Amphetamines were originally developed in 1920. Their vasoconstrictive properties allowed them to be initially used for the treatment of nasal congestion (7). Their emergence as performance enhancers occurred during World War II when German soldiers used amphetamines to delay fatigue and enhance their alertness while on patrol duty (13).

Amphetamines are structurally similar to endogenous catecholamines such as epinephrine, and are believed to enhance the release of neurotransmitters, especially norepinephrine (8). Therefore, much of their ergogenic effects are believed to be due to stimulation of the sympathetic nervous system. Peak plasma concentration is achieved very rapidly after intravenous administration of amphetamines, whereas the maximum concentration after oral ingestion usually occurs within 2 hours (14). Although the question of whether amphetamines truly enhance athletic performance is debated in the literature, the available studies and anecdotal reports strongly suggest that amphetamines are truly efficacious for their purported uses, especially in sports where speed, power, and endurance are essential (9,13,15,16,17,18). Available research reveals that the ergogenic effects are partially obtained through (a) prolonging the time to exhaustion, (b) increasing tolerance to strenuous exercise, (c) blunting pain perception and symptoms of fatigue, and (d) increasing aggression, which may increase the potential for injury in contact sports (19).

Many possible adverse side effects of amphetamine use are related to their effects on the CNS. Neurological symptoms and behavioral effects include restlessness, insomnia, anxiety, tremor, confusion, agitation, irritability, paranoia, hallucinations, increased aggressiveness, and a potential for psychological addiction (9,17). Cardiovascular complications include a lower threshold for arrhythmias, provocation of angina, hypertension, headaches, tachycardia, and palpitations. Adverse gastrointestinal side effects include abdominal pain, decreased appetite, and vomiting. Thermoregulatory disturbances may be caused by a decrease in the ability to sense the body’s limitation, and thereby may lead to the increased incidence of (or predisposition to) heat illness, including heatstroke (7,9,20). An abrupt cessation of amphetamines can result in chronic fatigue, lethargy, and depression (6,21). There have even been case reports where excessive doses have led to convulsions, coma, strokes, and death; while long-term exposure to amphetamines has resulted in dyskinesias, compulsive behavior, and paranoid delusional states (7,8,9,13,19,22).

It was not until the death of Danish cyclist Kurt Enemar Jensen at the 1960 Summer Olympic Games in Rome that a considerable international anti-doping movement was initiated (23). Many were stunned by the fact that Jensen and two of his fellow teammates became ill after ingesting amphetamine and Roniacol (a cough syrup) for performance enhancement. Jensen ultimately died and his two teammates were admitted to an Italian hospital in critical condition. In another incident, Tommy Simpson, a notable British cyclist, died during the thirteenth day of the Tour de France in 1967. At the time of his death, a vial of amphetamines was found in his possession (24). The following year, amphetamine abuse was believed to play a major role in the deaths of yet another cyclist, Yves Mottin, as well as a soccer player, Jean-Louis Quadri (24). These incidents helped generate considerable anti-doping sentiment and began a cascade of significant worldwide anti-doping legislation. From that point forward, a gradual evolution in collective thinking also began; drug use for performance enhancement was no longer considered just a matter of personal choice. Instead, it became an unethical act that clearly carried significant health risks. It also directly induced others to use ergogenic substances in order to compete equitably (25,26).

Caffeine is undoubtedly the most widely consumed stimulant in the world. This is in part due to its widespread social use, and availability to people of all ages. It is present in many different types of beverages, including coffee, cola drinks, hot chocolate, and tea (6,27). It may also be the most widely abused drug in sports, as it is routinely consumed by most sports competitors (28). Caffeine is a methylxanthine derivative related to theophylline and theobromine, which occurs naturally in many species of plants and is found in cocoa, coffee beans, and tea leaves. It is also found in many prescription and nonprescription medications such as analgesics, and weight-loss and cold preparations (27). Approximately 80% of the adult population in the United States drinks coffee or tea on a daily basis. Furthermore, coffee accounts for 90% of the caffeine consumed in the United States, where an average of approximately 210 mg of caffeine/person/day is consumed (29).

