 1980, Manfred Donike,
the head of an IOC-approved drug testing laboratory in Cologne, West Germany, developed a
method for detecting testosterone by comparing the testosterone-to-epitestosterone ratio (T:E ratio)
(4). Because the use of testosterone results in an increase in testosterone levels without a
concomitant increase in epitestosterone, athletes who possessed a T:E ratio of 6:1 were suggested to
be doping. After the 1980 Olympics in Moscow, the T:E ratio was determined and it was found that
20% of all athletes tested had a T:E ratio at, or above, 6:1 (29). Of the female athletes tested, 7.1%
had a T:E ratio at, or above, 6:1 (4). After the development of the T:E ratio test, the IOC
implemented the protocol as part of its doping controls. The advent of the T:E ratio test caused
significant problems for the state-instituted doping program of the GDR. During a 1981 meeting in
the GDR, it was determined that a program to find alternatives to exogenous testosterone
administration was needed and that testosterone was to be replaced by its precursors (i.e.,
androstenedione, dihydrotestosterone, dihydroandrostenedione, or dehydroepiandrosterone) (4). By
1982, scientists from the GDR had determined that three days after the injection of 25 mg of
testosterone propionate, the T:E ratio would be below the 6:1 cutoff used by drug testers.
Additionally, it was discovered that hCG and clomiphene did not alter the T:E ratio (4). By 1983, the
GDR had determined a method for simultaneously injecting testosterone and epitestosterone, which
consistently kept the T:E ratio below the 6:1 cutoff. With this information, the GDR had a method
that allowed them to circumvent doping controls.

The T:E ratio test was first administered at the 1983 Pan American Games in Caracas, Venezuela,
where a total of 15 athletes tested positive (11 weightlifters, 1 cyclist, 1 fencer, 1 sprinter, and 1 shot
putter) (4). There may have been more positive tests but 12 American athletes chose to withdraw
before competing and thus, avoided being tested. Journalists and commentators seemed shocked by
the apparent doping problems that were brought to light by the 1983 Pan American Games (4). At
this time, journalists began reporting that androgens were not only a part of Olympic sports such as
weightlifting but were also a part of every other professional sport in the United States. More
disturbing was the fact that collegiate and professional sport organizations, and even professional
bodybuilding, were doing nothing to curb the use of androgens (4). For example, it has been
speculated that between 50 and 75% of offensive and defensive linemen in the National Football
League (NFL) used steroids during the 1980s, but the precise level of use will probably never be
known (4).

Although the T:E ratio test was implemented at the 1984 Olympics in Los Angeles, the most
famous positive test for androgen occurred at the 1988 Seoul Olympics when Canadian sprinter, and
then worlds fastest man, Ben Johnson tested positive for stanozonol (4). This positive test sent
shock waves through the sporting community, ultimately resulting in the United States government
passing the Anti-Drug Abuse Act, which made it illegal to distribute or possess androgens (4).
Additionally, the IOC expanded the banned substance list to include diuretics, such as probenecid,
and other products typically used to mask androgen use (4). In 1990, the United States went a step
farther when it passed the first Anabolic Steroid Control Act and listed 27 steroids, along with their
muscle building salts, esters, and isomers, as class III drugs; simple possession could result in prison
time (4). As drug testing became more developed, the interest in the use of dietary supplements as
performance enhancement tools increased. In 1994, the FDA used the initiation of the DSHEA as
an opportunity to ban ephedra (4). In 1996, the prohormone androstenedione, which was first used
by the GDR in 1981, was introduced to the American market as a new dietary ingredient (4).
Because it was classified as a new dietary ingredient, it was not subject to regulation by the DSHEA
(4). In fact, androstenedione became a very popular dietary supplement when MLB player Mark
McGwire admitted to using it in 1998 (4). In 1999, the IOC took an unprecedented step and
convened the World Conference on Doping in Sport in Lausanne, Switzerland. Ultimately, this
conference served as the foundation for the formation of an international anti-doping initiative,
which resulted in the formation of the World Anti-Doping Agency (WADA) in 2001 (4).

By 2002, the WADA introduced the world anti-doping code, which contained three major parts: the
code, international standards, and models of best practice (4). The international standards serve as
the operational and technical areas that are contained within the anti-doping program and integrate
anti-doping agencies with the overall anti-doping code. The anti-doping code contains international
standards for laboratories, testing procedures, substances contained on prohibited lists, and
mechanisms and rules for therapeutic exemptions (4).

As a whole, the WADA oversees doping controls for international competitions including the
Olympics and World Championships as well as other sporting events that fall under the IOC (4).
These doping controls are not only performed at competitions but are also performed as no-notice,
out-of-competition controls. In this capacity, the WADA requires athletes to report their
whereabouts so that random drug testing can be conducted. If an athlete either fails a doping control
test or fails to show for testing, the WADA has the power to sanction that athlete, which ultimately
can withhold them from competition indefinitely depending upon the number of doping offenses.
Since 2000, the WADA has performed out-of-competition testing for sports, which are
encompassed under the IOC governance. However, professional sports in the United States have yet
to allow the WADA to perform in or out-of-competition testing in their respective sports and it is
unlikely that they ever will. In 2003, a syringe containing an unknown compound was sent to the
United States Anti-Doping Agency (USDA) that would expose a doping program that could only be
compared with the program once run by the GDR (4).

