خواص دارویی و گیاهی
Oxandrolone, sold under the brand names Oxandrin and Anavar, among others, is an androgen and anabolic steroid (AAS) medication which is used to help promote weight gain in various situations, to help offset protein catabolism caused by long-term corticosteroid therapy, to support recovery from severe burns, to treat bone pain associated with osteoporosis, to aid in the development of girls with Turner syndrome, and for other indications.[4][5][6] It is taken by mouth.[4]
Side effects of oxandrolone include symptoms of masculinization such as acne, increased hair growth, voice changes, and increased sexual desire.[4] The drug is a synthetic androgen and anabolic steroid, hence is an agonist of the androgen receptor (AR), the biological target of androgens such as testosterone and dihydrotestosterone.[4][7] It has strong anabolic effects and weak androgenic effects, which give it a mild side effect profile and make it especially suitable for use in women.[4]
Oxandrolone was first described in 1962 and was introduced for medical use in 1964.[4] It is used mostly in the United States.[4][8] In addition to its medical use, oxandrolone is used to improve physique and performance.[4][9] The drug is a controlled substance in many countries, so nonmedical use is generally illicit.[4][10][11][12]
Oxandrolone has been researched and prescribed as a treatment for a wide variety of conditions. It is FDA-approved for treating bone pain associated with osteoporosis, aiding weight gain following surgery or physical trauma, during chronic infection, or in the context of unexplained weight loss, and counteracting the catabolic effect of long-term corticosteroid therapy.[13][14] As of 2016[update], it is often prescribed off-label to quicken recovery from severe burns, aid the development of girls with Turner syndrome, and counteract HIV/AIDS-induced wasting. 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.[5][6] It is also used in the treatment of idiopathic short stature, anemia, hereditary angioedema, alcoholic hepatitis, and hypogonadism.[15][16]
Medical research has established the effectiveness of oxandrolone in aiding the development of girls with Turner syndrome. Although oxandrolone has long been used to accelerate growth in children with idiopathic short stature, it is unlikely to increase adult height, and in some cases may even decrease it. Oxandrolone has, therefore, largely been replaced by growth hormone for this use.[17] Children with idiopathic short stature or Turner syndrome are given doses of oxandrolone far smaller than those given to people with burns to minimize the likelihood of virilization and premature maturation.[17][18]
قرص oxandrolone چیست
Many bodybuilders and athletes use oxandrolone for its muscle-building effects.[4] It is much more anabolic than androgenic, so women and those seeking less intense steroid regimens use it particularly often.[4] Many also value oxandrolone’s low hepatotoxicity relative to most other orally active AAS.[4]
Like other AAS, oxandrolone may worsen hypercalcemia by increasing osteolytic bone resorption.[13] When taken by pregnant women, oxandrolone may have unintended effects such as masculinization on the fetus.[13]
Women who are administered oxandrolone may experience virilization, irreversible development of masculine features such as voice deepening, hirsutism, menstruation abnormalities, male-pattern hair loss, and clitoral enlargement.[17][13][18] Oxandrolone may disrupt growth in children, reducing their adult height.[19][better source needed] Because of these side effects, doses given to women and children are minimized and people are usually monitored for virilization and growth abnormalities.[17][18] Like other androgens, oxandrolone can cause or worsen acne and priapism (unwanted or prolonged erections).[13][19] Oxandrolone can also reduce males’ fertility, another side effect common among androgens.[19] In an attempt to compensate for the exogenous increase in androgens, the body may reduce testosterone production via testicular atrophy and inhibition of gonadotropic activity.[13]
