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Anabolic steroid

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

Anabolic-androgenic steroids or AAS are a class of steroid hormones that are derivatives of the male hormone, testosterone. AAS increase protein synthesis within muscle cells, which results in anabolism (growth) of muscle size. In addition to anabolic effects, AAS have androgenic properties, including the development and maintenance of masculine characteristics.

Anabolic steroids were first discovered in the early 1930s and are now used widely in medicine to stimulate bone growth, appetite, puberty, and muscle growth. The most widespread medical uses of anabolic steroids are for chronic wasting conditions, such as cancer and AIDS. Anabolic steroids produce increases in protein synthesis, muscle mass, strength, appetite and bone growth. Anabolic steroids are controversial because of their use in competitive sports and their associated side effects. While serious health risks can be produced by long-term use or excessive doses of anabolic steroids, public understanding of the true risks remains limited. Anabolic steroids are considered controlled substances" in some countries, including the United States, Canada, The United Kingdom, Australia, Argentina and Brazil. The use of anabolic steroids is banned by all major sports bodies including the IOC, FIFA , UEFA, the NHL, the MLB, the NBA, the EAA and the NFL.

History

Performance enhancing substances have been used for thousands of years in traditional medicine by societies around the world; these natural substances were used with the aim of promoting vitality and strength. Historical commentaries on professional athletes in ancient Greece suggest that a wide variety of natural anabolic substances were used to promote muscle growth and enhance endurance.[1] The use of steroid hormones in particular pre-dates their isolation, with testicle extracts being shown to increase strength in the late 19th century.[2]

Modern pharmaceutical anabolic steroids are believed to have been inadvertently discovered by German scientists in the early 1930s, but at the time the discovery was not considered significant enough to warrant further study.[3] The first known reference to an anabolic steroid in a U.S. weightlifting/bodybuilding magazine is to testosterone propionate, in a letter to the editor of Strength and Health magazine in 1938. In the 1950s, scientific interest was rekindled, and methandrostenolone (Dianabol) was approved for use in the United States by the federal Food and Drug Administration in 1958 after promising trials had been conducted in other countries. Throughout the '50s, '60s, '70s and even '80s there was doubt that anabolic steroids produced anything more than a placebo effect. In a 1972 study,[4] participants were informed they would receive injections of anabolic steroids on a daily basis, but instead had actually been given a placebo. They reportedly could not tell the difference, and the perceived performance enhancement was similar to that of subjects taking the real anabolic compounds. This study had many flaws including inconsistent controls and insignificant doses. According to Geraline Lin, a researcher for the National Institute on Drug Abuse, at the time of the book's publishing in 1996, the results of the study remained unchallenged for 18 years.[5] In the 1996 study mentioned above, which was funded by the National Institutes of Health, the effect of high doses of testosterone enanthate (600 mg/week intramuscularly for 10 weeks) was examined. The results showed a clear increase in muscle mass and decrease in fat mass in those who took the testosterone opposed to the placebo. No adverse reactions were noted.[6]

Mechanisms of action

Further information: [[:Steroid hormone receptor, Steroid hormone]]

Biochemical mechanisms

Anabolic steroids are androgenic, which means they stimulate the formation of muscles (a process called myogenesis). Androgens are known to causes an increase in the size of muscle fibers. This increase in muscle mass is mostly due to larger skeletal muscles, and is caused by both increased production of muscle proteins as well as a decline in these protein's rate of breakdown.[7] It has also been hypothesized[8] 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.[9] High doses of testosterone in men also decreases the amount of fat in muscle, while increasing protein content. Steroids also decrease fat in other parts of the body, such as the abdomen. They do this through changing the number of cells that develop into fat-storage cells, turning these cells into muscle instead.

The main way in which steroid hormones interact with cells is by binding to proteins called steroid receptors. Once these proteins have bound to their steroid target, they move into the cell nucleus and directly change the expression of genes.[10] In the case of anabolic steroids, the receptor involved is called the androgen receptor. The mechanisms of action differ depending on the specific anabolic steroid. Different types of anabolic steroids bind to the androgen receptor to varying degrees depending on their chemical structure. Anabolic steroids such as methandrostenolone do not bind strongly to the androgen receptor and instead directly affect protein synthesis or glycogenolysis: while steroids such as oxandrolone bind tightly to the androgen receptor and act mostly on transcription.

