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Wikipedia

Anabolic steroid

March 20, 2023

This article is about androgens as medications. For androgens as natural hormones, see Androgen.

Anabolic steroids, also known more properly as anabolic–androgenic steroids (AAS),[1] are steroidal androgens that include natural androgens like testosterone as well as synthetic androgens that are structurally related and have similar effects to testosterone. They increase protein within cells, especially in skeletal muscles, and also have varying degrees of virilizing effects, including induction of the development and maintenance of masculine secondary sexual characteristics such as the growth of facial and body hair. The word anabolic, referring to anabolism, comes from the Greek ἀναβολή anabole, "that which is thrown up, mound". Androgens or AAS are one of three types of sex hormone agonists, the others being estrogens like estradiol and progestogens like progesterone.

Anabolic–androgenic steroids
Drug class
Chemical structure of the natural AAS testosterone (androst-4-en-17β-ol-3-one).
Class identifiers
SynonymsAnabolic steroids; Androgens
UseVarious
ATC codeA14A
Biological targetAndrogen receptor
Chemical classSteroids; Androstanes; Estranes
Clinical data
Drugs.comDrug Classes
External links
MeSHD045165
In Wikidata

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

Health risks can be produced by long-term use or excessive doses of AAS.[3][4] 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 dangerous changes in the structure of the left ventricle of the heart.[5] These risks are further increased when athletes take steroids alongside other drugs, causing significantly more damage to their bodies.[6] The effect of anabolic steroids on the heart can cause myocardial infarction and strokes.[6] Conditions pertaining to hormonal imbalances such as gynecomastia and testicular size reduction may also be caused by AAS.[7] In women and children, AAS can cause irreversible masculinization.[7]

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 unfair 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.[6] For many years, AAS have been by far the most detected doping substances in IOC-accredited laboratories.[8][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

 
Various AAS and related compounds

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

Androgenic

Other

Enhancing performance

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

Most steroid users are not athletes.[49] In the United States, between 1 million and 3 million people (1% of the population) are thought to have used AAS.[50] 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.[51] "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%.[52] 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,[53] though a 2007 study found that sharing of needles was extremely uncommon among individuals using AAS for non-medical purposes, less than 1%.[54] 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.[54] 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.[54] 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.[55]

AAS users tend to be unhappy with the portrayal of AAS as deadly in the media and in politics.[56] According to one study, AAS users also distrust their physicians and in the sample 56% had not disclosed their AAS use to their physicians.[57] 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.[54] 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.[58] A recent study in the Journal of Health Psychology showed that many users believed that steroids used in moderation were safe.[59]

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%.[60]

Dosages

General dosage ranges of anabolic steroids
Medication Route Dosage range[a]
Danazol Oral 100–800 mg/day
Drostanolone propionate Injection 100 mg 3 times/week
Ethylestrenol Oral 2–8 mg/day
Fluoxymesterone Oral 2–40 mg/day
Mesterolone Oral 25–150 mg/day
Metandienone Oral 2.5–15 mg/day
Metenolone acetate Oral 10–150 mg/day
Metenolone enanthate Injection 25–100 mg/week
Methyltestosterone Oral 1.5–200 mg/day
Nandrolone decanoate Injection 12.5–200 mg/week[b]
Nandrolone phenylpropionate Injection 6.25–200 mg/week[b]
Norethandrolone Oral 20–30 mg/day
Oxandrolone Oral 2.5–20 mg/day
Oxymetholone Oral 1–5 mg/kg/day or
50–150 mg/day
Stanozolol Oral 2–6 mg/day
Injection 50 mg up to
every two weeks
Testosterone Oral[c] 400–800 mg/day[b]
Injection 25–100 mg up to
three times weekly
Testosterone cypionate Injection 50–400 mg up to
every four weeks
Testosterone enanthate Injection 50–400 mg up to
every four weeks
Testosterone propionate Injection 25–50 mg up to
three times weekly
Testosterone undecanoate Oral 80–240 mg/day[b]
Injection 750–1000 mg up to
every 10 weeks
Trenbolone HBC Injection 75 mg every 10 days
Sources: [61][62][63][64][18][65][66][67][68][69]
  1. ^ Unless otherwise noted, given as a once daily/weekly dose
  2. ^ a b c d In divided doses
  3. ^ Studied for human use but never marketed, for comparison only

Available forms

See also: List of androgens/anabolic steroids

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),[70] nandrolone esters (typically nandrolone decanoate and nandrolone phenylpropionate), stanozolol, and metandienone (methandrostenolone).[1] 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.[1] Dihydrotestosterone (DHT), known as androstanolone or stanolone when used medically, and its esters are also notable, although they are not widely used in medicine.[66] Boldenone undecylenate and trenbolone acetate are used in veterinary medicine.[1]

Designer steroids are AAS that have not been approved and marketed for medical use but have been distributed through the black market.[71] Examples of notable designer steroids include 1-testosterone (dihydroboldenone), methasterone, trenbolone enanthate, desoxymethyltestosterone, tetrahydrogestrinone, and methylstenbolone.[71]

Routes of administration

 
A vial of injectable testosterone cypionate

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.[72] 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.[54]

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.[9][73]

Adverse effects

Known possible side effects of AAS include:[7][74][75][76][77]

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.[84] 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.[85] AAS such as testosterone also increase the risk of cardiovascular disease[3] or coronary artery disease.[86][87] Acne is fairly common among AAS users, mostly due to stimulation of the sebaceous glands by increased testosterone levels.[8][88] Conversion of testosterone to DHT can accelerate the rate of premature baldness for males genetically predisposed, but testosterone itself can produce baldness in females.[89]

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.[90]

Cancer

WHO organization International Agency for Research on Cancer (IARC) list AAS under Group 2A: Probably carcinogenic to humans.[91]

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.[5] Possible effects of these alterations in the heart are hypertension, cardiac arrhythmias, congestive heart failure, heart attacks, and sudden cardiac death.[92] These changes are also seen in non-drug-using athletes, but steroid use may accelerate this process.[93][94] 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.[95][96]

AAS use can cause harmful changes in cholesterol levels: Some steroids cause an increase in LDL cholesterol and a decrease in HDL cholesterol.[97]

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.[98]

Feminization

 
22-year-old man with gynecomastia not due to AAS use. Before and after gynecomastia surgery.
See also: Feminization (biology)

There are also sex-specific side effects of AAS. Development of breast tissue in males, a condition called gynecomastia (which is usually caused by high levels of circulating estradiol), may arise because of increased conversion of testosterone to estradiol by the enzyme aromatase.[99] Reduced sexual function and temporary infertility can also occur in males.[100][101][102] Another male-specific side-effect that can occur is testicular atrophy, caused by the suppression of natural testosterone levels, which inhibits production of sperm (most of the mass of the testes is developing sperm). This side-effect is temporary; the size of the testicles usually returns to normal within a few weeks of discontinuing AAS use as normal production of sperm resumes.[103]

Masculinization

See also: Virilization

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.[104] 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.[105]

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.[106]

Liver problems

High doses of oral AAS compounds can cause liver damage.[4] Peliosis hepatis has been increasingly recognised with the use of AAS.

Neuropsychiatric

 
Addiction experts in psychiatry, chemistry, pharmacology, forensic science, epidemiology, and the police and legal services engaged in delphic analysis regarding 20 popular recreational drugs. AAS were ranked 19th in dependence, 9th in physical harm, and 15th in social harm.[107]
See also: Anabolic–androgenic steroids abuse

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".[79] 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 abuse, but the prevalence and severity of these various effects remains poorly understood.[108] 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.[109] Mood disturbances (e.g. depression, [hypo-]mania, psychotic features) are likely to be dose- and drug-dependent, but AAS dependence or withdrawal effects seem to occur only in a small number of AAS users.[8]

Large-scale long-term studies of psychiatric effects on AAS users are not currently available.[108] In 2003, the first naturalistic long-term study on ten users, seven of which having completed the study, found a high incidence of mood disorders and substance abuse, but few clinically relevant changes in physiological parameters or laboratory measures were noted throughout the study, and these changes were not clearly related to periods of reported AAS use.[110] A 13-month study, which was published in 2006 and which involved 320 body builders and athletes suggests that the wide range of psychiatric side-effects induced by the use of AAS is correlated to the severity of abuse.[111]

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]

A 1996 randomized controlled trial, which involved 43 men, did not find an increase in the occurrence of angry behavior during 10 weeks of administration of testosterone enanthate at 600 mg/week, but this study screened out subjects that had previously abused steroids or had any psychiatric antecedents.[122][123] A trial conducted in 2000 using testosterone cypionate at 600 mg/week found that treatment significantly increased manic scores on the YMRS, and aggressive responses on several scales. The drug response was highly variable. However: 84% of subjects exhibited minimal psychiatric effects, 12% became mildly hypomanic, and 4% (2 subjects) became markedly hypomanic. The mechanism of these variable reactions could not be explained by demographic, psychological, laboratory, or physiological measures.[124]

A 2006 study of two pairs of identical twins, in which one twin used AAS 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.[125] A small-scale study of 10 AAS users found that cluster B personality disorders were confounding factors for aggression.[126]

The relationship between AAS use and depression is inconclusive. There have been anecdotal reports of depression and suicide in teenage steroid users,[127] but little systematic evidence. A 1992 review 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.[128] In the case of suicide, 3.9% of a sample of 77 those classified as AAS users reported attempting suicide during withdrawal (Malone, Dimeff, Lombardo, & Sample, 1995).[129]

Reproductive

Androgens such as testosterone, androstenedione and dihydrotestosterone are required for the development of organs in the male reproductive system, including the seminal vesicles, epididymis, vas deferens, penis and prostate.[130] AAS are testosterone derivatives designed to maximize the anabolic effects of testosterone.[131] AAS are consumed by elite athletes competing in sports like weightlifting, bodybuilding, and track and field.[132] Male recreational athletes take AAS to achieve an "enhanced" physical appearance.[133]

AAS consumption disrupts the hypothalamic–pituitary–gonadal axis (HPG axis) in males.[130] In the HPG axis, gonadotropin-releasing hormone (GnRH) is secreted from the arcuate nucleus of the hypothalamus and stimulates the anterior pituitary to secrete the two gonadotropins, follicle stimulating hormone (FSH) and luteinizing hormone (LH).[134] In adult males, LH stimulates the Leydig cells in the testes to produce testosterone which is required to form new sperm through spermatogenesis.[130] AAS consumption leads to dose-dependent suppression of gonadotropin release through suppression of GnRH from the hypothalamus (long-loop mechanism) or from direct negative feedback on the anterior pituitary to inhibit gonadotropin release (short-loop mechanism), leading to AAS-induced hypogonadism.[130]

Pharmacology

Mechanism of action

See also: Steroid hormone
 
The human androgen receptor bound to testosterone[135] The protein is shown as a ribbon diagram in red, green, and blue, with the steroid shown in white.

The pharmacodynamics of AAS are unlike peptide hormones. Water-soluble peptide hormones cannot penetrate the fatty cell membrane and only indirectly affect the nucleus of target cells through their interaction with the cell's surface receptors. However, as fat-soluble hormones, AAS are membrane-permeable and influence the nucleus of cells by direct action. The pharmacodynamic action of AAS begin when the exogenous hormone penetrates the membrane of the target cell and binds to an androgen receptor (AR) located in the cytoplasm of that cell. From there, the compound hormone-receptor diffuses into the nucleus, where it either alters the expression of genes[136] or activates processes that send signals to other parts of the cell.[137] Different types of AAS bind to the AAR with different affinities, depending on their chemical structure.[8]

The effect of AAS on muscle mass is caused in at least two ways:[138] first, they increase the production of proteins; second, they reduce recovery time by blocking the effects of stress hormone cortisol on muscle tissue, so that catabolism of muscle is greatly reduced. It has been hypothesized that this reduction in muscle breakdown may occur through AAS inhibiting the action of other steroid hormones called glucocorticoids that promote the breakdown of muscles.[139] AAS also affect the number of cells that develop into fat-storage cells, by favouring cellular differentiation into muscle cells instead.[140]

Anabolic and androgenic effects

Androgenic vs. anabolic activity
of androgens/anabolic steroids
Medication Ratioa
Testosterone ~1:1
Androstanolone (DHT) ~1:1
Methyltestosterone ~1:1
Methandriol ~1:1
Fluoxymesterone 1:1–1:15
Metandienone 1:1–1:8
Drostanolone 1:3–1:4
Metenolone 1:2–1:30
Oxymetholone 1:2–1:9
Oxandrolone 1:3–1:13
Stanozolol 1:1–1:30
Nandrolone 1:3–1:16
Ethylestrenol 1:2–1:19
Norethandrolone 1:1–1:20
Notes: In rodents. Footnotes: a = Ratio of androgenic to anabolic activity. Sources: See template.

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

Some examples of the anabolic effects of these hormones are increased protein synthesis from amino acids, increased appetite, increased bone remodeling and growth, and stimulation of bone marrow, which increases the production of red blood cells. Through a number of mechanisms AAS stimulate the formation of muscle cells and hence cause an increase in the size of skeletal muscles, leading to increased strength.[141][142][143]

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 size does not change due to steroids[medical citation needed] ), increased vocal cord size, increased libido, suppression of natural sex hormones, and impaired production of sperm.[144] Effects on women include deepening of the voice, facial hair growth, and possibly a decrease in breast size. Men may develop an enlargement of breast tissue, known as gynecomastia, testicular atrophy, and a reduced sperm count.[citation needed] 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 AAS have significant androgenic effects.[72]

A commonly used protocol for determining the androgenic:anabolic ratio, dating back to the 1950s, uses the relative weights of ventral prostate (VP) and levator ani muscle (LA) of male rats. The VP weight is an indicator of the androgenic effect, while the LA weight is an indicator of the anabolic effect. Two or more batches of rats are castrated and given no treatment and respectively some AAS of interest. The LA/VP ratio for an AAS is calculated as the ratio of LA/VP weight gains produced by the treatment with that compound using castrated but untreated rats as baseline: (LAc,t–LAc)/(VPc,t–VPc). The LA/VP weight gain ratio from rat experiments is not unitary for testosterone (typically 0.3–0.4), but it is normalized for presentation purposes, and used as basis of comparison for other AAS, which have their androgenic:anabolic ratios scaled accordingly (as shown in the table above).[145][146] In the early 2000s, this procedure was standardized and generalized throughout OECD in what is now known as the Hershberger assay.

Body composition and strength improvements

Body weight in men may increase by 2 to 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.[8]

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 ARs in the upper body.[citation needed] 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.[8]

Strength improvements in the range of 5 to 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 bench press.[8] For almost two decades, it was assumed that AAS exerted significant effects only in experienced strength athletes.[147][148] A randomized controlled trial demonstrated, however, that even in novice athletes a 10-week strength training program accompanied by testosterone enanthate at 600 mg/week may improve strength more than training alone does.[8][122] This dose is sufficient to significantly improve lean muscle mass relative to placebo even in subjects that did not exercise at all.[122] The anabolic effects of testosterone enanthate were highly dose dependent.[8][149]

Dissociation of effects

Endogenous/natural AAS like testosterone and DHT and synthetic AAS mediate their effects by binding to and activating the AR.[1] On the basis of animal bioassays, the effects of these agents have been divided into two partially dissociable types: anabolic (myotrophic) and androgenic.[1] Dissociation between the ratios of these two types of effects relative to the ratio observed with testosterone is observed in rat bioassays with various AAS.[1] Theories for the dissociation include differences between AAS in terms of their intracellular metabolism, functional selectivity (differential recruitment of coactivators), and non-genomic mechanisms (i.e., signaling through non-AR membrane androgen receptors, or mARs).[1] Support for the latter two theories is limited and more hypothetical, but there is a good deal of support for the intracellular metabolism theory.[1]

The measurement of the dissociation between anabolic and androgenic effects among AAS is based largely on a simple but outdated and unsophisticated model using rat tissue bioassays.[1] It has been referred to as the "myotrophic–androgenic index".[1] In this model, myotrophic or anabolic activity is measured by change in the weight of the rat bulbocavernosus/levator ani muscle, and androgenic activity is measured by change in the weight of the rat ventral prostate (or, alternatively, the rat seminal vesicles), in response to exposure to the AAS.[1] The measurements are then compared to form a ratio.[1]

Intracellular metabolism

Testosterone is metabolized in various tissues by 5α-reductase into DHT, which is 3- to 10-fold more potent as an AR agonist, and by aromatase into estradiol, which is an estrogen and lacks significant AR affinity.[1] In addition, DHT is metabolized by 3α-hydroxysteroid dehydrogenase (3α-HSD) and 3β-hydroxysteroid dehydrogenase (3β-HSD) into 3α-androstanediol and 3β-androstanediol, respectively, which are metabolites with little or no AR affinity.[1] 5α-reductase is widely distributed throughout the body, and is concentrated to various extents in skin (particularly the scalp, face, and genital areas), prostate, seminal vesicles, liver, and the brain.[1] In contrast, expression of 5α-reductase in skeletal muscle is undetectable.[1] Aromatase is highly expressed in adipose tissue and the brain, and is also expressed significantly in skeletal muscle.[1] 3α-HSD is highly expressed in skeletal muscle as well.[66]

Natural AAS like testosterone and DHT and synthetic AAS are analogues and are very similar structurally.[1] For this reason, they have the capacity to bind to and be metabolized by the same steroid-metabolizing enzymes.[1] According to the intracellular metabolism explanation, the androgenic-to-anabolic ratio of a given AR agonist is related to its capacity to be transformed by the aforementioned enzymes in conjunction with the AR activity of any resulting products.[1] For instance, whereas the AR activity of testosterone is greatly potentiated by local conversion via 5α-reductase into DHT in tissues where 5α-reductase is expressed, an AAS that is not metabolized by 5α-reductase or is already 5α-reduced, such as DHT itself or a derivative (like mesterolone or drostanolone), would not undergo such potentiation in said tissues.[1] Moreover, nandrolone is metabolized by 5α-reductase, but unlike the case of testosterone and DHT, the 5α-reduced metabolite of nandrolone has much lower affinity for the AR than does nandrolone itself, and this results in reduced AR activation in 5α-reductase-expressing tissues.[1] As so-called "androgenic" tissues such as skin/hair follicles and male reproductive tissues are very high in 5α-reductase expression, while skeletal muscle is virtually devoid of 5α-reductase, this may primarily explain the high myotrophic–androgenic ratio and dissociation seen with nandrolone, as well as with various other AAS.[1]

Aside from 5α-reductase, aromatase may inactivate testosterone signaling in skeletal muscle and adipose tissue, so AAS that lack aromatase affinity, in addition to being free of the potential side effect of gynecomastia, might be expected to have a higher myotrophic–androgenic ratio in comparison.[1] In addition, DHT is inactivated by high activity of 3α-HSD in skeletal muscle (and cardiac tissue), and AAS that lack affinity for 3α-HSD could similarly be expected to have a higher myotrophic–androgenic ratio (although perhaps also increased long-term cardiovascular risks).[1] In accordance, DHT, mestanolone (17α-methyl-DHT), and mesterolone (1α-methyl-DHT) are all described as very poorly anabolic due to inactivation by 3α-HSD in skeletal muscle, whereas other DHT derivatives with other structural features like metenolone, oxandrolone, oxymetholone, drostanolone, and stanozolol are all poor substrates for 3α-HSD and are described as potent anabolics.[66]

The intracellular metabolism theory explains how and why remarkable dissociation between anabolic and androgenic effects might occur despite the fact that these effects are mediated through the same signaling receptor, and why this dissociation is invariably incomplete.[1] In support of the model is the rare condition congenital 5α-reductase type 2 deficiency, in which the 5α-reductase type 2 enzyme is defective, production of DHT is impaired, and DHT levels are low while testosterone levels are normal.[150][151] Males with this condition are born with ambiguous genitalia and a severely underdeveloped or even absent prostate gland.[150][151] In addition, at the time of puberty, such males develop normal musculature, voice deepening, and libido, but have reduced facial hair, a female pattern of body hair (i.e., largely restricted to the pubic triangle and underarms), no incidence of male pattern hair loss, and no prostate enlargement or incidence of prostate cancer.[151][152][153][154][155] They also notably do not develop gynecomastia as a consequence of their condition.[153]

Relative affinities of nandrolone and related steroids at the androgen receptor
Compound rAR (%) hAR (%)
Testosterone 38 38
5α-Dihydrotestosterone 77 100
Nandrolone 75 92
5α-Dihydronandrolone 35 50
Ethylestrenol ND 2
Norethandrolone ND 22
5α-Dihydronorethandrolone ND 14
Metribolone 100 110
Sources: See template.

