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Steroids are amazing.
[[Image:Sex hormone binding globulin.jpg|thumb|Crystal structure of human [[sex hormone-binding globulin]], transporting [[Dihydrotestosterone|5α-dihydrotestosterone]]<ref name="pmid10675319">{{cite journal
|author=Grishkovskaya I, Avvakumov GV, Sklenar G, Dales D, Hammond GL, Muller YA
|title=Crystal structure of human sex hormone-binding globulin: steroid transport by a laminin G-like domain
|journal=EMBO J.
|volume=19
|issue=4
|pages=504–12
|year=2000
|pmid=10675319
|doi=10.1093/emboj/19.4.504
|pmc=305588
}}</ref>]]
'''Anabolic steroids''', officially known as '''anabolic-androgen steroids''' ('''AAS''') or colloquially simply as "steroids", are drugs which mimic the effects of the [[androgen|male sex hormones]] [[testosterone]] and [[dihydrotestosterone]]. They increase [[Protein biosynthesis|protein synthesis]] within cells, which results in the buildup of [[cell (biology)|cellular]] [[tissue (biology)|tissue]] ([[anabolism]]), especially in [[muscle]]s. Anabolic steroids also have [[androgen]]ic and [[virilization|virilizing]] properties, including the development and maintenance of [[Masculinity|masculine]] characteristics such as the growth of the [[vocal fold|vocal cords]] and body hair. The word ''anabolic'' comes from the Greek ἀναβολή ''anabole'', "that which is thrown up, mound", and the word ''androgenic'' from the Greek ἀνδρός ''andros'', "of a man" + -γενής ''-genes'', "born".

Anabolic steroids were first isolated, identified and [[chemical synthesis|synthesized]] in the 1930s, and are now used therapeutically in medicine to stimulate bone growth and appetite, induce male [[puberty]], and treat chronic [[wasting]] conditions, such as [[cancer]] and [[AIDS]]. The [[American College of Sports Medicine]] acknowledges that AAS, in the presence of adequate diet, can contribute to increases in body weight, often as lean mass increases, and that the gains in muscular strength achieved through high-intensity exercise and proper diet can be additionally increased by the use of AAS in some individuals.<ref>Michael Powers, "Performance-Enhancing Drugs" in Joel Houglum, in Gary L. Harrelson, Deidre Leaver-Dunn, "Principles of Pharmacology for Athletic Trainers", SLACK Incorporated, 2005, ISBN 1-55642-594-5, p. 330</ref>

Some health risks can be produced by long-term use or excessive doses of anabolic steroids. These effects include harmful changes in [[cholesterol]] levels (increased [[low-density lipoprotein]] and decreased [[high-density lipoprotein]]), [[Acne vulgaris|acne]], [[high blood pressure]], [[hepatotoxicity|liver damage]] (mainly with oral steroids), and dangerous changes in the structure of the [[left ventricle]] of the heart.

[[Ergogenic aid|Ergogenic]] uses for anabolic steroids in sports and [[bodybuilding]] are controversial because of their adverse effects and the potential to gain an advantage conventionally considered "cheating." Their use is referred to as [[Doping in sport|doping]] and banned by all major sporting bodies. For many years AAS have been by far the most detected doping substances in [[IOC]]-accredited laboratories.<ref name=hk515>Hartgens and Kuipers (2004), p. 515</ref><ref name=Kicman/> In countries where AAS are [[controlled substances]], there is often a [[black market]] in which smuggled or even [[counterfeit drugs]] are sold to users.

== History ==
=== Isolation of gonadal AAS ===
[[Image:Testosterone.svg|thumb|Chemical structure of the natural anabolic hormone [[testosterone]],
17β-hydroxy-4-androsten-3-one]]

The use of [[gonadal]] [[steroid]]s pre-dates their identification and isolation. Medical use of [[testicle]] extract began in the late 19th century while its effects on strength were still being studied.<ref>{{cite journal |author=Kuhn CM |title=Anabolic steroids |journal=Recent Prog. Horm. Res. |volume=57 |issue= |pages=411–34 |year=2002 |pmid=12017555 |url=http://rphr.endojournals.org/cgi/content/full/57/1/411 |doi=10.1210/rp.57.1.411}}</ref> The isolation of gonadal steroids can be traced back to 1931 when [[Adolf Butenandt]], a chemist in [[Marburg]], purified 15 milligrams of the male hormone [[androstenone]] from tens of thousands of litres of urine. This steroid was subsequently [[chemical synthesis|synthesized]] in 1934 by [[Leopold Ruzicka]], a chemist in [[Zurich]].<ref name = "PMID7817189"/>

