Anabolic steroids , also known more precisely as anabolic-androgenic steroids ( AAS ), are steroid androgens that include natural androgens such as testosterone and synthetics. androgens that are structurally related and have effects similar to testosterone. They are anabolic and increase proteins in cells, especially in skeletal muscle, and also have varying levels of androgenic and virilizing effects, including developmental induction and maintenance of secondary sexual characteristics of masculine such as facial and body hair growth. The word anabolic , referring to anabolism, is derived from the Greek ??????? anabole , "thrown, mound". Androgens or AASs are one of three types of sex hormones agonists; others are estrogens such as estradiol and progestogens such as progesterone.
AAS was synthesized in the 1930s, and is now used therapeutically in medicine to stimulate muscle growth and appetite, induce male puberty and treat chronic wasting conditions, such as cancer and AIDS abstracts (. The American College of Sports Medicine recognizes that AAS, in the presence of an adequate diet, can contribute to weight gain, often increases lean mass and that increased muscle strength achieved through high intensity exercise and proper diet can also be improved. by using AAS in some individuals.
Health risks can be produced with long-term use or excessive doses of AAS. These effects include harmful changes in cholesterol levels (increased low density lipoproteins and decreased high density lipoprotein), acne, high blood pressure, liver damage (especially with most oral AAS), and harmful changes in the left ventricular structure of the heart. Conditions related to hormonal imbalances such as gynecomastia and a reduction in testicular size can also be caused by AAS. In women and children, AAS can cause irreversible masculinization.
The use of Ergogenic for AAS in sports, racing, and bodybuilding as a performance-enhancing drug is controversial due to its adverse effects and potential for unfair advantage in physical competition. Its use is referred to as doping and is prohibited by most sports bodies. Over the years, AAS has become the most detectable doping substance in laboratories accredited by the IOC. In countries where AAS is a controlled substance, there is often a black market in which drugs are smuggled, produced in secret or even forged sold to the user.
Video Anabolic steroid
Usage
Medical
Since the discovery and synthesis of testosterone in the 1930s, AAS has been used by doctors for various purposes, with varying degrees of success. It can be broadly grouped into anabolic, androgenic, and other uses.
Anabolic
- Bone marrow stimulation: Over the decades, AAS is a mainstay of therapy for hypoplastic anemia due to leukemia or renal failure, especially aplastic anemia. AAS has largely been replaced in this setting by synthetic protein hormones (such as epoetin alpha) which selectively stimulate the growth of blood cell precursors.
- Stimulation of growth: AAS may be used by pediatric endocrinologists to treat children with growth failure. However, the availability of synthetic growth hormone, which has fewer side effects, makes this a secondary treatment.
- Appetite stimulation and preservation and increased muscle mass: AAS has been given to people with chronic waste conditions such as cancer and AIDS.
- Stimulation of lean body mass and prevention of bone loss in elderly men, as some studies show. However, the 2006 placebo-controlled trial of low-dose testosterone supplementation in elderly men with low testosterone levels found no benefit in body composition, physical performance, insulin sensitivity, or quality of life.
- Prevention or treatment of osteoporosis in postmenopausal women. Nandrolone decanoate is approved for this use. Although they have been indicated for these indications, AAS sees very little use for this purpose because of their virilizing side effects.
Androgenic
- Androgen replacement therapy for men with low testosterone levels; also effective in increasing libido for elderly men.
- Induction of male puberty: Androgens are given to many depressed boys about extreme puberty delays. Testosterone is now almost the only androgen used for this purpose and has been shown to increase height, weight, and fat-free mass in boys with delayed puberty. masculine hormone treatment for transgender men, other transmasculine people, and intersex people, resulting in secondary sexual characteristics of masculine such as deepening of voice, increased bone and muscle mass, masculine fat distribution, facial and body hair, and clitoral enlargement, as well as changes mental as well as alleviation of gender dysphoria and increased sex drive.
More
- Treatment of breast cancer in women, although they are now very rarely used for this purpose because of their virilizing side effects.
- In low doses as a component of hormone therapy for postmenopausal and transgender women, for example to increase energy, well-being, libido, and quality of life, as well as to reduce hot flashes. Testosterone is usually used for this purpose, although methyltestosterone is also used.
- Male hormonal contraception; currently experimental, but potential to be used as an effective, safe, reliable, and reversible male contraceptive.
Improved performance
Most steroid users are not athletes. Between 1 million and 3 million people (1% of the population) are estimated to have used AAS in the United States. Studies in the United States have shown that AAS users tend to be mostly middle-class heterosexual men with an average age of about 25 who are noncompetitive and non-athlete bodybuilders and use drugs for beauty purposes. "Among children aged 12 to 17, the use of steroids and similar drugs jumped 25 percent from 1999 to 2000, with 20 percent saying they used it for looks rather than exercise, a study by Blue Cross Blue Shield insurer found." (Eisenhauer) Another study found that non-medical AAS use among students was at or less than 1%. According to a recent survey, 78.4% of steroid users were non-competitive bodybuilders and non-athletes, while about 13% reported unsafe injection practices such as reusing needles, sharing needles and sharing of multidose bottles, although a 2007 study found sharing a needle is not very common among individuals who use AAS for non-medical purposes, less than 1%. Another study in 2007 found that 74% of non-medical AAS users have post-graduate degrees and more have completed college and fewer are failing to finish high school than expected from the general public. The same study found that individuals who use AAS for non-medical purposes have higher employment rates and higher household incomes than the general population. AAS users tend to examine the drugs they use more than users of other controlled substances; however, the primary sources consulted by steroid users include friends, non-medical handbooks, internet-based forums, blogs, and fitness magazines, which can provide inaccurate or inaccurate information.
AAS users tend to be unhappy with AAS depictions as deadly in the media and in politics. According to one study, AAS users also do not trust their doctors and in a 56% sample did not disclose their AAS usage to their doctors. Other studies in 2007 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% had no confidence in their physicians, 92% felt that the medical community's knowledge of the use Non-medical AAS is lacking, and 99% feel that the public has an exaggerated view of the side effects of using AAS. A recent study also showed that long-term AAS users were more likely to have symptoms of muscle dysmorphia and also showed stronger support for a more conventional male role. A recent study in the Journal of Health Psychology shows that many users believe that the steroids used in moderation are safe.