Eventually, the compound in the syringe was isolated and determined to be tetrahydrogestrinone
(THG), which was, at the time, an undetectable steroid (4). After its isolation, the drug source was
linked to the Bay Area Laboratory Co-Operative (BALCO), and the subsequent scandal associated
with THG exposed a widespread doping problem in American sports (4). By 2004, a second
designer steroid known as madol was isolated by the University of California, Los Angeles (UCLA)
laboratory (4). The discovery of these designer steroid compounds suggested that unscrupulous
athletes and scientists were still trying to circumvent the drug testing controls much like the GDR
did in the 1980s. In 2004, the United States Senate held hearings on the abuse of androgens and
their precursors by athletes. By the end of 2004, a new Anabolic Steroid Control Act was
implemented, which contained 26 new steroid compounds, including many of the steroid precursors
such as androstenedione and androstenediol. Additionally, designer steroids such as THG were also
added to the controlled substance list (4). Another change in doping controls occurred in 2005 when
the WADA lowered the T:E ratio, which indicated an adverse analytical finding from 6:1 to 4:1 (4).
According to the change, if an athlete tested positive for an elevated T:E ratio (4:1), then a follow-up
test would be implemented that used an Isotope Ratio Mass Spectrometry (IRMS) procedure (4).
Ultimately, the IRMS procedure was suggested to be an accurate way to determine if synthetic
doping products were taken by an athlete (4). The advent of these new testing procedures resulted in
some interesting doping findings in 2006.

In 2006, the sporting world was rocked by another doping scandal. Before the 2006 Tour de France,
the Spanish Civil Guard began investigating Dr. Eufemiano Fuentes for providing doping products
to cyclists and athletes from other sports (4). The investigation resulted in several high-level cyclists
being excluded from the Tour de France in 2006 and some were subsequently sanctioned. At the
end of the 2006 Tour de France, it was revealed that the winner, American Floyd Landis, tested
positive for an abnormal T:E ratio and in 2008 he was stripped of his title under the suspicion of
using testosterone (4).

Up to this point, it was widely believed that androgen use was limited to strength and power
athletes. However, evidence from this event revealed that androgen use was also prevalent in
endurance-based sporting events. In 2007, Marion Jones admitted to taking banned drugs, including
THG, during the 2000 Olympics in Sydney, Australia (4). What was unique about the Marion Jones
case was that she was proven guilty of doping without ever testing positive for performance-
enhancing substances. She was initially linked to the BALCO scandal in 2004 and repeatedly denied
using anabolic steroids, but in 2007, she admitted to using performance-enhancing drugs before and
during the 2000 Olympics. By the end of 2007, an independent report on androgen use in
professional baseball was released, which suggested that the use of androgens and other
performance-enhancing drugs was a serious problem (4).

What are Anabolic-Androgenic Steroids and How do they Work?

Drugs which mimic the effects of the male sex hormones testosterone and dihydrotestosterone are
known as AAS, or steroids. AAS increase protein synthesis within cells, which results in the buildup
of cellular tissue (anabolism), especially in muscles.

Physiologically, elevations in testosterone concentrations stimulate protein synthesis, which results in

improvements in muscle size, body mass, and strength (3,6). In addition, testosterone and its
synthetic derivatives are responsible for the development and maturation of male secondary sex
characteristics (e.g., increase in body hair, masculine voice, development of male pattern baldness,
sperm production, aggressiveness). These androgenic properties include the full development of the
primary sexual characteristics of males. As a result, it is more accurate to refer to synthetic
derivatives of testosterone as AAS. However, they are also referred to as androgens, androgenic
steroids, or simply anabolic steroids. Secretion of testosterone occurs primarily in the interstitial
Leydig cells in the testicles. Several other steroid hormones with anabolic-androgenic properties are
produced in the testicles (e.g., dihydrotestosterone, androstenedione). Testosterone and these other
male sex hormones are also secreted in significantly smaller amounts from the adrenal glands and
ovaries. Many of the ergogenic aids on the market today are precursors for testosterone.

The physiological changes that testosterone regulates have made it one of the drugs of choice for
strength/power athletes or other athletes interested in increasing muscle mass. However,
testosterone itself is a very poor ergogenic aid. Rapid degradation occurs when testosterone is given
either orally or through injectable administration (4). Thus, chemical modifications of testosterone
are necessary to retard the degradation of androgenic and anabolic effects at lower concentrations
(4). Once these modifications occurred, anabolic steroid use through either oral or injectable
administration became possible.

Athletes typically use AAS in a stacking regimen, in which they administer several different drugs
simultaneously. The rationale for stacking is to increase the potency of each drug. That is, the
potency of one anabolic agent may be enhanced when it is consumed simultaneously with another
anabolic agent. Athletes use both oral and injectable compounds. Most users take AAS in a cyclic
pattern, meaning that they use the drugs for several weeks or months and alternate these cycles with
periods of discontinued use. Often athletes administer the drugs in a pyramid (step-up) pattern in
which dosages are steadily increased over the course of several weeks. Toward the end of the cycle,
the athlete steps down to reduce the likelihood of negative side effects. At this point, some
athletes discontinue use or perhaps initiate another cycle of different drugs (i.e., drugs that may
increase endogenous testosterone production, taken to prevent the undesirable drop in testosterone
concentrations that follows the removal of the pharmaceutical agents). A recent study showed that
the typical steroid regimen involved an average of 3.1 agents, with a typical cycle ranging from 5
10 weeks (4). The reported dosage varied from 5 29 times greater than physiological replacement
doses (4). These higher pharmacological dosages are necessary for eliciting the gains that an athlete
desires.