Administration

A vial of the injectable anabolic steroid, depo-testosterone cypionate

There are three common routes for the administration of anabolic steroids: oral (for steroids in pill form), injectable, and transdermal. Oral administration is most convenient, but the steroid must be chemically modified so that the liver cannot break it down before it reaches the blood stream. However, these formulations can cause liver damage in high doses.[11] 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 place on the skin, may also be used to deliver a time-released dose through the skin and into the bloodstream.

Anabolic and androgenic effects

The biochemical functions of androgens such as testosterone are vast. Processes affected can be maintenance of muscle and bone mass later in adulthood including stimulating pubertal growth spurts, inducing hair growth, sebaceous gland oil production, and sexuality (especially in fetal development). These effects are caused by steroids binding to androgen receptors and causing changes in gene expression or activating the conversion of cellular signals through the modification of proteins due to the addition of phosphate.[12]

Anabolic Steroids produce numerous anabolic and androgenic effects. Most anabolic steroids work in two simultaneous ways. First, they work by binding to the androgen receptor and increasing the cellular production of proteins. Second, they also reduce recovery time by blocking the effects of the stress hormone in the body, cortisol, on muscle tissue. As a result, catabolism of the body's muscle mass is greatly reduced. Some examples of the anabolic effects of these hormones include increased protein synthesis from amino acids, increased muscle mass and strength,[13][14][15] increased appetite, increased bone remodeling and growth, as well as stimulation of bone marrow increasing production of red blood cells. Some examples of the virilizing/androgenic effects include 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, as well as impaired production of sperm.[16]

Side effects

Big Muscles

Minimization of side effects

Further information: [[:Steroid cycle, Post-cycle therapy]]

Typically, bodybuilders, athletes and sportsmen who use anabolic steroids try to minimize their negative side effects. For example, users may increase their amount of cardiovascular exercise to help negate the effects of hypertrophy|changes in the left ventricle.[17] Some androgens will convert to estrogen, potentially causing some combination of the side effects listed above. During a steroid cycle, users tend to take drugs used to prevent the conversion of estrogen, otherwise known as aromatisation which include aromatase inhibitor and/or selective estrogen receptor modulators (SERMs); these drugs affect aromatisation and estrogen receptor binding respectively. The SERM tamoxifen is of particular interest because it prevents binding to the estrogen receptor in the breast, reducing the risk of gynecomastia.[18]

Furthermore, to combat the natural testosterone suppression and to restore proper function of numerous glands involved, what is known as 'post-cycle therapy' or PCT. PCT takes place after the course of the use of anabolic steroids. It typically consists of a combination of the following drugs, depending on which protocol is used:

The aim of PCT is to return the body's endogenous hormonal balance to its original state within the shortest period of time. People prone to premature hair loss that can be exacerbated by steroid use have been known to take the prescription drug finasteride for prolonged periods of time. Finasteride reduces the conversion of testosterone to DHT, the latter having much higher potency for alopecia. Finasteride is useless in the cases when steroid is not converted into a more androgenic derivative.[21] Since anabolic steroids can be toxic to the liver or can cause increases in blood pressure or cholesterol, many users consider it ideal to get frequent blood work tests and blood pressure tests to make sure their blood pressure or cholesterol are still within normal levels.

Medical uses

Various anabolic steroids and related compounds.

Anabolic steroids were used by physicians for many purposes from the discovery of synthetic testosterone in the 1930s to the 1950s with varying success. One of the initial medical uses of steroids was treatment of chronic wasting, such as was experienced by Nazi concentration camp prisoners and prisoners of war. During World War II, German scientists worked on synthesizing other anabolic steroids, and ran experiments on human prisoners, as well as with their own soldiers. They had hoped to increase the aggressive tendencies of their troops. Adolf Hitler's own physician reported that Hitler had been given testosterone derivative injections to treat various ailments.[22]

  • Bone marrow stimulation: For decades, anabolic steroids were the mainstay of therapy for hypoplastic anemias not due to nutrient deficiency, especially aplastic anemia. Anabolic steroids are slowly being replaced by synthetic protein hormones (such as epoetin alfa) that selectively stimulate growth of blood cell precursors.
  • Growth stimulation: Anabolic steroids were used heavily by pediatric endocrinologists for children with growth failure from the 1960s through the 1980s. Availability of synthetic growth hormone and increasing social stigmatization of anabolic steroids led to discontinuation of this use.
  • Stimulation of appetite and preservation and increase of muscle mass: Anabolic steroids have been given to people with chronic wasting conditions such as cancer and AIDS.[23][24]
  • Induction of male puberty: Androgens are given to many boys distressed about extreme delay of puberty. Testosterone is now nearly the only androgen used for this purpose and has been shown to increase height, weight, and fat free mass in boys with delayed puberty.[25]
  • Testosterone enanthate has frequently been used as a male contraceptive and it is thought that in the near future it could be used as a safe, reliable, and reversible male contraceptive.[26][27]
  • Anabolic steroids have been shown to help fight many age related problems in elderly men including increasing lean body mass and decreasing bone resorption.[28][29][neutrality is disputed]
  • Used in hormone replacement therapy for men with low levels of testosterone and is also effective in improving libido for elderly males.[30][31][32][33]
  • Used to treat gender dysmorphia (the belief that one was born the wrong gender) by producing secondary male characteristics, such as a deeper, voice increased bone and muscle mass, facial hair, increased levels of red blood cells and clitoral enlargement in female-to-male patients.