AAS has been used by men and women in various types of professional sports to achieve competitive advantage or to aid recovery from injury. These sports include bodybuilding, weight lifting, shot put and tracks and other fields, cycling, baseball, wrestling, mixed martial arts, boxing, soccer and cricket. Such use is prohibited by the rules of the governing bodies of most sports. The use of AAS occurs among teenagers, especially by those who participate in competitive sports. It has been suggested that the prevalence of use among high school students in the US may be as high as 2.7%. Male students use AAS more often than female students and, on average, those who participate in sports use steroids more often than those who do not.
Available form
The most common AAS used in medicine is testosterone and many esters (but commonly testosterone undecanoate, testosterone enanthate, testosterone cypionate, and testosterone propionate), nandrolone esters (usually nandrolone decanoate and nandrolone phenylpropionate), stanozolol, and metandienone (methandrostenolone). Others that are also available and used in general but at lower levels include methyltestosterone, oxandrolone, mesterolone, and oxymetholone, and drostanolone propionate (dromostanolone propionate), methenolone (methylandrostenolone) ester (especially methenolone acetate and enamin methenolone), and fluoxymesterone. Dihydrotestosterone (DHT), known as androstanolone or stanolone when used medically, and esters are also notorious, although they are not widely used in medicine. Boldenone undecylenate and trenbolone acetate are used in veterinary medicine.
Designer steroids are AAS that have not been approved and marketed for medical purposes but have been distributed through the black market. Examples of famous steroids include 1-testosterone (dihydroboldenone), methasterone, trenbolone enanthate, desoxymethyltestosterone, tetrahydrogestrinone, and methylstenbolone.
Administrative route
There are four common forms in which AAS is given: oral pills; injectable steroids; cream/gel for topical application; and skin patches. Oral administration is the most convenient. Testosterone given by mouth is quickly absorbed, but is mostly converted into an inactive metabolite, and only about one sixth is available in active form. To be active enough when given by mouth, testosterone derivatives are alkylated at 17? position, such as methyltestosterone and fluoxymesterone. This modification reduces the ability of the liver to break down this compound before it reaches the systemic circulation.
Testosterone can be administered parenterally, but has a more irregular absorption time and greater activity in the muscle in the form of enanthate, undecanoate, or cypionate ester. The derivative is hydrolysed to release free testosterone at the injection site; the absorption rate (and thus the injection schedule) varies between different esters, but medical injections are usually done anywhere between semi-weekly to once every 12 weeks. More frequent schedules may be desirable to maintain a more constant level of hormones in the system. The injected steroids are usually given to the muscles, not the veins, to avoid sudden changes in the amount of drugs in the bloodstream. In addition, since testosterone ester is dissolved in oil, intravenous injection has the potential to cause dangerous embolism (blood clots) in the bloodstream.
The transdermal patch (adhesive patch placed on the skin) can also be used to provide a stable dose through the skin and into the bloodstream. Creams and gel containing testosterone applied daily on the skin are also available, but inefficient absorption (about 10%, varies between individuals) and these treatments tend to be more expensive. Individuals who are physically active and/or often bathed may not be good candidates, as the drug can be washed and can take up to six hours to fully absorb. There is also the risk that an intimate partner or child may come into contact with the app site and accidentally position itself; children and women are very sensitive to testosterone and can suffer the effects of masculinization and unwanted health, even from small doses. Injection is the most common method used by individuals who manage AAS for non-medical purposes.
Traditional administrative routes do not have a different effect on drug efficacy. Studies show that the anabolic nature of AAS is relatively similar despite differences in pharmacokinetic principles such as first-flow metabolism. However, an AAS form that is available orally can cause liver damage in high doses.
Maps Anabolic steroid
Adverse effects
Known possible side effects from AAS include:
- dermatologist/integument: skin, acne vulgaris, acne conglobata, seborrhea, stretch marks (due to rapid muscle enlargement), hypertrichosis (oily hair growth) oily, androgenic alopecia (hair loss pattern, baldness scalp ), fluid retention/edema.
- Reproductive/endocrine: changes in libido, reversible infertility, hypogonadotropic hypogonadism.
- Male-specific :. Spontaneous erections, nocturnal emission, priapism, erectile dysfunction, gynecomastia (mostly with aromatizable and therefore estrogenic AAS), oligospermia/azoospermia, testicular atrophy, intratesticular leiomyosarcoma, prostate hypertrophy, prostate cancer
- Specific women: masculinisation, deepened irreversible sound, hirsutism (excessive growth of facial hair/body), menstrual disorders (eg, anovulation, oligomenore, amenorrhea, dysmenorrhea), clitoral enlargement, breast atrophy, uterine atrophy, teratogenic ).
- Children only: premature epiphyseal closure and short stature, premature puberty in boys, delayed puberty, and contrasexual precontual sex in girls.
- Psychiatry/neurological :. Mood swings, irritability, aggression, violent behavior, impulsiveness, hypomania/mania, euphoria, depression, anxiety, dysphoria, suicide, delusions, psychosis, withdrawal, dependence, neurotoxicity, cognitive impairment
- Musculoskeletal: muscle hypertrophy, muscle strain, tendon rupture, rhabdomyolysis.
- Cardiovascular: dyslipidemia (eg, elevated levels of LDL , lowers the HDL level, reduces < title apolipoprotein A1 apo-A1, atherosclerosis, hypertension, left ventricular hypertrophy, cardiomyopathy, myocardial hypertrophy, polycythemia/erythrocytosis, arrhythmias, thrombosis (eg embolism, stroke), myocardial infarction, sudden death.
- Liver: increased liver function tests ( AST , ALT , bilirubin, LDH , ALP ), hepatotoxicity, jaundice, liver steatosis, hepatocellular adenoma, hepatocellular carcinoma, cholestasis, hepatic peliosis; all most or exclusive with 17? -Alated AAS.
