Anabolic–androgenic steroids
Drug class
Chemical structure of the natural AAS testosterone (androst-4-en-17β-ol-3-one).
Class identifiers
Synonyms	Anabolic steroids; Androgens
Use	Various
ATC code	A14A
Biological target	Androgen receptor
Chemical class	Steroids; Androstanes; Estranes
Clinical data
Drugs.com	Drug Classes
External links
MeSH	D045165
Legal status
Legal status	CA: Schedule IV UK: Class C US: Schedule III Controlled in many countries
In Wikidata

Anabolic steroids, also known as anabolic-androgenic steroids (AAS), are a class of drugs that are structurally related to testosterone, the main male sex hormone, and produce effects by binding to the androgen receptor. Anabolic steroids have a number of medical uses,^[1] but are also used by athletes to increase muscle size, strength, and performance.

Health risks can be produced by long-term use or excessive doses of AAS.^[2][3] 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 most oral AAS), and left ventricular hypertrophy.^[4] These risks are further increased when athletes take steroids alongside other drugs, causing significantly more damage to their bodies.^[5] The effect of anabolic steroids on the heart can cause myocardial infarction and strokes.^[5] Conditions pertaining to hormonal imbalances such as gynecomastia and testicular size reduction may also be caused by AAS.^[6] In women and children, AAS can cause irreversible masculinization.^[6]

Ergogenic uses for AAS in sports, racing, and bodybuilding as performance-enhancing drugs are controversial because of their adverse effects and the potential to gain advantage in physical competitions. Their use is referred to as doping and banned by most major sporting bodies. Athletes have been looking for drugs to enhance their athletic abilities since the Olympics started in Ancient Greece.^[5] For many years, AAS have been by far the most detected doping substances in IOC-accredited laboratories.^[7][8] Anabolic steroids are classified as Schedule III controlled substances in many countries.^[9] In countries where AAS are controlled substances, there is often a black market in which smuggled, clandestinely manufactured or even counterfeit drugs are sold to users.

Uses

Medical

Since the discovery and synthesis of testosterone in the 1930s, AAS have been used by physicians for many purposes, with varying degrees of success. These can broadly be grouped into anabolic, androgenic, and other uses.

Anabolic

• Bone marrow stimulation: For decades, AAS were the mainstay of therapy for hypoplastic anemias due to leukemia, kidney failure or aplastic anemia.^[10]
• Growth stimulation: AAS can be used by pediatric endocrinologists to treat children with growth failure.^[11] However, the availability of synthetic growth hormone, which has fewer side effects, makes this a secondary treatment.
• Stimulation of appetite and preservation and increase of muscle mass: AAS have been given to people with chronic wasting conditions such as cancer and AIDS.^[12][13]
• Stimulation of lean body mass and prevention of bone loss in elderly men, as some studies indicate.^[14][15][16] However, a 2006 placebo-controlled trial of low-dose testosterone supplementation in elderly men with low levels of testosterone found no benefit on body composition, physical performance, insulin sensitivity, or quality of life.^[17]
• Prevention or treatment of osteoporosis in postmenopausal women.^[18][19] Nandrolone decanoate is approved for this use.^[20] Although they have been indicated for this indication, AAS saw very little use for this purpose due to their virilizing side effects.^[18][21]
• Aiding weight gain following surgery or physical trauma, during chronic infection, or in the context of unexplained weight loss.^[22][23]
• Counteracting the catabolic effect of long-term corticosteroid therapy.^[22][23]
• Oxandrolone improves both short-term and long-term outcomes in people recovering from severe burns, and is well-established as a safe treatment for this indication.^[24][25]
• Treatment of idiopathic short stature, hereditary angioedema, alcoholic hepatitis, and hypogonadism.^[26][27]
• Methyltestosterone is used in the treatment of delayed puberty, hypogonadism, cryptorchidism, and erectile dysfunction in males, and in low doses to treat menopausal symptoms (specifically for osteoporosis, hot flashes, and to increase libido and energy), postpartum breast pain and engorgement, and breast cancer in women.^[28][29][30]

Androgenic

• Androgen replacement therapy for men with low levels of testosterone; also effective in improving libido for elderly males.^{[31][32][33][34]}
• 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.^[35]
• Masculinizing hormone therapy for transgender men, other transmasculine people, and intersex people, by producing masculine secondary sexual characteristics such as a voice deepening, increased bone and muscle mass, masculine fat distribution, facial and body hair, and clitoral enlargement, as well as mental changes such as alleviation of gender dysphoria and increased sex drive.^{[36][37][38][39][40]}

