Steroids

Anabolic steroids are not mysterious wonder drugs; they are simply man-made versions of the primary male sex hormone, testosterone.

Hormones are one of the body's major regulatory mechanisms. Both men and women have natural hormones that serve as the controllers of the almost infinite number of chemical reactions that take place within our bodies. Hormones actively "turn on" or "turn off" a gene so as to alter the supply of cell components or influence the rate of chemical processes in the body. For example, hormones can tell muscle cells to produce specific proteins from raw materials within the body so that muscle tissue mass will increase. Hormones also can activate genes in skin cells to influence the growth of facial hair. Hormones regulate the supply of raw materials within the cells and often work directly to speed up or slow down certain biochemical reaction rates.

Two organs in the brain, the pituitary and the hypothalamus, control many hormonal functions. The thyroid gland and the pancreas also produce hormones. The group of hormones that are produced by the adrenal gland and ovaries in women, and the adrenal gland and testes in men, consist of a special type of lipid (fat) called steroids, which comes from a Greek word that means solid. The human body is capable of producing more than 600 different types of steroids, including testosterone, and a number of them exhibit male hormone-like activities. This family of compounds is known as androgens. The word androgen is derived from the Greek roots andro (meaning male) and gen (meaning to produce) and refers to male sex hormones.

The natural supply of testosterone in adult males is produced by the Leydig cells located within the testes. (Women and young boys do have a small amount of testosterone in their bodies that is produced by the adrenal gland.) Very little testosterone is stored within the body so that production must be more or less continuous. Testosterone is responsible for both the androgenic (masculinizing) and anabolic (tissue-building) effects that take place during puberty and continue in adulthood. It is the significant increase in the production of testosterone in a young male that precipitates puberty.

Anabolic steroids are primarily a consequence of research to develop drugs that would separate the tissue-building capability of testosterone from its masculinizing properties. This separation has never been fully achieved. Consequently, the proper name for this class of hormones is anabolic-androgenic steroids, although they are usually referred to simply as anabolic steroids or steroids.

Don't confuse anabolic steroids with corticosteroids such as prednisone or cortisone. Corticosteriods are hormones produced by the adrenal glands, and their biological properties are quite different from those of anabolic steroids. Corticosteroids like prednisone or cortisone are potent anti-inflammatory drugs used in medicine to treat conditions such as asthma and muscle strains and sprains. Their effect is catabolism (protein metabolism or breakdown) rather than anabolism (tissue protein building).

Mechanisms of action

Anabolic steroids were adopted initially by athletes in power sports such as weight lifting and football to increase strength and muscularity. From the beginning, these athletes consistently reported that the drugs also reduced their recovery time between workouts. That meant that they were able to work out more frequently, for longer periods of time, and with greater intensity. These observations by athletes very likely played an important role in the diffusion of anabolic steroids among sprinters in a variety of sports and, thereafter, to endurance athletes.

The truth is that anabolic steroids work. That is to say that anabolic steroids, especially when used in conjunction with intense strength training, increase muscle mass and strength well beyond what can be achieved with training alone. Experts have suggested the following mechanisms to explain the performance-enhancing effects of anabolic steroids.

• An increase in protein synthesis
• Prevention of muscle tissue destruction caused by heavy work or exercise
• The effects on the central nervous system and the neuro-muscular junctions
• Increased aggressiveness
• The placebo effect

How anabolic steroids work is most likely explained by a combination of these mechanisms.

In the normal way of things, two things can happen when athletes such as wrestlers, runners, or swimmers stress their bodies through training at high levels of intensity over prolonged periods. First, their natural production of testosterone can drop precipitously, often to levels as low as those of a castrated man. Second, the body responds by releasing another type of steroid called glucocorticoids, which are not anabolic (tissue building) but catabolic, meaning that they break down muscle tissue. A popular theory holds that a visible sign of overtraining is muscle wasting.