- Kidney: renal hypertrophy, nephropathy, acute renal failure (secondary to rhabdomyolysis), segmental focal glomerulosclerosis, renal cell carcinoma.
- Other: glucose intolerance, insulin resistance, immune dysfunction.
Physiological
Depending on the length of drug abuse, it is possible that the immune system may be damaged. Most of these side effects depend on the dose, the most common being the increase in blood pressure, especially in those with pre-existing hypertension. In addition to changes in cardiac morphology that can alter cardiovascular inefficiency is irreversible.
AAS has been shown to change fasting blood sugar and glucose tolerance tests. AAS such as testosterone also increases the risk of cardiovascular disease or coronary artery disease. Acne is quite common among AAS users, largely due to the stimulation of the sebaceous glands by elevated levels of testosterone. Conversion of testosterone into DHT can speed up the rate of premature baldness for men who have a genetic predisposition, but testosterone itself can produce baldness in women.
A number of severe side effects can occur if adolescents use AAS. For example, AAS can prematurely stop bone lengthening (early epiphyseal fusion by increasing estrogen metabolite levels), resulting in stunted growth. Other effects include, but are not limited to, accelerated bone maturation, increased frequency and duration of erections, and early sexual development. The use of AAS in adolescence is also correlated with healthier worse attitudes.
Cancer
The WHO Organization, International Agency for Research on Cancer (IARC) lists AAS under Group 2A: May be carcinogenic in humans.
Cardiovascular
Other side effects may include changes in the heart structure, such as left ventricular enlargement and thickening, which interfere with contraction and relaxation, and therefore reduce the volume of blood released. Possible effects of these changes in the heart are hypertension, cardiac arrhythmias, congestive heart failure, heart attacks, and sudden cardiac death. This change is also seen in athletes who do not use drugs, but the use of steroids can speed up this process. However, the relationship between left ventricular structure changes and decreased cardiac function, as well as connection to steroid use has been debated.
The use of AAS can cause harmful changes in cholesterol levels: Some steroids cause an increase in "bad" LDL cholesterol and a decrease in "good" HDL cholesterol. In addition, steroids provoke a rapid increase in weight and increased blood pressure, both of which make the user more susceptible to cardiovascular events.
Growth defects
The use of AAS in adolescents accelerates bone maturation and can reduce adult height in high doses. Low doses of AAS such as oxandrolone are used in the treatment of short idiopathic stature, but this may only speed up maturation rather than increase adult height.
Feminization
There are also special side effects from AAS. The development of breast tissue in men, a condition called gynecomastia (usually caused by high circulating estradiol levels), may arise from the increased conversion of testosterone to estradiol by the aromatase enzyme. Reduces sexual function and infertility while also can occur in men. Another male-specific side effect that can occur is testicular atrophy, caused by suppression of natural testosterone levels, which inhibits sperm production (most of the testicular mass is developing sperm). These side effects are temporary; testicular size usually returns to normal within a few weeks after stopping the use of AAS as a normal production of sperm resumes.
Masculinization
Specific side effects in women include increased body hair, deepening of the sound permanently, enlarged clitoris, and temporary decrease in the menstrual cycle. Changes in fertility and ovarian cysts can also occur in women. When taken during pregnancy, AAS can affect fetal development by causing the development of male features in female fetuses and female features in the male fetus.
Kidney problems
Kidney tests showed that nine out of ten steroid users developed a condition called segmental focal glomerulosclerosis, a type of scarring in the kidneys. Kidney damage to bodybuilders has similarities to those seen in obese patients who are not healthy, but appear to be more severe.
Liver issues
High doses of oral AAS compounds may cause liver damage. Pelangiosis of the hepatis has become increasingly recognized by the use of AAS.
Neuropsychiatric
The 2005 review on CNS Drugs stipulates that "significant psychiatric symptoms including aggression and violence, mania, and more rarely psychosis and suicide have been linked to steroid abuse." Long-term steroid users may develop symptoms of dependence and withdrawal upon termination of AAS ". High AAS concentrations, comparable to those likely to be supported by many recreational AAS users, produce apoptotic effects on neurons, raising the specter of potentially irreversible neurotoxicity. The use of recreational AAS appears to be associated with potentially prolonged effects of psychiatry, including dependency syndrome, mood disorders, and progression to other forms of substance abuse, but the prevalence and severity of these effects are still poorly understood. There is no evidence that steroid dependence evolves from the therapeutic use of AAS to treat medical disorders, but examples of AAS dependency have been reported among weightlifters and bodybuilders who chronically administer supraphysiologic doses. Mood disorders (eg depression, [hypo-] mania, psychotic features) tend to depend on doses and medications, but AAS reliance or AAS draw effect seems to occur only in a small number of AAS users.
Large-scale long-term psychiatric effects on AAS users are currently unavailable. In 2003, the first naturalistic long-term study on ten users, seven of whom completed the study, found a high incidence of mood disorders and substance abuse, but few clinically relevant changes in physiological parameters or laboratory measurements were noted during the study, and these changes are not clearly related to the reported period of AAS use. A 13-month study, published in 2006 and involving 320 body builders and athletes showed that the various psychiatric side effects caused by the use of AAS correlate with the severity of abuse.
Diagnostic Statement Statement
DSM-IV List General diagnostic criteria for personality disorder guidelines that "Patterns should not be better taken into account as manifestations of other mental disorders, or the direct physiological effects of a substance (eg drugs or drugs) or general medical conditions (eg head trauma). ". As a result, AAS users may be misdiagnosed by psychiatrists who are not informed of their habits.
Personality profile
Cooper, Noakes, Dunne, Lambert, and Rochford identified that individuals using AAS were more likely to score higher (4.7), antisocial (3.8 times), paranoid (3.4 times), skizotypal ( 3.1 times), histrionic (2.9 times). times), passive-aggressive (2.4 times), and narcissistic (1,6 times) personality profiles from non-users. Other studies have shown that antisocial personality disorder is slightly more likely among AAS users than among non-users (Pope & Katz, 1994). Bipolar dysfunction, substance dependence, and behavioral disorders have also been linked to the use of AAS.