Functional selectivity

An animal study found that two different kinds of androgen response elements could differentially respond to testosterone and DHT upon activation of the AR.[156][157] Whether this is involved in the differences in the ratios of anabolic-to-myotrophic effect of different AAS is unknown however.[156][157][1]

Non-genomic mechanisms

Testosterone signals not only through the nuclear AR, but also through mARs, including ZIP9 and GPRC6A.[158][159] It has been proposed that differential signaling through mARs may be involved in the dissociation of the anabolic and androgenic effects of AAS.[1] Indeed, DHT has less than 1% of the affinity of testosterone for ZIP9, and the synthetic AAS metribolone and mibolerone are ineffective competitors for the receptor similarly.[159] This indicates that AAS do show differential interactions with the AR and mARs.[159] However, women with complete androgen insensitivity syndrome (CAIS), who have a 46,XY ("male") genotype and testes but a defect in the AR such that it is non-functional, are a challenge to this notion.[160] They are completely insensitive to the AR-mediated effects of androgens like testosterone, and show a perfectly female phenotype despite having testosterone levels in the high end of the normal male range.[160] These women have little or no sebum production, incidence of acne, or body hair growth (including in the pubic and axillary areas).[160] Moreover, CAIS women have lean body mass that is normal for females but is of course greatly reduced relative to males.[161] These observations suggest that the AR is mainly or exclusively responsible for masculinization and myotrophy caused by androgens.[160][161][162] The mARs have however been found to be involved in some of the health-related effects of testosterone, like modulation of prostate cancer risk and progression.[159][163]

Antigonadotropic effects

Changes in endogenous testosterone levels may also contribute to differences in myotrophic–androgenic ratio between testosterone and synthetic AAS.[66] AR agonists are antigonadotropic – that is, they dose-dependently suppress gonadal testosterone production and hence reduce systemic testosterone concentrations.[66] By suppressing endogenous testosterone levels and effectively replacing AR signaling in the body with that of the exogenous AAS, the myotrophic–androgenic ratio of a given AAS may be further, dose-dependently increased, and this hence may be an additional factor contributing to the differences in myotrophic–androgenic ratio among different AAS.[66] In addition, some AAS, such as 19-nortestosterone derivatives like nandrolone, are also potent progestogens, and activation of the progesterone receptor (PR) is antigonadotropic similarly to activation of the AR.[66] The combination of sufficient AR and PR activation can suppress circulating testosterone levels into the castrate range in men (i.e., complete suppression of gonadal testosterone production and circulating testosterone levels decreased by about 95%).[48][164] As such, combined progestogenic activity may serve to further increase the myotrophic–androgenic ratio for a given AAS.[66]

GABAA receptor modulation

Some AAS, such as testosterone, DHT, stanozolol, and methyltestosterone, have been found to modulate the GABAA receptor similarly to endogenous neurosteroids like allopregnanolone, 3α-androstanediol, dehydroepiandrosterone sulfate, and pregnenolone sulfate.[1] It has been suggested that this may contribute as an alternative or additional mechanism to the neurological and behavioral effects of AAS.[1][165][166][167][168][169][170]

Comparison of AAS

AAS differ in a variety of ways including in their capacities to be metabolized by steroidogenic enzymes such as 5α-reductase, 3-hydroxysteroid dehydrogenases, and aromatase, in whether their potency as AR agonists is potentiated or diminished by 5α-reduction, in their ratios of anabolic/myotrophic to androgenic effect, in their estrogenic, progestogenic, and neurosteroid activities, in their oral activity, and in their capacity to produce hepatotoxicity.[66][1][171]

Pharmacological properties of major anabolic steroids
Compound Class 5α-R AROM 3-HSD AAR Estr Prog Oral Hepat
Androstanolone DHT – – + * – – – –
Boldenone T – ± – ** ± – – –
Drostanolone DHT – – – *** – – – –
Ethylestrenol 19-NT; 17α-A + (↓) ± – *** + + + +
Fluoxymesterone T; 17α-A + (↑) – – * – – + +
Mestanolone DHT; 17α-A – – + * – – + +
Mesterolone DHT – – + * – – ± –
Metandienone T; 17α-A – ± – ** + – + +
Metenolone DHT – – – ** – – ± –
Methyltestosterone T; 17α-A + (↑) + – * + – + +
Nandrolone 19-NT + (↓) ± – *** ± + – –
Norethandrolone 19-NT; 17α-A + (↓) ± – *** + + + +
Oxandrolone DHT; 17α-A – – – *** – – + ±
Oxymetholone DHT; 17α-A – – – *** + – + +
Stanozolol DHT; 17α-A – – – *** – – + +
Testosterone T + (↑) + – * + – ±a –
Trenbolone 19-NT – – – *** – + – –
Key: + = Yes. ± = Low. – = No. ↑ = Potentiated. ↓ = Inactivated. *** = High. ** = Moderate. * = Low. Abbreviations: 5α-R = Metabolized by 5α-reductase. AROM = Metabolized by aromatase. 3-HSD = Metabolized by 3α- and/or 3β-HSD. AAR = Anabolic-to-androgenic ratio (amount of anabolic (myotrophic) effect relative to androgenic effect). Estr = Estrogenic. Prog = Progestogenic. Oral = Oral activity. Hepat = Hepatotoxicity. Footnotes: a = As testosterone undecanoate. Sources: See template.
Relative affinities of anabolic steroids and related steroids
Steroid Chemical name Relative binding affinities (%)
PR AR ER GR MR SHBG CBG
Androstanolone DHT 1.4–1.5 60–120 <0.1 <0.1–0.3 0.15 100 0.8
Boldenone Δ1-T <1 50–75 ? <1 ? ? ?
Danazol 2,3-Isoxazol-17α-Ety-T 9 8 ? <0.1a ? 8 10
Dienolone ∆9-19-NT 17 134 <0.1 1.6 0.3 ? ?
Dimethyldienolone ∆9-7α,17α-DiMe-19-NT 198 122 0.1 6.1 1.7 ? ?
Dimethyltrienolone ∆9,11-7α,17α-DiMe-19-NT 306 180 0.1 22 52 ? ?
Drostanolone 2α-Me-DHT ? ? ? ? ? 39 ?
Ethisterone 17α-Ety-T 35 0.1 <1.0 <1.0 <1.0 25–92 0.3
Ethylestrenol 3-DeO-17α-Et-19-NT ? ? ? ? ? <1 ?
Fluoxymesterone 9α-F-11β-OH-17α-Me-T ? ? ? ? ? ≤3 ?
Gestrinone ∆9,11-17α-Ety-18-Me-19-NT 75–76 83–85 <0.1–10 77 3.2 ? ?
Levonorgestrel 17α-Ety-18-Me-19-NT 170 84–87 <0.1 14 0.6–0.9 14–50 <0.1
Mestanolone 17α-Me-DHT 5–10 100–125 ? <1 ? 84 ?
Mesterolone 1α-Me-DHT ? ? ? ? ? 82–440 ?
Metandienone ∆1-17α-Me-T ? ? ? ? ? 2 ?
Metenolone ∆1-1-Me-DHT ? ? ? ? ? 3 ?
Methandriol 17α-Me-A5 ? ? ? ? ? 40 ?
Methasterone 2α,17α-DiMe-DHT ? ? ? ? ? 58 ?
Methyldienolone ∆9-17α-Me-19-NT 71 64 <0.1 6 0.4 ? ?
Methyltestosterone 17α-Me-T 3 45–125 <0.1 1–5 ? 5–64 <0.1
Methyl-1-testosterone ∆1-17α-Me-DHT ? ? ? ? ? 69 ?
Metribolone ∆9,11-17α-Me-19-NT 208–210 199–210 <0.1 10–26 18 0.2–0.8 ≤0.4
Mibolerone 7α,17α-DiMe-19-NT 214 108 <0.1 1.4 2.1 6 ?
Nandrolone 19-NT 20 154–155 <0.1 0.5 1.6 1–16 0.1
Norethandrolone 17α-Et-19-NT ? ? ? ? ? 3 ?
Norethisterone 17α-Ety-19-NT 155–156 43–45 <0.1 2.7–2.8 0.2 5–21 0.3
Norgestrienone ∆9,11-17α-Ety-19-NT 63–65 70 <0.1 11 1.8 ? ?
Normethandrone 17α-Me-19-NT 100 146 <0.1 1.5 0.6 7 ?
Oxandrolone 2-Oxa-17α-Me-DHT ? ? ? ? ? <1 ?
Oxymetholone 2-OHMeEne-17α-Me-DHT ? ? ? ? ? ≤3 ?
RU-2309 (17α-Me-THG) ∆9,11-17α,18-DiMe-19-NT 230 143 <0.1 155 36 ? ?
Stanozolol 2,3-Pyrazol-17α-Me-DHT ? ? ? ? ? 1–36 ?
Testosterone T 1.0–1.2 100 <0.1 0.17 0.9 19–82 3–8
1-Testosterone ∆1-DHT ? ? ? ? ? 98 ?
Tibolone 7α-Me-17α-Ety-19-N-5(10)-T 12 12 1 ? ? ? ?
Δ4-Tibolone 7α-Me-17α-Ety-19-NT 180 70 1 <1 2 1–8 <1
Trenbolone ∆9,11-19-NT 74–75 190–197 <0.1 2.9 1.33 ? ?
Trestolone 7α-Me-19-NT 50–75 100–125 ? <1 ? 12 ?
Notes: Values are percentages (%). Reference ligands (100%) were progesterone for the PR, testosterone for the AR, estradiol for the ER, dexamethasone for the GR, aldosterone for the MR, dihydrotestosterone for SHBG, and cortisol for CBG. Footnotes: a = 1-hour incubation time (4 hours is standard for this assay; may affect affinity value). Sources: See template.
Parenteral durations of androgens/anabolic steroids
Medication Form Major brand names Duration
Testosterone Aqueous suspension Andronaq, Sterotate, Virosterone 2–3 days
Testosterone propionate Oil solution Androteston, Perandren, Testoviron 3–4 days
Testosterone phenylpropionate Oil solution Testolent 8 days
Testosterone isobutyrate Aqueous suspension Agovirin Depot, Perandren M 14 days
Mixed testosterone estersa Oil solution Triolandren 10–20 days
Mixed testosterone estersb Oil solution Testosid Depot 14–20 days
Testosterone enanthate Oil solution Delatestryl 14–28 days
Testosterone cypionate Oil solution Depovirin 14–28 days
Mixed testosterone estersc Oil solution Sustanon 250 28 days
Testosterone undecanoate Oil solution Aveed, Nebido 100 days
Testosterone buciclated Aqueous suspension 20 Aet-1, CDB-1781e 90–120 days
Nandrolone phenylpropionate Oil solution Durabolin 10 days
Nandrolone decanoate Oil solution Deca Durabolin 21–28 days
Methandriol Aqueous suspension Notandron, Protandren 8 days
Methandriol bisenanthoyl acetate Oil solution Notandron Depot 16 days
Metenolone acetate Oil solution Primobolan 3 days
Metenolone enanthate Oil solution Primobolan Depot 14 days
Note: All are via i.m. injection. Footnotes: a = TP, TV, and TUe. b = TP and TKL. c = TP, TPP, TiCa, and TD. d = Studied but never marketed. e = Developmental code names. Sources: See template.
Pharmacokinetics of testosterone esters
Testosterone ester Form Route Tmax t1/2 MRT
Testosterone undecanoate Oil-filled capsules Oral ? 1.6 hours 3.7 hours
Testosterone propionate Oil solution Intramuscular injection ? 0.8 days 1.5 days
Testosterone enanthate Castor oil solution Intramuscular injection 10 days 4.5 days 8.5 days
Testosterone undecanoate Tea seed oil solution Intramuscular injection 13.0 days 20.9 days 34.9 days
Testosterone undecanoate Castor oil solution Intramuscular injection 11.4 days 33.9 days 36.0 days
Testosterone buciclatea Aqueous suspension Intramuscular injection 25.8 days 29.5 days 60.0 days
Notes: Testosterone cypionate has similar pharmacokinetics to Testosterone enanthate. Footnotes: a = Never marketed. Sources: See template.

5α-Reductase and androgenicity

Testosterone can be robustly converted by 5α-reductase into DHT in so-called androgenic tissues such as skin, scalp, prostate, and seminal vesicles, but not in muscle or bone, where 5α-reductase either is not expressed or is only minimally expressed.[1] As DHT is 3- to 10-fold more potent as an agonist of the AR than is testosterone, the AR agonist activity of testosterone is thus markedly and selectively potentiated in such tissues.[1] In contrast to testosterone, DHT and other 4,5α-dihydrogenated AAS are already 5α-reduced, and for this reason, cannot be potentiated in androgenic tissues.[1] 19-Nortestosterone derivatives like nandrolone can be metabolized by 5α-reductase similarly to testosterone, but 5α-reduced metabolites of 19-nortestosterone derivatives (e.g., 5α-dihydronandrolone) tend to have reduced activity as AR agonists, resulting in reduced androgenic activity in tissues that express 5α-reductase.[1] In addition, some 19-nortestosterone derivatives, including trestolone (7α-methyl-19-nortestosterone (MENT)), 11β-methyl-19-nortestosterone (11β-MNT), and dimethandrolone (7α,11β-dimethyl-19-nortestosterone), cannot be 5α-reduced.[172] Conversely, certain 17α-alkylated AAS like methyltestosterone are 5α-reduced and potentiated in androgenic tissues similarly to testosterone.[1][66] 17α-Alkylated DHT derivatives cannot be potentiated via 5α-reductase however, as they are already 4,5α-reduced.[1][66]

The capacity to be metabolized by 5α-reductase and the AR activity of the resultant metabolites appears to be one of the major, if not the most important determinant of the androgenic–myotrophic ratio for a given AAS.[1] AAS that are not potentiated by 5α-reductase or that are weakened by 5α-reductase in androgenic tissues have a reduced risk of androgenic side effects such as acne, androgenic alopecia (male-pattern baldness), hirsutism (excessive male-pattern hair growth), benign prostatic hyperplasia (prostate enlargement), and prostate cancer, while incidence and magnitude of other effects such as muscle hypertrophy, bone changes,[173] voice deepening, and changes in sex drive show no difference.[1][174]

Aromatase and estrogenicity

Testosterone can be metabolized by aromatase into estradiol, and many other AAS can be metabolized into their corresponding estrogenic metabolites as well.[1] As an example, the 17α-alkylated AAS methyltestosterone and metandienone are converted by aromatase into methylestradiol.[175] 4,5α-Dihydrogenated derivatives of testosterone such as DHT cannot be aromatized, whereas 19-nortestosterone derivatives like nandrolone can be but to a greatly reduced extent.[1][176] Some 19-nortestosterone derivatives, such as dimethandrolone and 11β-MNT, cannot be aromatized due to steric hindrance provided by their 11β-methyl group, whereas the closely related AAS trestolone (7α-methyl-19-nortestosterone), in relation to its lack of an 11β-methyl group, can be aromatized.[176] AAS that are 17α-alkylated (and not also 4,5α-reduced or 19-demethylated) are also aromatized but to a lesser extent than is testosterone.[1][177] However, it is notable that estrogens that are 17α-substituted (e.g., ethinylestradiol and methylestradiol) are of markedly increased estrogenic potency due to improved metabolic stability,[175] and for this reason, 17α-alkylated AAS can actually have high estrogenicity and comparatively greater estrogenic effects than testosterone.[175][66]

The major effect of estrogenicity is gynecomastia (woman-like breasts).[1] AAS that have a high potential for aromatization like testosterone and particularly methyltestosterone show a high risk of gynecomastia at sufficiently high dosages, while AAS that have a reduced potential for aromatization like nandrolone show a much lower risk (though still potentially significant at high dosages).[1] In contrast, AAS that are 4,5α-reduced, and some other AAS (e.g., 11β-methylated 19-nortestosterone derivatives), have no risk of gynecomastia.[1] In addition to gynecomastia, AAS with high estrogenicity have increased antigonadotropic activity, which results in increased potency in suppression of the hypothalamic-pituitary-gonadal axis and gonadal testosterone production.[178]

Progestogenic activity

Many 19-nortestosterone derivatives, including nandrolone, trenbolone, ethylestrenol (ethylnandrol), metribolone (R-1881), trestolone, 11β-MNT, dimethandrolone, and others, are potent agonists of the progesterone receptor (PR) and hence are progestogens in addition to AAS.[1][179] Similarly to the case of estrogenic activity, the progestogenic activity of these drugs serves to augment their antigonadotropic activity.[179] This results in increased potency and effectiveness of these AAS as antispermatogenic agents and male contraceptives (or, put in another way, increased potency and effectiveness in producing azoospermia and reversible male infertility).[179]

Oral activity and hepatotoxicity

Non-17α-alkylated testosterone derivatives such as testosterone itself, DHT, and nandrolone all have poor oral bioavailability due to extensive first-pass hepatic metabolism and hence are not orally active.[1] A notable exception to this are AAS that are androgen precursors or prohormones, including dehydroepiandrosterone (DHEA), androstenediol, androstenedione, boldione (androstadienedione), bolandiol (norandrostenediol), bolandione (norandrostenedione), dienedione, mentabolan (MENT dione, trestione), and methoxydienone (methoxygonadiene) (although these are relatively weak AAS).[180][181] AAS that are not orally active are used almost exclusively in the form of esters administered by intramuscular injection, which act as depots and function as long-acting prodrugs.[1] Examples include testosterone, as testosterone cypionate, testosterone enanthate, and testosterone propionate, and nandrolone, as nandrolone phenylpropionate and nandrolone decanoate, among many others (see here for a full list of testosterone and nandrolone esters).[1] An exception is the very long-chain ester testosterone undecanoate, which is orally active, albeit with only very low oral bioavailability (approximately 3%).[182] In contrast to most other AAS, 17α-alkylated testosterone derivatives show resistance to metabolism due to steric hindrance and are orally active, though they may be esterified and administered via intramuscular injection as well.[1]

In addition to oral activity, 17α-alkylation also confers a high potential for hepatotoxicity, and all 17α-alkylated AAS have been associated, albeit uncommonly and only after prolonged use (different estimates between 1 and 17%),[183][184] with hepatotoxicity.[1][185][186] In contrast, testosterone esters have only extremely rarely or never been associated with hepatotoxicity,[184] and other non-17α-alkylated AAS only rarely,[citation needed] although long-term use may reportedly still increase the risk of hepatic changes (but at a much lower rate than 17α-alkylated AAS and reportedly not at replacement dosages).[183][187][70][additional citation(s) needed] In accordance, D-ring glucuronides of testosterone and DHT have been found to be cholestatic.[188]

Aside from prohormones and testosterone undecanoate, almost all orally active AAS are 17α-alkylated.[189] A few AAS that are not 17α-alkylated are orally active.[1] Some examples include the testosterone 17-ethers cloxotestosterone, quinbolone, and silandrone,[citation needed] which are prodrugs (to testosterone, boldenone (Δ1-testosterone), and testosterone, respectively), the DHT 17-ethers mepitiostane, mesabolone, and prostanozol (which are also prodrugs), the 1-methylated DHT derivatives mesterolone and metenolone (although these are relatively weak AAS),[1][70] and the 19-nortestosterone derivatives dimethandrolone and 11β-MNT, which have improved resistance to first-pass hepatic metabolism due to their 11β-methyl groups (in contrast to them, the related AAS trestolone (7α-methyl-19-nortestosterone) is not orally active).[1][179] As these AAS are not 17α-alkylated, they show minimal potential for hepatotoxicity.[1]

Neurosteroid activity

DHT, via its metabolite 3α-androstanediol (produced by 3α-hydroxysteroid dehydrogenase (3α-HSD)), is a neurosteroid that acts via positive allosteric modulation of the GABAA receptor.[1] Testosterone, via conversion into DHT, also produces 3α-androstanediol as a metabolite and hence has similar activity.[1] Some AAS that are or can be 5α-reduced, including testosterone, DHT, stanozolol, and methyltestosterone, among many others, can or may modulate the GABAA receptor, and this may contribute as an alternative or additional mechanism to their central nervous system effects in terms of mood, anxiety, aggression, and sex drive.[1][165][166][167][168][169][170]

Chemistry

See also: List of androgens/anabolic steroids, List of androgen esters, and Structure–activity relationships of anabolic steroids

AAS are androstane or estrane steroids. They include testosterone (androst-4-en-17β-ol-3-one) and derivatives with various structural modifications such as:[1][190][66]

As well as others such as 1-dehydrogenation (e.g., metandienone, boldenone), 1-substitution (e.g., mesterolone, metenolone), 2-substitution (e.g., drostanolone, oxymetholone, stanozolol), 4-substitution (e.g., clostebol, oxabolone), and various other modifications.[1][190][66]

Structural aspects of androgens and anabolic steroids
Classes Androgen Structure Chemical name Features
Testosterone 4-Hydroxytestosteronea
 
 4-Hydroxytestosterone –
Androstenediola
 
 5-Androstenediol (androst-5-ene-3β,17β-diol) Prohormone
Androstenedionea
 
 4-Androstenedione (androst-4-ene-3,17-dione) Prohormone
Boldenone
 
 1-Dehydrotestosterone –
Boldionea
 
 1-Dehydro-4-androstenedione Prohormone
Clostebol
 
 4-Chlorotestosterone –
Cloxotestosterone
 
 Testosterone 17-chloral hemiacetal ether Ether
Prasterone
 
 5-Dehydroepiandrosterone (androst-5-en-3β-ol-17-one) Prohormone
Quinbolone
 
 1-Dehydrotestosterone 17β-cyclopentenyl enol ether Ether
Silandronea
 
 Testosterone 17β-trimethylsilyl ether Ether
Testosterone
 
 Androst-4-en-17β-ol-3-one –
17α-Alkylated testosterone Bolasterone
 
 7α,17α-Dimethyltestosterone –
Calusterone
 
 7β,17α-Dimethyltestosterone –
Chlorodehydromethylandrostenediola
 
 1-Dehydro-4-chloro-17α-methyl-4-androstenediol Prohormone
Chlorodehydromethyltestosterone
 
 1-Dehydro-4-chloro-17α-methyltestosterone –
Chloromethylandrostenediola
 
 4-Chloro-17α-methyl-4-androstenediol –
Enestebola
 
 1-Dehydro-4-hydroxy-17α-methyltestosterone –
Ethyltestosteronea
 
 17α-Ethyltestosterone –
Fluoxymesterone
 
 9α-Fluoro-11β-hydroxy-17α-methyltestosterone –
Formebolone
 
 1-Dehydro-2-formyl-11α-hydroxy-17α-methyltestosterone –
Hydroxystenozolea
 
 17α-Methyl-2'H-androsta-2,4-dieno[3,2-c]pyrazol-17β-ol Ring-fused
Metandienone
 
 1-Dehydro-17α-methyltestosterone –
Methandriol
 
 17α-Methyl-5-androstenediol Prohormone
Methylclostebola
 
 4-Chloro-17α-methyltestosterone –
Methyltestosterone
 
 17α-Methyltestosterone –
Methyltestosterone hexyl ether
 
 17α-Methyltestosterone 3-hexyl enol ether Ether
Oxymesterone
 
 4-Hydroxy-17α-methyltestosterone –
Penmesterol
 
 17α-Methyltestosterone 3-cyclopentyl enol ether Ether
Tiomesterone
 
 1α,7α-Diacetylthio-17α-methyltestosterone –
Other 17α-substituted testosterone Danazol
 
 2,3-Isoxazol-17α-ethynyltestosterone Ring-fused
Dihydrotestosterone 1-Testosteronea
 
 1-Dehydro-4,5α-dihydrotestosterone –
Androstanolone
 
 4,5α-Dihydrotestosterone –
Bolazine
 
 C3 azine dimer of drostanolone Dimer
Drostanolone
 
 2α-Methyl-4,5α-dihydrotestosterone –
Epitiostanol
 
 2α,3α-Epithio-3-deketo-4,5α-dihydrotestosterone Ring-fused
Mepitiostane
 
 2α,3α-Epithio-3-deketo-4,5α-dihydrotestosterone 17β-(1-methoxycyclopentane) ether Ring-fused; Ether
Mesabolonea
 
 1-Dehydro-4,5α-Dihydrotestosterone 17β-(1-methoxycyclohexane) ether Ether
Mesterolone
 
 1α-Methyl-4,5α-dihydrotestosterone –
Metenolone
 
 1-Dehydro-1-methyl-4,5α-dihydrotestosterone –
Prostanozola
 
 2'H-5α-Androst-2-eno[3,2-c]pyrazol-17β-ol 17β-tetrahydropyran ether Ether
Stenbolone
 
 1-Dehydro-2-methyl-4,5α-dihydrotestosterone –
17α-Alkylated dihydrotestosterone Androisoxazole
 
 17α-Methyl-5α-androstano[3,2-c]isoxazol-17β-ol Ring-fused
Desoxymethyltestosteronea
 