Although the evidence is incomplete, scientists have speculated that anabolic steroids inhibit or block the catabolic effects of these glucocorticoids. If this theory is correct, a runner could endure more miles of road work per week and consequently lower her times, or a weight lifter could work out more often and do more sets and reps and achieve greater muscle and strength gains. Some experts have gone so far as to theorize that this anticatabolic mechanism may be the most important factor in untangling the performance effects of anabolic steroids. Beyond helping negate the muscle breakdown effects of glucocorticoids, anabolic steroids help replenish testosterone levels depleted by intense training.

The anabolic effect of steroids comes through increasing protein synthesis through their attachment to receptors in target tissues, which include skeletal and heart muscle, skin, testes, prostate, and various areas of the brain. Then these newly formed hormone receptor complexes interact with other receptor sites on the chromosomes and, through this hormonal chain action, ultimately result in the formation of various enzyme, structural (bone), and contractile (muscle) proteins. Obviously, the effect on muscle growth is of the greatest interest to steroid users. An "overload" of anabolic steroids causes an increase in the production of proteins, which in turn become building blocks for new cells.

The response to anabolic steroids, both positive and negative, varies significantly among men and women. With regard to skeletal muscle, anabolic steroids have a significantly greater impact on females (young and old), old males, and prepubescent males than they do on young adult males. Even within these groups there is variation in muscle response to anabolic steroids, most likely due to variations among individuals in the proportion of slow-twitch and fast-twitch muscle fibers (individuals with a higher percentage of fast-twitch fibers demonstrate greater response). Furthermore, even though all skeletal muscles respond to anabolic steroids, the sensitivity of individual muscles to steroids varies significantly. The pectoral muscles and shoulder girdle appear to be the most sensitive in males, probably because of the higher proportion of fast-twitch fibers in these muscle groups.

Many steroid users have reported increased energy levels and aggressiveness. Researchers have used several different types of psychological testing to discover whether this change is a factor that could account for some performance gains that are attributed to steroids. Whereas much of the discussion of steroid-induced aggression has focused on the negative side, little attention has been paid to the fact that appropriately channeled increased aggression is a part of most of athletics. In fact, such aggression is valued in sports such as football and wrestling because, in the eyes of many coaches, it is associated with improved performance. Likewise, it is logical to assume that an athlete doing strength training or conditioning in a more aggressive manner and with more energy would achieve better results. In addition, there is a widely held belief that increased aggression allows an athlete to better tolerate the pain and discomfort associated with intense training.

Although studies have demonstrated that anabolic steroids can affect both the central nervous system and neuromuscular junctions, the relationship between these findings and the increased aggressiveness and energy levels reported by athletes is not well understood. These findings do, however, raise the possibility that there could be a biochemical foundation for the aggressiveness some steroid users display. A corollary to this theory is the assertion that when a large, heavily muscled individual acts in an aggressive manner, he will receive more attention than a small person who behaves aggressively, because the large man can do more damage.

The term placebo effect refers to changes, either physical or psychological, that occur when an individual takes an inert substance that he believes will have a therapeutic effect. This medical phenomenon has been observed since the days of the ancient Greeks. Many people mistakenly believe that any benefit attributed to a placebo resides only in a person's imagination. This belief may hold true for some cases, but others have improvement based on objective clinical standards.

Although our understanding of the mind's effect on the body is still in its infancy, the effect is no less real. Thus, it seems likely that at least some athletes who take steroids see and realize gains because they expect to see them. Regardless of the mechanism, the overpowering response reported by athletes who use steroids over the past 40 years is far greater than what could be expected from the placebo effect alone, however.

How steroids were developed

The search for the source of human strength is ancient. For hundreds of years before the word hormone came into the language, strength and power were linked with male sex organs. Primitive people commonly ate animal organs, sometimes even those of humans, in the belief that they could improve their strength, courage, or sexual function. As early as 140 BC, a healer in India advocated eating testicle tissue as a cure for impotence.

The practice of human castration, which probably originated about 2000 BC in Babylon, provided evidence that loss of the testicles meant that males lost not only their fertility, but also their strength, their power, and their aggressiveness. Animal castration provided similar evidence. Even though Aristotle (300 BC) knew nothing about the secretion of sex hormones, he still was able to clearly describe the effect of castration on a bird.