After ingestion, caffeine reaches peak blood levels in approximately 30 to 60 minutes (8). It acts as a potent CNS stimulant, increasing arousal or level of consciousness, reducing fatigue, and decreasing motor reaction time when concentrations of 85 to 200 mg are consumed (7). Most believe the ergogenic dose is between 250 and 350 mg (8). Therefore, the IOC and the National Collegiate Athletic Association (NCAA) initially placed limits on caffeine ingestion. At present, caffeine is treated as a controlled substance by the NCAA. Certain amounts are tolerated because of its presence in commonly ingested beverages, but excessive amounts constitute grounds for disqualification (30). Before the formation of WADA, the IOC’s acceptable urine concentration was up to 12 μg/mL, whereas the NCAA’s is currently up to 15 μg/mL. To reach these levels, most athletes would have to drink six to eight cups of coffee in one sitting (approximately 600–800 mg of caffeine), 2 to 3 hours before testing. Because the ergogenic effects are gained well below these accepted limits, some question these organizations’ motives and raise ethical issues regarding the ergogenic use of caffeine (28). Furthermore, some argue that caffeine should be added to the banned substance list, which would thereby require athletes to abstain from caffeine ingestion 48 to 72 hours before competition. Interestingly however, caffeine is no longer prohibited at any concentration by WADA.

Over the years, there has been conflicting data in the literature concerning the in vivo reproducibility of caffeine’s ergogenic effects. Although some have questioned the true ergogenic value of caffeine, athletes and coaches have believed in and used caffeine as an ergogenic aid for years. Only relatively recently has the true ergogenic value of caffeine, especially regarding short-term (<5 minutes) high-intensity (>100% maximal aerobic power [VO₂ max]) exercise (STHIX) been significantly borne out in published research. What the evidence has more clearly supported is the notion that caffeine is ergogenic during prolonged (>30 minutes), moderate intensity (∼75%–80% VO_{2 max}) exercise. For example, in one study, the run time to exhaustion at 85% of VO_{2 max} in elite runners increased by 44% following the ingestion of an acceptable, under-the-limit dose of caffeine (31).

Information concerning STHIX has often been dismissed, even when positive results were shown. The early in vivo studies on humans found little evidence for a performance-enhancing effect on STHIX. On the other hand, early animal invitro and insitu studies revealed that caffeine could increase muscle force production through CNS stimulation, enhanced neuromuscular transmission, and/or enhanced muscle fiber contractility (32). More recently however, a number of well-controlled studies have indicated that caffeine can improve performance during STHIX and repeated bouts of STHIX. One such study examined the effects of caffeine ingested at 6 mg/kg on the performance of repeated bouts of cycling at 100% VO₂ max (33). This study showed that the cycle time to exhaustion was significantly improved with caffeine and that epinephrine and lactate (muscle and blood) levels were increased with use of caffeine. Interestingly, muscle glycogen stores did not vary between the placebo and caffeine groups. Therefore, the authors concluded that STHIX was not associated with glycogen sparing, and may in fact have been due to elevated epinephrine levels which increased muscle glycogenolysis at this intensity, thereby increasing anaerobic energy provision. Ultimately, although both adrenaline and lactate (muscle and blood) levels were elevated following caffeine ingestion and STHIX, the significance of these elevations is unclear. Caffeine also appears to influence electrolyte handling and substrate use, which may also further affect anaerobic performance (32).