Non-medical use and abuse

Studies have shown anabolic steroid users tend to be mostly middle class heterosexual men with a median age of 27. Most users do not compete in any sports. Anabolic steroid users often are stereotyped as uneducated or 'muscle heads' by popular media and culture, however studies on steroid users have shown them to be the most educated drug users out of all users of controlled substances.[34] Anabolic steroid users also tend to research the drugs they are taking more than any other group of users of controlled substances. Moreover, anabolic steroid users tend to be disillusioned by the portrayal of anabolic steroids as "deadly" in the media and in politics.[35]

Anabolic steroids have been used by men and women in many different kinds of professional sports (cricket, track and field, weightlifting, bodybuilding, shot put, cycling, baseball, wrestling, mixed martial arts, boxing, football, etc.) to attain a competitive edge or to assist in recovery from injury. Steroids used to obtain competitive advantage are prohibited by the rules of the governing bodies of many sports.

Anabolic steroid use seems to occur among adolescents especially by those in sports. It has been suggested that the prevalence of use among high school students in the United States may be as high as 2.7%.[36] Male students used more than female students and those who participated in sports used more often than those who did not on average.

It is extremely difficult to determine what percent of the population in general have actually used anabolic steroids, but the number seems to be fairly low. The demographics of steroid users tend to be mostly males generally around the age of 25[37] and noncompetitive bodybuilders and non-athletes who use the drugs for cosmetic purposes. According to a recent study, 78.4% of steroid users were noncompetitive bodybuilders and non-athletes while only about 13% reported unsafe injection practices such as reusing needles, sharing needles, and sharing multidose vials.[38]

Misconceptions and controversies

Anabolic steroids, like many other drugs, have been at the center of controversy, consequently there are many popular misconceptions concerning their effects and side effects. One such common misconception in popular culture and the media is that anabolic steroids are highly dangerous and users' mortality rates are high. However, anabolic steroids are used widely in the medical field without any serious health risks to patients,[39][40][41][42] and no serious health defects have been identified that are caused by the long-term use of anabolic steroids. While risk of death is present as a side-effect of many drugs, the risk of premature death from either the medical or illegal use of anabolic steroids seems to be extremely low.[42][39][43] Former assistant professor at the University of Toronto Mauro Di Pasquale has stated “As used by most people, including athletes, the adverse effects of anabolic steroids appear to be minimal,".[44] One possible origin of the idea that steroids are extremely dangerous is from claims that Lyle Alzado died from brain cancer caused by anabolic steroids. Alzado himself had claimed that his cancer was caused by anabolic steroids. However, although steroids can cause liver cancer,[45] there is no published evidence that anabolic steroids cause either brain cancer or the specific type of T-cell lymphoma that caused his death.[46] Indeed, Alzado's doctors stated that anabolic steroids did not contribute to his death.[47]

Other examples include the misconception that anabolic steroids can ‘shrink’ the male penis. It is likely that this idea came from the real side effect of anabolic steroids known as testicular atrophy, in which the use of anabolic steroids causes sperm production to fall. Since developing sperm makes up much of the mass of testicles, this temporarily reduces their size, as less sperm is developing. The testicles return to a normal size after steroid use is halted and sperm production resumes.[48]

Other purported side effects include the idea that anabolic steroids have caused many teenagers to commit suicide.[49] While lower levels of testosterone have been known to cause depression, and ending a steroid cycle temporarily lowers testosterone levels, the hypothesis that anabolic steroids are responsible for suicides among teenagers remains unproven. Although teen bodybuilders have been using steroids since at least the early 1960s, only a few cases suggesting a link between steroids and suicide have been reported in the medical literature.[50]