In the 1930s it was already known that the [[testes]] contained a more powerful [[androgen]] than [[androstenone]], and three groups of scientists, funded by competing [[pharmaceutical companies]] in the Netherlands, [[Nazi Germany]] and Switzerland, raced to isolate it.<ref name = "PMID7817189">{{cite journal
|author=Hoberman JM, Yesalis CE
|title=The history of synthetic testosterone
|journal=Scientific American
|volume=272
|issue=2
|pages=76–81
|year=1995
|pmid=7817189
|doi=10.1038/scientificamerican0295-76
|doi=10.1038/scientificamerican0295-76
}}</ref><ref name = "PMID11176375">{{cite journal
}}</ref><ref name = "PMID11176375">{{cite journal

Revision as of 01:37, 1 December 2010

File:Sex hormone binding globulin.jpg
Crystal structure of human sex hormone-binding globulin, transporting 5α-dihydrotestosterone[1]

Anabolic steroids, officially known as anabolic-androgen steroids (AAS) or colloquially simply as "steroids", are drugs which mimic the effects of the male sex hormones testosterone and dihydrotestosterone. They increase protein synthesis within cells, which results in the buildup of cellular tissue (anabolism), especially in muscles. Anabolic steroids also have androgenic and virilizing properties, including the development and maintenance of masculine characteristics such as the growth of the vocal cords and body hair. The word anabolic comes from the Greek ἀναβολή anabole, "that which is thrown up, mound", and the word androgenic from the Greek ἀνδρός andros, "of a man" + -γενής -genes, "born".

Anabolic steroids were first isolated, identified and synthesized in the 1930s, and are now used therapeutically in medicine to stimulate bone growth and appetite, induce male puberty, and treat chronic wasting conditions, such as cancer and AIDS. The American College of Sports Medicine acknowledges that AAS, in the presence of adequate diet, can contribute to increases in body weight, often as lean mass increases, and that the gains in muscular strength achieved through high-intensity exercise and proper diet can be additionally increased by the use of AAS in some individuals.[2]

Some health risks can be produced by long-term use or excessive doses of anabolic steroids. These effects include harmful changes in cholesterol levels (increased low-density lipoprotein and decreased high-density lipoprotein), acne, high blood pressure, liver damage (mainly with oral steroids), and dangerous changes in the structure of the left ventricle of the heart.

Ergogenic uses for anabolic steroids in sports and bodybuilding are controversial because of their adverse effects and the potential to gain an advantage conventionally considered "cheating." Their use is referred to as doping and banned by all major sporting bodies. For many years AAS have been by far the most detected doping substances in IOC-accredited laboratories.[3][4] In countries where AAS are controlled substances, there is often a black market in which smuggled or even counterfeit drugs are sold to users.

History

Isolation of gonadal AAS

File:Testosterone.svg
Chemical structure of the natural anabolic hormone testosterone, 17β-hydroxy-4-androsten-3-one

The use of gonadal steroids pre-dates their identification and isolation. Medical use of testicle extract began in the late 19th century while its effects on strength were still being studied.[5] The isolation of gonadal steroids can be traced back to 1931 when Adolf Butenandt, a chemist in Marburg, purified 15 milligrams of the male hormone androstenone from tens of thousands of litres of urine. This steroid was subsequently synthesized in 1934 by Leopold Ruzicka, a chemist in Zurich.[6]

In the 1930s it was already known that the testes contained a more powerful androgen than androstenone, and three groups of scientists, funded by competing pharmaceutical companies in the Netherlands, Nazi Germany and Switzerland, raced to isolate it.[6][7] This hormone was first identified by Karoly Gyula David, E. Dingemanse, J. Freud and Ernst Laqueur in a May 1935 paper "On Crystalline Male Hormone from Testicles (Testosterone)."[8] They named the hormone testosterone, from the stems of testicle and sterol, and the suffix of ketone. The chemical synthesis of testosterone was achieved in August that year, when Butenandt and G. Hanisch published a paper describing "A Method for Preparing Testosterone from Cholesterol."[9] Only a week later, the third group, Ruzicka and A. Wettstein, announced a patent application in a paper "On the Artificial Preparation of the Testicular Hormone Testosterone (Androsten-3-one-17-ol)."[10] Ruzicka and Butenandt were offered the 1939 Nobel Prize in Chemistry for their work, but the Nazi government forced Butenandt to decline the honor, although he accepted the prize after the end of World War II.[6][7]

Clinical trials on humans, involving either oral doses of methyltestosterone or injections of testosterone propionate, began as early as 1937.[6] Testosterone propionate is mentioned in a letter to the editor of Strength and Health magazine in 1938; this is the earliest known reference to an anabolic steroid in a U.S. weightlifting or bodybuilding magazine.[6] There are often reported rumors that German soldiers were administered anabolic steroids during the Second World War, the aim being to increase their aggression and stamina, but these are, as yet, unproven.[11] Adolf Hitler himself, according to his physician, was injected with testosterone derivatives to treat various ailments.[12] AAS were used in experiments conducted by the Nazis on concentration camp inmates,[12] and later by the allies attempting to treat the malnourished victims that survived Nazi camps.[11]

Development of synthetic AAS

Chemical structure of the synthetic steroid Methandrostenolone (Dianabol). 17α-methylation (upper right corner) enhances oral bioavailability.