Unlike some AAS, oxandrolone does not generally cause gynecomastia because it is not aromatized into estrogenic metabolites.[20] However, although no reports of gynecomastia were made in spite of widespread use, oxandrolone was reported in a publication in 1991 to have been associated with 33 cases of gynecomastia in adolescent boys treated with it for short stature.[21][22] The gynecomastia developed during oxandrolone therapy in 19 of the boys and after the therapy was completed in 14 of the boys, and 10 of the boys had transient gynecomastia, while 23 had persistent gynecomastia that necessitated mastectomy.[21][22] Though transient gynecomastia is a natural and common occurrence in pubertal boys, the gynecomastia associated with oxandrolone was of a late/delayed onset and was persistent in a high percentage of the cases.[21][22] As such, the researchers stated, “although oxandrolone cannot be implicated as stimulatory [in] gynecomastia”, a possible relationship should be considered in clinicians using oxandrolone in adolescents for growth stimulation.[21][22]
Uniquely among 17α-alkylated AAS, oxandrolone shows little to no hepatotoxicity, even at high doses.[23] No cases of severe hepatotoxicity have been singularly attributed to oxandrolone.[23] However, elevated liver enzymes have been observed in some people, particularly with high doses and/or prolonged treatment, although they return to normal ranges following discontinuation.[23]
Oxandrolone greatly increases warfarin’s blood-thinning effect, sometimes dangerously so.[24] In April 2004, Savient Pharmaceuticals published a safety alert through the FDA warning healthcare professionals of this.[25] Oxandrolone can also inhibit the metabolism of oral hypoglycemic agents.[13] It may worsen edema when taken alongside corticosteroids or adrenocorticotropic hormone.[13]
Like other AAS, oxandrolone is an agonist of the androgen receptor, similar to androgens such as testosterone and DHT.[4] The relative binding affinity of oxandrolone for the androgen receptor is about 0.8% of that of metribolone.[26] Activation of the androgen receptor stimulates protein synthesis, which increases muscle growth, lean body mass, and bone mineral density.[6]
Compared to testosterone and many other AAS, oxandrolone is less androgenic relative to its strength as an anabolic.[4][27] Oxandrolone has about 322 to 633% of the anabolic potency and 24% of the androgenic potency of methyltestosterone.[4] Similarly, oxandrolone has as much as 6 times the anabolic potency of testosterone and has significantly reduced androgenic potency in comparison.[4] The reduced ratio of anabolic to androgenic activity of oxandrolone often motivates its medical use in children and women because less androgenic effect implies less risk of virilization.[4] The bodybuilding community also considers this fact when choosing between AAS.[4]
As oxandrolone is already 5α-reduced, it is not a substrate for 5α-reductase, hence is not potentiated in androgenic tissues such as the skin, hair follicles, and prostate gland.[4] This is involved in its reduced ratio of anabolic to androgenic activity.[4] Due to the substitution of one of the carbon atoms with an oxygen atom at the C2 position in the A ring, oxandrolone is resistant to inactivation by 3α-hydroxysteroid dehydrogenase in skeletal muscle.[4] This is in contrast to DHT, and is thought to underlie the preserved anabolic potency with oxandrolone.[4] Because it is 5α-reduced, oxandrolone is not a substrate for aromatase, hence cannot be aromatized into metabolites with estrogenic activity.[4] Oxandrolone similarly possesses no progestogenic activity.[4]
Oxandrolone is, uniquely, far less hepatotoxic than other 17α-alkylated AAS, which may be due to differences in metabolism.[23][4][1][3]
The oral bioavailability of oxandrolone is 97%.[2] Its plasma protein binding is 94 to 97%.[2] The drug is metabolized primarily by the kidneys and to a lesser extent by the liver.[1][2] Oxandrolone is the only AAS that is not primarily or extensively metabolized by the liver, and this is thought to be related to its diminished hepatotoxicity relative to other AAS.[1][3] Its elimination half-life is reported as 9.4 to 10.4 hours, but is extended to 13.3 hours in the elderly.[2][3] About 28% of an oral dose of oxandrolone is eliminated unchanged in the urine and 3% is excreted in the feces.[3]
Oxandrolone is a synthetic androstane steroid and a 17α-alkylated derivative of DHT.[28][29][4] It is also known as 2-oxa-17α-methyl-5α-dihydrotestosterone (2-oxa-17α-methyl-DHT) or as 2-oxa-17α-methyl-5α-androstan-17β-ol-3-one, and is DHT with a methyl group at the C17α position and the C2 carbon replaced with an oxygen atom.[28][29][4] Closely related AAS include the marketed AAS mestanolone (17α-methyl-DHT), oxymetholone (2-hydroxymethylene-17α-methyl-DHT), and stanozolol (a 2,3-pyrazole A ring-fused derivative of 17α-methyl-DHT) and the never-marketed/designer AAS desoxymethyltestosterone (3-deketo-17α-methyl-δ2-DHT), methasterone (2α,17α-dimethyl-DHT), methyl-1-testosterone (17α-methyl-δ1-DHT), and methylstenbolone (2,17α-dimethyl-δ1-DHT).[28][29][4]