In 1889, a French physician named Charles-Edouard Brown-Sequard performed a series of experiments in which he injected extracts made from animal testes into dogs and even himself. He reported an improvement in general health, muscular strength, appetite, regulation of the intestinal tract, and mental faculties. This experiment was not scientifically controlled, and today his results have been attributed to the placebo effect. However, his work stimulated other researchers to follow in his footsteps. In the continuing quest for youth and vigor, injections of animal testicle extracts and even the surgical implantation of monkey testicles became very popular in mainstream medicine until the early 1930s. Thereafter, the practice dwindled and died out as a result of the work of responsible scientists who debunked these claims of rejuvenation.

Most scientists of the late 1700s and early 1800s believed that the nervous system was the mediator of the changes that occurred after castration. Then in 1849, a German scientist named Berthold did a simple but elegant experiment with six roosters. He showed that the changes in the combs and wattles that occurred when roosters were castrated could be prevented if the removed testes were transplanted into the bird's abdominal cavity. This experiment made it clear that the active masculinizing substance was produced in the bloodstream and did not involve the central nervous system.

A burst of research activity that began in the 1920s on hormones and the endocrine system, and on male hormones specifically, led to an important series of observations about how hormonal control occurs, what it does, and which hormones are responsible for specific functions. By 1935, testosterone had been isolated, its chemical structure identified, and the basic nature of its anabolic and androgenic effects had been recognized.

The next major figure in hormonal research was the man most experts consider the father of anabolic steroids, Dr. Charles Kochakian. In the early 1930s, Dr. Kochakian showed that a hormone-like extract from male urine stimulated a strong positive nitrogen balance in castrated dogs. This finding was important because positive nitrogen balance indicates the synthesis of new tissue (proteins) in dogs and in humans. Thus, the anabolic or tissue-building properties of testosterone were established. A subsequent series of studies in rats showed similar results, and again, the positive nitrogen balance was associated with an increase in nonfat body weight.

Once researchers discovered that testosterone stimulates the protein-synthesizing or tissue-building process, it was immediately clear that there could be important medical applications if the tissue-building properties could be isolated. Throughout the 1940s, scientists grappled with the problem of getting the tissue-building effects of testosterone without also getting the masculinizing effects. The notion of a drug that could stimulate the development of new tissue was extremely attractive during World War II because it could aid in wound healing and perhaps save lives. Thus, the project took on new significance.

Dr. Kochakian soon became concerned about possible misuse of anabolic steroids, and he has warned that a complete split of the hormonal properties is not possible. "There is no such thing as a pure anabolic steroid," he has written. "All of the modified steroids still retain sufficient virilizing (masculinizing) activity to make them objectionable as therapeutic agents, especially in children and women."

While experiments to find a testosterone preparation that would stimulate tissue-building continued, other researchers worked to alter the chemical structure of testosterone. The addition of esters, which are formed from an alcohol and an acid when water is removed, was one method used to chemically alter the testosterone molecule. Some of these testosterone esters proved to be useful for treating protein deficiency in both humans and in horses. Almost 60 years later, these same testosterone esters are one of the chief drugs that athletes use.

Health consequences of steroid use

The undesirable physical health consequences that are most often associated with abuse of anabolic steroids include the following:

• Cosmetic changes
• Heart disease
• Infertility
• Liver toxicity
• Musculoskeletal injuries
• Prostate problems
• Stroke

Physical appearance

Oily skin and acne, which can cause scarring, are among the most frequently observed side effects of steroid use among athletes. Another is changes in hair patterns, such as increased body hair growth and an acceleration in male pattern baldness in those predisposed to it. Breast enlargement (gynecomastia) in men or shrinkage of breast tissue in women are side effects considered by most to be unwanted.
Many of these effects are permanent and, not surprisingly, distressing to the individual, although none is considered a serious risk to life or limb. The most serious threat to appearance is the very real possibility that chronic steroid use, especially prior to puberty or in early adolescence, could cause the premature closure of the growth plates of the long bones so that adult stature is significantly shorter than nature intended.