There are three major theories that explain the ergogenic effects of caffeine. First, caffeine has a direct effect on the CNS, which alters our perception of effort and/or affects the propagation of neural signals somewhere between the brain and the neuromuscular junction (28). It thereby decreases fatigue and improves our level of consciousness. Second, caffeine is believed to increase muscle force production through direct CNS stimulation, enhanced neuromuscular transmission, and enhanced muscle fiber contractility. Caffeine causes this by increasing permeability of the sarcoplasmic reticulum to calcium, thereby increasing the amount of intracellular calcium available for muscular contraction (13). Third, caffeine has the ability to increase circulating levels of free fatty acids (FFA) because of an increase in lipolysis. Oxidation of fatty acids then provides the initial energy source, leaving glycogen available for later use (34). Caffeine thereby reduces an individual’s dependence on muscle glycogen as a fuel source during prolonged exercise, and improves endurance (9). Ultimately, caffeine increases the production of plasma catecholamines, including epinephrine, which is undoubtedly linked to many of its purported effects. These effects include increased psychological arousal, increased cardiac output, enhanced muscle contractility, and an increased mobilization and utilization of FFA during exercise (30).

The possible adverse side effects of using caffeine include anxiety, irritability, restlessness, inability to focus, tremor, headaches, insomnia, diuresis leading to fluid imbalances, gastrointestinal disturbances, hypertension, cholesterol abnormalities, tachycardia, and hyperesthesia (8,9,13). Caffeine can be lethal at doses of 3 to 10 g, causing delirium, seizures, tachycardia, and/or ventricular dysrhythmias (7,28).

Although tolerance to the performance-enhancing effects of caffeine has not been extensively studied, it appears that the derived ergogenic benefits may be significantly hampered in habitual consumers of caffeine (35). It has been suggested that in order for athletes to obtain the maximal ergogenic effect of caffeine, they should abstain from caffeine use at least 4 days before their competition to avoid a tolerance phenomenon (34). Additionally, the ingestion of caffeine should take place 3 to 4 hours before an endurance exercise, during peak plasma concentrations of FFAs rather than 1 hour or less before an event. If ingested an hour or less before competition, only the peak plasma concentration of caffeine is reached (36,37). However, some speculate that using caffeine 1 hour before competition also provides an effective ergogenic mechanism, especially in shorter length races, because in these instances it not only increases levels of epinephrine, but also increases psychological stimulation (30).

Finally, studies have shown that doses of up to 9 mg caffeine/kg body weight will produce peak plasma concentrations, with urine concentrations generally below the 12 μg/mL IOC limit (38) The optimal dose for performance enhancement appears to be between 3 and 6 mg/kg (28). At this level, side effects appear to be minimized and urine concentrations will not approach illegal limits. Many studies have been performed on the appropriate ergogenic levels even before the American cycling team used caffeine suppositories for performance enhancement in the 1984 Olympics (39). Not surprisingly, given the research available at that time, none of the American cyclists tested positive for caffeine. In fact, only a few athletes with illegal caffeine levels have been detected in Olympic competitions. Those athletes included an Australian pentathlete in 1988, two German swimmers in 1992, and Italian cyclists in 1992 and 1994 (28).

Sympathomimetic amines are CNS stimulants and include ephedrine, pseudoephedrine, norpseudoephedrine, and phenylpropanolamine (PPA). The prototypical sympathomimetics, ephedrine and PPA, were found in many OTC common cold remedies. PPA was also a common ingredient in diet pills, until it was taken off the market by the FDA because of an increased risk of hemorrhagic stroke in women (40). These drugs, also known as amphetamine look-alikes, were often combined with caffeine in the early 1970s. Unfortunately, use of these stimulants can have significant side effects, especially in larger doses. They include tachycardia, palpitations, arrhythmias, anginal pain, hypertension, intracranial hemorrhage, restlessness, anxiety, insomnia, headaches, anorexia, dizziness, confusion, delirium, respiratory difficulty, nausea, vomiting, urinary retention, hallucinations, psychosis, and possible addiction (13,41,42,43).