Oxandrolone was first made by Raphael Pappo and Christopher J. Jung while at Searle Laboratories (now part of Pfizer). The researchers first described the drug in 1962.[4][30][31] They were immediately interested in oxandrolone’s very weak androgenic effects relative to its anabolic effects.[30][4] It was introduced as a pharmaceutical drug in the United States in 1964.[4]
The drug was prescribed to promote muscle regrowth in disorders which cause involuntary weight loss, and is used as part of treatment for HIV/AIDS.[4] It had also been shown to be partially successful in treating cases of osteoporosis.[4] However, in part due to bad publicity from its illicit use by bodybuilders, production of Anavar was discontinued by Searle Laboratories in 1989.[4] It was picked up by Bio-Technology General Corporation, which changed its name to Savient Pharmaceuticals, which following successful clinical trials in 1995, released it under the brand name Oxandrin.[4] BTG subsequently won approvals for orphan drug status by the Food and Drug Administration for treating alcoholic hepatitis, Turner syndrome, and HIV-induced weight loss.[4] It is also indicated as an offset to protein catabolism caused by long-term administration of corticosteroids.[4]
Oxandrolone is the generic name of the drug and its INN, USAN, USP, BAN, DCF, DCIT, and JAN, while ossandrolone is or was formerly the DCIT.[28][29][32][8][33]
The original brand name of oxandrolone was Anavar, which was marketed in the United States and the Netherlands.[4][34] This product was eventually discontinued and replaced in the United States with a new product named Oxandrin, which is the sole remaining brand name for oxandrolone in the United States.[4][35] Oxandrolone has also been sold under the brand names Antitriol (Spain), Anatrophill (France), Lipidex (Brazil), Lonavar (Argentina, Australia, Italy), Protivar, and Vasorome (Japan), among others.[4][29][34][36] Additional brand names exist for products that are manufactured for the steroid black market.[4]
Among those using oxandrolone for nonmedical purposes, it is often referred to colloquially as “Var”, a shortened form of the brand name Anavar.[37][38][39][self-published source]
Oxandrolone is one of the few AAS that remain available for medical use in the United States.[35] The others (as of November 2017) are testosterone, testosterone cypionate, testosterone enanthate, testosterone undecanoate, methyltestosterone, fluoxymesterone, nandrolone decanoate, and oxymetholone.[35]
Outside of the United States, the availability of oxandrolone is quite limited.[4][8] With the exception of Moldova, it is no longer available in Europe.[4] Oxandrolone is available in some less-regulated markets in Asia such as Malaysia.[4] It is also available in Mexico.[4] Historically, oxandrolone has been marketed in Argentina, Australia, Brazil, France, Italy, Japan, and Spain, but it appears to no longer be available in these countries.[4][29][34][8]
In the United States, oxandrolone is categorized as a Schedule III controlled substance under the Controlled Substances Act along with many other AAS.[10] It is a Schedule IV controlled substance in Canada,[11] and a Schedule 4 controlled drug in the United Kingdom.[12]
Oxandrolone is sometimes used as a doping agent in sports. Cases of doping with oxandrolone by professional athletes have been reported.
An androgen (from Greek andr-, the stem of the word meaning “man”) is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors.[1] This includes the embryological development of the primary male sex organs, and the development of male secondary sex characteristics at puberty. Androgens are synthesized in the testes, the ovaries, and the adrenal glands.
Androgens increase in both boys and girls during puberty.[2] The major androgen in males is testosterone.[3] Dihydrotestosterone (DHT) and androstenedione are of equal importance in male development.[3] DHT in utero causes differentiation of penis, scrotum and prostate. In adulthood, DHT contributes to balding, prostate growth, and sebaceous gland activity.
Although androgens are commonly thought of only as male sex hormones, females also have them, but at lower levels: they function in libido and sexual arousal. Also, androgens are the precursors to estrogens in both men and women.
In addition to their role as natural hormones, androgens are used as medications; for information on androgens as medications, see the androgen replacement therapy and anabolic steroid articles.