The development of muscle-building properties of testosterone was pursued in the 1940s, in the Soviet Union and in Eastern Bloc countries such as East Germany, where steroid programs were used to enhance the performance of Olympic and other amateur weight lifters. In response to the success of Russian weightlifters, the U.S. Olympic Team physician Dr. John Ziegler worked with synthetic chemists to develop an anabolic steroid with reduced androgenic effects.[13] Ziegler's work resulted in the production of methandrostenolone, which Ciba Pharmaceuticals marketed as Dianabol. The new steroid was approved for use in the U.S. by the Food and Drug Administration (FDA) in 1958. It was most commonly administered to burn victims and the elderly. The drug's off-label users were mostly bodybuilders and weight lifters. Although Ziegler prescribed only small doses to athletes, he soon discovered that those who abused Dianabol suffered from enlarged prostates and atrophied testes.[14] AAS were placed on the list of banned substances of the IOC in 1976, and a decade later the committee introduced 'out-of-competition' doping tests because many athletes used AAS in their training period rather than during competition.[3]

Three major ideas governed modifications of testosterone into a multitude of AAS: alkylation at 17-alpha position with methyl or ethyl group created orally active compounds because it slows the degradation of the drug by the liver, esterification of testosterone and nortestosterone at the 17-beta position allows the substance to be administered parenterally and increases the duration of effectiveness because agents soluble in oily liquids may be present in the body for several months, and finally alterations of the ring structure were applied for both oral and parenteral agents to seeking to obtain different anabolic to androgenic effect ratios.[15]

Pharmacology

Routes of administration

A vial of injectable testosterone cypionate

There are three common forms in which anabolic steroids are administered: oral pills, injectable steroids, and skin patches. Oral administration is the most convenient. Testosterone administered by mouth is rapidly absorbed, but it is largely converted to inactive metabolites, and only about 1/6 is available in active form. In order to be sufficiently active when given by mouth, testosterone derivatives are alkylated at the 17 position, e.g. methyltestosterone and fluoxymesterone. This modification reduces the liver's ability to break down these compounds before they reach the systemic circulation.

Testosterone can be administered parenterally, but it has more irregular prolonged absorption time and greater activity in propionate, enanthate, undecanoate or cypionate ester form. These derivatives are hydrolyzed to release free testosterone at the site of injection.[16] Injectable steroids are typically administered into the muscle, not into the vein, to avoid sudden changes in the amount of the drug in the bloodstream. Transdermal patches (adhesive patches placed on the skin) may also be used to deliver a steady dose through the skin and into the bloodstream. Injection is the most common method used by individuals administering anabolic steroids for non-medical purposes.[17]

The traditional routes of administration do not have differential effects on the efficacy of the drug. Studies indicate that the anabolic properties of anabolic steroids are relatively similar despite the differences in pharmacokinetic principles such as first-pass metabolism. However, the orally available forms of AAS may cause liver damage in high doses.[4][18]

Mechanism of action

See also: Steroid hormone
The human androgen receptor bound to testosterone[19] The protein is shown as a ribbon diagram in red, green and blue, with the steroid shown in white.

The pharmacodynamics of anabolic steroids are unlike peptide hormones. Water-soluble peptide hormones cannot penetrate the fatty cell membrane and only indirectly affect the nucleus of target cells through their interaction with the cell’s surface receptors. Conversely, as fat-soluble hormones, anabolic steroids are membrane permeable and influence the nucleus of cells by direct action. The pharmacodynamic action of anabolic steroids begin when the exogenous hormone penetrates the membrane of the target cell and binds to an androgen receptor located in the cytoplasm of that cell. From there, the compound hormone-receptor diffuses into the nucleus, where it either alters the expression of genes[20] or activates processes that send signals to other parts of the cell.[21] Different types of anabolic steroids bind to the androgen receptor with different affinities, depending on their chemical structure.[3] Some anabolic steroids such as methandrostenolone bind weakly to this receptor in vitro, but still exhibit androgenic effects in vivo. The reason for this discrepancy is not known.[22]

The effect of anabolic steroids on muscle mass is caused in at least two ways:[23] first, they increase the production of proteins; second, they reduce recovery time by blocking the effects of stress hormone cortisol on muscle tissue, so that catabolism of muscle is greatly reduced. It has been hypothesized that this reduction in muscle breakdown may occur through anabolic steroids inhibiting the action of other steroid hormones called glucocorticoids that promote the breakdown of muscles.[24] Anabolic steroids also affect the number of cells that develop into fat-storage cells, by favouring cellular differentiation into muscle cells instead.[25] Anabolic steroids can also decrease fat by increasing basal metabolic rate (BMR), since an increase in muscle mass increases BMR.