Moods and anxieties
Affective disorders have long been known as complications of AAS use. Case reports describe both hypomania and mania, along with irritability, excitement, carelessness, racing thinking and feelings of power and invincibility that do not meet the criteria for mania/hypomania. Of 53 bodybuilders using AAS, 27 (51%) reported nonspecific mood disorders.
Aggression and hypomania
From the mid-1980s onwards, the media reported " roid rage " as a side effect of AAS.
The 2005 review determined that some, but not all, randomized controlled studies have found that use of AAS correlates with hypomania and increases aggressiveness, but suggests that attempts to determine whether AAS use triggers violent behavior has failed, mainly because of high levels of participation. A 2008 study on a representative sample of young national adult males in the United States found an association between lifelong use of AAS and self-reported years and involvement in violent acts. Compared with individuals who did not use steroids, young adult men who used AAS reported greater involvement in violent behavior even after controlling for the effects of key demographic variables, previous violent behavior, and polydrug use. A 1996 review examining available blind study at the time also found that this has shown a link between aggression and steroid use, but shows that with an estimated over one million past or current steroid users in the United States at that time, a very percentage small of those using steroids appear to have suffered severe mental illness to produce clinical care or medical case reports.
A 1996 randomized controlled trial, involving 43 men, found no increase in anger behavior during 10 weeks of enanthate testosterone at 600 mg/week, but this study screened subjects who had previously misused steroids or had psychiatric antecedents. A trial conducted in 2000 using testosterone cypionate at 600 mg/week found that treatment significantly improved the bead score on YMRS, and aggressive responses at multiple scales. Drug responses vary widely. However: 84% of subjects showed minimal psychiatric effects, 12% became slightly hypomanic, and 4% (2 subjects) became hypomanic apparent. The mechanism of the reaction of these variables can not be explained by demographic, psychological, laboratory, or physiological measures.
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, steroid-using twins exhibited high levels of aggressiveness, hostility, anxiety, and paranoia not found in "controls" twin. A small-scale study of 10 AAS users found that cluster B personality disorder was a confounding factor for aggression.
The relationship between use of AAS and depression can not be inferred. There have been reports of anecdotal depression and suicide on users of adolescent steroids, but little systematic evidence. A 1992 review found that AAS may relieve and cause depression, and the cessation or decrease in use of AAS may also lead to depression, but requested additional studies because of different data. In the case of suicide, 3.9% of a sample of 77 people who were classified as AAS users reported attempting suicide during withdrawal (Malone, Dimeff, Lombardo, & Sample, 1995).
Reproduction
Androgens such as testosterone, androstenedione and dihydrotestosterone are necessary for the development of organs in the male reproductive system, including seminal vesicles, epididymis, vas deferens, penis and prostate. Anabolic-androgenic steroids (AAS) are testosterone derivatives designed to maximize the anabolic effects of testosterone. AAS is consumed by elite athletes competing in sports such as weightlifting, bodybuilding, and track and field. Male recreation athletes take AAS to achieve "enhanced" physical appearance.
AAS consumption interferes with the hypothalamus-pituitary-gonad axis (the gastrointestinal axis) in males. In the HPG axis, the gonadotropin-releasing hormone (GnRH) is secreted from the arcuate nucleus of the hypothalamus and stimulates the anterior pituitary (AP) to secrete two gonadotropins, follicle stimulating hormone (FSH) and luteinizing hormone (LH). In adult men, LH stimulates Leydig cells in the testes to produce the testosterone needed to form new sperm through spermatogenesis. AAS consumption causes dose-dependent depression of gonadotropin (FSH and LH) released by GnRH suppression of the hypothalamus (long loop mechanism) or from direct negative feedback on AP to inhibit gonadotropin release (short loop mechanism), leading to AAS. induced hypogonadism.
Pharmacology
Action mechanism
Pharmacodynamics AAS is not like a peptide hormone. The water-soluble peptide hormone can not penetrate the fat cell membrane and only indirectly affects the nucleus of the target cell through their interaction with the cell surface receptor. However, as the fat-soluble hormone, AAS is membrane-permeable and affects the cell nucleus by direct action. The AA pharmacodynamic action begins when exogenous hormones penetrate the target cell membrane and bind to the androgen receptor (AR) located in the cell's cytoplasm. From there, the hormone-compound receptor diffuses into the nucleus, where it alters gene expression or activates a process that sends signals to other parts of the cell. Different types of AAS bind to the AAR with different affinities, depending on their chemical structure. Some AASs such as metandienone bind weakly with these receptors are in vitro , but still show ARM-mediated effects in vivo . The reason for this difference is unknown.
The effect of AAS on muscle mass is caused in at least two ways: first, they increase protein production; second, they reduce recovery time by blocking the effects of stress hormone cortisol on muscle tissue, so muscle catabolism is greatly reduced. It has been hypothesized that this reduction in muscle damage can occur through AAS which inhibits the action of another steroid hormone called glucocorticoid that promotes muscle splitting. AAS also affects the number of cells that develop into fat storage cells, by supporting cellular differentiation into muscle cells instead. AAS can also decrease fat by increasing basal metabolic rate (BMR), as increased muscle mass increases BMR.
Anabolic and androgenic effects
As the name suggests, AAS has two different types of effects, but overlaps: anabolic , which means 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 of amino acids, increased appetite, increased remodeling and bone growth, and bone marrow stimulation, which increases the production of red blood cells. Through a number of AAS mechanisms stimulate the formation of muscle cells and hence lead to an increase in skeletal muscle size, which leads to increased strength.
The androgenic effects of AAS are numerous. Depending on the duration of use, the side effects of steroids can be irreversible. Affected processes include pubertal growth, sebaceous gland oil production, and sexuality (especially in fetal development). Some examples of virilizing effects are clitoral growth in women and penis in boys (adult penis size unchanged due to steroids), increased vocal cord size, increased libido, natural sex hormone suppression, and sperm production disruption.. Effects on women include deepening of voice, facial hair growth, and possibly decreased breast size. Men can develop breast tissue enlargement, known as gynecomastia, testicular atrophy, and reduced sperm count.
