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Anabolic steroid

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

Anabolic androgenic steroids are a class of natural and synthetic steroid hormones that promote cell growth and division, resulting in growth of several types of tissues, especially muscle and bone. Different anabolic androgenic steroids have varying combinations of androgenic and anabolic properties, and are often referred to in medical texts as AAS (anabolic/androgenic steroids). Anabolism is the metabolic process that builds larger molecules from smaller ones.

Anabolic steroids were first discovered in the early 1930s and have since been used for numerous medical purposes including stimulation of bone growth, appetite, puberty, and muscle growth. The most widespread use of anabolic steroids is their use for chronic wasting conditions, such as cancer and AIDS. Anabolic steroids can produce numerous physiological effects including increases in protein synthesis, muscle mass, strength, appetite and bone growth. Anabolic steroids have also been associated with numerous side effects when administered in excessive doses and these include elevated cholesterol (increase in LDL, decreased HDL levels), acne, elevated blood pressure, hepatotoxicity, and alterations in left ventricle morphology.

Today anabolic steroids are controversial because of their widespread use in competitive sports and their associated side effects. While there are numerous health issues associated with excessive anabolic steroid use, public understanding of the true risks remains limited. Anabolic steroids are controlled in a few countries including the United States, where they are listed as Schedule III in the Controlled Substances Act, as well as Canada and Britain who also have laws controlling their use and distribution.

Biochemical mechanism

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

The physiological effects of androgens such as testosterone and dihydrotestosterone are vast. When taken during pregnancy they can affect fetal development. Other things 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 signal transduction through protein kinases.[1]

General Description

Anabolic steroids are androgenic and therefore produce androgenic effects in the body. Androgens stimulate myogenesis which is the formation of muscular tissue. Androgens are known to cause hypertrophy of both types (I and II) of muscle fibers however the mechanism of this is not completely understood and there are a few accepted mechanisms through which this may occur. It's widely understood that supraphysiological doses of testosterone in non-hypogonadal men promotes nitrogen density and increases fat free mass (muscle mass) while at the same time decreasing fat, particularly abdominal fat. The increase in muscle mass is mostly skeletal muscle increases and are likely caused by an increase in the synthesis of muscle proteins or possibly a decline in the breakdown in muscle proteins.[2] It has also been hypothesized[3] that androgens regulate body composition by promoting the commitment of mesenchymal pluripotent cells into myogenic lineages and inhibiting their differentiation into adipogenic lineages. However, androgens may also play an anticatabolic role in inhibiting skeletal muscle atrophy through antiglucocorticoid action independent of the androgen receptor.[4]

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

Medical Disclaimer

There are three common routes for the administration of anabolic steroids: oral (for steroids in pill form), injectable, and transdermal. Oral administration, while perhaps the most convenient, suffer from the fact that they often need to be chemically modified(17 alpha-alkylated) so that the liver cannot break it down before it reaches the blood stream, this can cause hepatotoxicity in higher doses.[5] Injectable steroids are typically administered intramuscularly, to avoid sharp blood level changes. Finally, transdermal administration via creams, gels or transdermal patches is very convenient and is becoming more popular.

Anabolic and virilizing effects

Anabolic androgenic steroids produce anabolic and virilizing (also known as androgenic) effects. Most anabolic steroids work in two simultaneous ways. First, they work by binding to the androgen receptor and increasing protein synthesis. Second, they also reduce recovery time by blocking the effects of the stress hormone, 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[6][7][8], 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 (clitoral hypertrophy) in females and the penis in male children (the adult penis does not grow indefinitely 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 endogenous sex hormones, as well as impaired spermatogenesis.

Possible unwanted side effects

Anabolic steroids can cause many unwanted side effects. Most of the side effects are dose dependent and are caused by the chemical reactions of the hormones such as androgens metabolizing into other hormones which can interact with steroid receptors in including the estrogen, progesterone, and glucocorticoid receptors, producing additional (usually) unwanted effects. The most common side effects are elevated blood pressure especially in hypertensives,[9] Increases in cholesterol levels due to the fact that some steroids can cause an increase in LDL and decreased HDL levels.[10] This can cause an increase in risk of cardiovascular disease[11] or coronary artery disease[12] in men with high risk of bad cholesterol. Acne is fairly common among anabolic steroid users, mostly due to the increases in testosterone which can cause stimulation of the sebaceous gland.[13][14] Testosterones conversion to DHT (Dihydrotestosterone) can accelerate the rate of premature baldness for who are genetically predisposed. Other side effects can include altered left ventricle Morphology; Steroids can induce an unfavourable enlargement and thickening of the left ventricle, which loses its diastolic properties with the mass increase.[15] However the negative relation of left ventricle morphology to decreased cardiac function has been disputed.[16] Also hepatotoxicity which can be caused by particularly by high doses of oral anabolic steroid compounds that are 17-alpha-alkylated to increase their bioavailability and stability in the digestive system.[17]