 2-Dehydro-3-deketo-4,5α-dihydro-17α-methyltestosterone –
Furazabol
 
 17α-Methyl-5α-androstano[2,3-c][1,2,5]oxadiazol-17β-ol Ring-fused
Mebolazine
 
 C3 azine dimer of methasterone Dimer
Mestanolone
 
 4,5α-Dihydro-17α-methyltestosterone –
Methasteronea
 
 2α,17α-Dimethyl-4,5α-dihydrotestosterone –
Methyl-1-testosteronea
 
 1-Dehydro-4,5α-dihydro-17α-methyltestosterone –
Methyldiazinola
 
 3-Deketo-3-azi-4,5α-dihydro-17α-methyltestosterone –
Methylepitiostanola
 
 2α,3α-Epithio-3-deketo-4,5α-dihydro-17α-methyltestosterone –
Methylstenbolonea
 
 1-Dehydro-2,17α-dimethyl-4,5α-dihydrotestosterone –
Oxandrolone
 
 2-Oxa-4,5α-dihydro-17α-methyltestosterone –
Oxymetholone
 
 2-Hydroxymethylene-4,5α-dihydro-17α-methyltestosterone –
Stanozolol
 
 17α-Methyl-2'H-5α-androst-2-eno[3,2-c]pyrazol-17β-ol Ring-fused
19-Nortestosterone 11β-Methyl-19-nortestosteronea
 
 11β-Methyl-19-nortestosterone –
19-Nor-5-androstenediola
 
 19-Nor-5-androstenediol Prohormone
19-Nordehydroepiandrosteronea
 
 19-Nor-5-dehydroepiandrosterone Prohormone
Bolandiola
 
 19-Nor-4-androstenediol Prohormone
Bolandionea
 
 19-Nor-4-androstenedione Prohormone
Bolmantalatea
 
 19-Nortestosterone 17β-adamantoate Ester
Dienedionea
 
 9-Dehydro-19-nor-4-androstenedione Prohormone
Dienolonea
 
 9-Dehydro-19-nortestosterone –
Dimethandrolonea
 
 7α,11β-Dimethyl-19-nortestosterone –
Methoxydienonea
 
 2,5(10)-Didehydro-18-methyl-19-norepiandrosterone 3-methyl ether Prohormone; Ether
Nandrolone
 
 19-Nortestosterone –
Norclostebol
 
 4-Chloro-19-nortestosterone –
Oxabolone
 
 4-Hydroxy-19-nortestosterone –
Trestolonea
 
 7α-Methyl-19-nortestosterone –
Trenbolone
 
 9,11-Didehydro-19-nortestosterone –
Trendionea
 
 9,11-Didehydro-19-nor-4-androstenedione Prohormone
Trestionea
 
 7α-Methyl-19-nor-4-androstenedione Prohormone
17α-Alkylated 19-nortestosterone Dimethyltrienolonea
 
 7α,17α-Dimethyl-9,11-didehydro-19-nortestosterone –
Dimethyldienolonea
 
 7α,17α-Dimethyl-9-dehydro-19-nortestosterone –
Ethyldienolonea
 
 9-Dehydro-17α-ethyl-19-nortestosterone –
Ethylestrenol
 
 17α-Ethyl-3-deketo-19-nortestosterone –
Methyldienolonea
 
 9-Dehydro-17α-methyl-19-nortestosterone –
Methylhydroxynandrolonea
 
 4-Hydroxy-17α-methyl-19-nortestosterone –
Metribolonea
 
 9,11-Didehydro-17α-methyl-19-nortestosterone –
Mibolerone
 
 7α,17α-Dimethyl-19-nortestosterone –
Norboletonea
 
 17α-Ethyl-18-methyl-19-nortestosterone –
Norethandrolone
 
 17α-Ethyl-19-nortestosterone –
Normethandrone
 
 17α-Methyl-19-nortestosterone –
Propetandrol
 
 17α-Ethyl-19-nortestosterone 3-propionate Ester
RU-2309a
 
 9,11-Didehydro-17α,18-dimethyl-19-nortestosterone –
Tetrahydrogestrinonea
 
 9,11-Didehydro-17α-ethyl-18-methyl-19-nortestosterone –
Other 17α-substituted 19-nortestosterone Gestrinone
 
 9,11-Didehydro-17α-ethynyl-18-methyl-19-nortestosterone –
Tibolone
 
 5(10)-Dehydro-7α-methyl-17α-ethynyl-19-nortestosterone –
Vinyltestosteronea
 
 17α-Ethenyltestosterone –
Notes: Esters of androgens and anabolic steroids are mostly not included in this table; see here instead. Weakly androgenic progestins are mostly not included in this table; see here instead. Footnotes: a = Never marketed.
Structural properties of major testosterone esters
Androgen Structure Ester Relative
mol. weight		 Relative
T contentb		 logPc
Position(s) Moiet(ies) Type Lengtha
Testosterone   – – – – 1.00 1.00 3.0–3.4
Testosterone propionate   C17β Propanoic acid Straight-chain fatty acid 3 1.19 0.84 3.7–4.9
Testosterone isobutyrate   C17β Isobutyric acid Aromatic fatty acid – (~3) 1.24 0.80 4.9–5.3
Testosterone isocaproate   C17β Isohexanoic acid Branched-chain fatty acid – (~5) 1.34 0.75 4.4–6.3
Testosterone caproate   C17β Hexanoic acid Straight-chain fatty acid 6 1.35 0.75 5.8–6.5
Testosterone phenylpropionate   C17β Phenylpropanoic acid Aromatic fatty acid – (~6) 1.46 0.69 5.8–6.5
Testosterone cypionate   C17β Cyclopentylpropanoic acid Cyclic carboxylic acid – (~6) 1.43 0.70 5.1–7.0
Testosterone enanthate   C17β Heptanoic acid Straight-chain fatty acid 7 1.39 0.72 3.6–7.0
Testosterone decanoate   C17β Decanoic acid Straight-chain fatty acid 10 1.53 0.65 6.3–8.6
Testosterone undecanoate   C17β Undecanoic acid Straight-chain fatty acid 11 1.58 0.63 6.7–9.2
Testosterone buciclated   C17β Bucyclic acide Aromatic carboxylic acid – (~9) 1.58 0.63 7.9–8.5
Footnotes: a = Length of ester in carbon atoms for straight-chain fatty acids or approximate length of ester in carbon atoms for aromatic fatty acids. b = Relative testosterone content by weight (i.e., relative androgenic/anabolic potency). c = Experimental or predicted octanol/water partition coefficient (i.e., lipophilicity/hydrophobicity). Retrieved from PubChem, ChemSpider, and DrugBank. d = Never marketed. e = Bucyclic acid = trans-4-Butylcyclohexane-1-carboxylic acid. Sources: See individual articles.
Structural properties of major anabolic steroid esters
Anabolic steroid Structure Ester Relative
mol. weight		 Relative
AAS contentb		 Durationc
Position Moiety Type Lengtha
Boldenone undecylenate
 
 C17β Undecylenic acid Straight-chain fatty acid 11 1.58 0.63 Long
Drostanolone propionate
 
 C17β Propanoic acid Straight-chain fatty acid 3 1.18 0.84 Short
Metenolone acetate
 
 C17β Ethanoic acid Straight-chain fatty acid 2 1.14 0.88 Short
Metenolone enanthate
 
 C17β Heptanoic acid Straight-chain fatty acid 7 1.37 0.73 Long
Nandrolone decanoate
 
 C17β Decanoic acid Straight-chain fatty acid 10 1.56 0.64 Long
Nandrolone phenylpropionate
 
 C17β Phenylpropanoic acid Aromatic fatty acid – (~6–7) 1.48 0.67 Long
Trenbolone acetate
 
 C17β Ethanoic acid Straight-chain fatty acid 2 1.16 0.87 Short
Trenbolone enanthated
 
 C17β Heptanoic acid Straight-chain fatty acid 7 1.41 0.71 Long
Footnotes: a = Length of ester in carbon atoms for straight-chain fatty acids or approximate length of ester in carbon atoms for aromatic fatty acids. b = Relative androgen/anabolic steroid content by weight (i.e., relative androgenic/anabolic potency). c = Duration by intramuscular or subcutaneous injection in oil solution. d = Never marketed. Sources: See individual articles.

Detection in body fluids

The most commonly employed human physiological specimen for detecting AAS usage is urine, although both blood and hair have been investigated for this purpose. The AAS, whether of endogenous or exogenous origin, are subject to extensive hepatic biotransformation by a variety of enzymatic pathways. The primary urinary metabolites may be detectable for up to 30 days after the last use, depending on the specific agent, dose and route of administration. A number of the drugs have common metabolic pathways, and their excretion profiles may overlap those of the endogenous steroids, making interpretation of testing results a very significant challenge to the analytical chemist. Methods for detection of the substances or their excretion products in urine specimens usually involve gas chromatography–mass spectrometry or liquid chromatography-mass spectrometry.[191][192][193][194]

History

Introduction of various anabolic steroids
Generic name Class[a] Brand name Route[b] Intr.
Androstanolone[c][d] DHT Andractim PO,[e] IM, TD 1953
Boldenone undecylenate[f] Ester Equipoise[g] IM 1960s
Danazol Alkyl Danocrine PO 1971
Drostanolone propionate[e] DHT Ester Masteron IM 1961
Ethylestrenol[d] 19-NT Alkyl Maxibolin[g] PO 1961
Fluoxymesterone[d] Alkyl Halotestin[g] PO 1957
Mestanolone[e] DHT Alkyl Androstalone[g] PO 1950s
Mesterolone DHT Proviron PO 1967
Metandienone[d] Alkyl Dianabol PO, IM 1958
Metenolone acetate[d] DHT Ester Primobolan PO 1961
Metenolone enanthate[d] DHT Ester Primobolan Depot IM 1962
Methyltestosterone[d] Alkyl Metandren PO 1936
Nandrolone decanoate 19-NT Ester Deca-Durabolin IM 1962
Nandrolone phenylpropionate[d] 19-NT Ester Durabolin IM 1959
Norethandrolone[d] 19-NT Alkyl Nilevar[g] PO 1956
Oxandrolone[d] DHT Alkyl Oxandrin[g] PO 1964
Oxymetholone[d] DHT Alkyl Anadrol[g] PO 1961
Prasterone[h] Prohormone Intrarosa[g] PO, IM, vaginal 1970s
Stanozolol[e] DHT Alkyl Winstrol[g] PO, IM 1962
Testosterone cypionate Ester Depo-Testosterone IM 1951
Testosterone enanthate Ester Delatestryl IM 1954
Testosterone propionate Ester Testoviron IM 1937
Testosterone undecanoate Ester Andriol[g] PO, IM 1970s
Trenbolone acetate[f] 19-NT Ester Finajet[g] IM 1970s
  1. ^ DHT = dihydrotestosterone; 19-NT = 19-nortestosterone
  2. ^ IM = Intramuscular injection; PO = Oral (by mouth); TD = Transdermal
  3. ^ Also known as dihydrotestosterone
  4. ^ a b c d e f g h i j k Availability limited
  5. ^ a b c d No longer marketed
  6. ^ a b Available for veterinary use only
  7. ^ a b c d e f g h i j k Also marketed under other brand names
  8. ^ Also known as dehydroepiandrosterone

Discovery of androgens

The use of gonadal steroids pre-dates their identification and isolation. Extraction of hormones from urines began in China c. 100 BCE.[citation needed] Medical use of testicle extract began in the late 19th century while its effects on strength were still being studied.[144] The isolation of gonadal steroids can be traced back to 1931, when Adolf Butenandt, a chemist in Marburg, purified 15 milligrams of the male hormone androstenone from tens of thousands of litres of urine. This steroid was subsequently synthesized in 1934 by Leopold Ružička, a chemist in Zurich.[195]

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.[195][196] 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)."[197] 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."[198] 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)."[199] 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.[195][196]

Clinical trials on humans, involving either PO doses of methyltestosterone or injections of testosterone propionate, began as early as 1937.[195] There are often reported rumors that German soldiers were administered AAS during the Second World War, the aim being to increase their aggression and stamina, but these are, as yet, unproven.[118]: 6  Adolf Hitler himself, according to his physician, was injected with testosterone derivatives to treat various ailments.[200] AAS were used in experiments conducted by the Nazis on concentration camp inmates,[200] and later by the allies attempting to treat the malnourished victims that survived Nazi camps.[118]: 6  President John F. Kennedy was administered steroids both before and during his presidency.[201]

Development of synthetic AAS

The development of muscle-building properties of testosterone was pursued in the 1940s, in the Soviet Union and in Eastern Bloc countries such as East Germany, where steroid programs were used to enhance the performance of Olympic and other amateur weight lifters. In response to the success of Russian weightlifters, the U.S. Olympic Team physician John Ziegler worked with synthetic chemists to develop an AAS with reduced androgenic effects.[202] Ziegler's work resulted in the production of methandrostenolone, which Ciba Pharmaceuticals marketed as Dianabol. The new steroid was approved for use in the U.S. by the Food and Drug Administration (FDA) in 1958. It was most commonly administered to burn victims and the elderly. The drug's off-label users were mostly bodybuilders and weight lifters. Although Ziegler prescribed only small doses to athletes, he soon discovered that those having abused Dianabol developed enlarged prostates and atrophied testes.[203] AAS were placed on the list of banned substances of the International Olympic Committee (IOC) in 1976, and a decade later the committee introduced 'out-of-competition' doping tests because many athletes used AAS in their training period rather than during competition.[8]

Three major ideas governed modifications of testosterone into a multitude of AAS: Alkylation at C17α position with methyl or ethyl group created POly active compounds because it slows the degradation of the drug by the liver; esterification of testosterone and nortestosterone at the C17β 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 PO and parenteral agents to seeking to obtain different anabolic-to-androgenic effect ratios.[8]

Society and culture

Etymology

Androgens were discovered in the 1930s and were characterized as having effects described as androgenic (i.e., virilizing) and anabolic (e.g., myotrophic, renotrophic).[66][1] The term anabolic steroid can be dated as far back as at least the mid-1940s, when it was used to describe the at-the-time hypothetical concept of a testosterone-derived steroid with anabolic effects but with minimal or no androgenic effects.[204] This concept was formulated based on the observation that steroids had ratios of renotrophic to androgenic potency that differed significantly, which suggested that anabolic and androgenic effects might be dissociable.[204]

In 1953, a testosterone-derived steroid known as norethandrolone (17α-ethyl-19-nortestosterone) was synthesized at G. D. Searle & Company and was studied as a progestin, but was not marketed.[205] Subsequently, in 1955, it was re-examined for testosterone-like activity in animals and was found to have similar anabolic activity to testosterone, but only one-sixteenth of its androgenic potency.[205][206] It was the first steroid with a marked and favorable separation of anabolic and androgenic effect to be discovered, and has accordingly been described as the "first anabolic steroid".[207][208] Norethandrolone was introduced for medical use in 1956, and was quickly followed by numerous similar steroids, for instance nandrolone phenylpropionate in 1959 and stanozolol in 1962.[207][208][209][210] With these developments, anabolic steroid became the preferred term to refer to such steroids (over "androgen"), and entered widespread use.

Although anabolic steroid was originally intended to specifically describe testosterone-derived steroids with a marked dissociation of anabolic and androgenic effect, it is applied today indiscriminately to all steroids with AR agonism-based anabolic effects regardless of their androgenic potency, including even non-synthetic steroids like testosterone.[66][1][205] While many anabolic steroids have diminished androgenic potency in comparison to anabolic potency, there is no anabolic steroid that is exclusively anabolic, and hence all anabolic steroids retain at least some degree of androgenicity.[66][1][205] (Likewise, all "androgens" are inherently anabolic.)[66][1][205] Indeed, it is probably not possible to fully dissociate anabolic effects from androgenic effects, as both types of effects are mediated by the same signaling receptor, the AR.[1] As such, the distinction between the terms anabolic steroid and androgen is questionable, and this is the basis for the revised and more recent term anabolic–androgenic steroid (AAS).[66][1][205]

Legal status

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

The legal status of AAS 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., AAS are currently listed as Schedule III controlled substances under the Controlled Substances Act, which makes simple possession of such substances without a prescription a federal crime punishable by up to one year in prison for the first offense. Unlawful distribution or possession with intent to distribute AAS as a first offense is punished by up to ten years in prison.[211] In Canada, AAS and their derivatives are part of the Controlled Drugs and Substances Act and are Schedule IV substances, meaning that it is illegal to obtain or sell them without a prescription; however, possession is not punishable, a consequence reserved for schedule I, II, or III substances. Those guilty of buying or selling AAS in Canada can be imprisoned for up to 18 months.[212] Import and export also carry similar penalties.

In Canada, researchers have concluded that steroid use among student athletes is extremely widespread. A study conducted in 1993 by the Canadian Centre for Drug-Free Sport found that nearly 83,000 Canadians between the ages of 11 and 18 use steroids.[213] AAS are also illegal without prescription in Australia,[214] Argentina,[citation needed] Brazil,[citation needed] and Portugal,[citation needed] and are listed as Class C Controlled Drugs in the United Kingdom. AAS are readily available without a prescription in some countries such as Mexico and Thailand.

United States

 
Steroid pills intercepted by the US Drug Enforcement Administration during the Operation Raw Deal bust in September 2007

The history of the U.S. legislation on AAS goes back to the late 1980s, when the U.S. Congress considered placing AAS under the Controlled Substances Act following the controversy over Ben Johnson's victory at the 1988 Summer Olympics in Seoul. AAS were added to Schedule III of the Controlled Substances Act in the Anabolic Steroids Control Act of 1990.[215]

The same act also introduced more stringent controls with higher criminal penalties for offenses involving the illegal distribution of AAS and human growth hormone. By the early 1990s, after AAS 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, AAS 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.[216]

Even though they can still be prescribed by a medical doctor in the U.S, the use of anabolic steroids for injury recovery purposes has been a taboo subject, even amongst the majority of sports medicine doctors and endocrinologists.

United Kingdom

In the United Kingdom, AAS are classified as class C drugs for their illegal abuse potential, which puts them in the same class as benzodiazepines. AAS are in Schedule 4, which is divided in 2 parts; Part 1 contains most of the benzodiazepines and Part 2 contains the AAS.

Part 1 drugs are subject to full import and export controls with possession being an offence without an appropriate prescription. There is no restriction on the possession when it is part of a medicinal product. Part 2 drugs require a Home Office licence for importation and export unless the substance is in the form of a medicinal product and is for self-administration by a person.[217]

Status in sports

See also: Doping in sport
 
Legal status of AAS and other drugs with anabolic effects in Western countries

AAS are banned by all major sports bodies including Association of Tennis Professionals, Major League Baseball, Fédération Internationale de Football Association[218] the Olympics,[219] the National Basketball Association,[220] the National Hockey League,[221] World Wrestling Entertainment and the National Football League.[222] 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 AAS and precursors as well as all hormones and related substances.[223][224]

Usage

See also: Anabolic–androgenic steroids abuse

Law enforcement

United States federal law enforcement officials have expressed concern about AAS use by police officers. "It's a big problem, and from the number of cases, it's something we shouldn't ignore. It's not that we set out to target cops, but when we're in the middle of an active investigation into steroids, there have been quite a few cases that have led back to police officers," says Lawrence Payne, a spokesman for the United States Drug Enforcement Administration.[225] The FBI Law Enforcement Bulletin stated that "Anabolic steroid abuse by police officers is a serious problem that merits greater awareness by departments across the country".[226] It is also believed that police officers across the United Kingdom "are using criminals to buy steroids" which he claims to be a top risk factor for police corruption.

Professional wrestling

Main article: WWE § Wellness Program

Following the murder-suicide of Chris Benoit in 2007, the Oversight and Government Reform Committee investigated steroid usage in the wrestling industry.[227] The Committee investigated WWE and Total Nonstop Action Wrestling (now known as Impact Wrestling), asking for documentation of their companies' drug policies. WWE CEO and chairman, Linda and Vince McMahon respectively, both testified. The documents stated that 75 wrestlers—roughly 40 percent—had tested positive for drug use since 2006, most commonly for steroids.[228][229]

Economics

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

AAS 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.[230] In these countries, the majority of steroids are obtained illegally through black market trade.[231][232] These steroids are usually manufactured in other countries, and therefore must be smuggled across international borders. As with most significant smuggling operations, organized crime is involved.[233]

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.[234]

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 AAS are sometimes sold at gyms and competitions, and through the mail, but may also be obtained through pharmacists, veterinarians, and physicians.[235] In addition, a significant number of counterfeit products are sold as AAS, in particular via mail order from websites posing as overseas pharmacies. In the U.S., black-market importation continues from Mexico, Thailand, and other countries where steroids are more easily available, as they are legal.[236]

Research

AAS, alone and in combination with progestogens, have been studied as potential male hormonal contraceptives.[48] Dual AAS and progestins such as trestolone and dimethandrolone undecanoate have also been studied as male contraceptives, with the latter under active investigation as of 2018.[237][179][238]

Topical androgens have been used and studied in the treatment of cellulite in women.[239] Topical androstanolone on the abdomen has been found to significantly decrease subcutaneous abdominal fat in women, and hence may be useful for improving body silhouette.[239] However, men and hyperandrogenic women have higher amounts of abdominal fat than healthy women, and androgens have been found to increase abdominal fat in postmenopausal women and transgender men as well.[240]

