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Introduction Competition is in our blood. The human drive to compete-and-win—in the Ice Age hunters fighting to drag home the biggest woolly mammoth, the ancient Greek athlete aiming for a greater distance in the discus toss, and the modern weightlifter pushing for the gold medal—has been linked to steroid hormones, namely testosterone and its derivatives, circulating within us. In the latter half the last century, many looking for an added edge have turned to synthetic testosterone-like anabolic-androgenic steroids to build muscle and enhance competitive drive. The ingestion of substances for better performance is not new. Ancient Greek athletes took in lots of protein to build muscle. Norse warriors known as Beserkers looked to hallucinogenic mushrooms for inspiration in preparation for battle. The earliest documented modern "doping" with xenobiotics for enhanced performance is among swimmers in Amsterdam in the 1860s. In the decades that followed, doping with nonfoods such as strychnine, caffeine, cocaine, and heroin spread to other sports (24,4). The synthesis of testosterone in the 1930s sparked the introduction of anabolic steroids into competitive sports. In the 1952 Olympics, synthetic testosterone enhanced the Russian weightlifting team’s ability to pump metal, and heave off with a heap of medals. In 1958 the first anabolic steroids were developed by a U.S. pharmaceutical company. Use of anabolic steroids spread through the wide world of sports in the 1960s and 1970s and by the 1980s the drugs were discovered by nonathltetes in search of a better body (24,8). Reports from the 1990s have indicated use of steroids among college, high school, and even middle school students (24). Exact numbers of users are hard to come by because they rely on self-reporting of illicit drug use, but recent estimates put the number of non-medical anabolic steroid users in the U.S. at over 1 million (4). Most users are males, but the number of female users is increasing. Among participants in weightlifting competitions some have estimated the prevalence of steroid use at 75 percent (13). Getting truthful information about who uses anabolic steroid for non-medical purposes is just one obstacle to studying the drug’s effects. Megadosing is another factor that confounds useful studies. Doses used by athletes are inconsistent and far exceed therapeutic doses. Athletes attempting to bulk up reportedly consume doses 100 to 1,000 times those prescribed for medical purposes. The normal therapeutic daily dose is 1 to 5 milligrams. Also, combinations of steroids are usually used, a practice known as "stacking." This makes it difficult to track the effects of a single substance. And, steroids are often "stacked" with other drugs such as stimulants, depressants, painkillers, and anti-inflammatories. The supraphysiological doses of multiple drugs are cycled over a period of 4 to 48 weeks to achieve the desired effects and avoid detection. Cycling is often scheduled around performance events and testing periods. Individual abusers therefore have different types and levels of steroid concentrations from time to time and from each other (24, 8). There are over 100 anabolic steroids available (8). Far fewer are available on the black market. And those obtained on the black market are not regulated, so you never know what you are getting. Many are contaminated and may play a part in observed physiological reactions to the drug. Because of all of the above researchers have had great difficulty establishing cause-and-effect relationships (8). It is also difficult to determine whether steroids are addictive. One of the characteristics of dependency is self-administration over a placebo. Researchers study whether rats or mice will preferably self-administer the substance over a placebo even if there are immediate adverse effects. Animals do not self-administer anabolic steroids and humans cannot tell the difference between the drugs and placebo (2). The effects of the drug, desired and undesired, are too delayed. Nevertheless there is enough evidence of the toxic effects of steroids. And recent studies indicate that that the drugs affect the brain reward systems. Withdrawal systems are well documented. Steroids have been linked to pathologies of the cardiovascular, immune, endocrine, psychiatric, reproductive and urogenital systems. Steroid abuse can also lead to liver disease and cancer, and inreased risk of injury to tendons, ligaments and muscles. Men can experience atrophy of the testes, reduced sperm count, and abnormal breast growth. Women may experience irreversible masculinization: facial hair growth, deepened voice, enlargement of the clitoris, cessation of menstrual cycle, and breast reduction. Psychological effects include feelings of grandiosity and violent, aggressive —and even homicidal—episodes that have become known as "roid rages." What Are Anabolic Steroids? Anabolic-androgenic steroids are synthetic analogs of the endogenous steroid hormone testosterone. Testosterone is a member of the androgen family of steroid hormones, one of six families of mammalian steroid hormones. The other five are estrogens, progestins, mineralcorticoids, glucocorticoids, and vitamin D with its metabolites. Like all steroids, androgens, testosterone included, are biologically derived from