There are also side effects that are particular to sex and can include development of breast tissue in males, a condition called gynecomastia. This is usually caused by high levels of circulating estrogen; the result of the increased conversion of testosterone to estrogen via an aromatase enzyme.[18] Reduced sexual function and temporary infertility can also occur in males. [19][20][21] Another male specific side effect which can occur is testicular atrophy which is a temporary side effect that is due to decreases in natural testosterone levels inhibiting spermatogenesis. As most of the mass of the testes is developing sperm, the size of the testicles usually returns to normal within a few weeks of discontinuing anabolic steroid use when spermatogenesis resumes.[22] Female specific side effects that can occur include increases in body hair,deepening of the voice, enlarged clitoris (clitoral hypertrophy), as well as temporary decreases in menstrual cycles. A number of severe side effects can occur if adolescents use anabolic steroids which include but are not limited to stunted growth; Abuse of the agents may prematurely stop the lengthening of bones (premature epiphyseal fusion through increased levels of estrogen metabolites), accelerated bone maturation, increased frequency and duration of erections, precocious sexual development and development of extreme secondary sexual characteristics (hypervirilization), Phallic enlargement (hypergonadism or megalophallus) as well as increases in body hair.

Medical uses

Various anabolic steroids and related compounds.

Anabolic steroids were tried 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.[23]

  • 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.[24][25]
  • 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 but synthetic anabolic steroids were often used prior to the 1980s.
  • Testosterone enanthate may prove to be a useful, safe, reversible, effective method of male hormonal contraception in the near future.[26][27]
  • Used for age related problems in elderly people. Anabolic steroids have been shown to help in many age related problems in the elderly.[28]
  • Used in hormone replacement therapy for men with low levels of testosterone. (see hypogonadism)
  • Used for gender dysmorphia: whereby secondary male characteristics (puberty) are initiated in female-to-male diagnosed patients. Most commonly used testosterone derivatives are Sustanon and Testosterone Enanthate which cause the voice to deepen, increased bone and muscle mass, facial hair, increased levels of red blood cells and clitoral enlargement.

Use and abuse

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 also seems to occur among adolescents especially by those in sports. It has been suggested[29] that the prevalence of use among High school students in the United States may be as high as 2.7%. 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 between the ages 15-25 and noncompetitive bodybuilders and non-athletes who use for cosmetic reasons.[30]

Minimization of side effects

Typically, bodybuilders, athletes and sportsmen who use anabolic steroids try to minimize the negative side effects. For example, users may increase their amount of cardiovascular exercise to help negate the effects of left ventricle hypertrophy.[31]

Some androgens will aromatise and convert to estrogen, potentially causing some combination of the side effects listed above. During a steroid cycle users tend to take an aromatase inhibitor and/or a SERM; these drugs affect aromatisation and estrogen receptor binding respectively. The SERM tamoxifen, is of particular interest as it prevents binding to the estrogen receptor in the breast, reducing the risk of gynecomastia.[32]

Furthermore, to combat the natural testosterone suppression and to restore proper HPTA function, what is known as 'post-cycle therapy' (PCT) is self prescribed. PCT takes place after the course 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 space 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.[35]

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. Since anabolic steroids can increase cholesterol they increase the risk for heart attack in users. [10]

Anabolic steroids, like many other drugs, have been at the center of controversy and because of this there are many popular misconceptions and myths concerning their effects and side effects. As with many infamous drugs in popular culture, the misconceptions relating to anabolic steroids have likely arisen from misunderstandings of their actual side effects. One such example might include the misconception that anabolic steroids can ‘shrink’ one's penis. It is likely that this myth came from the real side effect of anabolic steroids known as testicular atrophy, in which the use of anabolic steroids causes reduced secretion of the gonadotropin luteinizing hormone and follicle stimulating hormone from the anterior pituitary, thus reducing testicle size. This side effect is temporary and the testicles return to normal soon after exogenous androgen administration is halted.[36]