Another condition that is frequently discussed as a possible side effect of anabolic steroids is known as ‘roid rage’, however there is no consensus in the medical literature if such a condition actually exists. Testosterone levels are indeed associated with aggression and hypomania, but the link between other anabolic steroids and aggression remains unclear.[51] While some studies have shown a correlation between manic symptoms and anabolic steroid use,[52] later studies have questioned these conclusions.[43] Currently, three blinded studies have demonstrated a link between aggression and steroid use, but with estimates of over 1 million past or current steroid users in the United states, 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.[53] In contrast, the majority of recent studies done on angry behavior and anabolic steroid use show little or no psychological effect, implying that either "roid rage" does not exist or that anabolic steroids' effects on aggression are often too small to be measured. Some studies however have shown a small correlation between marked hypomania and anabolic steroid use.[54] Here, only 50 individuals were studied, with two showing signs of marked hypomania. It has previously been theorized that some studies showing a correlation between angry behavior and steroid use are confounded by the fact that steroid users are likely to demonstrate cluster B personality disorders prior to administering steroids.[55] In addition, many case studies have concluded anabolic steroids have little or no real effect on increased aggressive behavior.[56][39][57][58]

Arnold Schwarzenegger is the subject of a urban legend regarding the side effects of anabolic steroids. Schwarzenegger has admitted to using anabolic steroids during his bodybuilding career for many years prior to them being made illegal,[59] and in 1997 he underwent surgery to correct a defect relating to his heart. Some have assumed this was due to anabolic steroids. Although anabolic steroids when abused can sometimes cause unfavorable enlargement and thickening of the left ventricle, Schwarzenegger was born with a congenital genetic defect in which his heart had a bicuspid aortic valve — in other words, whereas normal hearts have three cusps, his had only two, which can occasionally cause problems later in life.[60]

Further information: [[:War on Drugs, Controlled Substances Act]]

Anabolic steroids are controlled in some countries, while relatively uncontrolled in others. Some countries have stricter controls on the use and prescription of anabolic steroids than other countries. In the United States, the U.S. Congress placed anabolic steroids into Schedule III of the Controlled Substances Act in the Anabolic Steroid Control Act of 1990.[61] The act was amended on January 20, 2005, with the Anabolic Steroid Control Act of 2004. This amendment placed prohormones on the list of controlled substances, making possession of the banned substances without a prescription a federal crime punishable by up to seven years in prison.[62]

The United States has has a long history with the legleslation of the use of anabolic steroids. In the late 1980s, the U.S. Congress had been considering placing anabolic steroids under the Controlled Substances Act due to recent controversy over Ben Johnson's victory at the 1988 Summer Olympics in Seoul. During deliberations the AMA, DEA, FDA as well as the NIDA all opposed listing anabolic steroids as controlled substances citing the fact that use of these hormones simply doesn't lead to the physical or psychological dependence required for scheduling under the controlled substance act. However, the U.S. Congress in the Anabolic Steroid Control Act of 1990 placed anabolic steroids into Schedule III of the Controlled Substances Act.[61] At that time, Congress enacted more stringent controls with higher criminal penalties for offenses involving the illegal distribution of anabolic steroids and human growth hormone. This new legislation was enacted as part of the Anabolic Steroids Control Act. The Controlled Substances Act defines anabolic steroids as any drug or hormonal substance chemically and pharmacologically related to testosterone (other than estrogens, progestins, and corticosteroids) that promote muscle growth. By the early 1990s after anabolic steroids were scheduled in the United States, several pharmaceutical companies stopped manufacturing or marketing the products in the United States, including Ciba, Searle, Syntex and others.

In addition, an entire market for counterfeit drugs emerged at this time. Never seen in the previous 30 years of their availability on the U.S. market, computers and scanning technology made the ease of counterfeiting legitimate products by utilizing their original label design, and the market was flooded with products that contained everything from mere vegetable oil to toxic substances which unsuspecting users injected into themselves, of which some died as a result of blood poisoning, methanol poisoning or subcutaneous abscess. On January 20, 2005, the Anabolic Steroid Control Act of 2004 took effect, amending the Controlled Substance Act to place both anabolic steroids and prohormones on a list of controlled substances, making possession of the banned substances without a prescription a federal crime.[62]

In Canada anabolic steroids and their derivatives are part of the Controlled drugs and substances act and are considered "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.[63] Anabolic steroids are also illegal without prescription in Australia,[64] Argentina, Brazil and Portugal.[65] and are listed as Schedule 4 Controlled Drug in the United Kingdom.