Other

• Treatment of breast cancer in women, although they are now very rarely used for this purpose due to their marked virilizing side effects.^[41][18][42]
• In low doses as a component of hormone therapy for postmenopausal and transgender women, for instance to increase energy, well-being, libido, and quality of life, as well as to reduce hot flashes.^{[43][44][45][46]} Testosterone is usually used for this purpose, although methyltestosterone is also used.^[46][47]
• Male hormonal contraception; currently experimental, but potential for use as effective, safe, reliable, and reversible male contraceptives.^[48]
• Assistant in the treatment of Raynaud's Phenomenon and peripheral acrocyanosis. Testosterone and other anabolics tend to be potent vasodilators, which can significantly improve bloodflow in individuals prone to vasoconstriction.^[49]

Enhancing performance

Most steroid users are not athletes.^[50] In the United States, between 1 million and 3 million people (1% of the population) are thought to have used AAS.^[51] Studies in the United States have shown that AAS users tend to be mostly middle-class men with a median age of about 25 who are noncompetitive bodybuilders and non-athletes and use the drugs for cosmetic purposes.^[52] "Among 12- to 17-year-old boys, use of steroids and similar drugs jumped 25 percent from 1999 to 2000, with 20 percent saying they use them for looks rather than sports, a study by insurer Blue Cross Blue Shield found."(Eisenhauer) Another study found that non-medical use of AAS among college students was at or less than 1%.^[53] 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,^[54] though a 2007 study found that sharing of needles was extremely uncommon among individuals using AAS for non-medical purposes, less than 1%.^[55] Another 2007 study found that 74% of non-medical AAS users had post-secondary degrees and more had completed college and fewer had failed to complete high school than is expected from the general populace.^[55] The same study found that individuals using AAS for non-medical purposes had a higher employment rate and a higher household income than the general population.^[55] AAS users tend to research the drugs they are taking more than other controlled-substance users;^{[citation needed]} 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.^[56]

AAS users tend to be unhappy with the portrayal of AAS as deadly in the media and in politics.^[57] According to one study, AAS users also distrust their physicians and in the sample 56% had not disclosed their AAS use to their physicians.^[58] Another 2007 study had similar findings, showing that, while 66% of individuals using AAS 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 AAS use was lacking, and 99% felt that the public has an exaggerated view of the side-effects of AAS use.^[55] 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.^[59] A recent study in the Journal of Health Psychology showed that many users believed that steroids used in moderation were safe.^[60]

AAS 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. AAS 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%.^[61]

Dosages

Available forms

The AAS that have been used most commonly in medicine are testosterone and its many esters (but most typically testosterone undecanoate, testosterone enanthate, testosterone cypionate, and testosterone propionate),^[71] nandrolone esters (typically nandrolone decanoate and nandrolone phenylpropionate), stanozolol, and metandienone (methandrostenolone).^[72] Others that have also been available and used commonly but to a lesser extent include methyltestosterone, oxandrolone, mesterolone, and oxymetholone, as well as drostanolone propionate (dromostanolone propionate), metenolone (methylandrostenolone) esters (specifically metenolone acetate and metenolone enanthate), and fluoxymesterone.^[72] Dihydrotestosterone (DHT), known as androstanolone or stanolone when used medically, and its esters are also notable, although they are not widely used in medicine.^[67] Boldenone undecylenate and trenbolone acetate are used in veterinary medicine.^[72]

Designer steroids are AAS that have not been approved and marketed for medical use but have been distributed through the black market.^[73] Examples of notable designer steroids include 1-testosterone (dihydroboldenone), methasterone, trenbolone enanthate, desoxymethyltestosterone, tetrahydrogestrinone, and methylstenbolone.^[73]

Routes of administration

There are four common forms in which AAS 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 one-sixth is available in active form. In order to be sufficiently active when given by mouth, testosterone derivatives are alkylated at the 17α 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 muscle in enanthate, undecanoate, or cypionate ester form. These derivatives are hydrolyzed to release free testosterone at the site of injection; absorption rate (and thus injection schedule) varies among different esters, but medical injections are normally done anywhere between semi-weekly to once every 12 weeks. A more frequent schedule may be desirable in order to maintain a more constant level of hormone in the system.^[74] 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. In addition, because estered testosterone is dissolved in oil, intravenous injection has the potential to cause a dangerous 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 themselves; children and women are highly sensitive to testosterone and can develop unintended masculinization and health effects, even from small doses. Injection is the most common method used by individuals administering AAS for non-medical purposes.^[55]