Another common misconception purveyed in popular culture and the media includes the myth that anabolic steroids are highly dangerous and users' mortality rates are high. Anabolic steroids are used widely in the medical field without any serious health risks to users,[37][38][39] and no scientific evidence has shown any long-term serious health defects from proper use of anabolic steroids. While risk of death is present in many drugs, the risk of premature death from use of anabolic steroids seems to be extremely low.[40] It is possible this myth gained popularity 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, there is no medical evidence anabolic steroids can cause brain cancer and Alzado's doctors stated that anabolic steroids did not contribute to his death.[41]

More myths relating to purported side effects include claims that anabolic steroids have caused many teenagers to commit suicide. While lower levels of testosterone have been known to cause depression, and ending a steroid cycle is known to result in temporarily lower testosterone levels, the claim that anabolic steroids are responsible for specific suicides among teenagers is highly questionable. In the United States the estimated use of anabolic steroids among high school students was 2.8% in 1999. On the other hand, in the year 2000 in the United States, suicide was the third leading cause of death among 15- to 24-year-olds.[42] With the suicide rate this high among teenagers, concluding anabolic steroids are responsible for the suicides of teenagers who happened to be taking them prior to committing suicide is a post hoc logical fallacy. Also, even though 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. [43]

One of the most common misconceptions regarding the side effects of anabolic steroids is known as ‘roid rage’. There seems to be little or no evidence such a condition actually exists. Some early studies done have shown a slight correlation between manic symptoms and anabolic steroid use[44], however more comprehensive and recent studies have brought into question their methodology and conclusions. The majority of recent studies done on "angry behavior" and anabolic steroid use show no psychological effect, implying that either "roid rage" doesn't exist or that anabolic steroids' effects on aggression are too small to be measured. Many scientists and medical professionals conclude anabolic steroids have no real effect on increased aggressive behavior.[45][46][47][48][49]

Arnold Schwarzenegger is the subject of yet another myth regarding the purported side effects of anabolic steroids. Arnold Schwarzenegger has admitted to using anabolic steroids during his bodybuilding career for many years,[50] 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, Arnold 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.[51]

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 via this black market,[52][53] 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.[54][55]

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.

Distribution

In the United States and Canada, steroids are purchased just like any 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.[52][56][57]

History

Comments on professional athletes in ancient Greece suggest that a wide variety of natural steroidal substances were used to promote androgenic and anabolic growth. These may have ranged from testicular extracts to plant materials. Traditional medicine in general, in the West as well as in contemporary Asian medicine, has a wide pharmacopeia of substances intended to promote virility and masculine traits, though not entirely oriented towards muscle growth and athletic ability so much as sexual performance. In Chinese traditional medicine substances such as deer antler, tiger bone, bear gall bladder, ginseng and other roots and much more were all primarily consumed and were thought to bolster the male organism, though there is no scientific evidence such potions have any effect.

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. The first known reference to an anabolic steroid in a US weightlifting/bodybuilding magazine is testosterone propinate in a letter to the editor in 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 were anything more than a placebo effect. In a 1972 study,[58] participants were informed they would receive injections of anabolic steroids on a daily basis, but instead had actually been given 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 books' publishing in 1996, the results of the study remained unchallenged for 18 years.[59]

In the 1996 study mentioned above which was founded by the NIH it examined the effect of high doses of testosterone enanthate (600 mg/week intramuscularly for 10 weeks). 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.[60]

The U.S. Congress in the Anabolic Steroid Control Act of 1990 placed anabolic steroids into Schedule III of the Controlled Substances Act (CSA). The CSA defines anabolic steroids as any drug or hormonal substance chemically and pharmacologically related to testosterone (other than estrogens, progestins, and corticosteroids) that promotes 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.[61]

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, Germany, 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.[62] 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.[63]

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.[64] 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.

List of anabolic compounds commonly used as ergogenic aids

NB: Many of these products are no longer available from the original manufacturers and are now manufactured by underground laboratories in the United States, Mexico, and Canada, but are still widely available in certain countries, in most cases from a subsidiary of the original manufacturer (e.g. Schering, Organon).

See also

References

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Further reading

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