In a study on the dose-response curve of anabolic steroids, it was demonstrated that the total dose
of anabolic steroids has a logarithmic relationship to increases in lean body mass; low doses produce
only slight effects, but with a progressive augmentation of lean body mass with increasingly larger
doses (4). These results reinforce the philosophy that if a low dose is effective, then more must be
better. Athletes typically use higher doses of the substances than are prescribed for men with low
testosterone levels. Dianabol, for example, maintains normal secondary sexual characteristics in men
at a replacement dose of approximately 15 mg/day; athletes have reported using up to 300 mg/day
(4). This drug is not available for medical use in the United States but is still available through black
market sources. Testosterone enanthate, a testosterone ester and the main injectable steroid used by
athletes, is readily available in the United States and is used clinically for some rare diseases and for
replacement treatment. A replacement dose is approximately 75 100 mg/week administered every
one to two weeks. Injectable steroids are administered intramuscularly, typically by deep gluteal
injections. They are also more potent than oral steroids because of their route of delivery, and
because they do not require additional modification to protect them from immediate metabolism by
the liver.

Who Uses Anabolic Steroids?

Although results of several surveys suggest that anabolic steroid use appears to have been declining
over the last 20 years, steroids are among the top sport issues today because of accusations of
widespread use in many sports (1). Strength athletes are not the only users of steroids either. People
outside organized sports use steroids to enhance appearance rather than performance. A national
survey of male American high school seniors showed that 7% are using, or had used, anabolic
steroids (1). One third of admitted steroid users are not involved in school-sponsored sports and
more than one fourth stated that their main reason for using steroids was to improve appearance, as
opposed to athletic performance (1).

A subset of bodybuilders were described in a study as having an altered self-image and believed that
they looked small and weak even though they were large and muscular (1). These individuals used
ergogenic substances and weight training to increase their body size. This condition is known as
reverse anorexia nervosa. The bodybuilders from the study appeared to be substantially different
from competitive athletes in terms of their objectives.

Ergogenic Benefits
The purported ergogenic benefits commonly attributed to anabolic steroid use are increased muscle
mass, strength, and athletic performance. The degree and incidence of these changes vary,
depending greatly on the training status of the individual as well as other factors.

General effects of androgens (non-sex-linked tissues) (4):

Increases lean body mass
Increases cardio tissue
Decreases body fat percentage
Increases isometric and dynamic muscle strength and power
Enhances recovery ability between workouts
Increases protein synthesis, accretion, and nitrogen retention (and possible anti-catabolism)
Increases muscle cross-sectional area
Stimulates growth of epiphyseal plate
Increases erythropoiesis, hemoglobin, and hematocrit
Increased vasodilation
Increases bone mineral content, density, and markers of bone growth
Regulation of osteoblasts, bone matrix production, and organization
Increases glycogen and creatine phosphate storage
Increased lipolysis and low-density lipoproteins and decreases high-density lipoproteins
Increases neural transmission, neurotransmitter release, myelinization, and regrowth of
damaged peripheral nerves
Repression of myostatin
Behavior modification (e.g., aggression)
Acute elevations in skeletal intramuscular calcium concentrations

Muscle Mass and Strength

When anabolic steroids are given in dosages similar to those used by recreationally trained and
competitive athletes, increases in muscle protein synthesis are seen (1). These increases are likely
responsible for the increases observed in lean body mass in both recreationally trained and
competitive athletes taking anabolic steroids (1). Even when anabolic steroids are administered to
normal adult men not engaged in intensive resistance training, increases in body mass, including the
nonfat component, are observed (1). In a study of competitive powerlifters, body mass increased
more than 5 kg following 26 weeks of anabolic steroid administration (1). In comparison, the
control group, consisting of both powerlifters and bodybuilders, did not display any increase in body
mass during the same time period. A dose-response effect, resembling a logarithmic relationship,
was apparent between the concentration of exogenous anabolic steroid use and increases in lean
body mass (1). For some time it was postulated that increases in body mass with steroid use came
from an increase in body water (1). An increase in total body water is expected with an increase in
muscle mass, since water constitutes a majority of the cellular weight; however, anabolic steroids
may increase water retention as well by increasing interstitial and extracellular volume. Although
water retention may explain why not all weight that is gained is sustained after cessation of anabolic
steroid use, this issue is still not well understood. In a study of experienced male bodybuilders, an 8-
week cycle of nandrolone decanoate (200 mg/week, intramuscularly) resulted in a significant 2.2 kg
increase in body mass (2.6 kg increase in fat-free mass and 0.4 kg decrease in fat mass), with no
change in hydration of fat-free mass (4). In addition, the extracellular and intracellular water ratio
was unaltered. Even after six weeks of discontinued steroid use, the body mass of the bodybuilders
was still significantly greater than baseline levels (1.6 kg greater), yet no hydration changes were seen.
The increase in fat-free mass and possible reduction in fat mass may last for several months after
cessation of use (1). Thus, athletes may derive a benefit from steroid use even if they stop taking the
drugs long enough before competition to obtain a negative drug test. This is why unannounced,
year-round drug testing of some elite athletes is important for the prevention of unfair drug use.