قرص oxandrolone چیست
The main subset of androgens, known as adrenal androgens, is composed of 19-carbon steroids synthesized in the zona reticularis, the innermost layer of the adrenal cortex. Adrenal androgens function as weak steroids (though some are precursors), and the subset includes dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA-S), androstenedione (A4), and androstenediol (A5).
Besides testosterone, other androgens include:
Determined by consideration of all biological assay methods (circa 1970):[5]
Ovaries and adrenal gland produce much lower levels than the testes. Regarding the relative contributions of ovaries and adrenal gland to female androgen levels, in a study with six menstruating women the following observations have been made:[6]
During mammalian development, the gonads are at first capable of becoming either ovaries or testes.[7] In humans, starting at about week 4, the gonadal rudiments are present within the intermediate mesoderm adjacent to the developing kidneys. At about week 6, epithelial sex cords develop within the forming testes and incorporate the germ cells as they migrate into the gonads. In males, certain Y chromosome genes, particularly SRY, control development of the male phenotype, including conversion of the early bipotential gonad into testes. In males, the sex cords fully invade the developing gonads.
The mesoderm-derived epithelial cells of the sex cords in developing testes become the Sertoli cells, which will function to support sperm cell formation. A minor population of nonepithelial cells appear between the tubules by week 8 of human fetal development. These are Leydig cells. Soon after they differentiate, Leydig cells begin to produce androgens.
The androgens function as paracrine hormones required by the Sertoli cells to support sperm production. They are also required for masculinization of the developing male fetus (including penis and scrotum formation). Under the influence of androgens, remnants of the mesonephron, the Wolffian ducts, develop into the epididymis, vas deferens and seminal vesicles. This action of androgens is supported by a hormone from Sertoli cells, Müllerian inhibitory hormone (MIH), which prevents the embryonic Müllerian ducts from developing into fallopian tubes and other female reproductive tract tissues in male embryos. MIH and androgens cooperate to allow for movement of testes into the scrotum.
Before the production of the pituitary hormone luteinizing hormone (LH) by the embryo starting at about weeks 11–12, human chorionic gonadotrophin (hCG) promotes the differentiation of Leydig cells and their production of androgens at week 8. Androgen action in target tissues often involves conversion of testosterone to 5α-dihydrotestosterone (DHT).
At the time of puberty, androgen levels increase dramatically in males, and androgens mediate the development of masculine secondary sexual characteristics as well as the activation of spermatogenesis and fertility and masculine behavioral changes such as gynephilia and increased sex drive. Masculine secondary sexual characteristics include androgenic hair, voice deepening, emergence of the Adam’s apple, broadening of the shoulders, increased muscle mass, and penile growth.
During puberty, androgen, LH and follicle stimulating hormone (FSH) production increase and the sex cords hollow out, forming the seminiferous tubules, and the germ cells start to differentiate into sperm. Throughout adulthood, androgens and FSH cooperatively act on Sertoli cells in the testes to support sperm production.[8] Exogenous androgen supplements can be used as a male contraceptive. Elevated androgen levels caused by use of androgen supplements can inhibit production of LH and block production of endogenous androgens by Leydig cells. Without the locally high levels of androgens in testes due to androgen production by Leydig cells, the seminiferous tubules can degenerate, resulting in infertility. For this reason, many transdermal androgen patches are applied to the scrotum.
Males typically have less body fat than females. Recent results indicate androgens inhibit the ability of some fat cells to store lipids by blocking a signal transduction pathway that normally supports adipocyte function.[9] Also, androgens, but not estrogens, increase beta adrenergic receptors while decreasing alpha adrenergic receptors- which results in increased levels of epinephrine/ norepinephrine due to lack of alpha-2 receptor negative feedback and decreased fat accumulation due to epinephrine/ norepinephrine then acting on lipolysis-inducing beta receptors.
Males typically have more skeletal muscle mass than females. Androgens promote the enlargement of skeletal muscle cells and probably act in a coordinated manner to function by acting on several cell types in skeletal muscle tissue.[10] One cell type conveys hormone signals to generating muscle, the myoblast. Higher androgen levels lead to increased expression of androgen receptor. Fusion of myoblasts generates myotubes, in a process linked to androgen receptor levels.[11]
Circulating levels of androgens can influence human behavior because some neurons are sensitive to steroid hormones. Androgen levels have been implicated in the regulation of human aggression and libido. Indeed, androgens are capable of altering the structure of the brain in several species, including mice, rats, and primates, producing sex differences.[12]
Numerous reports have shown androgens alone are capable of altering the structure of the brain,[13] but identification of which alterations in neuroanatomy stem from androgens or estrogens is difficult, because of their potential for conversion.