Muscle and bone injuries

So far, the musculoskeletal injuries sustained by steroid users cannot be distinguished from those seen in strength athletes with extraordinary muscle development who do not use steroids. Animal studies suggest that the risk of tendon rupture may be increased in steroid users, however. There are several anecdotal reports of injuries in athletes whose muscle mass exceeded the strength of the attachment to bone. The most common type of injury that athletes sustain is damage to the ligaments and tendons.

Infertility

The reversible effect of steroid administration on male fertility has been studied for more than 20 years with a thought to using anabolic steroids as a male contraceptive. Taking synthetic sex hormones disrupts the normal hormonal process. Many steroid users report an increase in libido initially, but diminished sex drive is associated with prolonged use. Most men who self-administer high doses of steroids become infertile during the period of use and for some time afterwards, perhaps six months or more. Infertility cannot be reliably produced in all males, and not all steroids are equally effective. Several researchers believe there is a risk of sterility with prolonged use at high dosage levels, but no case has ever been reliably documented. A common problem related to the infertility issue is a significant reduction in the size of the testicles as a result of steroid use.

Heart disease

There are good reasons to believe that long-term abuse of anabolic steroids increases the incidence of heart disease, even though that fact has not yet been demonstrated unequivocally. Several known bodily changes in steroid users could explain this possible increased risk of heart disease.

Lipid levels

The use of anabolic steroids causes a reduction in the serum level of a type of blood fat known as HDLC (high-density lipoprotein cholesterol), probably because the steroids stimulate a liver enzyme that regulates fats in the blood. This reduction of the so-called "good cholesterol" is clinically significant and has been identified as a major risk factor for heart disease and stroke in epidemiological studies of men who are not steroid users. This reduction appears to be reversible; HDLC levels begin to recover within about a month after steroid use is discontinued.
Although this depression of HDLC has been documented in a number of studies of athletes taking steroids, it's not an inevitable consequence because not all steroids produce the effect to the same extent. Oral steroids have a significantly more pronounced negative impact on HDLC levels, probably because of their overall stressful impact upon the liver. A few studies have reported an increase in total cholesterol but most do not. It appears that the decrease in circulating HDLC is offset by an increase in low-density lipoprotein cholesterol (LDLC) so that the total cholesterol level remains the same.

Glucose tolerance

Some anabolic steroids can cause glucose intolerance which, like blood fat changes, is considered a risk factor for heart disease in itself. These steroids can also impair the body's mechanism for regulating the amount of insulin so that too much is produced. Researchers have suggested that testosterone and steroids increase the risk of heart disease through an effect on insulin.

Blood pressure

There have been claims that steroids cause high blood pressure, but this claim appears to be exaggerated, based on a few studies that demonstrated increases in blood pressure that were of little or no clinical significance.

Heart tissue

The effects of testosterone on the heart muscle of animals were first described more than 60 years ago, and evidence that anabolic steroids alter myocardial performance in animals was presented more than 40 years ago. These animal studies showed that the heart has androgen receptors and that anabolic steroids can cause cardiac dysfunction.
Enlargement of the heart (cardiomegaly) is not always a bad thing. Exercise itself causes an increase in heart size that is not dangerous but represents a physical adaptation by the heart muscle to increase the blood supply to meet increased physical demands. With each beat of a normal heart, the main pumping chamber (left ventricle) ejects between 50 and 80 percent of the blood in the chamber, depending on the activity level. This is called the ejection fraction. When the heart becomes larger because of disease or drug use, its efficiency diminishes; the ejection fraction may fall below 40 percent, which means that the heart pump is no longer efficient. When this happens, the individual will have fatigue and shortness of breath and be unable to sustain a high level of physical activity.
In 1988, the first case of cardiomyopathy (a medical term referring to heart disease) and stroke (cerebrovascular accident) associated with anabolic steroids was reported. Since then, other case reports have indicated that using anabolic steroids can cause this unhealthy enlargement and weakening of the main pumping chamber.