Ephedrine is still used in the treatment of asthma, hay fever, sinusitis, allergic rhinitis, urticaria, and other allergic disorders. It is also used as a pressor agent in hypotensive states and is found in a variety of OTC supplements (13,43). Ephedrine continues to be used as an ergogenic aid, because it tends to have amphetamine-like effects. Accordingly, athletes who use ephedrine report a significant boost of energy that increases the quality of their workouts and enhances their performance (42). Athletes also report using ephedrine alkaloids, including ephedra and ma huang, not only for their stimulant-like effects, but also for their thermogenic, fat-burning properties (41). Ephedrine achieves this thermogenic effect by stimulating the thyroid gland to transform the weaker thyroxine (T4) hormone into the more potent triiodothyronine (T3). When combined with caffeine and aspirin (which is referred to as the thermogenic stack) the thermogenic effect is significantly enhanced. Recent studies have confirmed many of the purported ergogenic effects of ephedrine, including prolonged time to exhaustion and decreased perception of exertion (44). To the general public, the use of caffeine-ephedrine stacking appears to be a recent trend; however the use of amphetamine “look-alikes” or ephedrine alkaloids, combined with caffeine, were knowingly used as ergogenic aids earlier than the 1970s. One of the more notable Olympic cases involving sympathomimetic use occurred at the 1972 Games when Rick DeMont, an American swimmer, was disqualified for taking medication containing ephedrine, reportedly for asthma (45). It is interesting to see that the use of caffeine and ephedrine stacking has come full circle. These substances are now more widely used than ever before by the general population because of their prevalence in OTC supplements.

As is the case with many of the OTC supplements, there has been an increased incidence of adverse side effects and/or death from ephedrine alkaloid toxicity. This is often due to an accidental overdose prompted by exaggerated off-label claims, and a belief that “natural” medicinal agents are inherently safe. It is important for individuals to realize that just because a supplement is labeled “natural” or is from a herbal source, it is not necessarily safe. A recent example is the OTC herbal product kava kava that has been found to cause serious liver toxicity. The FDA is now advising consumers of the potential risk of severe liver injury associated with the use of kava-containing dietary supplements (46).

The use of ephedrine alkaloids has been linked to many episodes of ephedrine toxicity and ephedrine-related
deaths, especially when taken in combination with caffeine (47). The FDA has received more than 80 reports of ephedra-linked deaths and at least 1,400 reports of adverse reactions since 1994 (48). One interesting study reviewed more than 140 documented cases submitted to the FDA (49). The authors found that 47% of these adverse events involved cardiovascular symptoms, with the most frequent being elevated blood pressure followed by palpitations, and/or tachycardia. Eighteen percent involved CNS side effects including stroke and seizure, 13 caused permanent disability, and at least 10 events resulted in death (49).

To reduce the number of adverse reactions due to nutritional supplements containing ephedrine, the FDA proposed appropriate marketing and labeling changes for these products in 1997 (50). Although their proposal did not ban OTC ephedrine-containing products, it was intended to make consumers more aware of safety concerns (50). Under the FDA’s guidelines, ephedrine manufacturers had to: (a) refrain from making supplements that contained more than 8 mg of ephedrine alkaloids per serving, (b) avoid using labels that suggested the use of more than 8 mg of ephedrine alkaloids in a 6-hour period or the total daily intake of more than 24 mg, (c) instruct consumers not to use ephedrine for longer than 7 days, (d) refrain from combining other stimulant ingredients, including caffeine, with ephedrine alkaloids, and (e) warn consumers that taking more than the recommended dosage of this product may result in a heart attack, stroke, seizure, or death (50). Owing to significant lobbying by supplement manufacturers, the FDA has since withdrawn these guidelines. However, as with many OTC supplements with a paucity of long-term safety and efficacy trials, the “FDA remains concerned that adverse effects are associated with long-term consumption of such products and with consumption of such products in excess of labeled serving sizes” (51).

With the surge in use of OTC supplements containing ephedrine alkaloids, there were numerous reports of collegiate and professional athletes suffering severe side effects after using these products. These included the collapse of at least 10 Northwestern University football players, including Rashidi Wheeler, who died after a rigorous preseason workout during August 2001. Another death believed to be related to the use of ephedra includes that of former Florida State University freshman Devaughn Darling, who collapsed and died in February 2001 after a workout. Although autopsy results were inconclusive, they did reveal ephedrine in his system (48). On September 27, 2001, the National Football League (NFL) also banned the use of ephedrine-containing products, decades after the NCAA and IOC had done so. The decision was in direct response to the August 1, 2001, death of Minnesota Vikings’ offensive lineman Korey Stringer, a professional football player who was believed to be using ephedrine during practice (52). Finally, following the national media frenzy that implicated ephedra in the death of a 23-year-old during a Baltimore Orioles training camp in February of 2003, along with the mounting evidence of more than 18,000 reports of adverse events and more than 100 deaths linked to the use of ephedra-containing products, the FDA banned its use on April 2, 2004.

