Anabolic Steroids

ANABOLIC STEROIDS

Anabolic steroids are synthetic versions of the naturally occurring male sex hormone, testosterone. They are more properly called anabolic-androgenic steroids (AASs), because they have both bodybuilding (anabolic) effects and masculinizing (androgenic) effects. The masculinizing effects of testosterone cause male characteristics to appear during puberty in boys, such as enlargement of the penis, hair growth on the face and pubic area, muscular development, and deepened voice. Females also produce natural testosterone, but ordinarily in much smaller amounts than males.

AASs are sometimes referred to simply as steroids. Steroid means only that a substance either resembles cholesterol in its chemical structure or is made from cholesterol in the body. Thus, AASs are one kind of steroid. (They are not to be confused with an entirely different group of steroids called corticosteroids—of which prednisone and cortisone are examples—which are commonly used to treat illnesses such as arthritis, colitis, and asthma. In contrast to anabolic steroids, corticosteroids can cause muscle tissue to be wasted.) AASs are also referred to as ergogenic drugs, which means performance-enhancing. Street or slang terms for AASs include "roids" and "juice."

Soon after testosterone was first isolated and synthesized in the laboratory in 1935, a number of synthetics were created to be used as medicines. The synthetic forms were developed because natural testosterone did not work very long when given as a pill or injection (it is subject to rapid breakdown in the body). Bodybuilders may have begun using AASs to build muscle size and strength as early as the 1940s. Olympic athletes started to use these drugs in the 1950s. Most of this use went undetected, however, because the technology of drug testing did not allow reliable detection of AASs in the urine until the 1976 Olympic Games. Even so, anabolic steroids did not become a household word until Canadian sprinter, Ben Johnson, tested positive for AASs at the Seoul Olympic Games in 1988. In the same year, a study reported that 6.6 percent of American male high school seniors had tried AASs. This study made it clear that elite athletes were not the only ones taking these drugs. By 1991, AASs were added by federal law to the list of Schedule III of the Controlled Substances Act. Schedule III Controlled Substances are recognized to have value as prescribed medicines, but also have a potential for abuse that may lead to either low to moderate physical dependence or high psychological dependence. Table 1 lists the names of some AASs that bodybuilders have used. Hundreds of AASs have been synthesized, and more comprehensive lists exist (Wright & Cowart, 1990; Yesalis, 2000).

Two naturally occurring steroids, dehydroepiandrosterone (DHEA) and androstenedione, are used by the body to make testosterone and estrogen (Corrigan, 1999). The benefits and adverse effects of synthetic DHEA and androstenedione are mostly unknown, but they are commonly believed to have anabolic and androgenic effects. Unlike other AASs, DHEA and androstenedione are neither regulated by the Food and Drug Administration nor listed as controlled substances in the United States. DHEA has been sold over-the-counter as a nutritional supplement in the United States since 1994, even though the International Olympic Committee, many U.S. sports organizations, and some countries such as Australia ban it.

GENERAL CHEMICAL STRUCTURE

Testosterone has a four-ring structure composed of nineteen carbon atoms. Accordingly, the carbon atoms are labeled by number from one to nineteen (see Figure 1). Many synthetic forms of testosterone are made by adding either an alkyl group or an ester to the seventeen-carbon atom. An alkyl group is a chain of carbon and hydrogen atoms. An ester is formed by reacting an acidic chain of carbon and hydrogen atoms to the-OH group on the seventeen-carbon atom. In general, when an alkyl group is added to the seventeen-carbon atom, the resulting drug can be taken as a pill; however, these so-called seventeen-alkylated AASs are relatively toxic to the liver and are more likely to cause negative effects on cholesterol levels. By contrast, when an ester is formed at the seventeen-carbon atom, an injectable form of testosterone is created that is less toxic to the liver and cholesterol levels. Other AASs are created by making modifications at other carbon atoms.

MEDICAL AND NONMEDICAL USES

AASs are prescribed by physicians to treat a variety of medical conditions (Bagatell & Bremner, 1996). The most accepted use is for treating boys and men unable to produce normal levels of their own testosterone, a condition known as testosterone deficiency orhypogonadism. AASs are also used to treat a rare skin condition called hereditary angioedema, certain forms of anemia (deficiency of red blood cells), advanced breast cancer, and endometriosis (a painful condition in females in which tissue usually found only in the uterus develops in other body parts). AASs are also combined with female hormones to treat distressing symptoms that can accompany menopause. Experimentally, AASs have been used to treat a condition in which bone loss occurs (osteoporosis), to treat impotency and low sexual desire, and as a male birth control pill. In addition, AASs have been used in the treatment of Acquired Immune Deficiency Syndrome (AIDS) to stimulate appetite, weight gain, strength, and improvements in mood. Most of these medical uses are uncommon, either because the conditions are rare (such as angioedema) or because other treatments are preferred (such as erythropoeitin for anemia). Nevertheless, AASs are important medicines to have available.