Stroke and heart attack

Steroid abuse has emerged as a possible cause of thrombotic stroke, the kind caused by a blood clot. The medical literature contains several case reports of athletes and one of a young man who secretly increased his intake of a form of testosterone that had been prescribed to help him mature (a legitimate use of the drug) that had this kind of stroke. In addition, several cases of stroke have been reported in Japanese men who received large doses of anabolic steroids as treatment for a type of anemia. Although no direct evidence exists, the clinical circumstances of these case reports is suspicious and suggests a possible relationship between steroid use and the risk of stroke. If a causal relationship does exist, it could represent the first evidence that steroids have potentially life-threatening short-term effects.

Prostate diseases

Women who take oral contraceptives, which also are sex hormones, have a slightly greater risk of breast cancer. The parallel in men may be a higher risk of prostate cancer as a result of taking steroids. Although it usually is a disease of older men, prostate cancer is the second leading cause of cancer death (after lung cancer) in American men. If steroids increase the risk, it is a matter of serious concern. Physicians know that prostate cancer is negatively affected by the male hormone testosterone; standard treatment for this disease already includes reducing or blocking testosterone within the body. One case report describes a bodybuilder who had prostate cancer at the early age of 40 years. It is quite possible that today's steroid abusers will face a higher risk for prostate cancer as they age.

Liver disease and cancer

Steroids definitely have a strong negative effect on liver function, which is not surprising because the liver is the principal site where steroids are cleared from the body. Virtually all changes in the structure of the liver have been associated with the use of a type of oral steroids known as 17 alpha-alkylated steroids. When steroids are taken by mouth, the liver is exposed to the full dose of the drug before it is distributed in the circulation. This exposure can be particularly dangerous in individuals who already have poor liver function from other causes. Anabolic steroid abuse can harm the liver in several ways.

Jaundice

Blockage of the bile flow, which causes jaundice (yellowing of the skin and the whites of the eyes), has been seen in patients with serious diseases who are being treated with anabolic steroids. The first suggestion that some anabolic steroids might cause liver problems came when physicians tried to use methyltestosterone (an anabolic steroid) to treat the severe itching associated with obstructive jaundice. Most patients with jaundice got worse. Although athletes have used steroids that have been associated with bile flow blockage and jaundice, most probably stop taking steroids when jaundice occurs. For these reasons and the fact there have been only a few documented clinical cases of jaundice in athletes, almost no information exists about this condition in healthy individuals.

Peliosis hepatis

Peliosis hepatis is a potentially life-threatening condition in which blood-filled cysts develop in the liver. Before the development of steroids, this condition was seen almost exclusively in patients with pulmonary tuberculosis. Now, more than 70 cases of peliosis have been reported in association with intake of male hormones. The reason that this condition is so dangerous is that it is not easily diagnosed and patients often have no symptoms. If the cysts rupture, the patient can die, with little or no warning, from internal hemorrhage.

Liver tumors

Taking anabolic steroids increases the risk of liver tumors. The type of tumor seen most often behaves more like a noncancerous, or benign, type of liver tumor. These benign tumors can still be life threatening, however. At least several of the steroid-related tumors were diagnosed because the tumors ruptured and caused serious or fatal internal bleeding. There is one report of a hepatocellular carcinoma in a steroid-using athlete who died from this metastatic cancer. Another athlete who used steroids died from internal hemorrhage after a type of tumor called an adenoma ruptured. A third patient also had an adenoma but survived after it was removed surgically.

Psychological effects

So much attention was given to the serious physical health consequences of anabolic steroid use that it was some time before researchers realized that the psychological and behavioral effects might be equally important. Anabolic steroids were used from the late 1930s until the mid-1980s as an accepted and seemingly successful treatment for mood and mental disorders, including psychosis and depression. The psychological effects of giving therapeutic dosages of anabolic steroids in clinical settings include an increase in mental alertness, mood elevation, improvements in memory and concentration, and reduction of fatigue sensations.