See also

References

  1. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac ad ae af ag ah ai aj ak al am an ao ap aq ar as at au av aw ax ay az ba bb bc bd be bf bg bh bi bj bk bl bm bn bo Kicman, A T (2008). "Pharmacology of anabolic steroids". British Journal of Pharmacology. 154 (3): 502–521. doi:10.1038/bjp.2008.165. PMC 2439524. PMID 18500378.
  2. ^ Powers M (2011). Houglum J, Harrelson GL (eds.). Performance-Enhancing Drugs. Principles of Pharmacology for Athletic Trainers (2nd ed.). SLACK Incorporated. p. 345. ISBN 978-1-55642-901-9. from the original on 2016-12-22. Retrieved 2016-10-17.
  3. ^ a b Barrett-Connor EL (1995). "Testosterone and risk factors for cardiovascular disease in men". Diabete Metab. 21 (3): 156–61. PMID 7556805.
  4. ^ a b Yamamoto Y, Moore R, Hess HA, Guo GL, Gonzalez FJ, Korach KS, Maronpot RR, Negishi M (2006). "Estrogen receptor alpha mediates 17alpha-ethynylestradiol causing hepatotoxicity". J Biol Chem. 281 (24): 16625–31. doi:10.1074/jbc.M602723200. PMID 16606610. S2CID 83319949.
  5. ^ a b De Piccoli B, Giada F, Benettin A, Sartori F, Piccolo E (1991). "Anabolic steroid use in body builders: an echocardiographic study of left ventricle morphology and function". Int J Sports Med. 12 (4): 408–12. doi:10.1055/s-2007-1024703. PMID 1917226.
  6. ^ a b c Green GA (September 2009). "Performance-enhancing drug use". Orthopedics. 32 (9): 647–649. doi:10.3928/01477447-20090728-39. PMID 19751025.
  7. ^ a b c Turillazzi E, Perilli G, Di Paolo M, Neri M, Riezzo I, Fineschi V (2011). "Side effects of AAS abuse: an overview". Mini Rev Med Chem. 11 (5): 374–89. doi:10.2174/138955711795445925. hdl:11392/2357154. PMID 21443513.
  8. ^ a b c d e f g h i j k Hartgens F, Kuipers H (2004). "Effects of androgenic-anabolic steroids in athletes". Sports Med. 34 (8): 513–54. doi:10.2165/00007256-200434080-00003. PMID 15248788. S2CID 15234016.
  9. ^ a b Kicman AT, Gower DB (July 2003). "Anabolic steroids in sport: biochemical, clinical and analytical perspectives". Ann. Clin. Biochem. 40 (Pt 4): 321–56. doi:10.1258/000456303766476977. PMID 12880534. S2CID 24339701. 
  10. ^ Basaria S, Wahlstrom JT, Dobs AS (November 2001). "Clinical review 138: Anabolic-androgenic steroid therapy in the treatment of chronic diseases". J. Clin. Endocrinol. Metab. 86 (11): 5108–17. doi:10.1210/jcem.86.11.7983. PMID 11701661.
  11. ^ Ranke MB, Bierich JR (1986). "Treatment of growth hormone deficiency". Clinics in Endocrinology and Metabolism. 15 (3): 495–510. doi:10.1016/S0300-595X(86)80008-1. PMID 2429792.
  12. ^ Grunfeld C, Kotler DP, Dobs A, Glesby M, Bhasin S (2006). "Oxandrolone in the treatment of HIV-associated weight loss in men: a randomized, double-blind, placebo-controlled study". J. Acquir. Immune Defic. Syndr. 41 (3): 304–14. doi:10.1097/01.qai.0000197546.56131.40. PMID 16540931. S2CID 25911263.
  13. ^ Berger JR, Pall L, Hall CD, Simpson DM, Berry PS, Dudley R (1996). "Oxandrolone in AIDS-wasting myopathy". AIDS. 10 (14): 1657–62. doi:10.1097/00002030-199612000-00010. PMID 8970686. S2CID 9832782.
  14. ^ Kenny AM, Prestwood KM, Gruman CA, Marcello KM, Raisz LG (2001). "Effects of transdermal testosterone on bone and muscle in older men with low bioavailable testosterone levels". J. Gerontol. A Biol. Sci. Med. Sci. 56 (5): M266–72. doi:10.1093/gerona/56.5.M266. PMID 11320105.
  15. ^ Baum NH, Crespi CA (2007). "Testosterone replacement in elderly men". Geriatrics. 62 (9): 14–8. PMID 17824721.
  16. ^ Francis RM (2001). "Androgen replacement in aging men". Calcif. Tissue Int. 69 (4): 235–8. doi:10.1007/s00223-001-1051-9. PMID 11730258. S2CID 24170276.
  17. ^ Nair KS, Rizza RA, O'Brien P, Dhatariya K, Short KR, Nehra A, Vittone JL, Klee GG, Basu A, Basu R, Cobelli C, Toffolo G, Dalla Man C, Tindall DJ, Melton LJ, Smith GE, Khosla S, Jensen MD (October 2006). "DHEA in elderly women and DHEA or testosterone in elderly men". N. Engl. J. Med. 355 (16): 1647–59. doi:10.1056/NEJMoa054629. PMID 17050889. S2CID 42844580.
  18. ^ a b c d Mangus BC, Miller MG (11 January 2005). Pharmacology Application in Athletic Training. F.A. Davis. pp. 151–. ISBN 978-0-8036-2027-8. from the original on 14 April 2021. Retrieved 25 June 2017.
  19. ^ Royal College of Physicians of London (1999). Osteoporosis: Clinical Guidelines for Prevention and Treatment. Royal College of Physicians. pp. 51–. ISBN 978-1-86016-079-0. from the original on 2021-04-14. Retrieved 2017-06-25.
  20. ^ Davis SR (1999). "The therapeutic use of androgens in women". J. Steroid Biochem. Mol. Biol. 69 (1–6): 177–84. doi:10.1016/s0960-0760(99)00054-0. PMID 10418991. S2CID 23520067.
  21. ^ William N. Taylor, M.D. (16 January 2002). Anabolic Steroids and the Athlete, 2d ed. McFarland. pp. 193–. ISBN 978-0-7864-1128-3. from the original on 14 April 2021. Retrieved 25 June 2017.
  22. ^ a b "Oxandrolone Tablets, USP – Rx only" (PDF). Drugs@FDA. U.S. Food and Drug Administration. 1 December 2006. (PDF) from the original on 26 August 2016. Retrieved 21 June 2016.
  23. ^ a b "Oxandrin (oxandrolone tablets, USP)" (PDF). Drugs@FDA. BTG Pharmaceuticals, U.S. Food and Drug Administration. 21 April 2003. (PDF) from the original on 1 March 2017. Retrieved 21 June 2016.
  24. ^ Li H, Guo Y, Yang Z, Roy M, Guo Q (June 2016). "The efficacy and safety of oxandrolone treatment for patients with severe burns: A systematic review and meta-analysis". Burns. 42 (4): 717–27. doi:10.1016/j.burns.2015.08.023. PMID 26454425. S2CID 24139354.
  25. ^ Rojas Y, Finnerty CC, Radhakrishnan RS, Herndon DN (December 2012). "Burns: an update on current pharmacotherapy". Expert Opinion on Pharmacotherapy. 13 (17): 2485–94. doi:10.1517/14656566.2012.738195. PMC 3576016. PMID 23121414.
  26. ^ Bork K (August 2012). "Current management options for hereditary angioedema". Current Allergy and Asthma Reports. 12 (4): 273–80. doi:10.1007/s11882-012-0273-4. PMID 22729959. S2CID 207323793.
  27. ^ Choi G, Runyon BA (May 2012). "Alcoholic hepatitis: a clinician's guide". Clinics in Liver Disease. 16 (2): 371–85. doi:10.1016/j.cld.2012.03.015. PMID 22541704.
  28. ^ Manuchair Ebadi (31 October 2007). Desk Reference of Clinical Pharmacology, Second Edition. CRC Press. pp. 434–. ISBN 978-1-4200-4744-8. from the original on 14 April 2021. Retrieved 27 July 2018.
  29. ^ Yagiela JA, Dowd FJ, Johnson B, Mariotti A, Neidle EA (19 March 2010). Pharmacology and Therapeutics for Dentistry – E-Book. Elsevier Health Sciences. pp. 569–. ISBN 978-0-323-07824-5. from the original on 14 April 2021. Retrieved 27 July 2018.
  30. ^ "Android® C-III Label" (PDF). (PDF) from the original on 2017-02-10. Retrieved 2018-07-27.
  31. ^ Shah K, Montoya C, Persons RK (April 2007). "Clinical inquiries. Do testosterone injections increase libido for elderly hypogonadal patients?". J Fam Pract. 56 (4): 301–3. PMID 17403329.
  32. ^ Yassin AA, Saad F (March 2007). "Improvement of sexual function in men with late-onset hypogonadism treated with testosterone only". J Sex Med. 4 (2): 497–501. doi:10.1111/j.1743-6109.2007.00442.x. PMID 17367445.
  33. ^ Arver S, Dobs AS, Meikle AW, Caramelli KE, Rajaram L, Sanders SW, Mazer NA (December 1997). "Long-term efficacy and safety of a permeation-enhanced testosterone transdermal system in hypogonadal men". Clin. Endocrinol. 47 (6): 727–37. doi:10.1046/j.1365-2265.1997.3071113.x. PMID 9497881. S2CID 31976796.
  34. ^ Nieschlag E, Büchter D, Von Eckardstein S, Abshagen K, Simoni M, Behre HM (December 1999). "Repeated intramuscular injections of testosterone undecanoate for substitution therapy in hypogonadal men". Clin. Endocrinol. 51 (6): 757–63. doi:10.1046/j.1365-2265.1999.00881.x. PMID 10619981. S2CID 19174381.
  35. ^ Arslanian S, Suprasongsin C (1997). "Testosterone treatment in adolescents with delayed puberty: changes in body composition, protein, fat, and glucose metabolism". J. Clin. Endocrinol. Metab. 82 (10): 3213–20. doi:10.1210/jcem.82.10.4293. PMID 9329341. S2CID 5031396.
  36. ^ Moore E, Wisniewski A, Dobs A (August 2003). "Endocrine treatment of transsexual people: a review of treatment regimens, outcomes, and adverse effects". J. Clin. Endocrinol. Metab. 88 (8): 3467–73. doi:10.1210/jc.2002-021967. PMID 12915619.
  37. ^ Genderqueer, Pansexual, LGBTQ: Will Gender Exist 100 Years From Now? – Rebooted 2014-12-09 at the Wayback Machine. October 24, 2013. Retrieved November 17, 2014.
  38. ^ Young people exploring nonbinary gender roles – SF Gate 2014-12-08 at the Wayback Machine. February 12, 2014. Retrieved November 17, 2014.
  39. ^ Warne GL, Grover S, Zajac JD (2005). "Hormonal therapies for individuals with intersex conditions: protocol for use". Treatments in Endocrinology. 4 (1): 19–29. doi:10.2165/00024677-200504010-00003. PMID 15649098. S2CID 71737774.
  40. ^ What is Intersex – An Intersex FAQ by Inter/Act – Inter/Act Youth 2014-12-07 at the Wayback Machine. September 12, 2014. Retrieved December 5, 2014.
  41. ^ Perry MC, Doll DC, Freter CE (30 July 2012). Perry's The Chemotherapy Source Book. Lippincott Williams & Wilkins. pp. 409–. ISBN 978-1-4698-0343-2. from the original on 14 April 2021. Retrieved 25 June 2017.
  42. ^ Allegra JC, Bertino J, Bonomi P, Byrne P, Carpenter J, Catalano R, Creech R, Dana B, Durivage H, Einhorn L (December 1985). "Metastatic breast cancer: preliminary results with oral hormonal therapy". Semin. Oncol. 12 (4 Suppl 6): 61–4. PMID 3909420.
  43. ^ Bachmann GA (1999). "Androgen cotherapy in menopause: evolving benefits and challenges". Am. J. Obstet. Gynecol. 180 (3 Pt 2): S308–11. doi:10.1016/S0002-9378(99)70724-6. PMID 10076169.
  44. ^ Kotz K, Alexander JL, Dennerstein L (2006). "Estrogen and androgen hormone therapy and well-being in surgically postmenopausal women". J Womens Health (Larchmt). 15 (8): 898–908. doi:10.1089/jwh.2006.15.898. PMID 17087613.
  45. ^ Garefalakis M, Hickey M (2008). "Role of androgens, progestins and tibolone in the treatment of menopausal symptoms: a review of the clinical evidence". Clin Interv Aging. 3 (1): 1–8. doi:10.2147/CIA.S1043. PMC 2544356. PMID 18488873.
  46. ^ a b Somboonporn W (2006). "Androgen and menopause". Curr. Opin. Obstet. Gynecol. 18 (4): 427–32. doi:10.1097/01.gco.0000233938.36554.37. PMID 16794424. S2CID 8030248.
  47. ^ Davis S (2001). "Testosterone deficiency in women". J Reprod Med. 46 (3 Suppl): 291–6. PMID 11304877.
  48. ^ a b c Nieschlag E (2010). "Clinical trials in male hormonal contraception" (PDF). Contraception. 82 (5): 457–70. doi:10.1016/j.contraception.2010.03.020. PMID 20933120. (PDF) from the original on 2020-12-05. Retrieved 2019-08-18.
  49. ^ "Most steroid users are not athletes: study". Reuters. Reuters. 2007-11-21. from the original on 2016-01-25. Retrieved 2014-01-03.
  50. ^ Sjöqvist F, Garle M, Rane A (May 2008). "Use of doping agents, in particular anabolic steroids, in sports and society". Lancet. 371 (9627): 1872–82. doi:10.1016/S0140-6736(08)60801-6. PMID 18514731. S2CID 10762429.
  51. ^ Yesalis CE, Kennedy NJ, Kopstein AN, Bahrke MS (1993). "Anabolic-androgenic steroid use in the United States". JAMA. 270 (10): 1217–21. doi:10.1001/jama.270.10.1217. PMID 8355384.
  52. ^ McCabe SE, Brower KJ, West BT, Nelson TF, Wechsler H (2007). "Trends in non-medical use of anabolic steroids by U.S. college students: Results from four national surveys". Drug and Alcohol Dependence. 90 (2–3): 243–51. doi:10.1016/j.drugalcdep.2007.04.004. PMC 2383927. PMID 17512138.
  53. ^ Parkinson AB, Evans NA (April 2006). "Anabolic androgenic steroids: a survey of 500 users". Med Sci Sports Exerc. 38 (4): 644–51. doi:10.1249/01.mss.0000210194.56834.5d. PMID 16679978.
  54. ^ a b c d e Cohen J, Collins R, Darkes J, Gwartney D (2007). "A league of their own: demographics, motivations and patterns of use of 1,955 male adult non-medical anabolic steroid users in the United States". J Int Soc Sports Nutr. 4: 12. doi:10.1186/1550-2783-4-12. PMC 2131752. PMID 17931410.
  55. ^ Copeland J, Peters R, Dillon P (March 1998). "A study of 100 anabolic-androgenic steroid users". Med. J. Aust. 168 (6): 311–2. doi:10.5694/j.1326-5377.1998.tb140177.x. PMID 9549549. S2CID 8699231.
  56. ^ Eastley T (January 18, 2006). "Steroid study debunks user stereotypes". ABC. from the original on 2014-07-16. Retrieved 2014-01-03.
  57. ^ Pope HG, Kanayama G, Ionescu-Pioggia M, Hudson JI (September 2004). "Anabolic steroid users' attitudes towards physicians". Addiction. 99 (9): 1189–94. doi:10.1111/j.1360-0443.2004.00781.x. PMID 15317640.
  58. ^ Kanayama G, Barry S, Hudson JI, Pope HG (April 2006). "Body image and attitudes toward male roles in anabolic-androgenic steroid users". Am J Psychiatry. 163 (4): 697–703. doi:10.1176/appi.ajp.163.4.697. PMID 16585446. S2CID 38738640.
  59. ^ Grogan S, Shepherd S, Evans R, Wright S, Hunter G (Nov 2006). "Experiences of Anabolic Steroid Use". Journal of Health Psychology. 11 (6): 845–856. doi:10.1177/1359105306069080. PMID 17035257. S2CID 5794238.
  60. ^ Hickson RC, Czerwinski SM, Falduto MT, Young AP (1990). "Glucocorticoid antagonism by exercise and androgenic-anabolic steroids". Medicine & Science in Sports & Exercise. 22 (3): 331–40. doi:10.1249/00005768-199006000-00010. PMID 2199753.
  61. ^ "Drugs@FDA: FDA Approved Drug Products". United States Food and Drug Administration. from the original on 16 November 2016. Retrieved 1 December 2019.
  62. ^ Richard Joseph Hamilton; Nancy Anastasi Duffy; Daniel Stone (2014). Tarascon Pharmacopoeia. Jones & Bartlett Publishers. pp. 174–. ISBN 978-1-284-05671-6. from the original on 2021-02-13. Retrieved 2020-09-13.
  63. ^ Susan M. Ford; Sally S. Roach (2010). Roach's Introductory Clinical Pharmacology. Lippincott Williams & Wilkins. pp. 499–. ISBN 978-1-60547-633-9. from the original on 2021-04-14. Retrieved 2020-09-13.
  64. ^ Thomas L. Lemke; David A. Williams (24 January 2012). Foye's Principles of Medicinal Chemistry. Lippincott Williams & Wilkins. pp. 1358–. ISBN 978-1-60913-345-0. from the original on 14 April 2021. Retrieved 13 September 2020.
  65. ^ John A. Thomas (6 December 2012). Drugs, Athletes, and Physical Performance. Springer Science & Business Media. pp. 20–. ISBN 978-1-4684-5499-4. from the original on 14 April 2021. Retrieved 13 September 2020.
  66. ^ a b c d e f g h i j k l m n o p q r s t William Llewellyn (2011). Anabolics. Molecular Nutrition Llc. ISBN 978-0-9828280-1-4. from the original on 2021-04-14. Retrieved 2016-12-02.
  67. ^ Burkett, Lee N.; Falduto, Michael T. (1984). "Steroid Use by Athletes in a Metropolitan Area". The Physician and Sportsmedicine. 12 (8): 69–74. doi:10.1080/00913847.1984.11701923. ISSN 0091-3847.
  68. ^ J. Bain; Wolf-Bernhard Schill; L. Schwarzstein (6 December 2012). Treatment of Male Infertility. Springer Science & Business Media. pp. 176–177. ISBN 978-3-642-68223-0. from the original on 13 February 2021. Retrieved 13 September 2020.
  69. ^ Snyder, P J (1984). "Clinical Use of Androgens". Annual Review of Medicine. 35 (1): 207–217. doi:10.1146/annurev.me.35.020184.001231. ISSN 0066-4219. PMID 6372655.
  70. ^ a b c Becker KL (2001). Principles and Practice of Endocrinology and Metabolism. Lippincott Williams & Wilkins. pp. 1185–1186. ISBN 978-0-7817-1750-2. from the original on 2020-05-17. Retrieved 2016-10-17.
  71. ^ a b Rahnema CD, Crosnoe LE, Kim ED (March 2015). "Designer steroids – over-the-counter supplements and their androgenic component: review of an increasing problem". Andrology. 3 (2): 150–5. doi:10.1111/andr.307. PMID 25684733. S2CID 6999218.
  72. ^ a b Chrousos GP (2012). "The Gonadal Hormones & Inhibitors". In Katzung BG (ed.). Basic & Clinical Pharmacology. New York London: McGraw-Hill Medical McGraw-Hill distributor. ISBN 978-0071764018.
  73. ^ Mutzebaugh C (1998). "Does the choice of alpha-AAS really make a difference?". HIV Hotline. 8 (5–6): 10–1. PMID 11366379.
  74. ^ Casavant MJ, Blake K, Griffith J, Yates A, Copley LM (2007). "Consequences of use of anabolic androgenic steroids". Pediatr. Clin. North Am. 54 (4): 677–90, x. doi:10.1016/j.pcl.2007.04.001. PMID 17723870.
  75. ^ Pope HG, Wood RI, Rogol A, Nyberg F, Bowers L, Bhasin S (2014). "Adverse health consequences of performance-enhancing drugs: an Endocrine Society scientific statement". Endocr. Rev. 35 (3): 341–75. doi:10.1210/er.2013-1058. PMC 4026349. PMID 24423981.
  76. ^ Fragkaki AG, Angelis YS, Koupparis M, Tsantili-Kakoulidou A, Kokotos G, Georgakopoulos C (2009). "Structural characteristics of anabolic androgenic steroids contributing to binding to the androgen receptor and to their anabolic and androgenic activities. Applied modifications in the steroidal structure". Steroids. 74 (2): 172–97. doi:10.1016/j.steroids.2008.10.016. PMID 19028512. S2CID 41356223.
  77. ^ Nieschlag E, Vorona E (2015). "MECHANISMS IN ENDOCRINOLOGY: Medical consequences of doping with anabolic androgenic steroids: effects on reproductive functions". Eur. J. Endocrinol. 173 (2): R47–58. doi:10.1530/EJE-15-0080. PMID 25805894.
  78. ^ Hall RC, Hall RC, Chapman MJ (2005). "Psychiatric complications of anabolic steroid abuse". Psychosomatics. 46 (4): 285–90. doi:10.1176/appi.psy.46.4.285. PMID 16000671.
  79. ^ a b Trenton AJ, Currier GW (2005). "Behavioural manifestations of anabolic steroid use". CNS Drugs. 19 (7): 571–95. doi:10.2165/00023210-200519070-00002. PMID 15984895. S2CID 32243658.
  80. ^ Vanberg P, Atar D (2010). "Androgenic anabolic steroid abuse and the cardiovascular system". Handbook of Experimental Pharmacology. 195 (195): 411–57. doi:10.1007/978-3-540-79088-4_18. ISBN 978-3-540-79087-7. PMID 20020375.
  81. ^ Achar S, Rostamian A, Narayan SM (2010). "Cardiac and metabolic effects of anabolic-androgenic steroid abuse on lipids, blood pressure, left ventricular dimensions, and rhythm". Am. J. Cardiol. 106 (6): 893–901. doi:10.1016/j.amjcard.2010.05.013. PMC 4111565. PMID 20816133.
  82. ^ Solimini R, Rotolo MC, Mastrobattista L, Mortali C, Minutillo A, Pichini S, Pacifici R, Palmi I (2017). "Hepatotoxicity associated with illicit use of anabolic androgenic steroids in doping". Eur Rev Med Pharmacol Sci. 21 (1 Suppl): 7–16. PMID 28379599.
  83. ^ Brenu EW, McNaughton L, Marshall-Gradisnik SM (2011). "Is there a potential immune dysfunction with anabolic androgenic steroid use?: A review". Mini Rev Med Chem. 11 (5): 438–45. doi:10.2174/138955711795445907. PMID 21443507.
  84. ^ Grace F, Sculthorpe N, Baker J, Davies B (2003). "Blood pressure and rate pressure product response in males using high-dose anabolic-androgenic steroids (AAS)". J Sci Med Sport. 6 (3): 307–12. doi:10.1016/S1440-2440(03)80024-5. PMID 14609147.
  85. ^ "DailyMed: About DailyMed". Dailymed.nlm.nih.gov. from the original on 2009-05-12. Retrieved 2008-11-03.
  86. ^ Bagatell CJ, Knopp RH, Vale WW, Rivier JE, Bremner WJ (1992). "Physiologic testosterone levels in normal men suppress high-density lipoprotein cholesterol levels". Annals of Internal Medicine. 116 (12 Pt 1): 967–73. doi:10.7326/0003-4819-116-12-967. PMID 1586105.
  87. ^ Mewis C, Spyridopoulos I, Kühlkamp V, Seipel L (1996). "Manifestation of severe coronary heart disease after anabolic drug abuse". Clinical Cardiology. 19 (2): 153–5. doi:10.1002/clc.4960190216. PMID 8821428. S2CID 37024092.
  88. ^ Melnik B, Jansen T, Grabbe S (2007). "Abuse of anabolic-androgenic steroids and bodybuilding acne: an underestimated health problem". Journal der Deutschen Dermatologischen Gesellschaft. 5 (2): 110–7. doi:10.1111/j.1610-0387.2007.06176.x. PMID 17274777. S2CID 13382470.
  89. ^ Vierhapper H, Maier H, Nowotny P, Waldhäusl W (July 2003). "Production rates of testosterone and of dihydrotestosterone in female pattern hair loss". Metab. Clin. Exp. 52 (7): 927–9. doi:10.1016/S0026-0495(03)00060-X. PMID 12870172.
  90. ^ Irving LM, Wall M, Neumark-Sztainer D, Story M (2002). "Steroid use among adolescents: findings from Project EAT". The Journal of Adolescent Health. 30 (4): 243–52. doi:10.1016/S1054-139X(01)00414-1. PMID 11927236.
  91. ^ "Known and Probable Human Carcinogens". American Cancer Society. 2011-06-29. from the original on 2014-11-17. Retrieved 2014-11-17.
  92. ^ Sullivan ML, Martinez CM, Gallagher EJ (1999). "Atrial fibrillation and anabolic steroids". The Journal of Emergency Medicine. 17 (5): 851–7. doi:10.1016/S0736-4679(99)00095-5. PMID 10499702.
  93. ^ Dickerman RD, Schaller F, McConathy WJ (1998). "Left ventricular wall thickening does occur in elite power athletes with or without anabolic steroid Use". Cardiology. 90 (2): 145–8. doi:10.1159/000006834. PMID 9778553. S2CID 22123696.
  94. ^ George KP, Wolfe LA, Burggraf GW (1991). "The 'athletic heart syndrome'. A critical review". Sports Medicine. 11 (5): 300–30. doi:10.2165/00007256-199111050-00003. PMID 1829849. S2CID 45280834.
  95. ^ Dickerman RD, Schaller F, Zachariah NY, McConathy WJ (1997). "Left ventricular size and function in elite bodybuilders using anabolic steroids". Clin J Sport Med. 7 (2): 90–3. doi:10.1097/00042752-199704000-00003. PMID 9113423. S2CID 42891343.
  96. ^ Salke RC, Rowland TW, Burke EJ (1985). "Left ventricular size and function in body builders using anabolic steroids". Medicine & Science in Sports & Exercise. 17 (6): 701–4. doi:10.1249/00005768-198512000-00014. PMID 4079743.
  97. ^ Tokar S (February 2006). "Liver Damage And Increased Heart Attack Risk Caused By Anabolic Steroid Use". University of California – San Francisco. from the original on 2011-06-14. Retrieved 2007-04-24.
  98. ^ Wit JM, Oostdijk W (2015). "Novel approaches to short stature therapy". Best Practice & Research. Clinical Endocrinology & Metabolism. 29 (3): 353–66. doi:10.1016/j.beem.2015.01.003. PMID 26051296.
  99. ^ Marcus R, Korenman SG (1976). "Estrogens and the human male". Annu Rev Med. 27: 357–70. doi:10.1146/annurev.me.27.020176.002041. PMID 779604.
  100. ^ Matsumoto AM (1990). "Effects of chronic testosterone administration in normal men: safety and efficacy of high dosage testosterone and parallel dose-dependent suppression of luteinizing hormone, follicle-stimulating hormone, and sperm production". J. Clin. Endocrinol. Metab. 70 (1): 282–7. doi:10.1210/jcem-70-1-282. PMID 2104626.
  101. ^ Hoffman JR, Ratamess NA (June 1, 2006). "Medical Issues Associated with Anabolic Steroid Use: Are they Exaggerated?" (PDF). Journal of Sports Science and Medicine. (PDF) from the original on 20 June 2007. Retrieved 2007-05-08.
  102. ^ Meriggiola MC, Costantino A, Bremner WJ, Morselli-Labate AM (2002). "Higher testosterone dose impairs sperm suppression induced by a combined androgen-progestin regimen". J. Androl. 23 (5): 684–90. doi:10.1002/j.1939-4640.2002.tb02311.x. hdl:1773/4474. PMID 12185103