Although there have been many discussions about the ethical and legal aspects of the use of AAS, a most poignant fact must not be forgotten—the use of AAS remains prevalent in the athletic community. Survey results among Americans indicate that AAS use is found in approximately 2% of students between the ages of 10 and 14, between 5% and 12% of high school males, and between 2% and 20% of college athletes (53,54,55). Estimates of AAS use in elite athletes (e.g., Olympians, professional football linemen) range from 44% to 99% (56). The 1993 Drug Abuse National Household Survey found that there are at least 1 million current or former AAS users in this country (others estimate >3 million), that males had higher levels of AAS use during their lifetime than females (0.9% and 0.1%, respectively), that the median age of first AAS use was 18 years, and, most alarmingly, that for the 12- to 17-year-old group the median age of initiation was 15 years (57). AAS use was highly correlated with self-reported aggressive behavior and crimes against property. Among the 12- to 34-year-old age group, steroid use was associated with the use of alcohol as well as illicit drugs (57). In another study, it was reported that 75% of all steroid users will have done so before their 17th birthday which means that most AAS use begins before high school ends (55).

It was reported to the NCAA that greater than 50% of college athletes who admitted to AAS usage began in high school (11). Buckley et al. conducted the first nationwide study of AAS use at the high school level in 1987 (55). AAS use was found in 6.6% of high school males. Of this group, approximately 40% reported doing five or more cycles, 38% had initiated use before age 16, 44% used more than one steroid at a time, and 38% used injectable AAS. No difference was found in rates between urban and rural areas. Interestingly, there was a significant difference by the size of enrollment, (i.e., the larger the high school, the higher the rate of reported AAS use). In a study of middle school students in Massachusetts (n = 965), 2.7% reported using steroids (58).

In 1985 Anderson and McKeag surveyed 2,039 NCAA athletes at 11 colleges and universities (11). The use of AAS was defined as use in the past 12 months. The greatest use was found among football players at 9%. Four percent of male track and field, and tennis and basketball players and 3% of male baseball players reported using AAS. The only women’s sport in which AAS were used was women’s swimming, in 1% of the athletes. In 1991 the survey was replicated (12). Again, 2,039 male and female athletes were surveyed from 11 colleges and universities (7 of the
original 11 schools participated). AAS use had increased only slightly over the preceding 4 years. This time the incidence of reported AAS use was 10% among football players, 4% for male track and field athletes, and 2% each for baseball, basketball and tennis. The use of AAS had increased in women’s sports. Now 1% of women who participated in track and field, basketball, and swimming admitted to AAS use. Among those athletes admitting to AAS use, 25% began using before college, 25% initiated use during the first year of college, and 50% began after the first year of college.

Why has the use of AAS become so prevalent among athletes? Yesalis’ 1987 study identified several reasons why athletes use steroids: 47.1% do so to improve athletic performance, 26.7% use AAS to improve their appearance, and 10.7% reported they do so to treat athletic injuries (55). AAS help athletes achieve size and strength gains when they are used concurrently with a proper diet and training regimen (59). However, studies have shown long-term AAS use may have detrimental consequences (59,60).

AAS are synthetic hormones that are analogs of testosterone, which athletes use in supraphysiological doses to give them the effects of high levels of testosterone. Like testosterone, these hormones are synthesized from the parent compound cholesterol. Various modifications made to the cholesterol compound yield AAS with differing properties. AAS as a group of compounds have a common structure based on the steroid nucleus, which consists of three six-member carbon rings and one five-member carbon ring. The naturally occurring steroids include male and female sex hormones (androgens and estrogens), the adrenal cortex hormones (corticosteroids), progesterone, bile salts, and sterols (cholesterol).