Anabolic and androgenic effects

Relative androgenic:anabolic
activity in animals[16]
Preparation Ratio
Testosterone 1:1
Methyltestosterone 1:1
Fluoxymesterone 1:2
Oxymetholone 1:3
Oxandrolone 1:3–1:13
Nandrolone decanoate 1:2.5–1:4

As the name suggests, anabolic-androgenic steroids have two different, but overlapping, types of effects: anabolic, meaning that they promote anabolism (cell growth), and androgenic (or virilising), meaning that they affect the development and maintenance of masculine characteristics.

Some examples of the anabolic effects of these hormones are increased protein synthesis from amino acids, increased appetite, increased bone remodeling and growth, and stimulation of bone marrow, which increases the production of red blood cells. Through a number of mechanisms anabolic steroids stimulate the formation of muscle cells and hence cause an increase in the size of skeletal muscles, leading to increased strength.[26][27][28]

The androgenic effects of AAS are numerous. Processes affected include pubertal growth, sebaceous gland oil production, and sexuality (especially in fetal development). Some examples of virilizing effects are growth of the clitoris in females and the penis in male children (the adult penis does not grow even when exposed to high doses of androgens), increased growth of androgen-sensitive hair (pubic, beard, chest, and limb hair), increased vocal cord size, deepening the voice, increased libido, suppression of natural sex hormones, and impaired production of sperm.[29]

The androgenic:anabolic ratio of an AAS is an important factor when determining the clinical application of these compounds. Compounds with a high ratio of androgenic to a anabolic effects are the drug of choice in androgen-replacement therapy (e.g. treating hypogonadism in males), whereas compounds with a reduced androgenic:anabolic ratio are preferred for anemia, osteoporosis, and to reverse protein loss following trauma, surgery or prolonged immobilization. Determination of androgenic:anabolic ratio is typically performed in animal studies, which has led to the marketing of some compounds claimed to have anabolic activity with weak androgenic effects. This disassociation is less marked in humans, where all anabolic steroids have significant androgenic effects.[16]

A commonly used protocol for determining the androgenic:anabolic ratio, dating back to the 1950s, uses the relative weights of ventral prostate (VP) and levator ani muscle (LA) of male rats. The VP weight is an indicator of the androgenic effect, while the LA weight is an indicator of the anabolic effect. Two or more batches of rats are castrated and given no treatment and respectively some AAS of interest. The LA/VP ratio for an AAS is calculated as the ratio of LA/VP weight gains produced by the treatment with that compound using castrated but untreated rats as baseline: (LAc,t–LAc)/(VPc,t–VPc). The LA/VP weight gain ratio from rat experiments is not unitary for testosterone (typically 0.3–0.4), but it's normalized for presentation purposes, and used as basis of comparison for other AAS, which have their androgenic:anabolic ratios scaled accordingly (as shown in the table above).[30][22] In the early 2000s this procedure was standardized and generalized throughout OECD in what is now known as the Hershberger assay.

Body composition and strength improvements

A review spanning more than three decades of experimental studies in men found that body weight may increase by 2–5 kg as a result of short term (<10 weeks) AAS use, which may be attributed mainly to an increase of lean mass. Animal studies also found that fat mass was reduced, but most studies in humans failed to elucidate significant fat mass decrements. The effects on lean body mass have been shown to be dose dependent. Both muscle hypertrophy and the formation of new muscle fibers have been observed. The hydration of lean mass remains unaffected by AAS use, although small increments of blood volume cannot be ruled out.[31]

The upper region of the body (thorax, neck, shoulders and upper arm) seems to be more susceptible for AAS than other body regions because of predominance of androgen receptors in the upper body. The largest difference in muscle fibre size between AAS users and non-users was observed in type I muscle fibres of the vastus lateralis and the trapezius muscle as a result of long-term AAS self-administration. After drug withdrawal the effects fade away slowly, but may persist for more than 6–12 weeks after cessation of AAS use.[31]

The same review observed strength improvements in the range of 5-20% of baseline strength, largely depending on the drugs and dose used as well as the administration period. Overall, the exercise where the most significant improvements were observed was the bench press.[32] For almost two decades it was assumed that AAS only exerted significant effects in experienced strength athletes, particularly based on the studies of Hervey and coworkers.[33][34] In 1996 a randomized controlled trial published in the New England Journal of Medicine demonstrated however that even in novice athletes a 10-week strength training program accompanied by testosterone enanthate at 600 mg/week may improve strength more than training alone does.[32][35] The same study found that dose was sufficient to significantly improve lean muscle mass relative to placebo even in subjects that did not exercise at all.[35] A 2001 study by the same first author, showed that the anabolic effects of testosterone enanthate were highly dose dependent.[31][36]