March 20, 2023
anabolic, steroid, this, article, about, androgens, medications, androgens, natural, hormones, androgen, also, known, more, properly, anabolic, androgenic, steroids, steroidal, androgens, that, include, natural, androgens, like, testosterone, well, synthetic, . This article is about androgens as medications For androgens as natural hormones see Androgen Anabolic steroids also known more properly as anabolic androgenic steroids AAS 1 are steroidal androgens that include natural androgens like testosterone as well as synthetic androgens that are structurally related and have similar effects to testosterone They increase protein within cells especially in skeletal muscles and also have varying degrees of virilizing effects including induction of the development and maintenance of masculine secondary sexual characteristics such as the growth of facial and body hair The word anabolic referring to anabolism comes from the Greek ἀnabolh anabole that which is thrown up mound Androgens or AAS are one of three types of sex hormone agonists the others being estrogens like estradiol and progestogens like progesterone Anabolic androgenic steroidsDrug classChemical structure of the natural AAS testosterone androst 4 en 17b ol 3 one Class identifiersSynonymsAnabolic steroids AndrogensUseVariousATC codeA14ABiological targetAndrogen receptorChemical classSteroids Androstanes EstranesClinical dataDrugs comDrug ClassesExternal linksMeSHD045165In WikidataAAS were synthesized in the 1930s and are now used therapeutically in medicine to stimulate muscle growth and appetite induce male puberty and treat chronic wasting conditions such as cancer and AIDS The American College of Sports Medicine acknowledges that AAS in the presence of adequate diet can contribute to increases in body weight often as lean mass increases and that the gains in muscular strength achieved through high intensity exercise and proper diet can be additionally increased by the use of AAS in some individuals 2 Health risks can be produced by long term use or excessive doses of AAS 3 4 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 dangerous changes in the structure of the left ventricle of the heart 5 These risks are further increased when athletes take steroids alongside other drugs causing significantly more damage to their bodies 6 The effect of anabolic steroids on the heart can cause myocardial infarction and strokes 6 Conditions pertaining to hormonal imbalances such as gynecomastia and testicular size reduction may also be caused by AAS 7 In women and children AAS can cause irreversible masculinization 7 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 unfair 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 6 For many years AAS have been by far the most detected doping substances in IOC accredited laboratories 8 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 Contents 1 Uses 1 1 Medical 1 1 1 Anabolic 1 1 2 Androgenic 1 1 3 Other 1 2 Enhancing performance 1 3 Dosages 1 4 Available forms 1 4 1 Routes of administration 2 Adverse effects 2 1 Physiological 2 1 1 Cancer 2 1 2 Cardiovascular 2 1 3 Growth defects 2 1 4 Feminization 2 1 5 Masculinization 2 1 6 Kidney problems 2 1 7 Liver problems 2 2 Neuropsychiatric 2 2 1 Diagnostic Statistical Manual assertion 2 2 2 Personality profiles 2 2 3 Mood and anxiety 2 2 4 Aggression and hypomania 2 3 Reproductive 3 Pharmacology 3 1 Mechanism of action 3 2 Anabolic and androgenic effects 3 2 1 Body composition and strength improvements 3 3 Dissociation of effects 3 3 1 Intracellular metabolism 3 3 2 Functional selectivity 3 3 3 Non genomic mechanisms 3 3 4 Antigonadotropic effects 3 4 GABAA receptor modulation 3 5 Comparison of AAS 3 5 1 5a Reductase and androgenicity 3 5 2 Aromatase and estrogenicity 3 5 3 Progestogenic activity 3 5 4 Oral activity and hepatotoxicity 3 5 5 Neurosteroid activity 4 Chemistry 4 1 Detection in body fluids 5 History 5 1 Discovery of androgens 5 2 Development of synthetic AAS 6 Society and culture 6 1 Etymology 6 2 Legal status 6 2 1 United States 6 2 2 United Kingdom 6 3 Status in sports 6 4 Usage 6 4 1 Law enforcement 6 4 2 Professional wrestling 6 5 Economics 7 Research 8 See also 9 References 10 Further reading 11 External linksUses EditMedical Edit Various AAS and related compounds 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 Edit 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 Edit 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 Edit 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 Enhancing performance Edit See also Ergogenic use of anabolic steroids Numerous vials of injectable AAS Most steroid users are not athletes 49 In the United States between 1 million and 3 million people 1 of the population are thought to have used AAS 50 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 51 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 52 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 53 though a 2007 study found that sharing of needles was extremely uncommon among individuals using AAS for non medical purposes less than 1 54 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 54 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 54 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 55 AAS users tend to be unhappy with the portrayal of AAS as deadly in the media and in politics 56 According to one study AAS users also distrust their physicians and in the sample 56 had not disclosed their AAS use to their physicians 57 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 54 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 58 A recent study in the Journal of Health Psychology showed that many users believed that steroids used in moderation were safe 59 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 60 Dosages Edit General dosage ranges of anabolic steroids Medication Route Dosage range a Danazol Oral 100 800 mg dayDrostanolone propionate Injection 100 mg 3 times weekEthylestrenol Oral 2 8 mg dayFluoxymesterone Oral 2 40 mg dayMesterolone Oral 25 150 mg dayMetandienone Oral 2 5 15 mg dayMetenolone acetate Oral 10 150 mg dayMetenolone enanthate Injection 25 100 mg weekMethyltestosterone Oral 1 5 200 mg dayNandrolone decanoate Injection 12 5 200 mg week b Nandrolone phenylpropionate Injection 6 25 200 mg week b Norethandrolone Oral 20 30 mg dayOxandrolone Oral 2 5 20 mg dayOxymetholone Oral 1 5 mg kg day or50 150 mg dayStanozolol Oral 2 6 mg dayInjection 50 mg up to every two weeksTestosterone Oral c 400 800 mg day b Injection 25 100 mg up tothree times weeklyTestosterone cypionate Injection 50 400 mg up toevery four weeksTestosterone enanthate Injection 50 400 mg up toevery four weeksTestosterone propionate Injection 25 50 mg up tothree times weeklyTestosterone undecanoate Oral 80 240 mg day b Injection 750 1000 mg up to every 10 weeksTrenbolone HBC Injection 75 mg every 10 daysSources 61 62 63 64 18 65 66 67 68 69 Unless otherwise noted given as a once daily weekly dose a b c d In divided doses Studied for human use but never marketed for comparison onlyAvailable forms Edit See also List of androgens anabolic steroids 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 70 nandrolone esters typically nandrolone decanoate and nandrolone phenylpropionate stanozolol and metandienone methandrostenolone 1 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 1 Dihydrotestosterone DHT known as androstanolone or stanolone when used medically and its esters are also notable although they are not widely used in medicine 66 Boldenone undecylenate and trenbolone acetate are used in veterinary medicine 1 Designer steroids are AAS that have not been approved and marketed for medical use but have been distributed through the black market 71 Examples of notable designer steroids include 1 testosterone dihydroboldenone methasterone trenbolone enanthate desoxymethyltestosterone tetrahydrogestrinone and methylstenbolone 71 Routes of administration Edit A vial of injectable testosterone cypionate 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 17a 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 72 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 54 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 9 73 Adverse effects EditKnown possible side effects of AAS include 7 74 75 76 77 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 78 79 Musculoskeletal muscle hypertrophy muscle strains tendon ruptures rhabdomyolysis Cardiovascular dyslipidemia e g increased LDL levels decreased HDL levels reduced apo A1 levels atherosclerosis hypertension left ventricular hypertrophy cardiomyopathy myocardial hypertrophy polycythemia erythrocytosis arrhythmias thrombosis e g embolism stroke myocardial infarction sudden death 80 81 Hepatic elevated liver function tests AST ALT bilirubin LDH ALP hepatotoxicity jaundice hepatic steatosis hepatocellular adenoma hepatocellular carcinoma cholestasis peliosis hepatis all mostly or exclusively with 17a alkylated AAS 82 Renal renal hypertrophy nephropathy acute renal failure secondary to rhabdomyolysis focal segmental glomerulosclerosis renal cell carcinoma Others glucose intolerance insulin resistance immune dysfunction 83 Physiological Edit 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 84 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 85 AAS such as testosterone also increase the risk of cardiovascular disease 3 or coronary artery disease 86 87 Acne is fairly common among AAS users mostly due to stimulation of the sebaceous glands by increased testosterone levels 8 88 Conversion of testosterone to DHT can accelerate the rate of premature baldness for males genetically predisposed but testosterone itself can produce baldness in females 89 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 90 Cancer Edit WHO organization International Agency for Research on Cancer IARC list AAS under Group 2A Probably carcinogenic to humans 91 Cardiovascular Edit 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 5 Possible effects of these alterations in the heart are hypertension cardiac arrhythmias congestive heart failure heart attacks and sudden cardiac death 92 These changes are also seen in non drug using athletes but steroid use may accelerate this process 93 94 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 95 96 AAS use can cause harmful changes in cholesterol levels Some steroids cause an increase in LDL cholesterol and a decrease in HDL cholesterol 97 Growth defects Edit 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 98 Feminization Edit 22 year old man with gynecomastia not due to AAS use Before and after gynecomastia surgery See also Feminization biology There are also sex specific side effects of AAS Development of breast tissue in males a condition called gynecomastia which is usually caused by high levels of circulating estradiol may arise because of increased conversion of testosterone to estradiol by the enzyme aromatase 99 Reduced sexual function and temporary infertility can also occur in males 100 101 102 Another male specific side effect that can occur is testicular atrophy caused by the suppression of natural testosterone levels which inhibits production of sperm most of the mass of the testes is developing sperm This side effect is temporary the size of the testicles usually returns to normal within a few weeks of discontinuing AAS use as normal production of sperm resumes 103 Masculinization Edit See also Virilization 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 104 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 105 Kidney problems Edit 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 106 Liver problems Edit High doses of oral AAS compounds can cause liver damage 4 Peliosis hepatis has been increasingly recognised with the use of AAS Neuropsychiatric Edit Addiction experts in psychiatry chemistry pharmacology forensic science epidemiology and the police and legal services engaged in delphic analysis regarding 20 popular recreational drugs AAS were ranked 19th in dependence 9th in physical harm and 15th in social harm 107 See also Anabolic androgenic steroids abuse 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 79 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 abuse but the prevalence and severity of these various effects remains poorly understood 108 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 109 Mood disturbances e g depression hypo mania psychotic features are likely to be dose and drug dependent but AAS dependence or withdrawal effects seem to occur only in a small number of AAS users 8 Large scale long term studies of psychiatric effects on AAS users are not currently available 108 In 2003 the first naturalistic long term study on ten users seven of which having completed the study found a high incidence of mood disorders and substance abuse but few clinically relevant changes in physiological parameters or laboratory measures were noted throughout the study and these changes were not clearly related to periods of reported AAS use 110 A 13 month study which was published in 2006 and which involved 320 body builders and athletes suggests that the wide range of psychiatric side effects induced by the use of AAS is correlated to the severity of abuse 111 Diagnostic Statistical Manual assertion Edit 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 Edit 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 amp Katz 1994 112 Bipolar dysfunction 114 substance dependency and conduct disorder have also been associated with AAS use 115 Mood and anxiety Edit 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 Edit 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 A 1996 randomized controlled trial which involved 43 men did not find an increase in the occurrence of angry behavior during 10 weeks of administration of testosterone enanthate at 600 mg week but this study screened out subjects that had previously abused steroids or had any psychiatric antecedents 122 123 A trial conducted in 2000 using testosterone cypionate at 600 mg week found that treatment significantly increased manic scores on the YMRS and aggressive responses on several scales The drug response was highly variable However 84 of subjects exhibited minimal psychiatric effects 12 became mildly hypomanic and 4 2 subjects became markedly hypomanic The mechanism of these variable reactions could not be explained by demographic psychological laboratory or physiological measures 124 A 2006 study of two pairs of identical twins in which one twin used AAS 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 125 A small scale study of 10 AAS users found that cluster B personality disorders were confounding factors for aggression 126 The relationship between AAS use and depression is inconclusive There have been anecdotal reports of depression and suicide in teenage steroid users 127 but little systematic evidence A 1992 review 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 128 In the case of suicide 3 9 of a sample of 77 those classified as AAS users reported attempting suicide during withdrawal Malone Dimeff Lombardo amp Sample 1995 129 Reproductive Edit Androgens such as testosterone androstenedione and dihydrotestosterone are required for the development of organs in the male reproductive system including the seminal vesicles epididymis vas deferens penis and prostate 130 AAS are testosterone derivatives designed to maximize the anabolic effects of testosterone 131 AAS are consumed by elite athletes competing in sports like weightlifting bodybuilding and track and field 132 Male recreational athletes take AAS to achieve an enhanced physical appearance 133 AAS consumption disrupts the hypothalamic pituitary gonadal axis HPG axis in males 130 In the HPG axis gonadotropin releasing hormone GnRH is secreted from the arcuate nucleus of the hypothalamus and stimulates the anterior pituitary to secrete the two gonadotropins follicle stimulating hormone FSH and luteinizing hormone LH 134 In adult males LH stimulates the Leydig cells in the testes to produce testosterone which is required to form new sperm through spermatogenesis 130 AAS consumption leads to dose dependent suppression of gonadotropin release through suppression of GnRH from the hypothalamus long loop mechanism or from direct negative feedback on the anterior pituitary to inhibit gonadotropin release short loop mechanism leading to AAS induced hypogonadism 130 Pharmacology EditMechanism of action Edit See also Steroid hormone The human androgen receptor bound to testosterone 135 The protein is shown as a ribbon diagram in red green and blue with the steroid shown in white The pharmacodynamics of AAS are unlike peptide hormones Water soluble peptide hormones cannot penetrate the fatty cell membrane and only indirectly affect the nucleus of target cells through their interaction with the cell s surface receptors However as fat soluble hormones AAS are membrane permeable and influence the nucleus of cells by direct action The pharmacodynamic action of AAS begin when the exogenous hormone penetrates the membrane of the target cell and binds to an androgen receptor AR located in the cytoplasm of that cell From there the compound hormone receptor diffuses into the nucleus where it either alters the expression of genes 136 or activates processes that send signals to other parts of the cell 137 Different types of AAS bind to the AAR with different affinities depending on their chemical structure 8 The effect of AAS on muscle mass is caused in at least two ways 138 first they increase the production of proteins second they reduce recovery time by blocking the effects of stress hormone cortisol on muscle tissue so that catabolism of muscle is greatly reduced It has been hypothesized that this reduction in muscle breakdown may occur through AAS inhibiting the action of other steroid hormones called glucocorticoids that promote the breakdown of muscles 139 AAS also affect the number of cells that develop into fat storage cells by favouring cellular differentiation into muscle cells instead 140 Anabolic and androgenic effects Edit vte Androgenic vs anabolic activityof androgens anabolic steroids Medication RatioaTestosterone 1 1Androstanolone DHT 1 1Methyltestosterone 1 1Methandriol 1 1Fluoxymesterone 1 1 1 15Metandienone 1 1 1 8Drostanolone 1 3 1 4Metenolone 1 2 1 30Oxymetholone 1 2 1 9Oxandrolone 1 3 1 13Stanozolol 1 1 1 30Nandrolone 1 3 1 16Ethylestrenol 1 2 1 19Norethandrolone 1 1 1 20Notes In rodents Footnotes a Ratio of androgenic to anabolic activity Sources See template As their name suggests AAS have two different but overlapping types of effects anabolic meaning that they promote anabolism cell growth and androgenic or virilizing meaning that they affect the development and maintenance of masculine characteristics Some examples of the anabolic effects of these hormones are increased protein synthesis from amino acids increased appetite increased bone remodeling and growth and stimulation of bone marrow which increases the production of red blood cells Through a number of mechanisms AAS stimulate the formation of muscle cells and hence cause an increase in the size of skeletal muscles leading to increased strength 141 142 143 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 size does not change due to steroids medical citation needed increased vocal cord size increased libido suppression of natural sex hormones and impaired production of sperm 144 Effects on women include deepening of the voice facial hair growth and possibly a decrease in breast size Men may develop an enlargement of breast tissue known as gynecomastia testicular atrophy and a reduced sperm count citation needed 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 AAS have significant androgenic effects 72 A commonly used protocol for determining the androgenic anabolic ratio dating back to the 1950s uses the relative weights of ventral prostate VP and levator ani muscle LA of male rats The VP weight is an indicator of the androgenic effect while the LA weight is an indicator of the anabolic effect Two or more batches of rats are castrated and given no treatment and respectively some AAS of interest The LA VP ratio for an AAS is calculated as the ratio of LA VP weight gains produced by the treatment with that compound using castrated but untreated rats as baseline LAc t LAc VPc t VPc The LA VP weight gain ratio from rat experiments is not unitary for testosterone typically 0 3 0 4 but it is normalized for presentation purposes and used as basis of comparison for other AAS which have their androgenic anabolic ratios scaled accordingly as shown in the table above 145 146 In the early 2000s this procedure was standardized and generalized throughout OECD in what is now known as the Hershberger assay Body composition and strength improvements Edit Body weight in men may increase by 2 to 5 kg as a result of short term lt 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 8 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 ARs in the upper body citation needed 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 8 Strength improvements in the range of 5 to 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 bench press 8 For almost two decades it was assumed that AAS exerted significant effects only in experienced strength athletes 147 148 A randomized controlled trial demonstrated however that even in novice athletes a 10 week strength training program accompanied by testosterone enanthate at 600 mg week may improve strength more than training alone does 8 122 This dose is sufficient to significantly improve lean muscle mass relative to placebo even in subjects that did not exercise at all 122 The anabolic effects of testosterone enanthate were highly dose dependent 8 149 Dissociation of effects Edit Endogenous natural AAS like testosterone and DHT and synthetic AAS mediate their effects by binding to and activating the AR 1 On the basis of animal bioassays the effects of these agents have been divided into two partially dissociable types anabolic myotrophic and androgenic 1 Dissociation between the ratios of these two types of effects relative to the ratio observed with testosterone is observed in rat bioassays with various AAS 1 Theories for the dissociation include differences between AAS in terms of their intracellular metabolism functional selectivity differential recruitment of coactivators and non genomic mechanisms i e signaling through non AR membrane androgen receptors or mARs 1 Support for the latter two theories is limited and more hypothetical but there is a good deal of support for the intracellular metabolism theory 1 The measurement of the dissociation between anabolic and androgenic effects