The traditional routes of administration do not have differential effects on the efficacy of the drug. Studies indicate that the anabolic properties of AAS 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.^[8][75]

Adverse effects

Known possible side effects of AAS include:^{[6][76][77][78][79]}

• Dermatological/integumental: oily skin, acne vulgaris, acne conglobata, seborrhea, stretch marks (due to rapid muscle enlargement), hypertrichosis (excessive body hair growth), androgenic alopecia (pattern hair loss; scalp baldness), fluid retention/edema.
• Reproductive/endocrine: libido changes, reversible infertility, hypogonadotropic hypogonadism.
• Male-specific: spontaneous erections, nocturnal emissions, priapism, erectile dysfunction, gynecomastia (mostly only with aromatizable and hence estrogenic AAS), oligospermia/azoospermia, testicular atrophy, intratesticular leiomyosarcoma, prostate hypertrophy, prostate cancer.
• Female-specific: masculinization, irreversible voice deepening, hirsutism (excessive facial/body hair growth), menstrual disturbances (e.g., anovulation, oligomenorrhea, amenorrhea, dysmenorrhea), clitoral enlargement, breast atrophy, uterine atrophy, teratogenicity (in female fetuses).
• Child-specific: premature epiphyseal closure and associated short stature, precocious puberty in boys, delayed puberty and contrasexual precocity in girls.
• Psychiatric/neurological: mood swings, irritability, aggression, violent behavior, impulsivity/recklessness, hypomania/mania, euphoria, depression, anxiety, dysphoria, suicidality, delusions, psychosis, withdrawal, dependence, neurotoxicity, cognitive impairment.^[80][81]
• Musculoskeletal: muscle hypertrophy, muscle strains, tendon ruptures, rhabdomyolysis.
• Cardiovascular: dyslipidemia (e.g., increased LDLTooltip low-density lipoprotein levels, decreased HDLTooltip high-density lipoprotein levels, reduced apo-A1Tooltip apolipoprotein A1 levels), atherosclerosis, elevated hematocrit, hypertension, left ventricular hypertrophy, cardiomyopathy, myocardial hypertrophy, polycythemia/erythrocytosis, arrhythmias, thrombosis (e.g., embolism, stroke), myocardial infarction, sudden death.^[82][83]
• Hepatic: elevated liver function tests (ASTTooltip aspartate aminotransferase, ALTTooltip alanine aminotransferase, bilirubin, LDHTooltip lactic dehydrogenase, ALPTooltip alkaline phosphatase), hepatotoxicity, jaundice, hepatic steatosis, hepatocellular adenoma, hepatocellular carcinoma, cholestasis, peliosis hepatis; all mostly or exclusively with 17α-alkylated AAS.^[84]
• Renal: renal hypertrophy, nephropathy, acute renal failure (secondary to rhabdomyolysis), focal segmental glomerulosclerosis, renal cell carcinoma.
• Others: glucose intolerance, insulin resistance, immune dysfunction.^[85]

Physiological

Depending on the length of drug use, there is a chance that the immune system can be damaged. Most of these side-effects are dose-dependent, the most common being elevated blood pressure, especially in those with pre-existing hypertension.^[86] In addition to morphological changes of the heart which may have a permanent adverse effect on cardiovascular efficiency.

AAS have been shown to alter fasting blood sugar and glucose tolerance tests.^[87] AAS such as testosterone also increase the risk of cardiovascular disease^[2] or coronary artery disease.^[88][89] Acne is fairly common among AAS users, mostly due to stimulation of the sebaceous glands by increased testosterone levels.^[7][90] Conversion of testosterone to DHT can accelerate the rate of premature baldness for males genetically predisposed, but testosterone itself can produce baldness in females.^[91]

A number of severe side effects can occur if adolescents use AAS. For example, AAS 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. AAS use in adolescence is also correlated with poorer attitudes related to health.^[92]

Cancer

WHO organization International Agency for Research on Cancer (IARC) list AAS under Group 2A: Probably carcinogenic to humans.^[93]

Cardiovascular

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, and therefore reducing ejected blood volume.^[4] Possible effects of these alterations in the heart are hypertension, cardiac arrhythmias, congestive heart failure, heart attacks, and sudden cardiac death.^[94] These changes are also seen in non-drug-using athletes, but steroid use may accelerate this process.^[95][96] 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.^[97][98]

AAS use can cause harmful changes in cholesterol levels: Some steroids cause an increase in LDL cholesterol and a decrease in HDL cholesterol.^[99]

Growth defects

AAS use in adolescents quickens bone maturation and may reduce adult height in high doses.^{[citation needed]} Low doses of AAS such as oxandrolone are used in the treatment of idiopathic short stature, but this may only quicken maturation rather than increasing adult height.^[100]