Athletic Performance

Initially, researchers examining the ergogenic benefits of exogenously administered anabolic steroids
were unable to see any significant performance effects (1). Consequently, the scientific and medical
communities suggested that anabolic steroids had little influence on athletic performance. This,
however, was contrary to anecdotal reports emanating from gyms that showed large strength
improvements in athletes using steroids. Upon further examination of the initial studies, several
methodological flaws became apparent. Several of these initial studies used physiological doses, in
contrast to the suprapharmacological doses that are typically taken by athletes self-administering
steroids. In essence, these subjects were shutting down their own endogenous production and
replacing it with an exogenous anabolic steroid. Another flaw in the studies was the method of
strength assessment. In several studies, strength performance was evaluated using a mode of exercise
that was different than the training stimulus. This lack of specificity likely masked any possible
training effect. In addition, several studies used subjects who had only minimal resistance training
experience. When exogenous androgens have been administered to experienced resistance-trained
athletes, significant strength gains have been reported (1).

Strength gains in experienced strength-trained athletes are generally quite small relative to those seen
in novice lifters but, when strength-trained athletes begin to use anabolic steroids, their strength
gains may be 200 300% higher than those typically seen in similarly trained athletes who are not
supplementing (1). In a case study of a bodybuilder who was cycling anabolic steroids, strength
levels were elevated during the times of the year when the athlete was using anabolic steroids (1).
During cycles when the athlete trained drug-free, strength levels tended to decline. Although well-
controlled studies using similar subject populations are still lacking, the results in this case study are
consistent with many of the anecdotal reports from competitive athletes. The principle mechanisms
that appear to be responsible for increasing strength and lean body mass are increases in protein
synthesis and inhibition of the catabolic effects resulting from high-intensity training (1). The anti-
catabolic activity of androgen administration is reflected by changes in the testosterone-to-cortisol
ratio (T:C ratio) (1). A higher T:C ratio will give an athlete the ability to maintain a higher intensity
and volume of training, but also enhance the recovery processes between exercise sessions. If an
athlete can train harder and for a longer duration, the stimulus presented to the muscle will result in
a greater physiological adaptation. Thus, steroids may be considered to have an indirect effect on
performance and size gains.

Psychological Effects

Anabolic steroid use is also associated with changes in aggression, arousal, and irritability. The East
Germans reportedly used anabolic steroids for this effect, delivering high doses to the central
nervous system by taking steroids through the nose (1). The issue has not been well studied, but
anecdotal reports suggest that this practice markedly increased aggressiveness and enhanced
performance among athletes (1). Elevations in arousal and self-esteem may be a positive side effect
for anabolic steroid users. Increases in aggressiveness can also be perceived as a benefit, especially
for athletes participating in contact sports. Increased aggressiveness may not be confined to athletic
performance, however. Anabolic steroid users experiencing increased aggressiveness may pose a
threat both to themselves and to those they come in contact with (1). Anabolic steroids are also
associated with mood swings and psychotic episodes. Studies have shown that nearly 60% of
anabolic steroid users experience increases in irritability and aggressiveness (1). A recent study
reported significant elevations in aggressiveness and manic scores following 12 weeks of
testosterone cypionate injections in a controlled double-blind, crossover study.

Interestingly, the results of this study were not uniform across all subjects. Most subjects showed
little psychological effect, and few developed prominent effects. A cause and effect relationship has
yet to be identified in anabolic steroid users, but it does appear that individuals who experience
psychological or behavioral changes recover when steroid use is discontinued (1). Furthermore,
psychosis may occur in some susceptible individuals or perhaps with doses that also activate
corticosteroid-specific responses (corticosteroids have been known to produce psychosis). Recent
literature suggests that the medical problems related to anabolic steroids may be somewhat
overstated considering that many of the side effects linked to abuse are reversible upon cessation (2).
It is important to note that there are differences between the side effects of anabolic steroid use
under medical supervision and those associated with abuse (i.e., consumption of many drugs at high
doses). Most of the information concerning adverse medical events associated with anabolic steroid
use has been acquired from athletes self-administering the drugs. Anecdotally, it appears that a
disproportionate magnitude of use and incidence of adverse events are evident in bodybuilders (who
are also known for consuming several other drugs, such as diuretics, thyroid hormones, insulin, and
anti-estrogens, that relieve some side effects but potentiate other risk factors) compared to
strength/power athletes.
Table 1. Common Adverse Effects from AAS Usage (1)
Affected System Adverse Effects
Lipid profile changes
Cardiovascular Elevated blood pressure
Decreased myocardial function
Gynecomastia
Decreased sperm count
Endocrine
Testicular atrophy
Impotence and transient infertility
Males
Decreased sperm count
Decreased testicular size
Females
Menstrual irregularities
Genitourinary
Clitoromegaly
Masculinization
Males and Females
Gynecomastia
Libido changes
Acne
Dermatological
Male pattern baldness
Hepatic Increased risk of liver tumors and damage
Premature epiphyseal plate closure
Musculoskeletal Increased risk of tendon tears
Intramuscular abscess
Mania
Depression
Psychological
Aggression
Mood swings

Please note that recent literature suggests that medical problems in Table 1 may be overstated and
are most likely reversible upon cessation of AAS usage. It is the contention of modern sports
scientists that the incidence of serious health problems associated with the use of androgens by
athletes has been exaggerated (6). Many myths and misinformation surround the usage of AAS
particularly when reported by mainstream press stating numerous reports of roid rage (conjecture
on the part of the press for media creation/attention rather than actual scientific fact).

Testosterone
Testosterone is the primary androgen hormone that interacts with skeletal muscle tissue. Although
testosterone affects both males and females, there are differences in the magnitude of responses for
each gender (1). Testosterone has both direct and indirect effects on muscle tissue. It can promote
growth hormone responses in the pituitary, which can influence protein synthesis in the muscle. The
potential interaction with other hormones demonstrates the highly interdependent nature of the
neuroendocrine-immune system in influencing the strength and size of skeletal muscle (1).