among AAS is based largely on a simple but outdated and unsophisticated model using rat tissue bioassays 1 It has been referred to as the myotrophic androgenic index 1 In this model myotrophic or anabolic activity is measured by change in the weight of the rat bulbocavernosus levator ani muscle and androgenic activity is measured by change in the weight of the rat ventral prostate or alternatively the rat seminal vesicles in response to exposure to the AAS 1 The measurements are then compared to form a ratio 1 Intracellular metabolism Edit Testosterone is metabolized in various tissues by 5a reductase into DHT which is 3 to 10 fold more potent as an AR agonist and by aromatase into estradiol which is an estrogen and lacks significant AR affinity 1 In addition DHT is metabolized by 3a hydroxysteroid dehydrogenase 3a HSD and 3b hydroxysteroid dehydrogenase 3b HSD into 3a androstanediol and 3b androstanediol respectively which are metabolites with little or no AR affinity 1 5a reductase is widely distributed throughout the body and is concentrated to various extents in skin particularly the scalp face and genital areas prostate seminal vesicles liver and the brain 1 In contrast expression of 5a reductase in skeletal muscle is undetectable 1 Aromatase is highly expressed in adipose tissue and the brain and is also expressed significantly in skeletal muscle 1 3a HSD is highly expressed in skeletal muscle as well 66 Natural AAS like testosterone and DHT and synthetic AAS are analogues and are very similar structurally 1 For this reason they have the capacity to bind to and be metabolized by the same steroid metabolizing enzymes 1 According to the intracellular metabolism explanation the androgenic to anabolic ratio of a given AR agonist is related to its capacity to be transformed by the aforementioned enzymes in conjunction with the AR activity of any resulting products 1 For instance whereas the AR activity of testosterone is greatly potentiated by local conversion via 5a reductase into DHT in tissues where 5a reductase is expressed an AAS that is not metabolized by 5a reductase or is already 5a reduced such as DHT itself or a derivative like mesterolone or drostanolone would not undergo such potentiation in said tissues 1 Moreover nandrolone is metabolized by 5a reductase but unlike the case of testosterone and DHT the 5a reduced metabolite of nandrolone has much lower affinity for the AR than does nandrolone itself and this results in reduced AR activation in 5a reductase expressing tissues 1 As so called androgenic tissues such as skin hair follicles and male reproductive tissues are very high in 5a reductase expression while skeletal muscle is virtually devoid of 5a reductase this may primarily explain the high myotrophic androgenic ratio and dissociation seen with nandrolone as well as with various other AAS 1 Aside from 5a reductase aromatase may inactivate testosterone signaling in skeletal muscle and adipose tissue so AAS that lack aromatase affinity in addition to being free of the potential side effect of gynecomastia might be expected to have a higher myotrophic androgenic ratio in comparison 1 In addition DHT is inactivated by high activity of 3a HSD in skeletal muscle and cardiac tissue and AAS that lack affinity for 3a HSD could similarly be expected to have a higher myotrophic androgenic ratio although perhaps also increased long term cardiovascular risks 1 In accordance DHT mestanolone 17a methyl DHT and mesterolone 1a methyl DHT are all described as very poorly anabolic due to inactivation by 3a HSD in skeletal muscle whereas other DHT derivatives with other structural features like metenolone oxandrolone oxymetholone drostanolone and stanozolol are all poor substrates for 3a HSD and are described as potent anabolics 66 The intracellular metabolism theory explains how and why remarkable dissociation between anabolic and androgenic effects might occur despite the fact that these effects are mediated through the same signaling receptor and why this dissociation is invariably incomplete 1 In support of the model is the rare condition congenital 5a reductase type 2 deficiency in which the 5a reductase type 2 enzyme is defective production of DHT is impaired and DHT levels are low while testosterone levels are normal 150 151 Males with this condition are born with ambiguous genitalia and a severely underdeveloped or even absent prostate gland 150 151 In addition at the time of puberty such males develop normal musculature voice deepening and libido but have reduced facial hair a female pattern of body hair i e largely restricted to the pubic triangle and underarms no incidence of male pattern hair loss and no prostate enlargement or incidence of prostate cancer 151 152 153 154 155 They also notably do not develop gynecomastia as a consequence of their condition 153 vte Relative affinities of nandrolone and related steroids at the androgen receptor Compound rAR hAR Testosterone 38 385a Dihydrotestosterone 77 100Nandrolone 75 925a Dihydronandrolone 35 50Ethylestrenol ND 2Norethandrolone ND 225a Dihydronorethandrolone ND 14Metribolone 100 110Sources See template Functional selectivity Edit An animal study found that two different kinds of androgen response elements could differentially respond to testosterone and DHT upon activation of the AR 156 157 Whether this is involved in the differences in the ratios of anabolic to myotrophic effect of different AAS is unknown however 156 157 1 Non genomic mechanisms Edit Testosterone signals not only through the nuclear AR but also through mARs including ZIP9 and GPRC6A 158 159 It has been proposed that differential signaling through mARs may be involved in the dissociation of the anabolic and androgenic effects of AAS 1 Indeed DHT has less than 1 of the affinity of testosterone for ZIP9 and the synthetic AAS metribolone and mibolerone are ineffective competitors for the receptor similarly 159 This indicates that AAS do show differential interactions with the AR and mARs 159 However women with complete androgen insensitivity syndrome CAIS who have a 46 XY male genotype and testes but a defect in the AR such that it is non functional are a challenge to this notion 160 They are completely insensitive to the AR mediated effects of androgens like testosterone and show a perfectly female phenotype despite having testosterone levels in the high end of the normal male range 160 These women have little or no sebum production incidence of acne or body hair growth including in the pubic and axillary areas 160 Moreover CAIS women have lean body mass that is normal for females but is of course greatly reduced relative to males 161 These observations suggest that the AR is mainly or exclusively responsible for masculinization and myotrophy caused by androgens 160 161 162 The mARs have however been found to be involved in some of the health related effects of testosterone like modulation of prostate cancer risk and progression 159 163 Antigonadotropic effects Edit Changes in endogenous testosterone levels may also contribute to differences in myotrophic androgenic ratio between testosterone and synthetic AAS 66 AR agonists are antigonadotropic that is they dose dependently suppress gonadal testosterone production and hence reduce systemic testosterone concentrations 66 By suppressing endogenous testosterone levels and effectively replacing AR signaling in the body with that of the exogenous AAS the myotrophic androgenic ratio of a given AAS may be further dose dependently increased and this hence may be an additional factor contributing to the differences in myotrophic androgenic ratio among different AAS 66 In addition some AAS such as 19 nortestosterone derivatives like nandrolone are also potent progestogens and activation of the progesterone receptor PR is antigonadotropic similarly to activation of the AR 66 The combination of sufficient AR and PR activation can suppress circulating testosterone levels into the castrate range in men i e complete suppression of gonadal testosterone production and circulating testosterone levels decreased by about 95 48 164 As such combined progestogenic activity may serve to further increase the myotrophic androgenic ratio for a given AAS 66 GABAA receptor modulation Edit Some AAS such as testosterone DHT stanozolol and methyltestosterone have been found to modulate the GABAA receptor similarly to endogenous neurosteroids like allopregnanolone 3a androstanediol dehydroepiandrosterone sulfate and pregnenolone sulfate 1 It has been suggested that this may contribute as an alternative or additional mechanism to the neurological and behavioral effects of AAS 1 165 166 167 168 169 170 Comparison of AAS Edit AAS differ in a variety of ways including in their capacities to be metabolized by steroidogenic enzymes such as 5a reductase 3 hydroxysteroid dehydrogenases and aromatase in whether their potency as AR agonists is potentiated or diminished by 5a reduction in their ratios of anabolic myotrophic to androgenic effect in their estrogenic progestogenic and neurosteroid activities in their oral activity and in their capacity to produce hepatotoxicity 66 1 171 vte Pharmacological properties of major anabolic steroids Compound Class 5a R AROM 3 HSD AAR Estr Prog Oral HepatAndrostanolone DHT Boldenone T Drostanolone DHT Ethylestrenol 19 NT 17a A Fluoxymesterone T 17a A Mestanolone DHT 17a A Mesterolone DHT Metandienone T 17a A Metenolone DHT Methyltestosterone T 17a A Nandrolone 19 NT Norethandrolone 19 NT 17a A Oxandrolone DHT 17a A Oxymetholone DHT 17a A Stanozolol DHT 17a A Testosterone T a Trenbolone 19 NT Key Yes Low No Potentiated Inactivated High Moderate Low Abbreviations 5a R Metabolized by 5a reductase AROM Metabolized by aromatase 3 HSD Metabolized by 3a and or 3b HSD AAR Anabolic to androgenic ratio amount of anabolic myotrophic effect relative to androgenic effect Estr Estrogenic Prog Progestogenic Oral Oral activity Hepat Hepatotoxicity Footnotes a As testosterone undecanoate Sources See template vte Relative affinities of anabolic steroids and related steroids Steroid Chemical name Relative binding affinities PR AR ER GR MR SHBG CBGAndrostanolone DHT 1 4 1 5 60 120 lt 0 1 lt 0 1 0 3 0 15 100 0 8Boldenone D1 T lt 1 50 75 lt 1 Danazol 2 3 Isoxazol 17a Ety T 9 8 lt 0 1a 8 10Dienolone 9 19 NT 17 134 lt 0 1 1 6 0 3 Dimethyldienolone 9 7a 17a DiMe 19 NT 198 122 0 1 6 1 1 7 Dimethyltrienolone 9 11 7a 17a DiMe 19 NT 306 180 0 1 22 52 Drostanolone 2a Me DHT 39 Ethisterone 17a Ety T 35 0 1 lt 1 0 lt 1 0 lt 1 0 25 92 0 3Ethylestrenol 3 DeO 17a Et 19 NT lt 1 Fluoxymesterone 9a F 11b OH 17a Me T 3 Gestrinone 9 11 17a Ety 18 Me 19 NT 75 76 83 85 lt 0 1 10 77 3 2 Levonorgestrel 17a Ety 18 Me 19 NT 170 84 87 lt 0 1 14 0 6 0 9 14 50 lt 0 1Mestanolone 17a Me DHT 5 10 100 125 lt 1 84 Mesterolone 1a Me DHT 82 440 Metandienone 1 17a Me T 2 Metenolone 1 1 Me DHT 3 Methandriol 17a Me A5 40 Methasterone 2a 17a DiMe DHT 58 Methyldienolone 9 17a Me 19 NT 71 64 lt 0 1 6 0 4 Methyltestosterone 17a Me T 3 45 125 lt 0 1 1 5 5 64 lt 0 1Methyl 1 testosterone 1 17a Me DHT 69 Metribolone 9 11 17a Me 19 NT 208 210 199 210 lt 0 1 10 26 18 0 2 0 8 0 4Mibolerone 7a 17a DiMe 19 NT 214 108 lt 0 1 1 4 2 1 6 Nandrolone 19 NT 20 154 155 lt 0 1 0 5 1 6 1 16 0 1Norethandrolone 17a Et 19 NT 3 Norethisterone 17a Ety 19 NT 155 156 43 45 lt 0 1 2 7 2 8 0 2 5 21 0 3Norgestrienone 9 11 17a Ety 19 NT 63 65 70 lt 0 1 11 1 8 Normethandrone 17a Me 19 NT 100 146 lt 0 1 1 5 0 6 7 Oxandrolone 2 Oxa 17a Me DHT lt 1 Oxymetholone 2 OHMeEne 17a Me DHT 3 RU 2309 17a Me THG 9 11 17a 18 DiMe 19 NT 230 143 lt 0 1 155 36 Stanozolol 2 3 Pyrazol 17a Me DHT 1 36 Testosterone T 1 0 1 2 100 lt 0 1 0 17 0 9 19 82 3 81 Testosterone 1 DHT 98 Tibolone 7a Me 17a Ety 19 N 5 10 T 12 12 1 D4 Tibolone 7a Me 17a Ety 19 NT 180 70 1 lt 1 2 1 8 lt 1Trenbolone 9 11 19 NT 74 75 190 197 lt 0 1 2 9 1 33 Trestolone 7a Me 19 NT 50 75 100 125 lt 1 12 Notes Values are percentages Reference ligands 100 were progesterone for the PR testosterone for the AR estradiol for the ER dexamethasone for the GR aldosterone for the MR dihydrotestosterone for SHBG and cortisol for CBG Footnotes a 1 hour incubation time 4 hours is standard for this assay may affect affinity value Sources See template vte Parenteral durations of androgens anabolic steroids Medication Form Major brand names DurationTestosterone Aqueous suspension Andronaq Sterotate Virosterone 2 3 daysTestosterone propionate Oil solution Androteston Perandren Testoviron 3 4 daysTestosterone phenylpropionate Oil solution Testolent 8 daysTestosterone isobutyrate Aqueous suspension Agovirin Depot Perandren M 14 daysMixed testosterone estersa Oil solution Triolandren 10 20 daysMixed testosterone estersb Oil solution Testosid Depot 14 20 daysTestosterone enanthate Oil solution Delatestryl 14 28 daysTestosterone cypionate Oil solution Depovirin 14 28 daysMixed testosterone estersc Oil solution Sustanon 250 28 daysTestosterone undecanoate Oil solution Aveed Nebido 100 daysTestosterone buciclated Aqueous suspension 20 Aet 1 CDB 1781e 90 120 daysNandrolone phenylpropionate Oil solution Durabolin 10 daysNandrolone decanoate Oil solution Deca Durabolin 21 28 daysMethandriol Aqueous suspension Notandron Protandren 8 daysMethandriol bisenanthoyl acetate Oil solution Notandron Depot 16 daysMetenolone acetate Oil solution Primobolan 3 daysMetenolone enanthate Oil solution Primobolan Depot 14 daysNote All are via i m injection Footnotes a TP TV and TUe b TP and TKL c TP TPP TiCa and TD d Studied but never marketed e Developmental code names Sources See template vte Pharmacokinetics of testosterone esters Testosterone ester Form Route Tmax t1 2 MRTTestosterone undecanoate Oil filled capsules Oral 1 6 hours 3 7 hoursTestosterone propionate Oil solution Intramuscular injection 0 8 days 1 5 daysTestosterone enanthate Castor oil solution Intramuscular injection 10 days 4 5 days 8 5 daysTestosterone undecanoate Tea seed oil solution Intramuscular injection 13 0 days 20 9 days 34 9 daysTestosterone undecanoate Castor oil solution Intramuscular injection 11 4 days 33 9 days 36 0 daysTestosterone buciclatea Aqueous suspension Intramuscular injection 25 8 days 29 5 days 60 0 daysNotes Testosterone cypionate has similar pharmacokinetics to Testosterone enanthate Footnotes a Never marketed Sources See template 5a Reductase and androgenicity Edit Testosterone can be robustly converted by 5a reductase into DHT in so called androgenic tissues such as skin scalp prostate and seminal vesicles but not in muscle or bone where 5a reductase either is not expressed or is only minimally expressed 1 As DHT is 3 to 10 fold more potent as an agonist of the AR than is testosterone the AR agonist activity of testosterone is thus markedly and selectively potentiated in such tissues 1 In contrast to testosterone DHT and other 4 5a dihydrogenated AAS are already 5a reduced and for this reason cannot be potentiated in androgenic tissues 1 19 Nortestosterone derivatives like nandrolone can be metabolized by 5a reductase similarly to testosterone but 5a reduced metabolites of 19 nortestosterone derivatives e g 5a dihydronandrolone tend to have reduced activity as AR agonists resulting in reduced androgenic activity in tissues that express 5a reductase 1 In addition some 19 nortestosterone derivatives including trestolone 7a methyl 19 nortestosterone MENT 11b methyl 19 nortestosterone 11b MNT and dimethandrolone 7a 11b dimethyl 19 nortestosterone cannot be 5a reduced 172 Conversely certain 17a alkylated AAS like methyltestosterone are 5a reduced and potentiated in androgenic tissues similarly to testosterone 1 66 17a Alkylated DHT derivatives cannot be potentiated via 5a reductase however as they are already 4 5a reduced 1 66 The capacity to be metabolized by 5a reductase and the AR activity of the resultant metabolites appears to be one of the major if not the most important determinant of the androgenic myotrophic ratio for a given AAS 1 AAS that are not potentiated by 5a reductase or that are weakened by 5a reductase in androgenic tissues have a reduced risk of androgenic side effects such as acne androgenic alopecia male pattern baldness hirsutism excessive male pattern hair growth benign prostatic hyperplasia prostate enlargement and prostate cancer while incidence and magnitude of other effects such as muscle hypertrophy bone changes 173 voice deepening and changes in sex drive show no difference 1 174 Aromatase and estrogenicity Edit Testosterone can be metabolized by aromatase into estradiol and many other AAS can be metabolized into their corresponding estrogenic metabolites as well 1 As an example the 17a alkylated AAS methyltestosterone and metandienone are converted by aromatase into methylestradiol 175 4 5a Dihydrogenated derivatives of testosterone such as DHT cannot be aromatized whereas 19 nortestosterone derivatives like nandrolone can be but to a greatly reduced extent 1 176 Some 19 nortestosterone derivatives such as dimethandrolone and 11b MNT cannot be aromatized due to steric hindrance provided by their 11b methyl group whereas the closely related AAS trestolone 7a methyl 19 nortestosterone in relation to its lack of an 11b methyl group can be aromatized 176 AAS that are 17a alkylated and not also 4 5a reduced or 19 demethylated are also aromatized but to a lesser extent than is testosterone 1 177 However it is notable that estrogens that are 17a substituted e g ethinylestradiol and methylestradiol are of markedly increased estrogenic potency due to improved metabolic stability 175 and for this reason 17a alkylated AAS can actually have high estrogenicity and comparatively greater estrogenic effects than testosterone 175 66 The major effect of estrogenicity is gynecomastia woman like breasts 1 AAS that have a high potential for aromatization like testosterone and particularly methyltestosterone show a high risk of gynecomastia at sufficiently high dosages while AAS that have a reduced potential for aromatization like nandrolone show a much lower risk though still potentially significant at high dosages 1 In contrast AAS that are 4 5a reduced and some other AAS e g 11b methylated 19 nortestosterone derivatives have no risk of gynecomastia 1 In addition to gynecomastia AAS with high estrogenicity have increased antigonadotropic activity which results in increased potency in suppression of the hypothalamic pituitary gonadal axis and gonadal testosterone production 178 Progestogenic activity Edit Many 19 nortestosterone derivatives including nandrolone trenbolone ethylestrenol ethylnandrol metribolone R 1881 trestolone 11b MNT dimethandrolone and others are potent agonists of the progesterone receptor PR and hence are progestogens in addition to AAS 1 179 Similarly to the case of estrogenic activity the progestogenic activity of these drugs serves to augment their antigonadotropic activity 179 This results in increased potency and effectiveness of these AAS as antispermatogenic agents and male contraceptives or put in another way increased potency and effectiveness in producing azoospermia and reversible male infertility 179 Oral activity and hepatotoxicity Edit Non 17a alkylated testosterone derivatives such as testosterone itself DHT and nandrolone all have poor oral bioavailability due to extensive first pass hepatic metabolism and hence are not orally active 1 A notable exception to this are AAS that are androgen precursors or prohormones including dehydroepiandrosterone DHEA androstenediol androstenedione boldione androstadienedione bolandiol norandrostenediol bolandione norandrostenedione dienedione mentabolan MENT dione trestione and methoxydienone methoxygonadiene although these are relatively weak AAS 180 181 AAS that are not orally active are used almost exclusively in the form of esters administered by intramuscular injection which act as depots and function as long acting prodrugs 1 Examples include testosterone as testosterone cypionate testosterone enanthate and testosterone propionate and nandrolone as nandrolone phenylpropionate and nandrolone decanoate among many others see here for a full list of testosterone and nandrolone esters 1 An exception is the very long chain ester testosterone undecanoate which is orally active albeit with only very low oral bioavailability approximately 3 182 In contrast to most other AAS 17a alkylated testosterone derivatives show resistance to metabolism due to steric hindrance and are orally active though they may be esterified and administered via intramuscular injection as well 1 In addition to oral activity 17a alkylation also confers a high potential for hepatotoxicity and all 17a alkylated AAS have been associated albeit uncommonly and only after prolonged use different estimates between 1 and 17 183 184 with hepatotoxicity 1 185 186 In contrast testosterone esters have only extremely rarely or never been associated with hepatotoxicity 184 and other non 17a alkylated AAS only rarely citation needed although long term use may reportedly still increase the risk of hepatic changes but at a much lower rate than 17a alkylated AAS and reportedly not at replacement dosages 183 187 70 additional citation s needed In accordance D ring glucuronides of testosterone and DHT have been found to be cholestatic 188 Aside from prohormones and testosterone undecanoate almost all orally active AAS are 17a alkylated 189 A few AAS that are not 17a alkylated are orally active 1 Some examples include the testosterone 17 ethers cloxotestosterone quinbolone and silandrone citation needed which are prodrugs to testosterone boldenone D1 testosterone and testosterone respectively the DHT 17 ethers mepitiostane mesabolone and prostanozol which are also prodrugs the 1 methylated DHT derivatives mesterolone and metenolone although these are relatively weak AAS 1 70 and the 19 nortestosterone derivatives dimethandrolone and 11b MNT which have improved resistance to first pass hepatic metabolism due to their 11b methyl groups in contrast to them the related AAS trestolone 7a methyl 19 nortestosterone is not orally active 1 179 As these AAS are not 17a alkylated they show minimal potential for hepatotoxicity 1 Neurosteroid activity Edit DHT via its metabolite 3a androstanediol produced by 3a hydroxysteroid dehydrogenase 3a HSD is a neurosteroid that acts via positive allosteric modulation of the GABAA receptor 1 Testosterone via conversion into DHT also produces 3a androstanediol as a metabolite and hence has similar activity 1 Some AAS that are or can be 5a reduced including testosterone DHT stanozolol and methyltestosterone among many others can or may modulate the GABAA receptor and this may contribute as an alternative or additional mechanism to their central nervous system effects in terms of mood anxiety aggression and sex