Adverse effects

Anabolic steroids can cause many adverse effects. Most of these side effects are dose-dependent, the most common being elevated blood pressure, especially in those with pre-existing hypertension,[37] and harmful changes in cholesterol levels: some steroids cause an increase in LDL cholesterol and a decrease in HDL cholesterol.[38] Anabolic steroids have been shown to alter fasting blood sugar and glucose tolerance tests.[39] Anabolic steroids such as testosterone also increase the risk of cardiovascular disease[40] or coronary artery disease.[41][42] Acne is fairly common among anabolic steroid users, mostly due to stimulation of the sebaceous glands by increased testosterone levels.[43][44] Conversion of testosterone to dihydrotestosterone (DHT) can accelerate the rate of premature baldness for males who are genetically predisposed, but testosterone itself can produce baldness in females.[45]

High doses of oral anabolic steroid compounds can cause liver damage, as the steroids are metabolized (17α-alkylated) in the digestive system to increase their bioavailability and stability.[46]

There are also sex-specific side effects of anabolic steroids. Development of breast tissue in males, a condition called gynecomastia (which is usually caused by high levels of circulating estradiol), may arise because of increased conversion of testosterone to estradiol by the enzyme aromatase.[47] Reduced sexual function and temporary infertility can also occur in males.[48][49][50] Another male-specific side effect which can occur is testicular atrophy, caused by the suppression of natural testosterone levels, which inhibits production of sperm (most of the mass of the testes is developing sperm). This side effect is temporary: the size of the testicles usually returns to normal within a few weeks of discontinuing anabolic steroid use as normal production of sperm resumes.[51] Female-specific side effects include increases in body hair, deepening of the voice, enlarged clitoris, and temporary decreases in menstrual cycles. When taken during pregnancy, anabolic steroids can affect fetal development by causing the development of male features in the female fetus and female features in the male fetus.[52]

A number of severe side effects can occur if adolescents use anabolic steroids.

For example, the steroids may prematurely stop the lengthening of bones (premature epiphyseal fusion through increased levels of estrogen metabolites), resulting in stunted growth. Other effects include, but are not limited to, accelerated bone maturation, increased frequency and duration of erections, and premature sexual development. Anabolic steroid use in adolescence is also correlated with poorer attitudes related to health.[53]

Other side effects can include alterations in the structure of the heart, such as enlargement and thickening of the left ventricle, which impairs its contraction and relaxation.[54] Possible effects of these alterations in the heart are hypertension, cardiac arrhythmias, congestive heart failure, heart attacks, and sudden cardiac death.[55] These changes are also seen in non-drug using athletes, but steroid use may accelerate this process.[56][57] However, both the connection between changes in the structure of the left ventricle and decreased cardiac function, as well as the connection to steroid use have been disputed.[58][59]

Psychiatric effects

A 2005 review in CNS Drugs determined that "significant psychiatric symptoms including aggression and violence, mania, and less frequently psychosis and suicide have been associated with steroid abuse. Long-term steroid abusers may develop symptoms of dependence and withdrawal on discontinuation of AAS".[60] High concentrations of AAS, comparable to those likely sustained by many recreational AAS users, produce apoptotic effects on neurons, raising the specter of possibly irreversible neuropsychiatric toxicity. Recreational AAS use appears to be associated with a range of potentially prolonged psychiatric effects, including dependence syndromes, mood disorders, and progression to other forms of substance abuse, but the prevalence and severity of these various effects remains poorly understood.[61] There is no evidence that steroid dependence develops from therapeutic use of anabolic steroids to treat medical disorders, but instances of AAS dependence have been reported among weightlifters and bodybuilders who chronically administered supraphysiologic doses.[62] Mood disturbances (e.g. depression, [hypo-]mania, psychotic features) are likely to be dose- and drug-dependent, but AAS dependence or withdrawal effects seem to occur only in a small number of AAS users.[63]

Large scale long term studies of psychiatric effects on AAS users are not currently available.[61] In 2003, the first naturalistic long term study on ten users, seven of which completed the study, found a high incidence of mood disorders and substance abuse, but few clinically relevant changes in physiological parameters or laboratory measures were noted throughout the study, and these changes were not clearly related to periods of reported AAS use.[64] A 13-month study, published in 2006 and which involved 320 body builders and athletes suggests that the wide range of psychiatric side effects induced by the use of AAS is correlated to the severity of abuse.[65]

Aggression and hypomania

From the mid-1980s onwards the popular press has been reporting "roid rage" as a side effect of AAS (the term being a play on the more established phenomenon of road rage).[66]