Testosterone precursors
The basis for the use of testosterone precursors, also called prohormones, as an ergogenic aid
evolved from a study showing a threefold increase in testosterone in healthy women who were given
100 mg of either androstenedione or dehydroepiandrosterone (1). Athletes have continued to
supplement with testosterone precursors such as androstenedione, androstenediol, and
dehydroepiandrosterone (DHEA) on the premise that they will increase testosterone concentrations
and achieve performance changes similar to those experienced by those taking anabolic steroids (1).
However, these precursors have relatively weak androgenic properties in themselves;
androstenedione and DHEA have only one fifth and one tenth the biological activity of
testosterone, respectively (1). Even if a large dose is ingested, most of these substances (similarly to
testosterone) are rapidly eliminated from circulation. Nevertheless, testosterone precursors were
officially listed as controlled substances in the Anabolic Steroid Control Act which mandated a
physicians prescription for these substances.

Studies examining the efficacy of testosterone precursors have produced varying results. No
significant differences in strength or body composition were seen in middle-aged men performing a
resistance training program while supplementing with either DHEA, androstenedione (100 mg), or a
placebo for three months (1). When DHEA supplementation (150 mg) was examined in a group of
younger males (19 29 years) on a two-weeks-on, one-week-off cycle for eight weeks, there were no
gains in strength or lean tissue (1). In addition, the investigators were unable to see any changes in
serum testosterone, estrone, estradiol, or lipid concentrations with supplementation. In studies using
higher dosages (300 mg) of androstenedione for eight weeks, using a similar two-weeks-on, one-
week-off protocol, no significant effects were observed in strength, muscle size, or testosterone
concentrations (1). However, androstenedione supplementation caused an increase in serum
concentrations of estradiol and estrone and was associated with lower high-density lipoprotein
levels. These results suggest that although performance changes may not occur in athletes taking this
supplement, they may be at higher risk for some of the side effects that are associated with anabolic
steroid use.

Recently, it has been concluded that these prohormones fall far short of providing the anabolic
effects generally associated with steroids (1). However, use of the prohormones has not been studied
in highly trained athletes. In addition, oral administration has been the primary method of taking
prohormones. A study demonstrated that 100 and 300 mg doses of oral androstenedione did
convert to testosterone; however, most of the conversion occurred in the liver, from which 89% of
the converted testosterone was excreted without reentry into the circulation (1). Thus, oral use of
prohormones may not be as effective as other means of intake (e.g., injection). All of this suggests
that continued study of the efficacy of precursors for testosterone are still needed; specifically
warranted is examination of other routes of ingestion in a trained competitive athletic population.

Human chorionic gonadotropin

Human chorionic Gonadotropin, or hCG, is a hormone obtained from the placenta of pregnant
women and is very closely related in structure and function to the luteinizing hormone. When
injected into men, hCG can increase testicular testosterone production; testosterone levels can
nearly double within four days after a large intramuscular injection (1). It is primarily used by athletes
who are finishing a cycle of anabolic steroids and are looking to activate their own endogenous
testosterone production (1). In addition, because hCG can stimulate endogenous testosterone
production, it can help stabilize the T:E ratio, which serves as an indicator of anabolic steroid use
(1). However, because hCG can increase testosterone levels, many of the side effects associated with
anabolic steroid use may become evident.

Insulin
Insulin is a very potent anabolic hormone. It is secreted by the pancreas in response to elevations in
blood glucose and amino acid concentrations. Its role is to facilitate the uptake of glucose and amino
acids into cells. Since insulin increases protein synthesis, it is considered an anabolic hormone; and
because it is a peptide hormone, its use as an ergogenic aid cannot be detected in the urine. It is
taken primarily by bodybuilders to potentiate the effects of growth hormone and insulin-like growth
factors. However, use among those who are not bodybuilders appears to be on the rise (1). The use
of insulin, though, comes with serious consequences. A major side effect is hypoglycemia (i.e., low
blood sugar), which can prove to be fatal.

Human growth hormone

Human growth hormone, or HGH, is a protein secreted from the anterior pituitary gland with
several important physiological functions that enhance its ergogenic effect. It is anabolic steroid due
to its stimulation of bone and skeletal muscle growth, but it also has important metabolic functions
such as maintaining blood glucose levels, increasing the uptake of glucose and amino acids into
muscle cells, and stimulating release of fatty acids from the fat cells (1). However, until 1986, the
only source of HGH was the pituitaries of human cadavers. Because HGH receptors are unable to
cross-react with growth hormone from animal sources, the financial cost of HGH was very high
before 1986. Although the use of cadaver growth hormone did not come without significant health
risks, these consequences did not prevent athletes from taking the supplement, but instead only
restricted use substantially. The development of recombinant HGH provided clinicians with a
relatively low-risk drug at a lower cost with greater availability. Clinicians can now prescribe
recombinant HGH to increase stature in normal children and alter body composition in normal
adults. However, since the 1980s, athletes have become well aware of the anabolic potential of HGH
and its ability to reduce body fat. The use of HGH by competitive athletes appears to be on the rise;
it is either taken alone or stacked with anabolic steroids (1). Even though recombinant technology
has increased the availability of HGH, its cost, especially on the black market, is extremely high.
humatrope, nutropin, norditropin, genotropin, serostim, saizen, and protropin are brand names of
HGH commonly used in the United States.