Nonmedically, AASs are used to enhance athletic performance, physical appearance, and fighting ability. Since society endows people who look physically fit and attractive with many benefits and recognition, some individuals see AASs as a means to those benefits. Three groups of AAS users have been described:

1. The athlete group aims to win at any cost. The athlete also believes, sometimes correctly, that the competition is using AASs. The anticipated rewards to the athlete are the glory of victory, social recognition and popularity, and financial incentives (college scholarships, major league contracts).
2. The aesthete group aims to create a beautiful body, as if to make the body into a work of art. Aesthetes may be competitive bodybuilders, or aspiring models, actors, or dancers. They put their bodies on display to obtain admiration and financial rewards.
3. This group of AAS users seeks to enhance their ability to fight or intimidate. They include body guards, security guards, prison guards, police, soldiers, bouncers, and gang members. These people depend on fighting for their very survival.

Whether AASs actually work to improve performance and appearance has been debated. Invariably, users believe AASs do work, but some scientific studies have failed to show an effect. However, there are serious limitations to how these studies were done and what they could show. In general, most researchers agree that AASs can work in some individuals to enhance muscle size and strength when combined with a proper exercise program and diet (Bagatell & Brenner, 1996; Bhasin et al., 1996). By contrast, AASs probably do not improve performance of aerobic or endurance activities (Yesalis, 2000).

CONSEQUENCES OF USE

AASs have been associated with a variety of undesirable effects. The most severe consequence attributed to their use is death. One study of mice given AASs revealed a shortened life span (Bronson & Matherne, 1997). In humans, the distinction between fatalities that occur among relatively healthy athletes who use AASs and patients with illnesses (such as anemia) who are prescribed AASs is important, because ill patients are already at a higher risk for an early death. Nevertheless, reported deaths in nonmedical steroid users (such as athletes and aesthetes) have occurred from liver disease, cancer, heart attacks, strokes, and suicide (Yesalis, 2000; Pope & Brower, 2000). Clearly, anyone using AASs should have their health monitored by a physician.

Psychiatric Effects.

Another serious, life-threatening consequence has been violent aggression toward other people. Both the medical literature and newspapers contain reports of previously mild-mannered individuals who committed murder and lesser assaults while taking AASs (Thiblin et al., 1997). Although reports of severe violence generate both alarm and widespread attention, the total number of such reports is small. Moreover, the effects of AASs on violent behavior vary widely depending on the social circumstances and the characteristics of the individual. Nevertheless, most but not all studies in humans have found that high doses of AASs increase feelings and thoughts of aggressiveness (Yesalis & Cowart, 1998). Although an increase in feelings and thoughts of violence does not always lead to violent behavior, it can be very distressing to the individual and to those around him or her. "Roid rage" is a slang expression used to describe the aggressive feelings, thoughts, and behaviors of AAS users.

Other psychiatric effects of AASs include mood swings and psychosis (Pope & Brower, 2000). AAS users commonly report that they feel energetic, confident, and even euphoric during a cycle of use. They may have a decreased need for sleep or find it difficult to sleep because of their high energy level. Such feelings may give way to feeling down, depressed, irritable, and tired between cycles of use. With continued use of high AAS doses, moods may shift suddenly, so that the user feels on top of the world one moment, irritable and aggressive the next, and then depressed or nervous. The appetite may also swing widely with cycles of use (Wright & Cowart, 1990). During a cycle on AASs, huge quantities of food may be consumed to support the body's requirements for muscle growth and energy. During the "off cycles," appetite may diminish.

The term "psychosis" means that a person cannot distinguish between what is real and what is not. For example, a person may believe that other people intend harm when no real threat exists; or a person may believe that an impossible, life-threatening stunt can be performed with no problem. Such false beliefs are called delusions. The psychotic person may also experience hallucinations, such as hearing a voice that is not there. Fortunately, most psychiatric effects of AASs tend to disappear soon after AASs are stopped, although a depressed mood may last for several months. Obviously, when suicides, homicides, or legal consequences from assault have occurred, they cannot be reversed simply by stopping one's use of AASs.

Effects on the Liver.