A 2005 review determined that some, but not all, randomized controlled studies have found that anabolic steroid use correlates with hypomania and increased aggressiveness, but pointed out that attempts to determine whether AAS use triggers violent behaviour have failed, primarily because of high rates of non-participation.[67] A 2008 study on a nationally representative sample of young adult males in the United States found an association between lifetime and past-year self-reported anabolic-androgenic steroid use and involvement in violent acts. Compared with individuals who did not use steroids, young adult males who used anabolic-androgenic steroids reported greater involvement in violent behaviors even after controlling for the effects of key demographic variables, previous violent behavior, and polydrug use.[68] A 1996 review examining the blind studies available at that time also found that these had demonstrated a link between aggression and steroid use, but pointed out that with estimates of over one million past or current steroid users in the United States at that time, an extremely small percentage of those using steroids appear to have experienced mental disturbance severe enough to result in clinical treatments or medical case reports.[69]

A 1996 randomized controlled trial, which involved 43 men, did not find an increase in the occurrence of angry behavior during 10 weeks of administration of testosterone enanthate at 600 mg/week, but this study screened out subjects that had previously abused steroids or had any psychiatric antecedents.[35][70] A trial conducted in 2000 using testosterone cypionate at 600 mg/week found that treatment significantly increased manic scores on the YMRS, and aggressive responses on several scales. The drug response was highly variable, however: 84% of subjects exhibited minimal psychiatric effects, 12% became mildly hypomanic, and 4% (2 subjects) became markedly hypomanic. The mechanism of these variable reactions could not be explained by demographic, psychological, laboratory, or physiological measures.[71]

A 2006 study of two pairs of identical twins, in which one twin used anabolic steroids and the other did not, found that in both cases the steroid-using twin exhibited high levels of aggressiveness, hostility, anxiety and paranoid ideation not found in the "control" twin.[72] A small scale study of 10 AAS users found that cluster B personality disorders were confounding factors for aggression.[73]

Depression and suicide

The relationship between AAS use and depression is inconclusive. There have been anecdotal reports of depression and suicide in teenage steroid users,[74] but little systematic evidence. A 1992 review found that anabolic-androgenic steroids may both relieve and cause depression, and that cessation or diminished use of anabolic-androgenic steroids may also result in depression, but called for additional studies due to disparate data.[75]

Addiction potential

In an animal study male rats developed a conditioned place preference to testosterone injections into the nucleus accumbens, an effect blocked by dopamine antagonists, which suggests that androgen reinforcement is mediated by the brain. Moreover, testosterone appears to act through the mesolimbic dopamine system, a common substrate for drugs of abuse. Nonetheless, androgen reinforcement is not comparable to that of cocaine, nicotine or heroin. Instead, testosterone resembles other mild reinforcers, such as caffeine, or benzodiazepines. The potential for androgen addiction remains to be determined.[76]

Medical and ergogenic uses

Medical uses

Various anabolic steroids and related compounds

Since the discovery and synthesis of testosterone in the 1930s, anabolic steroids have been used by physicians for many purposes, with varying degrees of success.

Ergogenic use and abuse

See also: Ergogenic use of anabolic steroids
Numerous vials of injectable anabolic steroids

Between 1 million and 3 million people (1% of the population) are thought to have misused AAS in the United States.

[92] Studies in the United States have shown anabolic steroid users tend to be mostly middle-class heterosexual men with a median age of about 25 who are noncompetitive bodybuilders and non-athletes and use the drugs for cosmetic purposes.[93] Another study found that non-medical use of AAS among college students was at or less than 1%.[94] According to a recent survey, 78.4% of steroid users were noncompetitive bodybuilders and non-athletes while about 13% reported unsafe injection practices such as reusing needles, sharing needles, and sharing multidose vials,[95] though a 2007 study found that sharing of needles was extremely uncommon among individuals using anabolic steroids for non-medical purposes, less than 1%.[17] Another 2007 study found that 74% of non-medical anabolic steroid users had secondary college degrees and more had completed college and less had failed to complete high school than is expected from the general populace.[17] The same study found that individuals using anabolic steroids for non-medical purposes had a higher employment rate and a higher household income than the general population.[17] Anabolic steroid users tend to research the drugs they are taking more than other controlled-substance users; however, the major sources consulted by steroid users include friends, non-medical handbooks, internet-based forums, blogs and fitness magazines, which can provide questionable or inaccurate information.[96]

Anabolic steroid users tend to be disillusioned by the portrayal of anabolic steroids as deadly in the media and in politics.[97] According to one study, AAS users also distrust their physicians and in the sample 56% had not disclosed their AAS use to their physicians.[98] Another 2007 study had similar findings, showing that while 66% of individuals using anabolic steroids for non-medical purposes were willing to seek medical supervision for their steroid use, 58% lacked trust in their physicians, 92% felt that the medical community's knowledge of non-medical anabolic steroid use was lacking and 99% felt that the public has an exaggerated view of the side effects of anabolic steroid use.[17] A recent study has also shown that long term AAS users were more likely to have symptoms of muscle dysmorphia and also showed stronger endorsement of more conventional male roles.[99]