The androgenic: Anabolic ratio of AAS is an important factor when determining the clinical application of this compound. Compounds with high androgenic ratios to anabolic effects are the drug of choice in androgen replacement therapy (eg, treating hypogonadism in men), whereas the androgenic compounds are reduced: anabolic ratios are preferred for anemia and osteoporosis, and to reversing proteins. lost after trauma, surgery, or prolonged immobilization. Androgenic determination: Anabolic ratios are usually performed in animal studies, which have led to the marketing of some compounds claimed to have anabolic activity with weak androgenic effects. This dissociation is less marked in humans, where all AAS have significant androgenic effects.
A protocol commonly used to determine androgenic: anabolic ratios, dating back to the 1950s, using the relative weights of ventral prostate (VP) and levator ani (LA) muscle in male rats. VP weight is an indicator of androgenic effects, whereas LA weight is an indicator of anabolic effects. Two or more castrated rats were castrated and treated and each of the AAS was of interest. The LA/VP ratio for AAS is calculated as the LA/VP weight gain ratio resulting from the treatment with the compound using castrated rats but not treated as baseline: (LA c, t -LA c )/(VP c, t -VP c ). The LA/VP weight gain ratio of the rat experiments was not uniform for testosterone (usually 0.3-0.4), but normalized for presentation purposes, and used as a comparative basis for other AASs, which had their androgens: anabolic-scale ratios suitable ( as shown in the table above). In early 2000, the procedure was standardized and generalized across the OECD in what is now known as the Hershberger test.
Body composition and strength increase
Weight gain in men can increase by 2-5 kgs as a result of short-term use of AAS (& lt; 10 weeks), which may be due primarily to the increase in lean mass. Animal studies have also found that fat mass decreases, but most research in humans fails to explain a significant reduction in fat mass. The effect on lean body mass has been shown to be dose-dependent. Both muscle hypertrophy and the formation of new muscle fibers have been observed. The slim lean hydration remains unaffected by the use of AAS, although a slight increase in blood volume can not be ruled out.
The upper body (chest, neck, shoulders, and upper arms) seems more susceptible to AAS than other body areas due to the dominance of ARS in the upper body. The largest differences in muscle fiber size between AAS and non-user users were observed in Type I muscle fibers from lateral and lateral trachezius muscles as a result of long-term AAS administration. After discontinuation of the drug, its effects slowly fade, but may persist for more than 6-12 weeks after discontinuation of AAS use.
An increase in strength in the range of 5-20% of baseline strength depends on the drug and dose used and the period of administration. Overall, the exercise in which the most significant improvement was observed was the bench press. For nearly two decades, it was assumed that AAS had a significant effect only on experienced strength athletes. A randomized controlled trial showed, however, that even in novice athletes a 10-week strength training program accompanied by testosterone enanthate at 600 mg/wk may increase strength over the training itself. This dose is sufficient to significantly increase lean muscle mass relative to placebo even on subjects who are not exercising at all. The anabolic effects of enanthate testosterone are highly dose dependent.
Dissociation effects
Endogenous AASs such as testosterone and DHT and synthetic AAS mediate their effects by binding and activating AR. On the basis of animal bioassays, the effects of these agents have been divided into two partially separated types: anabolic (myotrophic) and androgenic. The dissociation between the ratios of these two types of effects was observed in rat bioassay with various AAS relative to the ratio observed with testosterone. Explanations for dissociation include differences in intracellular metabolism, functional selectivity (coactivator recruitment), and non-genomic mechanisms (ie, signals through non-AR membrane androgen receptors, or mARs). Support for the latter two is limited and more hypothetical, but there is much support for the explanation of intracellular metabolism.
The dissociation measurements between the anabolic and androgenic effects among AASs are largely based on a simple, though somewhat sophisticated and outdated model involving rat tissue bioassays. This is called the androgenic-androgenic index. In this model, myotrophic activity was measured by weight changes in bulbocavernosus/levator ani muscle and androgenic activity was measured by changes in mouse ventral prostate (or, alternatively, rat seminal vesicles) in response to AAS exposure, and later measurements were compared and used to form ratio.
Intracellular metabolism
Testosterone is metabolized in various tissues by 5? -reductase to DHT, which is 3- to 10 times as strong as AR agonists, and by aromatase to estradiol, which is a significant estrogen and a deficiency of AR affinity. In addition, DHT is metabolized by 3? -hydroxysteroid dehydrogenase (3? -HSD) and 3? -hydroxysteroid dehydrogenase (3? -HSD) to 3? -androstanediol and 3? -androstanediol, respectively, which is a metabolite with little or no AR Affinity. 5? -Reductase is widely distributed throughout the body, and is concentrated into various areas of the skin (especially the scalp, facial-beard, pubic area, and genital area (penis and scrotum)), prostate, seminal vesicles, liver, and brain. Conversely, expression 5? -reductase in skeletal muscle is not detected. Aromatase is highly expressed in adipose and brain tissue, and is also expressed significantly in skeletal muscle. 3? -HSD is also highly expressed in skeletal muscle.
Natural AASs such as testosterone and DHT and synthetic AAS are analogue and very similar structurally. For this reason, they have the capacity to bind and be metabolized by the same steroid-sizing enzymes. According to the explanation of intracellular metabolism, the androgenic-to-anabolic ratio of the given AR agonist relates to its capacity to be altered by the enzymes in relation to the AR activity of each product produced. For example, whereas AR activity of testosterone is strongly reinforced by local conversion through 5? -reductase to DHT in tissue where 5-sucuctase is expressed, an AAS that is not metabolized by 5? -reductase or already 5? -reduced, such as DHT itself or a derivative (such as mesterolone or drostanolone), will not experience such potential in the network. In addition, nandrolone is metabolized by 5? -redasease, but unlike the case of testosterone and DHT, the reduced nandrolone metabolite 5 has a lower affinity for AR than nandrolone itself, and this results in decreased AR activation at 5? -the provision of a network of pengedapase. Like so-called "androgenic" tissues such as skin/hair follicles and male reproductive tissues are very high in 5-acetase expression, while skeletal muscles are almost without 5-ductuctase, this can primarily explain high myotrophic-androgenic ratios. and dissociation seen with nandrolone, as well as with various other AAS.