cholesterol. Cholesterol and all steroids consist of a phenanthrene ring structure with a pentano ring attached. The side-chain on the pentano ring of cholesterol is cleaved in the first and rate-limiting step of the production of steroid hormones. Enzymes modify the basic ring structure in the biosynthetic pathways that lead to the production of the various hormones. [Figures: Chemical structures of testosterone, phenanthrene, cholesterol. Orally active anabolic steroids: Fluoxymesterone, oxandrolone, stanozolol. Synthetic testosterone steroids: testosterone-proprionate, testosterone-enanthate, nandrolone-decanoate] The hyphenated adjective describing the drug (beginning of last paragraph) is derived from its two main functions. Anabolic means growing or building and refers to the steroid’s ability to stimulate protein anabolism. Androgenic means masculinizing and refers to the drug’s stimulation of secondary male sex characteristics. Those who use the drug for non-therapeutic purposes desire its anabolic effects. The other effects are written off as side effects. The drugs are therefore often simply referred to as anabolic steroids. Much like acetaminophen is termed an analgesic and not a liver damager. The biochemical mechanism for their muscle mass building action is largely unknown, as there are no endogenous receptors for androgens in muscle tissue. Some suspect, though, that anabolic steroids may compete with endogenous glucocorticoids for their receptors. Some anabolic steroids are administered orally and others are injected (25). Medical Uses Anabolic steroids also have clinical applications. They are FDA approved to treat men with androgen deficiency, anemia in patients with chronic renal failure or aplastic anemia (2). The are also approved for treatment of breast cancer, osteoporosis, endometriosis, and hereditary angioadema (24) as well as for bone marrow failure (17). The FDA has withdrawn approval for use after surgery to improve appetite and healing (24). Adverse Effects Cardiovascular Effects While anabolic steroids build skeletal muscle, they also thicken ventricle wall of the heart muscle. The supraphysiological consumption of steroids by athletes may stimulate the development of a grossly hypertrophied heart and consequently impaired diastolic function (8), especially when coupled with intense training. The thickened ventricle wall manifests itself as ventricular fibrillation. Animal studies have found that beating is completely stopped by anabolic steroids in myocardial cell cultures within 1 hour (8). Anabolic steroids decrease HDL (the "good" cholesterol) levels and increase the levels of LDL (the "bad" cholesterol), leading to the build up of lipid deposits in the arteries (16,20). Change in the lipoprotein profile is observed with both injected and ingested steroids. These effects stem from excess consumed steroid interfering with the carefully controlled feedback system (19). Anabolic steroid use also decreases the reduction of blood pressure during sleep (20) and increases the risk of severe coronary heart disease (21). Immunological Effects High doses of anabolic steroids can have significant effect on immune responses. In one study anabolic steroids were shown to significantly inhibit the production of antibodies in mice. They have also directly stimulated the production of the inflammatory cytokines IL-1b and TNF-a , but had no effect on IL-10 or IL-2 production. And corticotropin production in human peripheral blood lymphocytes after viral infection was significantly inhibited. Interferon production in human cells was also inhibited (17). Fearradez et al. (22) studied the effect of high doses of anabolic steroids on activity of immune cells in cultures of rat spleen and thymus lymphocytes. They reported impaired lymphocyte mobility and an inhibition of mitogen-induced proliferative response of 90 percent. They also showed that endurance training, as opposed to high-intensity training, counteracted the negative effects. Hepatoxicity Chronic use of high doses of anabolic steroids may cause liver damage and cancer. Boada et al. (23) examined the hepatic effects of high doses of the anabolic steroid stanozolol in rats. Steroid treatment decreased the levels of cytochrome P450 and Cytochrome b5, indicating reduced ability to metabolize xenobiotics. The livers exhibited inflammatory and degenerative lesions in centrilobular hepatocytes and there was also an increase in the percentage of S-phase cells among those cells, indicating an increased risk for liver cancer. Conclusion Anabolic steroids have toxic effects on wide variety of physiological systems, some of which were reviewed in this paper. Yet, their use is still prevalent, especially among weightlifters and bodybuilders. Perhaps, these users have made a conscious evaluation of risk verse benefit and are willing to accept the increased health risk in exchange for increased muscle mass and physical strength. However, many users are misinformed. Many users get their information on how to illicitly use the drugs from an underground steroid "bible." The handbook boasts, among other false claims, that the risk of side effects is non-existent in healthy athletes (8). Perhaps greater awareness of the actual risk in gyms can reduce the illicit use of anabolic steroids. References
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