AASs can affect the liver in various ways, but the seventeen-alkylated AASs are more toxic to the liver than other AASs. Most commonly, AASs cause the liver to release extra amounts of enzymes into the bloodstream that can be easily measured by a blood test. The liver enzymes usually return to normal levels when AASs are stopped. The liver also releases a substance called bilirubin, which in high amounts can cause the skin and eyes to turn yellow (a condition called jaundice). As many as 17 percent of patients treated with the seventeen-alkylated AASs develop jaundice (Yesalis, 2000). Nonmedical AAS users can also develop jaundice. Although untreated jaundice can be dangerous and even fatal, jaundice usually disappears within several weeks of stopping AASs. Jaundice can also signal other dangerous conditions of the liver, such as hepatitis, so a physician should always treat it. Another condition that occurs among patients treated with AASs is peliosis hepatis, in which little sacs of blood form in the liver. Death can occur from bleeding if one of the sacs ruptures. Finally, liver tumors may occur in 1 to 3 percent of individuals (including athletes) using high doses of the seventeen-alkylated AASs for more than two years (Yesalis, 2000). Rare cases of liver tumors have been reported with other types of AASs as well. Some of the tumors are cancerous, and although more than half of the tumors disappeared when AASs were stopped, others resulted in death.

Potential to Affect the Heart.

AASs can cause changes in cholesterol levels (Yesalis, 2000). Low amounts of a certain kind of cholesterol (high-density lipoprotein cholesterol) in the blood are known to increase the risk of heart attacks. AASs, especially the seventeen-alkylated ones, cause a lowering of this so-called good form of cholesterol. When AASs are stopped, however, cholesterol levels return to normal. Another risk factor for heart attacks and strokes is high blood pressure. Studies have shown that AASs can cause small increases in blood pressure, which return to normal when AASs are stopped. As a result of strenuous exercise, many athletes develop an enlarged heart that is not harmful. Some, but not all studies, suggest that AAS users can develop a harmful enlargement of the heart. As noted previously, heart attacks and strokes have been reported in AAS users, but studies are needed to determine if AAS users have a higher risk of heart attacks and strokes than non-users (Yesalis, 2000).

Sexual Side Effects.

AASs can alter the levels of several sex-related hormones in the body, resulting in many adverse effects (Wright & Cowart, 1990; Yesalis & Cowart, 1998). In males, the prostate gland can enlarge, making it difficult to urinate; the testes shrink; and sterility can occur. The effects on the prostate, the testes, and sterility reverse when AASs are stopped; however, at least one case of prostate cancer has been reported, an exception to reversibility. Males can also develop enlarged breast tissue from taking AASs, an effect medically termed "gynecomastia" (it is referred to by male users as "bitch tits"). Gynecomastia occurs because testosterone is chemically changed in the body to the female hormone, estrogen. Thus, the male user experiences higher amounts of estrogen than normal. Painful lumps in the male breast may persist after stopping AASs, and they sometimes require surgical removal. Females, however, may undergo shrinkage of their breasts, as a response to higher amounts of male hormone than normal. Menstrual periods become irregular and sterility can occur in females as well. Deepened voice and an enlarged clitoris are effects in females, which do not always reverse after stopping AASs. Women may also develop excessive hair growth in typically masculine patterns, such as on the chest and face. Finally, both males and females may experience increases and decreases in their desire for sex.

Other Effects.

In children of both sexes before the onset of puberty, AASs can initiate the characteristics of male puberty and cause the bones to stop growing prematurely. The latter effect can result in shorter adult heights than would otherwise occur. AASs can cause premature baldness in some individuals, and it can cause acne. The acne is reversible with cessation of AASs. Other possible effects include small increases in the number of red blood cells, worsening of a condition called sleep apnea (in which afflicted persons stop breathing for short intervals during sleep), and worsening of muscle twitches (known as tics) in those who are predisposed.

Patterns of Illicit Use.

AASs are commonly smuggled from countries where they are obtained over-the-counter without a prescription, and then sold illegally in the United States. Dealers and users typically connect in weight-lifting gyms. Users report that AASs are relatively easy to obtain.

Steroids are taken as pills, through skin patches, and by injection (Bagatell & Bremner, 1996). Injection occurs into large muscle groups (buttocks, thigh, or shoulder) or under the skin, but not into veins. Cases of acquired immune deficiency syndrome (AIDS) have been reported in steroid users due to needle sharing. Steroids are often taken in cycles of six to twelve weeks on the drugs, followed by six to twelve weeks off. At the beginning of a cycle, small doses are taken with the intent to build to larger doses, which are then tapered at the end of a cycle. Illicit users typically consume ten to one hundred times the amounts ordinarily prescribed for medical purposes, requiring them to combine or "stack" multiple steroid drugs. The actual dose cannot always be determined, however, because illicit steroids may contain both falsely labeled and veterinary preparations. (Drugs purchased on the illicit market do not always contain what the labels indicate, and law-enforcement officials have confiscated vials contaminated with bacteria.)