Anabolic steroids have been used by men and women in many different kinds of professional sports to attain a competitive edge or to assist in recovery from injury. These sports include bodybuilding, weightlifting, shot put and other track and field, cycling, baseball, wrestling, mixed martial arts, boxing, football, and cricket. Such use is prohibited by the rules of the governing bodies of most sports. Anabolic steroid use occurs among adolescents, especially by those participating in competitive sports. It has been suggested that the prevalence of use among high-school students in the U.S. may be as high as 2.7%.[100] Male students used anabolic steroids more frequently than female students and, on average, those who participated in sports used steroids more often than those who did not.

The use of anabolic steroids is banned by all major sporting bodies, including the International Olympic Committee, Major League Baseball, the National Football League, the National Basketball Association, the National Hockey League, World Wrestling Entertainment, Ultimate Fighting Championship, ICC, ITF, FIFA, FINA, UEFA, the European Athletic Association, and the Brazilian Football Confederation.

The legal status of anabolic steroids varies from country to country: some have stricter controls on their use or prescription than others though in many countries they are not illegal. In the U.S., anabolic steroids are currently listed as Schedule III controlled substances under the Controlled Substances Act, which makes the first offense simple possession of such substances without a prescription a federal crime punishable by up to one year in prison, and the unlawful distribution or possession with intent to distribute anabolic steroids punishable as a first offense by up to ten years in prison.[101] In Canada, anabolic steroids and their derivatives are part of the Controlled drugs and substances act and are Schedule IV substances, meaning that it is illegal to obtain or sell them without a prescription; however, possession is not punishable, a consequence reserved for schedule I, II or III substances. Those guilty of buying or selling anabolic steroids in Canada can be imprisoned for up to 18 months. Import and export also carry similar penalties.[102] Anabolic steroids are also illegal without prescription in Australia,[103] Argentina, Brazil and Portugal,[104] and are listed as Class C Controlled Drugs in the United Kingdom. On the other hand, anabolic steroids are readily available without a prescription in some countries such as Mexico and Thailand.

United States

Steroid pills intercepted by the US Drug Enforcement Administration during the "Operation raw deal" bust in September 2007.

The history of the U.S. legislation on anabolic steroids goes back to the late 1980s, when the U.S. Congress considered placing anabolic steroids under the Controlled Substances Act following the controversy over Ben Johnson's victory at the 1988 Summer Olympics in Seoul. During deliberations, the American Medical Association (AMA), Drug Enforcement Administration (DEA), Food and Drug Administration (FDA) as well as the National Institute on Drug Abuse (NIDA) all opposed listing anabolic steroids as controlled substances, citing the fact that use of these hormones does not lead to the physical or psychological dependence required for such scheduling under the Controlled Substance Act. Nevertheless, anabolic steroids were added to Schedule III of the Controlled Substances Act in the Anabolic Steroid Control Act of 1990.[105]

The same act also introduced more stringent controls with higher criminal penalties for offenses involving the illegal distribution of anabolic steroids and human growth hormone. By the early 1990s, after anabolic steroids were scheduled in the U.S., several pharmaceutical companies stopped manufacturing or marketing the products in the U.S., including Ciba, Searle, Syntex and others. In the Controlled Substances Act, anabolic steroids are defined to be any drug or hormonal substance chemically and pharmacologically related to testosterone (other than estrogens, progestins, and corticosteroids) that promote muscle growth. The act was amended by the Anabolic Steroid Control Act of 2004, which added prohormones to the list of controlled substances, with effect from January 20, 2005.[106]

Movement for decriminalization

After the Anabolic Steroid Control Act of 1990 listed anabolic steroids as Schedule III controlled substances in the U.S., a small movement has arisen that is highly critical of current laws concerning anabolic steroids. On June 21, 2005, Real Sports aired a segment discussing the legality and prohibition of anabolic steroids in America.[107] The show featured Gary I. Wadler, M.D., chairman of the U.S. Anti-Doping Agency and a prominent anti-steroid activist. When pressed for scientific evidence by correspondent Armen Keteyian that anabolic steroids are as "highly fatal" as is often claimed, Wadler admitted there was no evidence. Bryant Gumbel concluded the "hoopla" concerning the dangers of anabolic steroids in the media was "all smoke and no fire".[107] The show also featured John Romano, a pro-steroid activist who wrote "The Romano Factor", a pro-steroid column for bodybuilding magazine Muscular Development.

United Kingdom

In the United Kingdom, anabolic steroids are classified as class C drugs for their illegal abuse potential, which puts them in the same class as benzodiazepines. Anabolic steroids are in Schedule 4, which is divided in 2 parts; Part 1 contains most of the benzodiazepines and Part 2 contains the anabolic and androgenic steroids. There are no special controls on Schedule 4 drugs.