drive 1 165 166 167 168 169 170 Chemistry EditSee also List of androgens anabolic steroids List of androgen esters and Structure activity relationships of anabolic steroids AAS are androstane or estrane steroids They include testosterone androst 4 en 17b ol 3 one and derivatives with various structural modifications such as 1 190 66 17a Alkylation methyltestosterone metandienone fluoxymesterone oxandrolone oxymetholone stanozolol norethandrolone ethylestrenol 19 Demethylation nandrolone trenbolone norethandrolone ethylestrenol trestolone dimethandrolone 5a Reduction androstanolone drostanolone mestanolone mesterolone metenolone oxandrolone oxymetholone stanozolol 3b and or 17b esterification testosterone enanthate nandrolone decanoate drostanolone propionate boldenone undecylenate trenbolone acetateAs well as others such as 1 dehydrogenation e g metandienone boldenone 1 substitution e g mesterolone metenolone 2 substitution e g drostanolone oxymetholone stanozolol 4 substitution e g clostebol oxabolone and various other modifications 1 190 66 vte Structural aspects of androgens and anabolic steroids Classes Androgen Structure Chemical name FeaturesTestosterone 4 Hydroxytestosteronea 4 Hydroxytestosterone Androstenediola 5 Androstenediol androst 5 ene 3b 17b diol ProhormoneAndrostenedionea 4 Androstenedione androst 4 ene 3 17 dione ProhormoneBoldenone 1 Dehydrotestosterone Boldionea 1 Dehydro 4 androstenedione ProhormoneClostebol 4 Chlorotestosterone Cloxotestosterone Testosterone 17 chloral hemiacetal ether EtherPrasterone 5 Dehydroepiandrosterone androst 5 en 3b ol 17 one ProhormoneQuinbolone 1 Dehydrotestosterone 17b cyclopentenyl enol ether EtherSilandronea Testosterone 17b trimethylsilyl ether EtherTestosterone Androst 4 en 17b ol 3 one 17a Alkylated testosterone Bolasterone 7a 17a Dimethyltestosterone Calusterone 7b 17a Dimethyltestosterone Chlorodehydromethylandrostenediola 1 Dehydro 4 chloro 17a methyl 4 androstenediol ProhormoneChlorodehydromethyltestosterone 1 Dehydro 4 chloro 17a methyltestosterone Chloromethylandrostenediola 4 Chloro 17a methyl 4 androstenediol Enestebola 1 Dehydro 4 hydroxy 17a methyltestosterone Ethyltestosteronea 17a Ethyltestosterone Fluoxymesterone 9a Fluoro 11b hydroxy 17a methyltestosterone Formebolone 1 Dehydro 2 formyl 11a hydroxy 17a methyltestosterone Hydroxystenozolea 17a Methyl 2 H androsta 2 4 dieno 3 2 c pyrazol 17b ol Ring fusedMetandienone 1 Dehydro 17a methyltestosterone Methandriol 17a Methyl 5 androstenediol ProhormoneMethylclostebola 4 Chloro 17a methyltestosterone Methyltestosterone 17a Methyltestosterone Methyltestosterone hexyl ether 17a Methyltestosterone 3 hexyl enol ether EtherOxymesterone 4 Hydroxy 17a methyltestosterone Penmesterol 17a Methyltestosterone 3 cyclopentyl enol ether EtherTiomesterone 1a 7a Diacetylthio 17a methyltestosterone Other 17a substituted testosterone Danazol 2 3 Isoxazol 17a ethynyltestosterone Ring fusedDihydrotestosterone 1 Testosteronea 1 Dehydro 4 5a dihydrotestosterone Androstanolone 4 5a Dihydrotestosterone Bolazine C3 azine dimer of drostanolone DimerDrostanolone 2a Methyl 4 5a dihydrotestosterone Epitiostanol 2a 3a Epithio 3 deketo 4 5a dihydrotestosterone Ring fusedMepitiostane 2a 3a Epithio 3 deketo 4 5a dihydrotestosterone 17b 1 methoxycyclopentane ether Ring fused EtherMesabolonea 1 Dehydro 4 5a Dihydrotestosterone 17b 1 methoxycyclohexane ether EtherMesterolone 1a Methyl 4 5a dihydrotestosterone Metenolone 1 Dehydro 1 methyl 4 5a dihydrotestosterone Prostanozola 2 H 5a Androst 2 eno 3 2 c pyrazol 17b ol 17b tetrahydropyran ether EtherStenbolone 1 Dehydro 2 methyl 4 5a dihydrotestosterone 17a Alkylated dihydrotestosterone Androisoxazole 17a Methyl 5a androstano 3 2 c isoxazol 17b ol Ring fusedDesoxymethyltestosteronea 2 Dehydro 3 deketo 4 5a dihydro 17a methyltestosterone Furazabol 17a Methyl 5a androstano 2 3 c 1 2 5 oxadiazol 17b ol Ring fusedMebolazine C3 azine dimer of methasterone DimerMestanolone 4 5a Dihydro 17a methyltestosterone Methasteronea 2a 17a Dimethyl 4 5a dihydrotestosterone Methyl 1 testosteronea 1 Dehydro 4 5a dihydro 17a methyltestosterone Methyldiazinola 3 Deketo 3 azi 4 5a dihydro 17a methyltestosterone Methylepitiostanola 2a 3a Epithio 3 deketo 4 5a dihydro 17a methyltestosterone Methylstenbolonea 1 Dehydro 2 17a dimethyl 4 5a dihydrotestosterone Oxandrolone 2 Oxa 4 5a dihydro 17a methyltestosterone Oxymetholone 2 Hydroxymethylene 4 5a dihydro 17a methyltestosterone Stanozolol 17a Methyl 2 H 5a androst 2 eno 3 2 c pyrazol 17b ol Ring fused19 Nortestosterone 11b Methyl 19 nortestosteronea 11b Methyl 19 nortestosterone 19 Nor 5 androstenediola 19 Nor 5 androstenediol Prohormone19 Nordehydroepiandrosteronea 19 Nor 5 dehydroepiandrosterone ProhormoneBolandiola 19 Nor 4 androstenediol ProhormoneBolandionea 19 Nor 4 androstenedione ProhormoneBolmantalatea 19 Nortestosterone 17b adamantoate EsterDienedionea 9 Dehydro 19 nor 4 androstenedione ProhormoneDienolonea 9 Dehydro 19 nortestosterone Dimethandrolonea 7a 11b Dimethyl 19 nortestosterone Methoxydienonea 2 5 10 Didehydro 18 methyl 19 norepiandrosterone 3 methyl ether Prohormone EtherNandrolone 19 Nortestosterone Norclostebol 4 Chloro 19 nortestosterone Oxabolone 4 Hydroxy 19 nortestosterone Trestolonea 7a Methyl 19 nortestosterone Trenbolone 9 11 Didehydro 19 nortestosterone Trendionea 9 11 Didehydro 19 nor 4 androstenedione ProhormoneTrestionea 7a Methyl 19 nor 4 androstenedione Prohormone17a Alkylated 19 nortestosterone Dimethyltrienolonea 7a 17a Dimethyl 9 11 didehydro 19 nortestosterone Dimethyldienolonea 7a 17a Dimethyl 9 dehydro 19 nortestosterone Ethyldienolonea 9 Dehydro 17a ethyl 19 nortestosterone Ethylestrenol 17a Ethyl 3 deketo 19 nortestosterone Methyldienolonea 9 Dehydro 17a methyl 19 nortestosterone Methylhydroxynandrolonea 4 Hydroxy 17a methyl 19 nortestosterone Metribolonea 9 11 Didehydro 17a methyl 19 nortestosterone Mibolerone 7a 17a Dimethyl 19 nortestosterone Norboletonea 17a Ethyl 18 methyl 19 nortestosterone Norethandrolone 17a Ethyl 19 nortestosterone Normethandrone 17a Methyl 19 nortestosterone Propetandrol 17a Ethyl 19 nortestosterone 3 propionate EsterRU 2309a 9 11 Didehydro 17a 18 dimethyl 19 nortestosterone Tetrahydrogestrinonea 9 11 Didehydro 17a ethyl 18 methyl 19 nortestosterone Other 17a substituted 19 nortestosterone Gestrinone 9 11 Didehydro 17a ethynyl 18 methyl 19 nortestosterone Tibolone 5 10 Dehydro 7a methyl 17a ethynyl 19 nortestosterone Vinyltestosteronea 17a Ethenyltestosterone Notes Esters of androgens and anabolic steroids are mostly not included in this table see here instead Weakly androgenic progestins are mostly not included in this table see here instead Footnotes a Never marketed vte Structural properties of major testosterone esters Androgen Structure Ester Relativemol weight RelativeT contentb logPcPosition s Moiet ies Type LengthaTestosterone 1 00 1 00 3 0 3 4Testosterone propionate C17b Propanoic acid Straight chain fatty acid 3 1 19 0 84 3 7 4 9Testosterone isobutyrate C17b Isobutyric acid Aromatic fatty acid 3 1 24 0 80 4 9 5 3Testosterone isocaproate C17b Isohexanoic acid Branched chain fatty acid 5 1 34 0 75 4 4 6 3Testosterone caproate C17b Hexanoic acid Straight chain fatty acid 6 1 35 0 75 5 8 6 5Testosterone phenylpropionate C17b Phenylpropanoic acid Aromatic fatty acid 6 1 46 0 69 5 8 6 5Testosterone cypionate C17b Cyclopentylpropanoic acid Cyclic carboxylic acid 6 1 43 0 70 5 1 7 0Testosterone enanthate C17b Heptanoic acid Straight chain fatty acid 7 1 39 0 72 3 6 7 0Testosterone decanoate C17b Decanoic acid Straight chain fatty acid 10 1 53 0 65 6 3 8 6Testosterone undecanoate C17b Undecanoic acid Straight chain fatty acid 11 1 58 0 63 6 7 9 2Testosterone buciclated C17b Bucyclic acide Aromatic carboxylic acid 9 1 58 0 63 7 9 8 5Footnotes a Length of ester in carbon atoms for straight chain fatty acids or approximate length of ester in carbon atoms for aromatic fatty acids b Relative testosterone content by weight i e relative androgenic anabolic potency c Experimental or predicted octanol water partition coefficient i e lipophilicity hydrophobicity Retrieved from PubChem ChemSpider and DrugBank d Never marketed e Bucyclic acid trans 4 Butylcyclohexane 1 carboxylic acid Sources See individual articles vte Structural properties of major anabolic steroid esters Anabolic steroid Structure Ester Relativemol weight RelativeAAS contentb DurationcPosition Moiety Type LengthaBoldenone undecylenate C17b Undecylenic acid Straight chain fatty acid 11 1 58 0 63 LongDrostanolone propionate C17b Propanoic acid Straight chain fatty acid 3 1 18 0 84 ShortMetenolone acetate C17b Ethanoic acid Straight chain fatty acid 2 1 14 0 88 ShortMetenolone enanthate C17b Heptanoic acid Straight chain fatty acid 7 1 37 0 73 LongNandrolone decanoate C17b Decanoic acid Straight chain fatty acid 10 1 56 0 64 LongNandrolone phenylpropionate C17b Phenylpropanoic acid Aromatic fatty acid 6 7 1 48 0 67 LongTrenbolone acetate C17b Ethanoic acid Straight chain fatty acid 2 1 16 0 87 ShortTrenbolone enanthated C17b Heptanoic acid Straight chain fatty acid 7 1 41 0 71 LongFootnotes a Length of ester in carbon atoms for straight chain fatty acids or approximate length of ester in carbon atoms for aromatic fatty acids b Relative androgen anabolic steroid content by weight i e relative androgenic anabolic potency c Duration by intramuscular or subcutaneous injection in oil solution d Never marketed Sources See individual articles Detection in body fluids Edit The most commonly employed human physiological specimen for detecting AAS usage is urine although both blood and hair have been investigated for this purpose The AAS whether of endogenous or exogenous origin are subject to extensive hepatic biotransformation by a variety of enzymatic pathways The primary urinary metabolites may be detectable for up to 30 days after the last use depending on the specific agent dose and route of administration A number of the drugs have common metabolic pathways and their excretion profiles may overlap those of the endogenous steroids making interpretation of testing results a very significant challenge to the analytical chemist Methods for detection of the substances or their excretion products in urine specimens usually involve gas chromatography mass spectrometry or liquid chromatography mass spectrometry 191 192 193 194 History EditIntroduction of various anabolic steroids Generic name Class a Brand name Route b Intr Androstanolone c d DHT Andractim PO e IM TD 1953Boldenone undecylenate f Ester Equipoise g IM 1960sDanazol Alkyl Danocrine PO 1971Drostanolone propionate e DHT Ester Masteron IM 1961Ethylestrenol d 19 NT Alkyl Maxibolin g PO 1961Fluoxymesterone d Alkyl Halotestin g PO 1957Mestanolone e DHT Alkyl Androstalone g PO 1950sMesterolone DHT Proviron PO 1967Metandienone d Alkyl Dianabol PO IM 1958Metenolone acetate d DHT Ester Primobolan PO 1961Metenolone enanthate d DHT Ester Primobolan Depot IM 1962Methyltestosterone d Alkyl Metandren PO 1936Nandrolone decanoate 19 NT Ester Deca Durabolin IM 1962Nandrolone phenylpropionate d 19 NT Ester Durabolin IM 1959Norethandrolone d 19 NT Alkyl Nilevar g PO 1956Oxandrolone d DHT Alkyl Oxandrin g PO 1964Oxymetholone d DHT Alkyl Anadrol g PO 1961Prasterone h Prohormone Intrarosa g PO IM vaginal 1970sStanozolol e DHT Alkyl Winstrol g PO IM 1962Testosterone cypionate Ester Depo Testosterone IM 1951Testosterone enanthate Ester Delatestryl IM 1954Testosterone propionate Ester Testoviron IM 1937Testosterone undecanoate Ester Andriol g PO IM 1970sTrenbolone acetate f 19 NT Ester Finajet g IM 1970s DHT dihydrotestosterone 19 NT 19 nortestosterone IM Intramuscular injection PO Oral by mouth TD Transdermal Also known as dihydrotestosterone a b c d e f g h i j k Availability limited a b c d No longer marketed a b Available for veterinary use only a b c d e f g h i j k Also marketed under other brand names Also known as dehydroepiandrosteroneDiscovery of androgens Edit The use of gonadal steroids pre dates their identification and isolation Extraction of hormones from urines began in China c 100 BCE citation needed Medical use of testicle extract began in the late 19th century while its effects on strength were still being studied 144 The isolation of gonadal steroids can be traced back to 1931 when Adolf Butenandt a chemist in Marburg purified 15 milligrams of the male hormone androstenone from tens of thousands of litres of urine This steroid was subsequently synthesized in 1934 by Leopold Ruzicka a chemist in Zurich 195 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 195 196 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 197 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 198 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 199 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 195 196 Clinical trials on humans involving either PO doses of methyltestosterone or injections of testosterone propionate began as early as 1937 195 There are often reported rumors that German soldiers were administered AAS during the Second World War the aim being to increase their aggression and stamina but these are as yet unproven 118 6 Adolf Hitler himself according to his physician was injected with testosterone derivatives to treat various ailments 200 AAS were used in experiments conducted by the Nazis on concentration camp inmates 200 and later by the allies attempting to treat the malnourished victims that survived Nazi camps 118 6 President John F Kennedy was administered steroids both before and during his presidency 201 Development of synthetic AAS Edit The development of muscle building properties of testosterone was pursued in the 1940s in the Soviet Union and in Eastern Bloc countries such as East Germany where steroid programs were used to enhance the performance of Olympic and other amateur weight lifters In response to the success of Russian weightlifters the U S Olympic Team physician John Ziegler worked with synthetic chemists to develop an AAS with reduced androgenic effects 202 Ziegler s work resulted in the production of methandrostenolone which Ciba Pharmaceuticals marketed as Dianabol The new steroid was approved for use in the U S by the Food and Drug Administration FDA in 1958 It was most commonly administered to burn victims and the elderly The drug s off label users were mostly bodybuilders and weight lifters Although Ziegler prescribed only small doses to athletes he soon discovered that those having abused Dianabol developed enlarged prostates and atrophied testes 203 AAS were placed on the list of banned substances of the International Olympic Committee IOC in 1976 and a decade later the committee introduced out of competition doping tests because many athletes used AAS in their training period rather than during competition 8 Three major ideas governed modifications of testosterone into a multitude of AAS Alkylation at C17a position with methyl or ethyl group created POly active compounds because it slows the degradation of the drug by the liver esterification of testosterone and nortestosterone at the C17b 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 PO and parenteral agents to seeking to obtain different anabolic to androgenic effect ratios 8 Society and culture EditEtymology Edit Androgens were discovered in the 1930s and were characterized as having effects described as androgenic i e virilizing and anabolic e g myotrophic renotrophic 66 1 The term anabolic steroid can be dated as far back as at least the mid 1940s when it was used to describe the at the time hypothetical concept of a testosterone derived steroid with anabolic effects but with minimal or no androgenic effects 204 This concept was formulated based on the observation that steroids had ratios of renotrophic to androgenic potency that differed significantly which suggested that anabolic and androgenic effects might be dissociable 204 In 1953 a testosterone derived steroid known as norethandrolone 17a ethyl 19 nortestosterone was synthesized at G D Searle amp Company and was studied as a progestin but was not marketed 205 Subsequently in 1955 it was re examined for testosterone like activity in animals and was found to have similar anabolic activity to testosterone but only one sixteenth of its androgenic potency 205 206 It was the first steroid with a marked and favorable separation of anabolic and androgenic effect to be discovered and has accordingly been described as the first anabolic steroid 207 208 Norethandrolone was introduced for medical use in 1956 and was quickly followed by numerous similar steroids for instance nandrolone phenylpropionate in 1959 and stanozolol in 1962 207 208 209 210 With these developments anabolic steroid became the preferred term to refer to such steroids over androgen and entered widespread use Although anabolic steroid was originally intended to specifically describe testosterone derived steroids with a marked dissociation of anabolic and androgenic effect it is applied today indiscriminately to all steroids with AR agonism based anabolic effects regardless of their androgenic potency including even non synthetic steroids like testosterone 66 1 205 While many anabolic steroids have diminished androgenic potency in comparison to anabolic potency there is no anabolic steroid that is exclusively anabolic and hence all anabolic steroids retain at least some degree of androgenicity 66 1 205 Likewise all androgens are inherently anabolic 66 1 205 Indeed it is probably not possible to fully dissociate anabolic effects from androgenic effects as both types of effects are mediated by the same signaling receptor the AR 1 As such the distinction between the terms anabolic steroid and androgen is questionable and this is the basis for the revised and more recent term anabolic androgenic steroid AAS 66 1 205 Legal status Edit Various compounds with anabolic and androgenic effects their relation with AAS The legal status of AAS 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 AAS are currently listed as Schedule III controlled substances under the Controlled Substances Act which makes simple possession of such substances without a prescription a federal crime punishable by up to one year in prison for the first offense Unlawful distribution or possession with intent to distribute AAS as a first offense is punished by up to ten years in prison 211 In Canada AAS and their derivatives are part of the Controlled Drugs and Substances Act and are Schedule IV substances meaning that it is illegal to obtain or sell them without a prescription however possession is not punishable a consequence reserved for schedule I II or III substances Those guilty of buying or selling AAS in Canada can be imprisoned for up to 18 months 212 Import and export also carry similar penalties In Canada researchers have concluded that steroid use among student athletes is extremely widespread A study conducted in 1993 by the Canadian Centre for Drug Free Sport found that nearly 83 000 Canadians between the ages of 11 and 18 use steroids 213 AAS are also illegal without prescription in Australia 214 Argentina citation needed Brazil citation needed and Portugal citation needed and are listed as Class C Controlled Drugs in the United Kingdom AAS are readily available without a prescription in some countries such as Mexico and Thailand United States Edit 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 AAS goes back to the late 1980s when the U S Congress considered placing AAS under the Controlled Substances Act following the controversy over Ben Johnson s victory at the 1988 Summer Olympics in Seoul AAS were added to Schedule III of the Controlled Substances Act in the Anabolic Steroids Control Act of 1990 215 The same act also introduced more stringent controls with higher criminal penalties for offenses involving the illegal distribution of AAS and human growth hormone By the early 1990s after AAS 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 AAS 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 216 Even though they can still be prescribed by a medical doctor in the U S the use of anabolic steroids for injury recovery purposes has been a taboo subject even amongst the majority of sports medicine doctors and endocrinologists United Kingdom Edit In the United Kingdom AAS are classified as class C drugs for their illegal abuse potential which puts them in the same class as benzodiazepines AAS are in Schedule 4 which is divided in 2 parts Part 1 contains most of the benzodiazepines and Part 2 contains the AAS Part 1 drugs are subject to full import and export controls with possession being an offence without an appropriate prescription There is no restriction on the possession when it is part of a medicinal product Part 2 drugs require a Home Office licence for importation and export unless the substance is in the form of a medicinal product and is for self administration by a person 217 Status in sports Edit See also Doping in sport Legal status of AAS and other drugs with anabolic effects in Western countries AAS are banned by all major sports bodies including Association of Tennis Professionals Major League Baseball Federation Internationale de Football Association 218 the Olympics 219 the National Basketball Association 220 the National Hockey League 221 World Wrestling Entertainment and the National Football League 222 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 AAS and precursors as well as all hormones and related substances 223 224 Usage Edit See also Anabolic androgenic steroids abuse Law enforcement Edit United States federal law enforcement officials have expressed concern about AAS use by police officers It s a big problem and from the number of cases it s something we shouldn t ignore It s not that we set out to target cops but when we re in the middle of an active investigation into steroids there have been quite a few cases that have led back to police officers says Lawrence Payne a spokesman for the United States Drug Enforcement Administration 225 The FBI Law Enforcement Bulletin stated that Anabolic steroid abuse by police officers is a serious problem that merits greater awareness by departments across the country 226 It is also believed that police officers across the United Kingdom are using criminals to buy steroids which he claims to be a top risk factor for police corruption Professional wrestling Edit Main article WWE Wellness Program Following the murder suicide of Chris Benoit in 2007 the Oversight and Government Reform Committee investigated steroid usage in the wrestling industry 227 The Committee investigated WWE and Total Nonstop Action Wrestling now known as Impact Wrestling asking for documentation of their companies drug policies WWE CEO and chairman Linda and Vince McMahon