There appear to be no studies on the efficacy of HGH in athletic populations (1). Most
investigations of HGH have focused on HGH as replacement therapy in growth hormone-deficient
adults or children. These studies have consistently shown positive alterations in body composition
(increases in lean body tissue with decreases in body fat) (1). In men with established growth
hormone deficiencies, nightly injections of recombinant HGH for six months resulted in an average
increase of 5.4 kg in lean body mass and a similar amount of fat loss (1). Most studies have not
addressed the effect of HGH therapy on muscle strength and performance. One study showed no
changes in isokinetic strength following 12 months of therapy (1). However, the subjects in that
study did not perform any resistance training during the course of treatment. A study involving
trained adults given growth hormone (three days per week for six weeks) showed modest changes in
body composition, but no strength assessment was performed (1). Nevertheless, anecdotal reports
suggest impressive musculoskeletal performance changes in athletes using HGH. Although the
scientific literature does not provide support for the efficacy of HGH use in athletic populations, it
is likely the inability to perform such studies (due to ethical constraints) limits much of our
understanding of HGH and human performance. However, as already noted, the use of HGH by
athletes appears to be increasing, owing to its perceived efficacy and the fact that it cannot be
detected in random drug tests.

HGH is a protein molecule. Injection is necessary to avoid the complete metabolization of HGH
and maintain its effectiveness. Oral ingestion does not result in any benefit. As a peptide hormone,
HGH is not detected in the urine via a drug test, and many athletes may opt to use it for this reason.
Many of the actions of HGH are mediated through insulin-like growth factor I (IGF-I), another
peptide hormone, which is produced and secreted from the liver in response to HGH stimulation
(1). Insulin-like growth factor I is now being synthesized and will likely produce the same effects as
HGH.

The use of HGH does, however, present some potential health risks. Excessive secretion of growth
hormone during childhood causes gigantism, a condition in which a person becomes abnormally tall.
After puberty, once linear growth has stopped, excess secretion of growth hormone causes
acromegaly, a disfiguring disease characterized by a widening of the bones, arthritis, organ
enlargement, and metabolic abnormalities. This is a potential risk for athletes who use HGH as an
ergogenic aid. In addition, these side effects may provide some indication that an athlete may be
using this drug. In clinical studies in growth hormone-deficient adults, side effects appear to be
minimal for up to two years of replacement therapy (1). However, athletes who supplement with
HGH generally use dosages that far exceed the doses commonly administered in replacement
treatment. Thus, one should not assume that HGH use is benign with regard to adverse medical
events in doses commonly used by an athletic population.

Erythropoietin
Erythropoietin, or EPO, is produced in the kidneys and stimulates the production of new red blood
cells. Its level increases in response to aerobic endurance exercise such as marathon running (1). In
certain types of anemia, especially in kidney patients with inadequate EPO production, recombinant
human EPO can improve the quality of life. Injections of EPO are generally associated with
elevations in both hematocrit and hemoglobin. When EPO was given to normal men during six
weeks of treatment, hematocrit levels increased by 44.5 50%, hemoglobin concentrations increased
by 10%, aerobic capacity increased 6 8%, and the time-to-exhaustion improved by up to 17% (1).
The enhanced oxygen-carrying capacity of the blood makes EPO an effective ergogenic aid for the
aerobic endurance athlete. The mechanism for increasing hemoglobin levels has been reported to be
related to the elevated hematocrit and a decrease in plasma volume (1). The change in plasma
volume is thought to be mediated by a downregulation of the renin-angiotensin-aldosterone axis (1).

The increase in hematocrit presents a significant health risk. Increases in red blood cell numbers
increase blood viscosity. This poses several problems that include increased risk of blood clotting,
elevations in systolic blood pressure, and a compromised thermoregulatory system (1). During
aerobic endurance events, the additional problem of dehydration could compound cardiovascular
risks by eliminating any safety margin in the balance between performance advantages from
artificially increased hematocrit and decrements from increased blood viscosity. The primary risk
associated with EPO is its lack of predictability compared to red blood cell infusion. Once EPO is
injected into the body, the stimulus for producing red blood cells is no longer under control.
Consequently, aerobic endurance athletes should stay away from this drug because of the significant
cardiovascular risk, leading to possible death, associated with its administration.

-Adrenergic agonists
Synthetic -adrenergic agonists, or -agonists, are substances chemically related to epinephrine, a
hormone produced in the adrenal medulla that regulates physiological effects, such as lipolysis (the
breakdown of fat) and thermogenesis (increased energy expenditure for heat production). -
Agonists were originally developed for the treatment of asthma and other life-threatening medical
conditions. Some of these compounds have been found to have specific effects on body
composition, such as increases in lean mass and decreases in stored fat; because of this, these drugs
are sometimes referred to as partitioning agents (1). The implicit proof of the effectiveness of -
agonists is demonstrated in their increased use in livestock. Without question, these drugs work in
the species for which they are intended, increasing protein synthesis and muscle mass and decreasing
fat mass through enhanced lipolysis and lowered lipogenesis (fat synthesis and storage) (1).