Natural testosterone is not effective when taken orally because of rapid first-pass liver metabolism. Similarly, natural testosterone injections undergo a relatively rapid rate of breakdown in the liver. Therefore, in an attempt to develop a more purely anabolic steroid, AAS are molecularly altered to resist this metabolic breakdown. The efficacy of orally administered AAS is greatly improved by alkylation at the 17 position (C-17 alpha-alkalization). This change decreases the first-pass metabolism by the liver and increases the AAS potency, although it also significantly increases the level of hepatotoxicity. The efficacy of parenteral or injectable AAS is enhanced by esterification of the 17-hydroxyl group. This modification yields a more lipid-soluble compound with extended activity. Parenteral AAS are suspended in oil or water. Suspending AAS in oil for injection helps them remain in the body for weeks or months. For example, testosterone cypionate (Depo) is detectable for at least 6 to 12 months. Oil-based AAS can also be administered transdermally. Water-based AAS such as stanozolol (Winstrol) are detectable for 5 to 12 months.

In men, testosterone acts in two ways—anabolically by stimulating nitrogen retention and muscle growth and androgenically, by promoting the development of secondary sexual characteristics. Endogenous testosterone plays a role in determining male sex characteristics. In utero, testosterone brings facial hair and a deepening of the voice during puberty, regulates the release of follicle stimulating-hormone (FSH) and luteinizing hormone (LH), increases protein synthesis, increases aggression, and increases sex drive. Testosterone is produced primarily by the Leydig cells of the testes and to some extent by the adrenals (usually <10% in males). Most of the daily testosterone production comes from the peripheral metabolism of prehormones (61,62). Serum testosterone levels are regulated by a negative feedback loop in response to low testosterone levels. In this loop, the hypothalamus releases gonadotrophin-releasing hormone that stimulates the pituitary to release gonadotrophins, which then act upon testosterone-producing sites (the testes and adrenals in males, and the ovaries and adrenals in females). FSH then downregulates the number of LH receptors.

The effects that compel athletes to take AAS stem from their anabolic nature. Anabolic refers to promoting the process of assimilation of nutritive matter and its conversion into living substance as well as promoting tissue growth by increasing the metabolic processes involved in protein synthesis. The anabolic effects that are sought by athletes include increased protein synthesis, decreased cortisol and adrenocorticotropic hormone (ACTH) release that is related to the inhibition of catabolic effects on skeletal muscle, promotion of a positive nitrogen balance that increases muscle mass, increased strength or force of muscle contraction (which may be a permanent increase if weight training is paired with a high protein diet [2.2 gm/kg/day]), inhibition of protein catabolism that may hasten recovery from injury; and stimulation of erythropoiesis that increases endurance due to the increase in red blood cell (RBC) mass. AAS use may also allow faster recovery time from repetitive, high-intensity workouts, enhance performance by increasing aggressiveness, and produce euphoria, thereby decreasing the sense of fatigue during training (59,60,63). Therefore, AAS can contribute to increases in lean body weight, strength, and endurance, if coupled with a proper diet and high-intensity exercise (64,65,66,67). Furthermore, the strength building effects of AAS are greater in athletes who have trained before AAS use than in those who have not trained (65). Two additional mechanisms theorized to result in the anabolic effects of AAS include increased messenger RNA and intracellular calcium concentration through the cAMP pathway, and increased acetylcholine release at the neuromuscular junction in the brain, thereby increasing monoamine levels which in turn increases aggression and energy (61,68). Therefore, Aas Can Contribute to Increases in Lean Body Weight, Strength, And Endurance, If Coupled with a Proper Diet and High-Intensity Exercise (64,65,66,67). Furthermore, The Strength Building Effects of Aas Are Greater in Athletes Who Have Trained before Aas Use Than in Those Who Have Not Trained (65). Two Additional Mechanisms Theorized to Result in the Anabolic Effects of Aas Include Increased Messenger Rna and Intracellular Calcium Concentration through the cAMP Pathway, And Increased Acetylcholine Release at the Neuromuscular Junction in the Brain, Thereby Increasing Monoamine Levels Which in Turn Increases Aggression and Energy (61,68).

