Anabolic steroids, technically known as anabolic-androgenic steroids (AAS) or colloquially as “steroids“, are drugs that mimic the effects of vocal cords, testicles, and body hair (secondary sexual characteristics). 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.[1]

Health risks can be produced by long-term use or excessive doses of anabolic steroids.testicular atrophy may also be caused by anabolic steroids.

counterfeit drugs are sold to users.

Contents

[edit] History

[edit] Isolation of gonadal AAS

Chemical structure of the natural anabolic hormone testosterone, 17β-hydroxy-4-androsten-3-one

The use of [8]

In the 1930s, it was already known that the testes contain a more powerful androgen than androstenone, and three groups of scientists, funded by competing pharmaceutical companies in the Netherlands, Germany, and Switzerland, raced to isolate it.[8][9] 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).”[10] 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.”[11] 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).”[12] 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.[8][9]

Clinical trials on humans, involving either oral doses of [13]

[edit] Development of synthetic AAS

Chemical structure of the synthetic steroid bioavailability.

The development of muscle-building properties of testosterone was pursued in the 1940s, in the Soviet Union and in [5]

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 alterations of the ring structure were applied for both oral and parenteral agents to seeking to obtain different anabolic to androgenic effect ratios.[17]

[edit] Pharmacology

[edit] Routes of administrations

A vial of injectable testosterone cypionate

There are four common forms in which anabolic steroids are administered: oral pills, injectable steroids, creams/gels for topical application, 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. fluoxymesterone. This modification reduces the liver’s ability to break down these compounds before they reach the systemic circulation.

Testosterone can be administered embolism (clot) 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. Testosterone-containing creams and gels that are applied daily to the skin are also available, but absorption is inefficient (roughly 10%, varying between individuals) and these treatments tend to be more expensive. Individuals who are especially physically active and/or bathe often may not be good candidates, since the medication can be washed off and may take up to six hours to be fully absorbed. There is also the risk that an intimate partner or child may come in contact with the application site and inadvertently dose himself or herself; children and women are highly sensitive to testosterone and can suffer unintended masculinization and health effects, even from small doses. Injection is the most common method used by individuals administering anabolic steroids for non-medical purposes.[19]

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 [20]

[edit] Mechanism of action

The human androgen receptor bound to testosterone[21] The protein is shown as a ribbon diagram in red, green, and blue, with the steroid shown in white.

The [24]

The effect of anabolic steroids on muscle mass is caused in at least two ways:basal metabolic rate (BMR), since an increase in muscle mass increases BMR.

[edit] Anabolic and androgenic effects

Relative androgenic:anabolic
activity in animals[18]
Preparation Ratio
Testosterone 1:1
Methyltestosterone 1:1
Fluoxymesterone 1:2
Oxymetholone 1:3
Oxandrolone 1:3–1:13
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 virilising), meaning that they affect the development and maintenance of masculine characteristics.

Some examples of the anabolic effects of these hormones are increased [30]

The androgenic effects of AAS are numerous. Depending on the length of use, the side effects of the steroid can be irreversible. 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, and will eventually get smaller 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.[31]

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 an 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 and 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.[18]

A commonly used protocol for determining the androgenic:anabolic ratio, dating back to the 1950s, uses the relative weights of ventral Hershberger assay.

[edit] 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.[33]

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 fiber size between AAS users and non-users was observed in type I muscle fibers 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.[33]

The same review observed strength improvements in the range of 5–20% of baseline strength, depending largely on the drugs and dose used as well as the administration period. Overall, the exercise where the most significant improvements were observed is the [38]

[edit] Adverse effects

Anabolic steroids can cause many [46]

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.[3]

There are also sex-specific side-effects of anabolic steroids. Development of breast tissue in males, a condition called [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 [58]

[edit] Psychiatric effects

A 2005 review in [62]

Large-scale long-term studies of psychiatric effects on AAS users are not currently available.[64]

[edit] Aggression and hypomania

From the mid-1980s onward, the media reported “roid rage” as a side-effect of AAS.[65]

A 2005 review determined that some, but not all, randomized controlled studies have found that anabolic steroid use correlates with [68]

A 1996 [70]

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]

[edit] 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]

[edit] 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.[75]

[edit] Medical and ergogenic uses

[edit] 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, for the treatment of:

It should be noted that although steroids do have medical uses, they may also have side effects – for example, the potential risk of citation needed].

[edit] Ergogenic use and abuse

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.[95]

Anabolic steroid users tend to be disillusioned by the portrayal of anabolic steroids as deadly in the media and in politics.[98]

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%.[99] Male students used anabolic steroids more frequently than female students and, on average, those that participated in sports used steroids more often than those that did not.

[edit] Legal and sport restrictions

[edit] Legal status

Various compounds with anabolic and androgenic effects, their relation with anabolic steroids

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 Thailand.

[edit] 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]

[edit] 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 doping regulations in sports.

[edit] Status in sports

Legal status of anabolic steroids and other compounds with anabolic effects in Western countries

Anabolic steroids are banned by all major sports bodies including [119]

[edit] 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 [123]

[edit] Illegal trade

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.[127]

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.[128]

In the U.S., Canada, and Europe, illegal steroids are sometimes purchased just as 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 and competitions, and through the mail, but may also be obtained through pharmacists, veterinarians, and physicians.[130]

[edit] See also

131.Tygart, Travis T. “Steroids, the Media, and Youth.” Prevention Researcher Integrated Research Services, Inc., Vol. 16 Supplement. December 2009: 7–9. SIRS Researcher. Web. 25 Oct 2010.

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Tygart, Travis T. “Steroids, the Media, and Youth.” Prevention Researcher Integrated Research Services, Inc., Vol. 16 Supplement. December 2009: 7–9. SIRS Researcher. Web. 25 Oct 2010.

Eisenhauer, Lisa. “Do I Look OK?.” St. Louis Post-Dispatch (St. Louis, MO). Nov. 7 2005: HF1+. SIRS Researcher. Web. 25 Oct 2010.

[edit] Further reading

  • D. Kochakian, Charles (2000). Anabolic Steroids in Sport and Exercise. Human Kinetics. ISBN 0-88011-786-9.
  • Daniels, R. C. (February 1, 2003). The Anabolic Steroid Handbook. Richard C Daniels. p. 80. ISBN 0-9548227-0-6.
  • Gallaway, Steve (January 15, 1997). The Steroid Bible. Belle Intl; 3rd Sprl edition. p. 125. ISBN 1-890342-00-9.
  • Llewellyn, William (January 28, 2007). ANABOLICS 2007 : Anabolic Steroid Reference Manual (6th Ed.). Body of Science. p. 988. ISBN 978-0-9679304-6-6.
  • Roberts, Anthony; Brian Clapp (January 2006). Anabolic Steroids: Ultimate Research Guide. Anabolic Books, LLC. p. 394. ISBN 1-59975-100-3.
  • Yesalis, Charles E. (July 2000). Anabolic Steroids in Sport and Exercise. Human Kinetics Publishers; 2nd edition. p. 493. ISBN 0-88011-786-9.
  • Sigmarsson, Victor (January 15, 2007). Inside Secrets: The Bodybuilder’s Guide To Buying Steroids On The Internet!. SA LABS LLC ; 2nd edition. p. 7. ISBN 978-1-4507-5402-6.

Tygart, Travis T. “Steroids, the Media, and Youth.” Prevention Researcher Integrated Research Services, Inc., Vol. 16 Supplement. December 2009: 7–9. SIRS Researcher. Web. 25 Oct 2010.

[edit] External links



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