In addition to 5-ductase, aromatase can inactivate the signaling of testosterone in skeletal muscle and adipose tissue, so AASs that have no aromatase affinity, apart from being free of potential gynecomastia side-effects, may be expected to have higher myotrophic-androgenic ratios. compared. In addition, DHT is not active by high activity 3? -HSD in skeletal muscle (and heart tissue), and AAS is less affinity for 3? -HSD can also be expected to have higher myotrophic-androgenic ratios (although it may also increase long-term cardiovascular risk). Accordingly, DHT, mestanolone (17? -methyl-DHT), and m cholesterolone (1? -metil-DHT) are all described as very bad anabolic because of inactivation by 3? -HSD in skeletal muscle, whereas other DHT derivatives with other structural features such as metenolone, oxandrolone, oxymetholone, drostanolone, and stanozolol are all bad substrates for 3? -HSD and is described as a strong anabolic.
The theory of intracellular metabolism explains how and why the remarkable dissociation between anabolic and androgenic effects can occur despite the fact that this effect is mediated through the same signal receptor, and of course why dissociation is always incomplete. To support this model is a rare condition of the deficient type 2 defectase 2, where enzyme 5? -the type 2 defective, damaged production of DHT, and low DHT levels while normal testosterone levels. Men with this condition are born with ambiguous genitals and the prostate gland is very undeveloped or even absent. In addition, at puberty, such men develop normal muscles, deepening sounds, and libido, but it has reduced facial hair, the female pattern of body hair (ie, largely confined to the pubic and armpit triangles), none the incidence of male pattern of hair loss, and no prostate enlargement or prostate cancer incidence. Nor do they develop gynecomastia as a consequence of their condition.
Functional selectivity
An animal study found that two different types of androgen response elements could respond to testosterone and DHT differently after AR activation. Whether this is involved in the difference in the ratio of anabolic-to-myotropic effects of different AAS is unknown.
Non-genomic mechanism
Testosterone signals not only through nuclear AR, but also through mars, including ZIP9 and GPRC6A. It has been proposed that differential signaling through mARs may be involved in the dissociation of anabolic and androgenic effects of AAS. Indeed, DHT has less than 1% of testosterone affinity for ZIP9, and AAS metabololone synthetic and mibolerone are ineffective competitors for the same receptor, indicating that AAS does show differential interaction with AR and mars. However, women with complete androgen insensitivity syndrome (CAIS), which has a male genotype (46, XY) and testes but a defect in AR so that it does not work (and therefore are not at all sensitive to the AR-mediated effects of androgens such as testosterone), show phenotype females are perfect despite having testosterone levels at the upper end of the normal male range. In addition, these women showed little or no sebum production, acne, and body hair growth (including the genital area and axilla). In addition, CAIS women have normal non-fat body mass for women but of course greatly reduced for men. This observation indicates that AR is primarily or exclusively responsible for masculinization and myotrophy caused by androgens. In any case, mARs have been found to be involved in several other effects of testosterone such as risk modulation and prostate cancer progression.
Antigonadotropic Effects
Changes in endogenous testosterone levels may also contribute to the androgen-andotrophic-ratio differences between testosterone and synthetic AAS. AR agonists are antigonadotropic - that is, they depend on doses to suppress the production of gonadal testosterone and therefore reduce the concentration of systemic testosterone. By suppressing endogenous testosterone levels and effectively replacing AR signaling in the body with exogenous AAS, the myotrophic-androgenic comparison of the AAS given may be further, the dose-dependent increase, and this may therefore be an additional mechanism that contributes to the andotropic-androgenic ratio difference in between different AAS. In addition, some AASs, such as 19-nortestosterone derivatives such as nandrolone, are also potential progestogen, and progesterone receptor activation (PR) is the same antigonadotropic with AR activation. A considerable combination of AR and PR activations suppresses testosterone levels in the male castrate range (ie, complete emphasis on testosterone gonad production and circulating testosterone levels decreases by about 95%). Thus, joint progestogenic activity may serve to further increase the andotropic-androgenic ratio for the given AAS.
GABA A receptor modulation
Some AASs, such as testosterone, DHT, stanozolol, and methyltestosterone, have been found to modulate GABA receptors A similar to endogenous neurosteroids such as allopregnanolone, 3? -androstanediol, dehydroepiandrosterone sulfate, and pregnenolone sulfate. It has been suggested that this may contribute as an alternative or additional mechanism for the neurological and behavioral effects of AAS.
AAS comparison
AAS differs in various ways including in their capacity to be metabolized by steroidogenic enzymes such as 5? -duktuktase, 3-hydroxisteroid dehydrogenase, and aromatase, does their potential as an AR agonist have potential or decrease by 5? -reduction, in their ratio to the anabolic/myotropic to androgenic effects, in their estrogenic, progestogenic, and neurosteroid activity, in their oral activity, and in their capacity to produce hepatotoxicity.