Clenbuterol, a 2-agonist, is generally used to reverse bronchial constriction. In recent years, athletes
use it as an ergogenic aid to increase lean muscle tissue and reduce subcutaneous fat (1). This is
based on studies from a rodent model that demonstrates that clenbuterol can increase muscle
protein synthesis (1). Though studies in humans are limited, several findings have indicated an
ergogenic potential of 2-agonists for strength improvements (1). Athletes generally use clenbuterol
in doses twice the recommended amounts administered for clinical purposes, in a cyclic fashion
(three-weeks-on alternated with three-weeks-off, with a two-days-on, two-days-off cycle during the
on week) (1). It is believed that this cycling regimen avoids 2-receptor downregulation (1).
Athletes consume clenbuterol in a capsule form, in contrast to the inhalation route that is often used
for relieving bronchial constriction. Although a number of potential side effects have been suggested
(i.e., transient tachycardia, hyperthermia, tremors, dizziness, palpitations, and malaise), actual
documented events are quite limited. In addition, the scarcity of data on the ergogenic benefits of
clenbuterol in humans makes determining its efficacy difficult.

-Blockers
-Blockers are a class of drug that block the -adrenergic receptors, preventing the catecholamines
(i.e., norepinephrine and epinephrine) from binding. -Blockers are generally prescribed by
cardiologists for the treatment of a wide variety of cardiovascular diseases, including hypertension.
The ergogenic benefit of these drugs may reside in their ability to reduce anxiety and tremors during
performance (1). Thus, athletes who rely on steady, controlled movements during performance (e.g.,
archers or marksmen) would appear to benefit from these drugs. In addition, it has been suggested
that -blockers improve physiological adaptations from aerobic endurance training by causing an
upregulation of -adrenergic receptors (1). This may result in an exaggerated response to
sympathetic discharge during intense exercise upon cessation of supplementation. Several studies
have shown that -blockers can improve both slow and fast shooting accuracy (1). In addition, the
dose taken appears to have significant effects on the magnitude of improvement. Shooters who were
administered -blockers in two different doses (40 mg and 80 mg of oxprenolol, respectively)
showed that the group taking the higher dose shot with greater accuracy (1). In certain sports,
however, some degree of anxiety may be important. A study reported that bowlers whose
performance was improved during blockade with oxprenolol had significantly greater heart rates
before, during, and after competition than subjects whose performance did not improve while on -
blockers (1). -Blockers may also have an ergolytic effect (reduced performance) (1). Studies have
shown that -blockers impair the cardiovascular response to exercise by reducing oxygen and
substrate delivery to exercising muscles (1). Risks associated with these drugs include
bronchospasms in individuals with asthma, light-headedness (due to decreases in blood pressure),
increased fatigue, and hypoglycemia in type 2 diabetics (-blockers can increase insulin secretion) (1).

Designer Steroids

Designer steroids are compounds which are generally not tested by the WADA because they are not
on the official testing protocols; they are in fact considered undetectable (3). A designer steroid can
be classified in one of two ways: a steroid previously identified but never marketed or approved for
human use or a new steroid entity that has never been documented in the scientific literature (3).
Once a designer steroid is detected, new drug testing procedures/protocols are developed, placed
into drug screening practices, and often retrospective testing on frozen urine samples are undertaken
(3). As of now, only three designer steroids have been noted in the scientific literature.

In 2002, the first so-called designer steroid, norbolethone, was isolated in the urine samples of two
female athletes by the UCLA Olympic Analytical Laboratory (3). Norbolethone was originally
documented some 30 years ago (3). A research study hypothesized that norbolethone was never
marketed because of toxic effects in animal studies and/or reports of the drug causing menstrual
irregularities (3). Research conducted on norbolethone in the 1960s reported that the drug had an
anabolic activity that was 20 times higher than its androgenic activity thus, making this drug very
attractive to athletes looking to gain a competitive edge (3). After its discovery, a new drug testing
protocol was developed for norbolethone, which was subsequently added to the list of banned
substances presented by the WADA and is currently tested for during drug screenings (3).

The second and most famous designer steroid is tetrahydrogestrinone, or THG (3). This drug
brought national attention to what it often referred to as the BALCO scandal. The BALCO scandal
and its implications brought national attention to the problems associated with sports doping (3).

THG was discovered in 2003 by the UCLA Olympic Analytical Laboratory after a syringe with an
unknown anabolic compound was anonymously sent to the USADA (3). Unlike norbolethone,
THG was a new chemical entity and would have remained undetectable if the syringe containing it
had not been sent to the USADA (3). THG is closely related to gestrinone, a progestin, and
trenbolone, a veterinarian androgen (3). A small modification of gestrinone resulted in the creation
of THG (3). Since THG is a new steroid entity, there is very little information about the safety and
anabolic effects of this drug (3).

A recent research study was the first to demonstrate that THG is a potent androgen with progestin-
like properties (3). Additionally, another study confirmed that THG is a potent androgen and also
demonstrated that it has a high binding affinity for glucocorticoid receptors, which may suggest that
it is also an anti-catabolic drug (3). There are no scientific studies on the side effects of THG, but
due to its similarities to gestrinone, side effects of THG might be similar to those noted for
gestrinone (3). In women who have been treated with gestrinone, several androgenic side effects
have been reported including increased presence of acne, weight gain, voice change, and hirsutism
(heavy hair growth) (3). In order to screen for THG in athletes, a reliable testing protocol was
developed that added to the test battery conducted by the WADA (3).