Status in sports

See also: Doping (sport)

Anabolic steroids are banned by all major sports bodies including the Olympics,[66] the NBA,[67] the NHL,[68] as well as the NFL.[69] 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.[70] Spain has passed an anti-doping law which would create a national anti-doping agency.[71] Italy passed a law in 2000 where penalties range up to 3 years in prison if an athlete has tested positive for banned substances.[72] 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,[73] France,[74] the Netherlands[75] as well as Sweden.[76]

Illegal trade in anabolic steroids

Since anabolic steroids are often produced in different countries than in which they are distributed, they must be smuggled across international borders. Like most significant smuggling operations, sophisticated organized crime is involved, often in conjunction with other smuggling efforts (including other illegal drugs). Unlike psychoactive recreational drugs such as cannabis and heroin, there have not been many high profile cases of individual smugglers of anabolic steroids being caught. The majority of those using illegally obtain the drugs through this black market,[77][78] and more specifically, pharmacists, veterinarians, and physicians. Anabolic steroids purchased through the black market may be counterfeit, or originally manufactured for veterinary applications. Which in and of itself isn't dangerous except for the fact they are sometimes produced and handled in cruder and less sterile environments.[79][80]

Production

Anabolic steroids need sophisticated pharmaceutical processes and equipment to produce, so they are produced by legitimate pharmaceutical companies or underground laboratories with large overheads. Common problems associated with illegal drug trades, such as chemical substitutions, cutting, and diluting, affect illegal anabolic steroids such that when it reaches distribution the quality may be questionable or possibly dangerous. In the 1990s most US producers such as Ciba, Searle and Syntex stopped making and marketing anabolic steroids within the US. However, in many other regions, particularly Eastern Europe, they are still produced in quantity. European anabolic steroids are the source of most medical grade anabolic steroids sold illegally in North America. However, anabolic steroids are still in wider use for veterinary purposes, and many illegal anabolic steroids are actually veterinary grade.[81]

Distribution

In the United States, Canada and Europe, steroids are purchased just like any other illegal drug, through dealers who are able to obtain the drugs from a number of sources. Most users would prefer to buy from legitimate sources but cannot because of the restrictive laws against steroid possession. Counterfeit steroids are a common solution to the lack of legal availability in the United States and Canada, although black-market importation continues from Mexico, Thailand and other countries where steroids are more easily available and, in many countries, not illegal at all. Many people produce fake steroids and attempt to sell them over the Internet which causes a wide variety of health concerns.

Most illicit anabolic steroids are now sold at gyms, competitions, and through the mail. For the most part, these substances are smuggled into the United States. In addition, a significant number of counterfeit products are sold as anabolic steroids, particularly via mail order from websites posing as overseas pharmacies. In addition to the recreational use of anabolic steroids, users in Great Britain have been shown to consume illicit drugs as well, such as cannabis, and cocaine.[77][82][83]

Movement for decriminalization

Anabolic steroids are Schedule III controlled substances in the United States and are strictly regulated in some other countries. (It is perhaps worth noting that anabolic steroids are readily available without a prescription in some other countries such as Mexico and Thailand.) However, since the U.S. Congress passed the Anabolic Steroid Control Act of 1990, 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.[84] 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 he claims, Wadler admitted there was no evidence. Gumbel concluded the 'hoopla' concerning the dangers of anabolic steroids in the media was 'all smoke and no fire.' The show also featured John Romano, a pro-steroid activist who authors 'The Romano Factor,' a pro-steroid column for bodybuilding magazine Muscular Development.[85]

In July 2005 Philip Sweitzer, an attorney and author, published an open letter to the Members of the House Committee on Government Reform, and the Senate Committee on Commerce et al. In it he criticized lawmakers' actions in scheduling anabolic steroids, as well as criticized their 'disregard of scientific reality for symbolic effect.' He also pleaded for the consideration of the decriminalization of anabolic steroids and asked for a new policy direction.[86] Several other legal reviewers have criticized controlled substance status for anabolic steroids, including lawyer Rick Collins whose book, Legal Muscle, is one of the most detailed published resources on anabolic steroids and the law. Collins opposes non-medical teen steroid use or steroid use to cheat in sports, but advocates wider discretion for physicians in the case of mature adults. In 2006 he argued at "PUMPED", a steroid seminar in Manhattan, that the risks associated with anabolic steroids in the media are overtly biased as well as incredibly misinformed. He also argues that anabolic steroid criminalization increases the risks associated with anabolic steroids due to impurities in the black market.[87][88] However, the U.S. government's position since the late 1980s has been and continues to be that the risks of steroid use are 'too great' to allow them to be decriminalized or unregulated.

See also

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Further reading


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