5? -Reductase and androgenicity
Testosterone can be changed strongly by 5? -reductase to DHT in so-called androgenic tissues such as skin, scalp, prostate, and seminal vesicles, but not in muscle or bone, where 5-reductase is not expressed or only minimal states. Because DHT is 3- to 10 times more potent as an AR agonist than testosterone, the AR agonist activity of testosterone thus has a clear and potent potential in the tissue. In contrast to testosterone, DHT and 4.5? -dihydrogenated AAS is 5-reduced, and for this reason, can not be reinforced in androgenic tissue. 19-Nortestosterone derivatives such as nandrolone can be metabolized by 5? -testasease is similar to testosterone, but the reduced metabolite of the 19-nortestosterone derivative (eg, 5 -dihydronandrolone) tends to have reduced activity as an AR agonist, thus reducing the androgenic activity in the expressed tissue 5? -reductase. In addition, some 19-nortestosterone derivatives, including trestolone (7? -methyl-19-nortestosterone (MENT)), 11? -methyl-19-nortestosterone (11? -MNT), and dimethrolone (7 ?, 11? -dimethyl -19-nortestosterone), can not be 5? -reduced. Conversely, 17? AAS alkylated like methyltestosterone is 5? -produced and potentially in androgenic tissue similar to testosterone. 17? -Activity Derived DHT can not be amplified through 5? -reductase however, since they are already 4.5? -reduced.
Capacity to be metabolized by 5? -the deductase and activity of AR from the resulting metabolite appears to be one of the major factors, if not the most important determinant of the androgenic-myotropic ratios for the given AAS. AAS not reinforced by 5? -reductase or are attenuated by 5? androgenic-reductase in the androgenic tissue has a reduced risk of androgenic side effects such as acne, androgenic alopecia (male pattern baldness), hirsutism (male pattern over growth), benign prostatic hyperplasia (prostate enlargement), and prostate cancer, while the incidence and magnitude of other effects muscle hypertrophy, bone changes, deepening of voice, and changes in sex drive do not show any difference.
Aromatase and estrogenicity
Testosterone can be metabolized by aromatase to estradiol, and many other AAS can be metabolized to an appropriate estrogenic metabolite as well. For example, 17-metiltestosterone AAS is alkylated and metandienone is converted by aromatase to methylestradiol. 4.5? Derivatives -Dihydrogenated from testosterone like DHT can not be aromatized, whereas 19-turbine nortestosterone such as nandrolone can but to a greatly reduced level. Some 19-nortestosterone derivatives, such as dimetandrolon and 11? -MNT, can not be aromatized because of the steric hindrances provided by their 11 -ethyl group, whereas the closely related AAS trestolone (7? -metil-19-nortestosterone), in relation to the lack of the 11 -ethyl group, can be aromatized. AAS aged 17? -alkylation (and neither 4.5? -caused or 19-demetilation) is also aromatized but to a lesser degree than testosterone. However, it should be noted that estrogen is 17? -lubstitution (eg, ethinylestradiol and methylestradiol) is a marked increase in estrogenic potential due to increased metabolic stability, and for this reason, 17? -AAA certification can actually have a higher and relatively greater estrogenicity. an estrogenic effect than testosterone.
The main effect of estrogenicity is gynecomastia (breast like woman). AAS that has a high potential for aromatization such as testosterone and especially methyltestosterone shows high risk of gynecomastia at fairly high doses, while AAS with a reduced aromatization potential such as nandrolone has a much lower risk (although potentially significant at high doses). In contrast, the AAS is reduced by 4.5, and some other AAS (eg, 11? -Testable 19-nortestosterone derived), have no risk of gynecomastia. In addition to gynecomastia, AAS with high estrogen has increased antigonadotropic activity, resulting in increased potency in suppression of the hypothalamus-pituitary-gonad axis and the production of gonadal testosterone.
Progestogenic activity
Many 19-nortestosterone derivatives, including nandrolone, trenbolone, ethylestrenol (ethylnandrol), metribolone (R-1881), trestolone, 11? -MNT, dimethandrolone, and others, are strong agonists of progesterone (AR) receptors and hence are progestogens in addition to AAS. Similarly for the case of estrogenic activity, progestogenic activity of these drugs serves to increase their antigonadotropic activity. This results in increased potency and effectiveness of this AAS as an antispermatogenic agent and male contraceptive (or, in other ways, an increased potency and effectiveness in generating reversible azoospermia and male infertility).
Oral activity and hepatotoxicity
Non-17? The alkylated testosterone derivatives such as testosterone itself, DHT, and nandrolone all have poor oral bioavailability due to careful metabolism of the first stomach and are therefore inactive orally. Important exceptions to this are AAS which is a precursor of androgens or prohormones, including dehydroepiandrosterone (DHEA), androstenediol, androstenedione, boldione (androstadienedione), bolandiol (norandrostenediol), bolandione (norandrostenedione), dienedione, mentabolan (MENT dione, trestione) and methoxydienone (methoxygonadiene) (although this is a relatively weak AAS). Orally inactive AAS is used almost exclusively in ester form given by intramuscular injection, which acts as a depot and serves as a long-acting prodrug. Examples include testosterone, such as testosterone cypionate, testosterone enanthate, and testosterone propionate, and nandrolone, as nandrolone phenylpropionate and nandrolone decanoate, among many others (see here for a complete list of testosterone and nandrolone esters). The exception is a very long, long-acting testosterone ester, which is orally active, although only with very low oral bioavailability (about 3%). Unlike most other AASs, 17-alkylated testosterone derivatives exhibit resistance to metabolism due to steric and active resistance orally, although they can be esterified and administered by intramuscular injection as well.
In addition to oral activity, 17? alkylation also provides high potential for hepatotoxicity, and all alkylated 17-AAS has been associated, although not common and only after long-term use (estimates varying between 1 and 17%), with hepatotoxicity. Conversely, testosterone esters are only rarely or never associated with hepatotoxicity, and non-17? AAS is alkylated rarely, although long-term use is reported to still increase the risk of liver change (but to a much lower level than 17? -Alated AAS and reported not at substitute dose). Appropriate, D-ring glucuronides from testosterone and DHT have been found to be cholestatic.
In addition to prohormones and testosterone undecanoate, almost all AAS that are orally active are 17? -alkylation. Some AAS that is not 17? -alkillation active orally. Some examples include testosterone 17-ether cloxotestosterone, quinbolone, and silandrone, which are prodrugs (for testosterone, boldenone (? 1 -testosterone), and testosterone, respectively), DHT 17-ether mepitiostane, mesabolone, and prostanozole (which are also prodrugs), 1-methylated DHT derivatives m cholesterolone and methenolone (although this is a relatively weak AAS), and 19-nortestosterone derivatives dimethandrolone and 11? -MNT, which has increased resistance to first-pass liver metabolism because they are 11? -methyl groups (in contrast to those, the associated AAS trestolone (7? -methyl-19-nortestosterone) are not verbally active). Because the AAS is not 17-alkylated, they exhibit minimal potential for hepatotoxicity.