Status in sports

See also: Use of performance-enhancing drugs in sport

Anabolic steroids are banned by all major sports bodies including Fédération Internationale de Football Association[108] the Olympics,[109] the National Basketball Association,[110] the National Hockey League,[111] as well as the National Football League.[112] The World Anti-Doping Agency (WADA) maintains the list of performance-enhancing substances used by many major sports bodies and includes all anabolic agents, which includes all anabolic steroids and precursors as well as all hormones and related substances.[113][114] Spain has passed an anti-doping law creating a national anti-doping agency.[115] Italy passed a law in 2000 where penalties range up to three years in prison if an athlete has tested positive for banned substances.[116] In 2006, Russian President Vladimir Putin signed into law ratification of the International Convention Against Doping in Sport which would encourage cooperation with WADA. Many other countries have similar legislation prohibiting anabolic steroids in sports including Denmark,[117] France,[118] the Netherlands[119] and Sweden.[120]

Detection of use

The most commonly employed human physiological specimen for detecting anabolic steroid usage is urine, although both blood and hair have been investigated for this purpose. The anabolic steroids, whether of endogenous or exogenous origin, are subject to extensive hepatic biotransformation by a variety of enzymatic pathways. The primary urinary metabolites may be detectable for up to 30 days after the last use, depending on the specific agent, dose and route of administration. A number of the drugs have common metabolic pathways, and their excretion profiles may overlap those of the endogenous steroids, making interpretation of testing results a very significant challenge to the analytical chemist. Methods for detection of the substances or their excretion products in urine specimens usually involve gas chromatography-mass spectrometry or liquid chromatography-mass spectrometry.[121][122][123][124]

Illegal trade

Main article: Illegal trade in anabolic steroids
Several large buckets containing tens of thousands of Anabolic steroid vials confiscated by the DEA during "Operation Raw Deal" in 2007.

Anabolic steroids are frequently produced in pharmaceutical laboratories, but in nations where stricter laws are present, they are also produced in small home made underground laboratories, usually from raw substances imported from abroad.[125] In these countries the majority of steroids are obtained illegally through black market trade.[126][127] These steroids are usually manufactured in other countries, and therefore must be smuggled across international borders. Like most significant smuggling operations, organized crime is involved.[128]

In the late 2000s the worldwide trade in illicit AAS increased significantly, and authorities announced record captures on three continents. In 2006 Finnish authorities announced a record seizure of 11.8 million AAS tablets. A year later the DEA seized 11.4 million units of AAS in the largest U.S seizure ever. In the first three months of 2008, Australian customs reported a record 300 seizures of AAS shipments.[129]

In the U.S., Canada and Europe, illicit steroids are sometimes purchased just like any other illegal drug, through dealers who are able to obtain the drugs from a number of sources. Illegal anabolic steroids are sometimes sold at gyms, competitions, and through the mail, but may also be obtained through pharmacists, veterinarians, and physicians.[130] In addition, a significant number of counterfeit products are sold as anabolic steroids, particularly via mail order from websites posing as overseas pharmacies. In the U.S., black market importation continues from Mexico, Thailand, and other countries where steroids are more easily available as they are legal.[131]

See also

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Further reading

  • D. Kochakian, Charles (2000). Anabolic Steroids in Sport and Exercise. Human Kinetics. ISBN 0880117869. {{cite book}}: Cite has empty unknown parameter: |coauthors= (help)
  • Daniels, R. C. (February 1, 2003). The Anabolic Steroid Handbook. Richard C Daniels. p. 80. ISBN 0-9548227-0-6. {{cite book}}: Cite has empty unknown parameter: |coauthors= (help)
  • Gallaway, Steve (January 15, 1997). The Steroid Bible. Belle Intl; 3rd Sprl edition. p. 125. ISBN 1-890342-00-9. {{cite book}}: Cite has empty unknown parameter: |coauthors= (help)
  • Llewellyn, William (January 28, 2007). ANABOLICS 2007 : Anabolic Steroid Reference Manual (6th Ed.). Body of Science. p. 988. ISBN 978-0967930466. {{cite book}}: Cite has empty unknown parameter: |coauthors= (help)
  • Roberts, Anthony (2006). Anabolic Steroids: Ultimate Research Guide. Anabolic Books, LLC. p. 394. ISBN 1-59975-100-3. {{cite book}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  • Yesalis, Charles E. (2000). Anabolic Steroids in Sport and Exercise. Human Kinetics Publishers; 2nd edition. p. 493. ISBN 0-88011-786-9. {{cite book}}: Cite has empty unknown parameter: |coauthors= (help); Unknown parameter |month= ignored (help)

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