The third designer steroid is a compound known as madol or desoxymethyltestosterone (DMT) (3).
The UCLA Olympic Analytical Laboratory isolated this steroid in 2004 from an oily product
allegedly containing an anabolic steroid that was not on any of the WADA testing protocols. Later,
in 2005, a group of scientists from Montreal discovered a designer steroid which they labeled as
DMT, however when looking at the chemical structure this drug was in fact madol (3). As with
norbolethone, madol was first reported in scientific literature in the 1960s and was never marketed
or approved for use by humans. Presently, there is no known safety or efficacy data for madol, but
when looking at early studies in rat models, madols anabolic activity was reported as being 160% of
that reported for testosterone and its androgenic activity was 60% that of testosterone (3). Currently,
the WADA has added screening procedures for madol to its drug testing protocols (3).

The entrepreneurial exploits of those who have developed these designer drugs (unscrupulous
chemists) suggests that the manipulation of the steroid skeleton can result in custom designed
androgens with the express purpose of yielding the benefits on androgens while allowing the
individual to avoid the punitive effects of a failed drug test (3). It is likely that many more drugs are
being developed covertly so that athletes can beat current drug screening practices.

Education and Awareness

One of the primary issues that arise when attempting to educate athletes on steroid use is that
steroids typically have positive social connotations. This opposes what is seen in the use of
recreational drugs like cocaine, marijuana, or ecstasy. These recreational drugs are perceived to have
a self-destructive tendency associated with their use. At the same time it is often portrayed that
steroids will enable an athlete to win a game, get more muscular, or become more physically
attractive; all of which are typically perceived as positive todays society. It is a challenge when
educating athletes to the adverse effects of anabolic steroids because of their inherent positive
effects; those effects being real or otherwise.

What Does Not Work

Some educational and prevention models for anabolic steroid use have been attempted in an effort
to quell usage (3). These attempts have included:
Scare tactics
Didactic discussions
Campaigns such as Just Say No
Drug testing
Threats

Each of these tactics has had little effect and in some cases, possibly the reverse effects the program
was hoping to achieve. For instance, scare tactics and threats are often perceived by athletes as a
challenge; drug testing has never been scientifically proven to work, and purely informational
handouts, statistics, and lectures do not appeal to the social values of the athlete. For all of these
reasons a more strategic approach is suggested.

What Does Work

Social-psychological interventions are programs that focus on improving behavior within a group
(society) and how that group perceives the environment (3). It has been suggested that when
implementing a social-psychological program the components are age appropriate, contain multiple
years of intervention, have detailed lesson plans, teach norms of drug use, and use interactive
teaching methods (3). This type of intervention strategy was used for the Athletes Training and
Learning to Avoid Steroids (ATLAS) program (3).

ATLAS is multi-component universal intervention program that focuses on risk and protective
factors of anabolic steroid use (3). ATLAS takes advantage of the unique properties of an athletic
team to deter drug use and promote healthy nutrition and exercise as alternatives to drug use in
sports. ATLAS targets male adolescent use of anabolic steroids, alcohol, and other drugs and sport
supplements, while improving healthy nutrition and exercise practices. Compared with controls of
the ATLAS program, experimental subjects were significantly less interested in trying steroids after
the intervention, were less likely to want to use AAS even if their friends used them, were less likely
to believe steroid use was a good idea, believed steroids were more dangerous, had better knowledge
of alternatives to steroid use, had improved body images, increased their knowledge of diet
supplements, and had less belief that AAS were as beneficial (3).

Initiatives of the National Strength and Conditioning Association

The NSCA was one of the first organizations to take a stance against the use of AAS (4). In a joint
effort between the NSCA and the nutritional supplement company EAS, owned by Abbott Ross
Laboratories, a new steroid education and awareness campaign will be implemented throughout the
United States (3). NSCA volunteers will assist at state and national conferences to help spread
information as it relates to anabolic steroid usage. There are three primary tenants of the program:
Steroid education: What are anabolic steroids, how they work, how does the body produce
them, anabolic steroids history and what the research is saying about their use.
Strength and conditioning: Fundamental principles of strength and conditioning, and
strategies that promote muscle growth and improve athletic performance are addressed.
Nutrition: The six essential nutrients are covered; caloric balance, meal timing and
reasonable supplementation are also covered.

The depth of the information presented will depend on the target audience. Strength and
conditioning coaches will need to be well prepared when speaking to high level or professional
athletes because of the unique environment they train and compete in. This may differ from parents
of youth athletes who could be more interested in the signs that predispose their children to
anabolic steroid use.

References
1. Baechle, T, and Earle, R. Essentials of Strength Training and Conditioning. (3rd ed.) Champaign,
IL, Human Kinetics; 42199, 2008.
2. Berning, J, Adams, K, and Stamford, B. Anabolic steroid usage in athletics: Facts, fiction,
and public relations. Journal of Strength and Conditioning Research 18(4): 908917, 2004.
3. Cinea, K. Steroids: Special report (special issue). NSCAs Performance Training Journal 124,
2006.
4. Hoffman, J, Kraemer, W, Bhasin, S, Storer, T, Ratamess, N, Haff, G, Willoughby, D, and
Rogol, A. Position stand on androgen and human growth hormone use. Journal of Strength and
Conditioning Research 23(5 Suppl): S1S59, 2009. Review. Erratum in: Journal of Strength and
Conditioning Research 24(2): 585, 2010.
5. Koziris, L. Anabolic-androgenic steroids. Journal of Strength and Conditioning Research 29(1): 74
75, 2007.
6. Roundtable: Anabolic androgenic steroids: Part I. National Strength and Conditioning Association
Journal 28(6): 4255, 2006.
7. Roundtable: Anabolic androgenic steroids: Part II. National Strength and Conditioning Association
Journal 29(1): 5057, 2007.