Other research has shown that testosterone has a significant effect on both the development and function of the nervous system. It appears that the effect of testosterone/anabolic steroids on brain function results in an elevation of norepinephrine (nature's version of adrenaline) levels in the brain. Anabolic steroids also have been shown to elicit changes in brain activity similar to those seen with amphetamines and tricyclic antidepressants.

The relationship between natural testosterone levels and dominance and aggressive behavior in various species of animals is well known. Of course, as we move up the evolutionary scale, social learning plays a significantly greater role in behavior. Although the relationship between testosterone and aggression is quite pronounced in mice and rats, the association is somewhat less consistent in monkeys, apes, and especially man. Nevertheless, a number of studies have looked at naturally occurring testosterone levels in men, and many, but not all, have shown an association between elevated testosterone levels and increases in both subjectively perceived aggressive behavior and observed aggressive behavior.

Although most scientists apparently agree that anabolic steroids, especially at high doses, seem to increase aggressiveness, not all studies reached this conclusion. Although three prospective, blinded studies documenting aggression or adverse overt behavior resulting from steroid use have been reported, two recent clinical trials, in which fairly substantial doses of steroids were administered to volunteers over a period of weeks, didn't detect any widespread demonstrable sexual or psychological effects.

Dependence

In classic drug addiction, changes within the brain and body cause a craving for the abused drug, and physical withdrawal symptoms occur when use is discontinued. For instance, cocaine produces dependence through a mechanism called "primary reinforcement." Taking the drug stimulates the parts of the brain that are involved with reward, and a user feels pleasure or euphoria.

Although steroids don't appear to produce that type of immediate high, many users do say they feel pleasure from using the drugs over a period of time. The "high" they feel just occurs over a longer period of time. Some researchers have reported mood elevation in patients who were taking steroids for medical reasons, but it is still unclear whether steroids can cause the type of physical and/or psychological dependence that occurs with cocaine use.

We do know that anabolic steroids enter the brain and become attached to certain receptor sites. One study demonstrated that steroids can affect the same neurotransmitters that are involved in the action of cocaine and other stimulants on the brain. If steroids do have the potential to cause physical dependence, educational programs or penalties alone would not be enough to turn an addicted user away from the drugs.

The area of mood and behavior has the most potential for drug dependence. Most investigators now agree that steroids, especially at high doses, apparently can increase aggressiveness, but the studies in the medical literature are not uniform in this conclusion. Because most steroid users begin taking steroids for their effects on the body, they may not be fully aware of the possible mood-altering properties as well.

The experts say that there is some evidence that steroids can lead to dependence. The next step then is to examine that evidence and define dependence. Psychiatrists are very specific in their definitions of "psychoactive substance dependence" caused by using drugs that alter mood, thinking, or behavior. To meet the psychiatric criteria for drug dependency, a user must have at least three of the following symptoms for at least one month before a diagnosis of substance-dependency is made:

• Takes more of the substance than intended
• Wants to stop or cut down use but is unable to do so
• Spends a lot of time on substance-related activity
• Is frequently intoxicated or suffering from withdrawal symptoms when expected to function or when physically hazardous
• Replaces social, work, or leisure activities with drug use
• Continues drug use despite problems caused or worsened by use
• Exhibits tolerance
• Has withdrawal symptoms
• Uses the substance to relieve or avoid withdrawal symptoms

A number of studies of bodybuilders who use steroids have shown that 25 percent to more than 50 percent exhibit attitudes and behaviors that meet these criteria and are indicative of dependence on these drugs. There have been reports that for many in bodybuilding, where physical development is the purpose of the activity, taking steroids is an integral part of the lifestyle and subculture.

Whatever views anyone may hold regarding the potential for steroid addiction, scientific discussion of the subject has no meaning to an individual user who finds himself unable to stop behavior that he knows is clearly causing harm. The question then becomes one of offering help appropriately. If we believe that steroids produce dependence, we need to understand the mechanism of how this dependence happens in order to prevent and treat it.

Comments