Steroid users commonly take other drugs, each with their own risks, to manage the unpleasant side effects of steroids, to increase the body-building effects, and/or to avoid detection by urine testing (Wright & Cowart, 1990). For example, estrogen blockers, such as tamoxifen or clomiphene, are taken to prevent breast enlargement. Water pills (diuretics) are taken both to dilute the urine prior to drug testing and to eliminate fluid retention so that muscles will look more defined. Human chorionic gonadotropin (HCG) is an injectable, nonsteroidal hormone that stimulates the testicles to produce more testosterone and to prevent them from shrinking. Human growth hormone is another nonsteroidal hormone that is taken to increase muscle and body size.

Addictive Potential.

As with other drugs of abuse, dependence on AASs occurs when a user reports several of the following symptoms: Inability to stop or cut down use, taking more drugs than intended, continued use despite having negative effects, tolerance, and withdrawal. "Tolerance" refers to needing more of a drug to get the same effect that was previously obtained with smaller doses, or of having diminished effects with the same dose. In terms of the anabolic effects, tolerance was demonstrated in animals in the 1950s. In recent studies, 12 to 18 percent of nonmedical AAS users reported tolerance (Yesalis, 2000; Copeland et al., 2000). Whether tolerance develops to the mood-altering effects of AASs is unknown. Withdrawal refers to the uncomfortable effects users experience when they stop taking AASs. As noted previously, many of the undesirable effects reverse when AASs are stopped, however, others can begin—such as depressed mood, fatigue, loss of appetite, difficulty sleeping, restlessness, decreased sex drive, headaches, muscle aches, and a desire for more AASs (Copeland et al., 2000). The depression can become so severe that suicidal thoughts occur. The risk of suicide described previously is thought to be highest during the withdrawal period.

Studies indicate that between 14 and 57 percent of nonmedical AAS users develop dependence on AASs (Yesalis, 2000), and rare cases have been reported in women (Copeland et al., 2000). These studies support the addition of AASs to the list of Schedule III controlled substances. Nevertheless, AASs may differ from other drugs of abuse in several ways. First, neither physical nor psychological dependence on AASs has been reported to occur when AASs are prescribed for treating medical conditions. This differentiates the AASs from the opioid pain killers and the sedative-hypnotics. Second, dependence may develop primarily to the muscle-altering effects of AASs, rather than the mood-altering effects. Some researchers have questioned whether AASs produce dependence at all, because most definitions of dependence require that drugs be taken primarily for their mood-altering effects. Third, AAS users appear more preoccupied with their bodies and how they look than do users of other drugs of dependence.

SUMMARY

The anabolic-androgenic steroids are related to the male sex hormone, testosterone. They have both masculinizing and bodybuilding effects. AASs are useful to treat a variety of mostly uncommon medical conditions. They are sometimes used for the nonmedical purposes of enhancing athletic performance and physical appearance. Most researchers agree with users that AASs can increase muscle size and strength in some individuals when combined with a proper exercise program and diet. Many are also concerned about the potential for harmful effects with AASs, especially when the patterns of illicit use are considered. Drugs obtained on the illicit market may be contaminated, falsely labeled, or may contain substances not approved for human use. Multiple steroid and nonsteroidal drugs are combined, and AAS doses may exceed therapeutic doses by ten to one hundred times. Although the seventeen-alkylated AASs are commonly used because pills are more convenient than injections, they are more toxic to the liver and cholesterol levels than the injectable testosterone esters. Nevertheless, injections carry their own risks from improper injection techniques to dirty and shared needles.

The most serious side effects of AASs seem relatively uncommon, such as deaths or near-deaths from liver disease, heart attacks, strokes, cancer, suicide, and homicidal aggression. Most other side effects appear to be reversible when AASs are stopped, such as altered cholesterol levels, some liver effects, most psychiatric effects, testicular shrinkage, sterility, high blood pressure, and acne. Exceptions to reversibility include lumps in the male breast, deepened voice and enlarged clitoris in females, and cessation of bone growth in children. Moreover, some individuals may develop dependence on AASs, making it difficult for them to stop using. Stopping use can also produce distressing withdrawal symptoms, the worst of which is suicidal depression. Finally, studies of the long-term effects of using AASs are lacking, so safety cannot be assumed with the high-dose use of these drugs.

BIBLIOGRAPHY

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Kirk J. Brower