respectively both testified The documents stated that 75 wrestlers roughly 40 percent had tested positive for drug use since 2006 most commonly for steroids 228 229 Economics Edit Main article Illegal trade in anabolic steroids Several large buckets containing tens of thousands of AAS vials confiscated by the DEA during Operation Raw Deal in 2007 AAS 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 230 In these countries the majority of steroids are obtained illegally through black market trade 231 232 These steroids are usually manufactured in other countries and therefore must be smuggled across international borders As with most significant smuggling operations organized crime is involved 233 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 234 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 AAS are sometimes sold at gyms and competitions and through the mail but may also be obtained through pharmacists veterinarians and physicians 235 In addition a significant number of counterfeit products are sold as AAS in particular via mail order from websites posing as overseas pharmacies In the U S black market importation continues from Mexico Thailand and other countries where steroids are more easily available as they are legal 236 Research EditAAS alone and in combination with progestogens have been studied as potential male hormonal contraceptives 48 Dual AAS and progestins such as trestolone and dimethandrolone undecanoate have also been studied as male contraceptives with the latter under active investigation as of 2018 237 179 238 Topical androgens have been used and studied in the treatment of cellulite in women 239 Topical androstanolone on the abdomen has been found to significantly decrease subcutaneous abdominal fat in women and hence may be useful for improving body silhouette 239 However men and hyperandrogenic women have higher amounts of abdominal fat than healthy women and androgens have been found to increase abdominal fat in postmenopausal women and transgender men as well 240 See also EditSelective androgen receptor modulator Antiandrogen Mossman Pacey paradox Steroid rosacea Steroid use in Bollywood Bigger Stronger Faster Juiced Wild Times Rampant Roids Smash Hits amp How Baseball Got Big List of androgens anabolic steroids available in the United StatesReferences Edit a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac ad ae af ag ah ai aj ak al am an ao ap aq ar as at au av aw ax ay az ba bb bc bd be bf bg bh bi bj bk bl bm bn bo Kicman A T 2008 Pharmacology of anabolic steroids British Journal of Pharmacology 154 3 502 521 doi 10 1038 bjp 2008 165 PMC 2439524 PMID 18500378 Powers M 2011 Houglum J Harrelson GL eds Performance Enhancing Drugs Principles of Pharmacology for Athletic Trainers 2nd ed SLACK Incorporated p 345 ISBN 978 1 55642 901 9 Archived from the original on 2016 12 22 Retrieved 2016 10 17 a b Barrett Connor EL 1995 Testosterone and risk factors for cardiovascular disease in men Diabete Metab 21 3 156 61 PMID 7556805 a b Yamamoto Y Moore R Hess HA Guo GL Gonzalez FJ Korach KS Maronpot RR Negishi M 2006 Estrogen receptor alpha mediates 17alpha ethynylestradiol causing hepatotoxicity J Biol Chem 281 24 16625 31 doi 10 1074 jbc M602723200 PMID 16606610 S2CID 83319949 a b De Piccoli B Giada F Benettin A Sartori F Piccolo E 1991 Anabolic steroid use in body builders an echocardiographic study of left ventricle morphology and function Int J Sports Med 12 4 408 12 doi 10 1055 s 2007 1024703 PMID 1917226 a b c Green GA September 2009 Performance enhancing drug use Orthopedics 32 9 647 649 doi 10 3928 01477447 20090728 39 PMID 19751025 a b c Turillazzi E Perilli G Di Paolo M Neri M Riezzo I Fineschi V 2011 Side effects of AAS abuse an overview Mini Rev Med Chem 11 5 374 89 doi 10 2174 138955711795445925 hdl 11392 2357154 PMID 21443513 a b c d e f g h i j k Hartgens F Kuipers H 2004 Effects of androgenic anabolic steroids in athletes Sports Med 34 8 513 54 doi 10 2165 00007256 200434080 00003 PMID 15248788 S2CID 15234016 a b Kicman AT Gower DB July 2003 Anabolic steroids in sport biochemical clinical and analytical perspectives Ann Clin Biochem 40 Pt 4 321 56 doi 10 1258 000456303766476977 PMID 12880534 S2CID 24339701 Basaria S Wahlstrom JT Dobs AS November 2001 Clinical review 138 Anabolic androgenic steroid therapy in the treatment of chronic diseases J Clin Endocrinol Metab 86 11 5108 17 doi 10 1210 jcem 86 11 7983 PMID 11701661 Ranke MB Bierich JR 1986 Treatment of growth hormone deficiency Clinics in Endocrinology and Metabolism 15 3 495 510 doi 10 1016 S0300 595X 86 80008 1 PMID 2429792 Grunfeld C Kotler DP Dobs A Glesby M Bhasin S 2006 Oxandrolone in the treatment of HIV associated weight loss in men a randomized double blind placebo controlled study J Acquir Immune Defic Syndr 41 3 304 14 doi 10 1097 01 qai 0000197546 56131 40 PMID 16540931 S2CID 25911263 Berger JR Pall L Hall CD Simpson DM Berry PS Dudley R 1996 Oxandrolone in AIDS wasting myopathy AIDS 10 14 1657 62 doi 10 1097 00002030 199612000 00010 PMID 8970686 S2CID 9832782 Kenny AM Prestwood KM Gruman CA Marcello KM Raisz LG 2001 Effects of transdermal testosterone on bone and muscle in older men with low bioavailable testosterone levels J Gerontol A Biol Sci Med Sci 56 5 M266 72 doi 10 1093 gerona 56 5 M266 PMID 11320105 Baum NH Crespi CA 2007 Testosterone replacement in elderly men Geriatrics 62 9 14 8 PMID 17824721 Francis RM 2001 Androgen replacement in aging men Calcif Tissue Int 69 4 235 8 doi 10 1007 s00223 001 1051 9 PMID 11730258 S2CID 24170276 Nair KS Rizza RA O Brien P Dhatariya K Short KR Nehra A Vittone JL Klee GG Basu A Basu R Cobelli C Toffolo G Dalla Man C Tindall DJ Melton LJ Smith GE Khosla S Jensen MD October 2006 DHEA in elderly women and DHEA or testosterone in elderly men N Engl J Med 355 16 1647 59 doi 10 1056 NEJMoa054629 PMID 17050889 S2CID 42844580 a b c d Mangus BC Miller MG 11 January 2005 Pharmacology Application in Athletic Training F A Davis pp 151 ISBN 978 0 8036 2027 8 Archived from the original on 14 April 2021 Retrieved 25 June 2017 Royal College of Physicians of London 1999 Osteoporosis Clinical Guidelines for Prevention and Treatment Royal College of Physicians pp 51 ISBN 978 1 86016 079 0 Archived from the original on 2021 04 14 Retrieved 2017 06 25 Davis SR 1999 The therapeutic use of androgens in women J Steroid Biochem Mol Biol 69 1 6 177 84 doi 10 1016 s0960 0760 99 00054 0 PMID 10418991 S2CID 23520067 William N Taylor M D 16 January 2002 Anabolic Steroids and the Athlete 2d ed McFarland pp 193 ISBN 978 0 7864 1128 3 Archived from the original on 14 April 2021 Retrieved 25 June 2017 a b Oxandrolone Tablets USP Rx only PDF Drugs FDA U S Food and Drug Administration 1 December 2006 Archived PDF from the original on 26 August 2016 Retrieved 21 June 2016 a b Oxandrin oxandrolone tablets USP PDF Drugs FDA BTG Pharmaceuticals U S Food and Drug Administration 21 April 2003 Archived PDF from the original on 1 March 2017 Retrieved 21 June 2016 Li H Guo Y Yang Z Roy M Guo Q June 2016 The efficacy and safety of oxandrolone treatment for patients with severe burns A systematic review and meta analysis Burns 42 4 717 27 doi 10 1016 j burns 2015 08 023 PMID 26454425 S2CID 24139354 Rojas Y Finnerty CC Radhakrishnan RS Herndon DN December 2012 Burns an update on current pharmacotherapy Expert Opinion on Pharmacotherapy 13 17 2485 94 doi 10 1517 14656566 2012 738195 PMC 3576016 PMID 23121414 Bork K August 2012 Current management options for hereditary angioedema Current Allergy and Asthma Reports 12 4 273 80 doi 10 1007 s11882 012 0273 4 PMID 22729959 S2CID 207323793 Choi G Runyon BA May 2012 Alcoholic hepatitis a clinician s guide Clinics in Liver Disease 16 2 371 85 doi 10 1016 j cld 2012 03 015 PMID 22541704 Manuchair Ebadi 31 October 2007 Desk Reference of Clinical Pharmacology Second Edition CRC Press pp 434 ISBN 978 1 4200 4744 8 Archived from the original on 14 April 2021 Retrieved 27 July 2018 Yagiela JA Dowd FJ Johnson B Mariotti A Neidle EA 19 March 2010 Pharmacology and Therapeutics for Dentistry E Book Elsevier Health Sciences pp 569 ISBN 978 0 323 07824 5 Archived from the original on 14 April 2021 Retrieved 27 July 2018 Android C III Label PDF Archived PDF from the original on 2017 02 10 Retrieved 2018 07 27 Shah K Montoya C Persons RK April 2007 Clinical inquiries Do testosterone injections increase libido for elderly hypogonadal patients J Fam Pract 56 4 301 3 PMID 17403329 Yassin AA Saad F March 2007 Improvement of sexual function in men with late onset hypogonadism treated with testosterone only J Sex Med 4 2 497 501 doi 10 1111 j 1743 6109 2007 00442 x PMID 17367445 Arver S Dobs AS Meikle AW Caramelli KE Rajaram L Sanders SW Mazer NA December 1997 Long term efficacy and safety of a permeation enhanced testosterone transdermal system in hypogonadal men Clin Endocrinol 47 6 727 37 doi 10 1046 j 1365 2265 1997 3071113 x PMID 9497881 S2CID 31976796 Nieschlag E Buchter D Von Eckardstein S Abshagen K Simoni M Behre HM December 1999 Repeated intramuscular injections of testosterone undecanoate for substitution therapy in hypogonadal men Clin Endocrinol 51 6 757 63 doi 10 1046 j 1365 2265 1999 00881 x PMID 10619981 S2CID 19174381 Arslanian S Suprasongsin C 1997 Testosterone treatment in adolescents with delayed puberty changes in body composition protein fat and glucose metabolism J Clin Endocrinol Metab 82 10 3213 20 doi 10 1210 jcem 82 10 4293 PMID 9329341 S2CID 5031396 Moore E Wisniewski A Dobs A August 2003 Endocrine treatment of transsexual people a review of treatment regimens outcomes and adverse effects J Clin Endocrinol Metab 88 8 3467 73 doi 10 1210 jc 2002 021967 PMID 12915619 Genderqueer Pansexual LGBTQ Will Gender Exist 100 Years From Now Rebooted Archived 2014 12 09 at the Wayback Machine October 24 2013 Retrieved November 17 2014 Young people exploring nonbinary gender roles SF Gate Archived 2014 12 08 at the Wayback Machine February 12 2014 Retrieved November 17 2014 Warne GL Grover S Zajac JD 2005 Hormonal therapies for individuals with intersex conditions protocol for use Treatments in Endocrinology 4 1 19 29 doi 10 2165 00024677 200504010 00003 PMID 15649098 S2CID 71737774 What is Intersex An Intersex FAQ by Inter Act Inter Act Youth Archived 2014 12 07 at the Wayback Machine September 12 2014 Retrieved December 5 2014 Perry MC Doll DC Freter CE 30 July 2012 Perry s The Chemotherapy Source Book Lippincott Williams amp Wilkins pp 409 ISBN 978 1 4698 0343 2 Archived from the original on 14 April 2021 Retrieved 25 June 2017 Allegra JC Bertino J Bonomi P Byrne P Carpenter J Catalano R Creech R Dana B Durivage H Einhorn L December 1985 Metastatic breast cancer preliminary results with oral hormonal therapy Semin Oncol 12 4 Suppl 6 61 4 PMID 3909420 Bachmann GA 1999 Androgen cotherapy in menopause evolving benefits and challenges Am J Obstet Gynecol 180 3 Pt 2 S308 11 doi 10 1016 S0002 9378 99 70724 6 PMID 10076169 Kotz K Alexander JL Dennerstein L 2006 Estrogen and androgen hormone therapy and well being in surgically postmenopausal women J Womens Health Larchmt 15 8 898 908 doi 10 1089 jwh 2006 15 898 PMID 17087613 Garefalakis M Hickey M 2008 Role of androgens progestins and tibolone in the treatment of menopausal symptoms a review of the clinical evidence Clin Interv Aging 3 1 1 8 doi 10 2147 CIA S1043 PMC 2544356 PMID 18488873 a b Somboonporn W 2006 Androgen and menopause Curr Opin Obstet Gynecol 18 4 427 32 doi 10 1097 01 gco 0000233938 36554 37 PMID 16794424 S2CID 8030248 Davis S 2001 Testosterone deficiency in women J Reprod Med 46 3 Suppl 291 6 PMID 11304877 a b c Nieschlag E 2010 Clinical trials in male hormonal contraception PDF Contraception 82 5 457 70 doi 10 1016 j contraception 2010 03 020 PMID 20933120 Archived PDF from the original on 2020 12 05 Retrieved 2019 08 18 Most steroid users are not athletes study Reuters Reuters 2007 11 21 Archived from the original on 2016 01 25 Retrieved 2014 01 03 Sjoqvist F Garle M Rane A May 2008 Use of doping agents in particular anabolic steroids in sports and society Lancet 371 9627 1872 82 doi 10 1016 S0140 6736 08 60801 6 PMID 18514731 S2CID 10762429 Yesalis CE Kennedy NJ Kopstein AN Bahrke MS 1993 Anabolic androgenic steroid use in the United States JAMA 270 10 1217 21 doi 10 1001 jama 270 10 1217 PMID 8355384 McCabe SE Brower KJ West BT Nelson TF Wechsler H 2007 Trends in non medical use of anabolic steroids by U S college students Results from four national surveys Drug and Alcohol Dependence 90 2 3 243 51 doi 10 1016 j drugalcdep 2007 04 004 PMC 2383927 PMID 17512138 Parkinson AB Evans NA April 2006 Anabolic androgenic steroids a survey of 500 users Med Sci Sports Exerc 38 4 644 51 doi 10 1249 01 mss 0000210194 56834 5d PMID 16679978 a b c d e Cohen J Collins R Darkes J Gwartney D 2007 A league of their own demographics motivations and patterns of use of 1 955 male adult non medical anabolic steroid users in the United States J Int Soc Sports Nutr 4 12 doi 10 1186 1550 2783 4 12 PMC 2131752 PMID 17931410 Copeland J Peters R Dillon P March 1998 A study of 100 anabolic androgenic steroid users Med J Aust 168 6 311 2 doi 10 5694 j 1326 5377 1998 tb140177 x PMID 9549549 S2CID 8699231 Eastley T January 18 2006 Steroid study debunks user stereotypes ABC Archived from the original on 2014 07 16 Retrieved 2014 01 03 Pope HG Kanayama G Ionescu Pioggia M Hudson JI September 2004 Anabolic steroid users attitudes towards physicians Addiction 99 9 1189 94 doi 10 1111 j 1360 0443 2004 00781 x PMID 15317640 Kanayama G Barry S Hudson JI Pope HG April 2006 Body image and attitudes toward male roles in anabolic androgenic steroid users Am J Psychiatry 163 4 697 703 doi 10 1176 appi ajp 163 4 697 PMID 16585446 S2CID 38738640 Grogan S Shepherd S Evans R Wright S Hunter G Nov 2006 Experiences of Anabolic Steroid Use Journal of Health Psychology 11 6 845 856 doi 10 1177 1359105306069080 PMID 17035257 S2CID 5794238 Hickson RC Czerwinski SM Falduto MT Young AP 1990 Glucocorticoid antagonism by exercise and androgenic anabolic steroids Medicine amp Science in Sports amp Exercise 22 3 331 40 doi 10 1249 00005768 199006000 00010 PMID 2199753 Drugs FDA FDA Approved Drug Products United States Food and Drug Administration Archived from the original on 16 November 2016 Retrieved 1 December 2019 Richard Joseph Hamilton Nancy Anastasi Duffy Daniel Stone 2014 Tarascon Pharmacopoeia Jones amp Bartlett Publishers pp 174 ISBN 978 1 284 05671 6 Archived from the original on 2021 02 13 Retrieved 2020 09 13 Susan M Ford Sally S Roach 2010 Roach s Introductory Clinical Pharmacology Lippincott Williams amp Wilkins pp 499 ISBN 978 1 60547 633 9 Archived from the original on 2021 04 14 Retrieved 2020 09 13 Thomas L Lemke David A Williams 24 January 2012 Foye s Principles of Medicinal Chemistry Lippincott Williams amp Wilkins pp 1358 ISBN 978 1 60913 345 0 Archived from the original on 14 April 2021 Retrieved 13 September 2020 John A Thomas 6 December 2012 Drugs Athletes and Physical Performance Springer Science amp Business Media pp 20 ISBN 978 1 4684 5499 4 Archived from the original on 14 April 2021 Retrieved 13 September 2020 a b c d e f g h i j k l m n o p q r s t William Llewellyn 2011 Anabolics Molecular Nutrition Llc ISBN 978 0 9828280 1 4 Archived from the original on 2021 04 14 Retrieved 2016 12 02 Burkett Lee N Falduto Michael T 1984 Steroid Use by Athletes in a Metropolitan Area The Physician and Sportsmedicine 12 8 69 74 doi 10 1080 00913847 1984 11701923 ISSN 0091 3847 J Bain Wolf Bernhard Schill L Schwarzstein 6 December 2012 Treatment of Male Infertility Springer Science amp Business Media pp 176 177 ISBN 978 3 642 68223 0 Archived from the original on 13 February 2021 Retrieved 13 September 2020 Snyder P J 1984 Clinical Use of Androgens Annual Review of Medicine 35 1 207 217 doi 10 1146 annurev me 35 020184 001231 ISSN 0066 4219 PMID 6372655 a b c Becker KL 2001 Principles and Practice of Endocrinology and Metabolism Lippincott Williams amp Wilkins pp 1185 1186 ISBN 978 0 7817 1750 2 Archived from the original on 2020 05 17 Retrieved 2016 10 17 a b Rahnema CD Crosnoe LE Kim ED March 2015 Designer steroids over the counter supplements and their androgenic component review of an increasing problem Andrology 3 2 150 5 doi 10 1111 andr 307 PMID 25684733 S2CID 6999218 a b Chrousos GP 2012 The Gonadal Hormones amp Inhibitors In Katzung BG ed Basic amp Clinical Pharmacology New York London McGraw Hill Medical McGraw Hill distributor ISBN 978 0071764018 Mutzebaugh C 1998 Does the choice of alpha AAS really make a difference HIV Hotline 8 5 6 10 1 PMID 11366379 Casavant MJ Blake K Griffith J Yates A Copley LM 2007 Consequences of use of anabolic androgenic steroids Pediatr Clin North Am 54 4 677 90 x doi 10 1016 j pcl 2007 04 001 PMID 17723870 Pope HG Wood RI Rogol A Nyberg F Bowers L Bhasin S 2014 Adverse health consequences of performance enhancing drugs an Endocrine Society scientific statement Endocr Rev 35 3 341 75 doi 10 1210 er 2013 1058 PMC 4026349 PMID 24423981 Fragkaki AG Angelis YS Koupparis M Tsantili Kakoulidou A Kokotos G Georgakopoulos C 2009 Structural characteristics of anabolic androgenic steroids contributing to binding to the androgen receptor and to their anabolic and androgenic activities Applied modifications in the steroidal structure Steroids 74 2 172 97 doi 10 1016 j steroids 2008 10 016 PMID 19028512 S2CID 41356223 Nieschlag E Vorona E 2015 MECHANISMS IN ENDOCRINOLOGY Medical consequences of doping with anabolic androgenic steroids effects on reproductive functions Eur J Endocrinol 173 2 R47 58 doi 10 1530 EJE 15 0080 PMID 25805894 Hall RC Hall RC Chapman MJ 2005 Psychiatric complications of anabolic steroid abuse Psychosomatics 46 4 285 90 doi 10 1176 appi psy 46 4 285 PMID 16000671 a b Trenton AJ Currier GW 2005 Behavioural manifestations of anabolic steroid use CNS Drugs 19 7 571 95 doi 10 2165 00023210 200519070 00002 PMID 15984895 S2CID 32243658 Vanberg P Atar D 2010 Androgenic anabolic steroid abuse and the cardiovascular system Handbook of Experimental Pharmacology 195 195 411 57 doi 10 1007 978 3 540 79088 4 18 ISBN 978 3 540 79087 7 PMID 20020375 Achar S Rostamian A Narayan SM 2010 Cardiac and metabolic effects of anabolic androgenic steroid abuse on lipids blood pressure left ventricular dimensions and rhythm Am J Cardiol 106 6 893 901 doi 10 1016 j amjcard 2010 05 013 PMC 4111565 PMID 20816133 Solimini R Rotolo MC Mastrobattista L Mortali C Minutillo A Pichini S Pacifici R Palmi I 2017 Hepatotoxicity associated with illicit use of anabolic androgenic steroids in doping Eur Rev Med Pharmacol Sci 21 1 Suppl 7 16 PMID 28379599 Brenu EW McNaughton L Marshall Gradisnik SM 2011 Is there a potential immune dysfunction with anabolic androgenic steroid use A review Mini Rev Med Chem 11 5 438 45 doi 10 2174 138955711795445907 PMID 21443507 Grace F Sculthorpe N Baker J Davies B 2003 Blood pressure and rate pressure product response in males using high dose anabolic androgenic steroids AAS J Sci Med Sport 6 3 307 12 doi 10 1016 S1440 2440 03 80024 5 PMID 14609147 DailyMed About DailyMed Dailymed nlm nih gov Archived from the original on 2009 05 12 Retrieved 2008 11 03 Bagatell CJ Knopp RH Vale WW Rivier JE Bremner WJ 1992 Physiologic testosterone levels in normal men suppress high density lipoprotein cholesterol levels Annals of Internal Medicine 116 12 Pt 1 967 73 doi 10 7326 0003 4819 116 12 967 PMID 1586105 Mewis C Spyridopoulos I Kuhlkamp V Seipel L 1996 Manifestation of severe coronary heart disease after anabolic drug abuse Clinical Cardiology 19 2 153 5 doi 10 1002 clc 4960190216 PMID 8821428 S2CID 37024092 Melnik B Jansen T Grabbe S 2007 Abuse of anabolic androgenic steroids and bodybuilding acne an underestimated health problem Journal der Deutschen Dermatologischen Gesellschaft 5 2 110 7 doi 10 1111 j 1610 0387 2007 06176 x PMID 17274777 S2CID 13382470 Vierhapper H Maier H Nowotny P Waldhausl W July 2003 Production rates of testosterone and of dihydrotestosterone in female pattern hair loss Metab Clin Exp 52 7 927 9 doi 10 1016 S0026 0495 03 00060 X PMID 12870172 Irving LM Wall M Neumark Sztainer D Story M 2002 Steroid use among adolescents findings from Project EAT The Journal of Adolescent Health 30 4 243 52 doi 10 1016 S1054 139X 01 00414 1 PMID 11927236 Known and Probable Human Carcinogens American Cancer Society 2011 06 29 Archived from the original on 2014 11 17 Retrieved 2014 11 17 Sullivan ML Martinez CM Gallagher EJ 1999 Atrial fibrillation and anabolic steroids The Journal of Emergency Medicine 17 5 851 7 doi 10 1016 S0736 4679 99 00095 5 PMID 10499702 Dickerman RD Schaller F McConathy WJ 1998 Left ventricular wall thickening does occur in elite power athletes with or without anabolic steroid Use Cardiology 90 2 145 8 doi 10 1159 000006834 PMID 9778553 S2CID 22123696 George KP Wolfe LA Burggraf GW 1991 The athletic heart syndrome A critical review Sports Medicine 11 5 300 30 doi 10 2165 00007256 199111050 00003 PMID 1829849 S2CID 45280834 Dickerman RD Schaller F Zachariah NY McConathy WJ 1997 Left ventricular size and function in elite bodybuilders using anabolic steroids Clin J Sport Med 7 2 90 3 doi 10 1097 00042752 199704000 00003 PMID 9113423 S2CID 42891343 Salke RC Rowland TW Burke EJ 1985 Left ventricular size and function in body builders using anabolic steroids Medicine amp Science in Sports amp Exercise 17 6 701 4 doi 10 1249 00005768 198512000 00014 PMID 4079743 Tokar S February 2006 Liver Damage And Increased Heart Attack Risk Caused By Anabolic Steroid Use University of California San Francisco Archived from the original on 2011 06 14 Retrieved 2007 04 24 Wit JM Oostdijk W 2015 Novel approaches to short stature therapy Best Practice amp Research Clinical Endocrinology amp Metabolism 29 3 353 66 doi 10 1016 j beem 2015 01 003 PMID 26051296 Marcus R Korenman SG 1976 Estrogens and the human male Annu Rev Med 27 357 70 doi 10 1146 annurev me 27 020176 002041 PMID 779604 Matsumoto AM 1990 Effects of chronic testosterone administration in normal men safety and efficacy of high dosage testosterone and parallel dose dependent suppression of luteinizing hormone follicle stimulating hormone and sperm production J Clin Endocrinol Metab 70 1 282 7 doi 10 1210 jcem 70 1 282 PMID 2104626 Hoffman JR Ratamess NA June 1 2006 Medical Issues Associated with Anabolic Steroid Use Are they Exaggerated PDF Journal of Sports Science and Medicine Archived PDF from the original on 20 June 2007 Retrieved 2007 05 08 Meriggiola MC Costantino A Bremner WJ Morselli Labate AM 2002 Higher testosterone dose impairs sperm suppression induced by a combined androgen progestin regimen J Androl 23 5 684 90 doi 10 1002 j 1939 4640 2002 tb02311 x hdl 1773 4474 PMID 12185103, wikipedia, wiki, book, books, 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