Neurosteroid activity
DHT, through its metabolites 3? -androstanediol (produced by 3? -hydroxysteroid dehydrogenase (3? -HSD)), is a neurosteroid that acts via a positive allosteric modulation of GABA receptors A . Testosterone, through conversion to DHT, also generates 3? -androstanediol as a metabolite and therefore have similar activity. Some AASs that can or 5-minus, including testosterone, DHT, stanozolol, and methyltestosterone, among many others, can or can modulate GABA receptors A , and these may contribute as an alternative or additional mechanism for the effects their central nervous system in terms of mood, anxiety, aggression, and sexual drive.
Chemistry
AAS is a steroid androstane or estrane. They include testosterone (androst-4-en-17? -ol-3-one) and derivatives with various structural modifications such as:
- 17? -Alkylation: methyltestosterone, metandienone, fluoxymesterone, oxandrolone, oxymetholone, stanozolol, norethandrolone, ethylestrenol
- 19-Demethylation: nandrolone, trenbolone, norethandrolone, ethylestrenol, trestolone, dimethandrolone
- 5? -Reduction: androstanolone, drostanolone, mestanolone, mesterolone, methenolone, oxandrolone, oxymetholone, stanozolol
- 3? - and/or 17? -esterification: testosterone enanthate, nandrolone decanoate, drostanolone propionate, boldenone undecylenate, trenbolone acetate
As well as others such as 1-dehydrogenation (eg, metandienone, boldenone), 1-substitution (eg, m cholesterolone, methenolone), 2-substitution (eg, drostanolone, oxymetholone, stanozolol), 4-substitution (eg, clostebol, oxabolone) , and various other modifications.
Detection in body fluids
The most commonly used human physiology specimen to detect the use of AAS is urine, although blood and hair have been studied for this purpose. The AAS, whether of endogenous or exogenous origin, is subject to extensive liver biotransformation by various enzymatic pathways. Primary urine metabolism can be detected up to 30 days after the last use, depending on the specific agent, dose and route of administration. A number of drugs have a common metabolic pathway, and their excretion profile can overlap from endogenous steroids, making interpretation of the test results a very significant challenge for analytical chemists. Methods for detecting substances or their excretion products in urine specimens usually involve gas chromatographic mass spectrometry or liquid chromatography mass spectrometry.
History
The discovery of androgens
The use of gonad steroid pre-date identification and their isolation. The medical use of testicular extracts began in the late 19th century while its effect on strength is still being studied. The gonad steroid isolation can be traced back to 1931, when Adolf Butenandt, a chemist in Marburg, purified 15 milligrams of androstenone male hormone from tens of thousands of liters of urine. This steroid was later synthesized in 1934 by Leopold Ru? I? Ka, a chemist in Zurich.
By the 1930s, it was well known that testes contained androgenene more powerful than androstenone, and three groups of scientists, funded by competing pharmaceutical companies in the Netherlands, Germany and Switzerland, rushed to isolate them. 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)." They named the testosterone hormone, from the stem of testicular and sterol, and the ketone suffix. Chemical synthesis of testosterone was achieved in August of that year, when Butenandt and G. Hanisch published a paper describing "Methods for Preparing Testosterone from Cholesterol." Only a week later, the third group, Ruzicka and A. Wettstein, announced a patent application in the paper "On Preparation Testosterone Testosterone Hormone Testosterone (Androsten-3-one-17-ol)." Ruzicka and Butenandt were offered the 1939 Nobel Prize in Chemistry for their work, but the Nazi government forced Butenandt to refuse honor, even though he received the prize after the end of World War II.
Clinical trials in humans, involving oral doses of methyltestosterone or testosterone propionate injections, begin as early as 1937. Testosterone propionate was mentioned in a letter to the editor of Strength and Health magazine in 1938; this is the earliest known reference to AAS in a weight lifting or bodybuilding magazine of the United States. There were often rumors that German soldiers were given the AAS during the Second World War, the aim was to increase their aggression and stamina, but this has not been proven. Adolf Hitler himself, according to his doctor, was injected with testosterone derivatives to treat various diseases. AAS was used in experiments conducted by the Nazis on concentration camp prisoners, and then by allies who sought to treat survivors of malnutrition that survived the Nazi camps. President John F. Kennedy was given steroids both before and during his presidency.
Development of synthetic AAS
Developmental properties of testosterone muscle builders were pursued in the 1940s, in the Soviet Union and in the Eastern Bloc countries such as East Germany, where steroid programs were used to improve the performance of Olympic and other weight lifers. In response to Russia's weight lifting success, US Olympic Team physician John Ziegler worked with a synthetic chemist to develop AAS by reducing androgenic effects. Ziegler's work resulted in the production of methandrostenolone, which Ciba Pharmaceuticals marketed as Dianabol. New steroids were approved for use in the United States by the Food and Drug Administration (FDA) in 1958. These drugs were most often given to burn victims and parents. Users who do not use drug labels are mostly bodybuilders and weight lifts. Although Ziegler only gave small doses to athletes, he soon found that those who experienced Dianabol abuse suffered from prostate enlargement and testes that stopped growing. AAS was placed on the IOC's list of prohibited substances in 1976, and a decade later the committee introduced an out-of-competition doping test because many athletes use AAS in their training periods rather than during the competition.
The three main ideas govern the modification of testosterone into many AAS: Alkylation in C17? position with methyl or ethyl groups made active compounds orally by slowing the degradation of the drug by the liver; esterification of testosterone and nortestosterone in C17? position allows the substance to be administered parenterally and increases the duration of effectiveness because the soluble agent in oily fluid may be present in the body for several months; and changes in the structure of the ring
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