Feminization

Although all anabolic steroids have androgenic effects, some of them paradoxically results in feminization, such as breast tissue in males, a condition called gynecomastia. These side effect are caused by the natural conversion of testosterone into estrogen and estradiol by the action of aromatase enzyme.^[101]

Prolonged use of androgenic-anabolic steroids by men results in a permanent shut down of their natural testosterone production due to an inhibition of the hypothalamic–pituitary–gonadal axis. This manifests in testicular atrophy, inhibition of the production of sperm, sexual function and infertility.^{[102][103][104]} A short (1-2 months) use of androgenic-anabolic steroids by men followed by a course of testosterone-boosting therapy (e.g. clomifene and human chorionic gonadotropin) usually results in return to normal testosterone production. ^[105])

Masculinization

Female-specific side effects include increases in body hair, permanent deepening of the voice, enlarged clitoris, and temporary decreases in menstrual cycles. Alteration of fertility and ovarian cysts can also occur in females.^[106] When taken during pregnancy, AAS can affect fetal development by causing the development of male features in the female fetus and female features in the male fetus.^[107]

Kidney problems

Kidney tests revealed that nine of the ten steroid users developed a condition called focal segmental glomerulosclerosis, a type of scarring within the kidneys. The kidney damage in the bodybuilders has similarities to that seen in morbidly obese patients, but appears to be even more severe.^[108]

Liver problems

High doses of oral AAS compounds can cause liver damage.^[3] Peliosis hepatis has been increasingly recognised with the use of AAS.

Neuropsychiatric

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".^[81] High concentrations of AAS, comparable to those likely sustained by many recreational AAS users, produce apoptotic effects on neurons,^{[citation needed]} raising the specter of possibly irreversible neurotoxicity. 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 use, but the prevalence and severity of these various effects remains poorly understood.^[110] There is no evidence that steroid dependence develops from therapeutic use of AAS to treat medical disorders, but instances of AAS dependence have been reported among weightlifters and bodybuilders who chronically administered supraphysiologic doses.^[111] Mood disturbances (e.g. depression, 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.^[7] Large-scale long-term studies of psychiatric effects on AAS users are not currently available.^[110]

Diagnostic Statistical Manual assertion

DSM-IV lists General diagnostic criteria for a personality disorder guideline that "The pattern must not be better accounted for as a manifestation of another mental disorder, or to the direct physiological effects of a substance (e.g. drug or medication) or a general medical condition (e.g. head trauma).". As a result, AAS users may get misdiagnosed by a psychiatrist not told about their habit.^[112]

Personality profiles

Cooper, Noakes, Dunne, Lambert, and Rochford identified that AAS-using individuals are more likely to score higher on borderline (4.7 times), antisocial (3.8 times), paranoid (3.4 times), schizotypal (3.1 times), histrionic (2.9 times), passive-aggressive (2.4 times), and narcissistic (1.6 times) personality profiles than non-users.^[113] Other studies have suggested that antisocial personality disorder is slightly more likely among AAS users than among non-users (Pope & Katz, 1994).^[112] Bipolar dysfunction,^[114] substance dependency, and conduct disorder have also been associated with AAS use.^[115]

Mood and anxiety

Affective disorders have long been recognised as a complication of AAS use. Case reports describe both hypomania and mania, along with irritability, elation, recklessness, racing thoughts and feelings of power and invincibility that did not meet the criteria for mania/hypomania.^[116] Of 53 bodybuilders who used AAS, 27 (51%) reported unspecified mood disturbance.^[117]

Aggression and hypomania

From the mid-1980s onward, the media reported "roid rage" as a side effect of AAS.^[118]: 23

A 2005 review determined that some, but not all, randomized controlled studies have found that AAS use correlates with hypomania and increased aggressiveness, but pointed out that attempts to determine whether AAS use triggers violent behavior have failed, primarily because of high rates of non-participation.^[119] 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 AAS use and involvement in violent acts. Compared with individuals that did not use steroids, young adult males that used AAS reported greater involvement in violent behaviors even after controlling for the effects of key demographic variables, previous violent behavior, and polydrug use.^[120] 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.^[121]

The relationship between AAS use and depression is inconclusive. A 1992 review^{[needs update]} found that AAS may both relieve and cause depression, and that cessation or diminished use of AAS may also result in depression, but called for additional studies due to disparate data.^[122] Zdroj:https://en.wikipedia.org?pojem=Anabolic-androgenic_steroid
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