For athletes, the less desirable effects of AAS stem from their androgenic properties. Androgenic refers to masculinization (i.e., stimulation of the development of male sex hormones and male secondary sexual characteristics). Androgenic effects include increased body and facial hair, deepening of the voice, increased sex drive, increased aggressiveness, male pattern baldness, and acne. Ultimately, AAS bind to androgen receptors, stimulate production
of RNA, and are anticatabolic because they improve the utilization of protein and inhibit the catabolic effect of glucocorticoids (59).

Athletes use AAS according to different regimens. One regimen is stacking or simultaneously using an average of five different AAS, in both oral and injectable forms, in 6- to 12- week cycles. Stacking is done because AAS users believe it will activate and saturate multiple steroid receptor sites, decrease the amount of each AAS necessary, decrease associated side effects, and provide synergistic benefits. Cycling is done to avoid developing a tolerance to AAS, avoid detection, decrease the incidence of harmful side effects associated with long-term AAS use, and allow the body to return to normal function between cycles. This last rationale for cycling is logical, given that endogenous testosterone levels, sperm production, and the entire hypothalamic-pituitary-gonadal axis are affected by AAS use; therefore, off-cycling allows these processes to return to normal. A type of drug regimen that involves stacking increasingly larger dosages of AAS, is commonly referred to as stacking the pyramid. There are numerous AAS regimens out there and they are becoming increasingly more complex.

AAS users employ dosages that may range from 40 to 100 times what is medically prescribed (63). The daily dose and route of AAS usage will depend on the cycle and stacking method used. AAS in dosages ranging from 50 to more than 200 mg/day are not unusual. The oral AAS preparations with shorter half-lives are typically taken up to three times daily. Parenteral injections vary anywhere from daily to weekly. AAS are taken along with other kinds of drugs that will prevent or counteract their androgenic effects, as well as extend their anabolic effects. Human chorionic gonadotrophin (hCG) is taken to counteract testicular atrophy; diuretics are taken to block water retention, create the “ripped” look and to circumvent detection; tamoxifen and other anti-estrogens are taken to block gynecomastia due to aromatization of the androgens; and antiacne medications are taken to resolve the acne that may develop in some AAS users (63). There have been reports that endocrinologists and steroid users have experimented with the use of prednisone to retard the anabolic gains that are lost after coming off AAS (69). While this is counterintuitive because cortisol is catabolic, the catabolic link may have more to do with endogenous ACTH. Not all of the combinations of AAS and other drugs are safe. In fact, some can be deadly. The riskiest use of AAS involves athletes who take multiple substances at one time while engaging in other self-destructive behaviors (63).

To avoid detection, athletes adjust their regimens according to the current knowledge of drug testing and discontinue use in a “safe” time period, make steroid alterations, and/or utilize masking techniques. Experienced users are knowledgeable about detection methods and event testing and can generally beat the system. Annual use patterns vary with the sport and the likelihood of being tested. Bodybuilders typically cycle on and off several times per year for several years, in a very systematic manner around competition dates. The typical 12-week cycle will include a pyramid with at least three to four different AAS. The athlete will then continue on other drugs which stop the rebound physiological bottoming out, prolong the anabolic and positive nitrogen balance, maintaining muscle and strength increases gained during the cycle.

Gains produced with AAS use are not made without significant risks. In one study, male mice were exposed for 6 months to four different types of AAS in levels that correspond to those that humans take (70). In addition to a control group that was not given any AAS, mice were given doses of AAS at 20 or 5 times the normal level for mice. One year after the end of the AAS exposure, 52% of the 20-time group had died, compared with only 35% of the 5-time group, and 12% of the control group.

AAS use leads to many cardiovascular side effects, including hypertension, in susceptible individuals (71

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