Evidence from neurogenesis (formation of new neurons) studies on male rats has shown that the hippocampus is a useful brain region to examine when determining the effects of androgens on behavior. To examine neurogenesis, wild-type male rats were compared with male rats that had testicular feminization mutation (TMF), a genetic disorder resulting in complete or partial insensitivity to androgens and a lack of external male genitalia.
Neural injections of Bromodeoxyuridine (BrdU) were applied to males of both groups to test for neurogenesis. Analysis showed that testosterone and dihydrotestosterone regulated adult hippocampal neurogenesis (AHN). Adult hippocampal neurogenesis was regulated through the androgen receptor in the wild-type male rats, but not in the TMF male rats. To further test the role of activated androgen receptors on AHN, flutamide, an antiandrogen drug that competes with testosterone and dihydrotestosterone for androgen receptors, and dihydrotestosterone were administered to normal male rats. Dihydrotestosterone increased the number of BrdU cells, while flutamide inhibited these cells.
Moreover, estrogens had no effect. This research demonstrates how androgens can increase AHN.[14]
Researchers also examined how mild exercise affected androgen synthesis which in turn causes AHN activation of N-methyl-D-aspartate (NMDA) receptors.
NMDA induces a calcium flux that allows for synaptic plasticity which is crucial for AHN.
Researchers injected both orchidectomized (ORX) (castrated) and sham castrated male rats with BrdU to determine if the number of new cells was increased. They found that AHN in male rats is increased with mild exercise by boosting synthesis of dihydrotestosterone in the hippocampus.
Again it was noted that AHN was not increase via activation of the estrogen receptors.[15]
Androgen regulation decreases the likelihood of depression in males. In preadolescent male rats, neonatal rats treated with flutamide developed more depression-like symptoms compared to control rats.
Again BrdU was injected into both groups of rats in order to see if cells were multiplying in the living tissue. These results demonstrate how the organization of androgens has a positive effect on preadolescent hippocampal neurogenesis that may be linked with lower depression-like symptoms.[16]
Social isolation has a hindering effect in AHN whereas normal regulation of androgens increases AHN. A study using male rats showed that testosterone may block social isolation, which results in hippocampal neurogenesis reaching homeostasis—regulation that keeps internal conditions stable. A Brdu analysis showed that excess testosterone did not increase this blocking effect against social isolation; that is, the natural circulating levels of androgens cancel out the negative effects of social isolation on AHN.[17]
Androgens have potential roles in relaxation of the myometrium via non-genomic, androgen receptor-independent pathways, preventing premature uterine contractions in pregnancy.[18]
Reduced ability of an XY-karyotype fetus to respond to androgens can result in one of several conditions, including infertility and several forms of intersex conditions.
Yolk androgen levels in certain birds have been positively correlated to social dominance later in life. See American coot.
Androgens bind to and activate androgen receptors (ARs) to mediate most of their biological effects.
Determined by consideration of all biological assay methods (circa 1970):[5]
5α-Dihydrotestosterone (DHT) was 2.4 times more potent than testosterone at maintaining normal prostate weight and duct lumen mass (this is a measure of epithelial cell function stimulation). Whereas DHT was equally potent as testosterone at preventing prostate cell death after castration.[19]
Androgens have also been found to signal through membrane androgen receptors, which are distinct from the classical nuclear androgen receptor.[20][21][22]
Androgens are synthesized from cholesterol and are produced primarily in the gonads (testicles and ovaries) and also in the adrenal glands. The testicles produce a much higher quantity than the ovaries. Conversion of testosterone to the more potent DHT occurs the prostate gland, liver, brain and skin.
Androgens are metabolized mainly in the liver.
A low testosterone level (hypogonadism) in men may be treated with testosterone administration. Prostate cancer may be treated by removing the major source of testosterone: testicle removal (orchiectomy); or agents which block androgens from accessing their receptor: antiandrogens.
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 are anabolic and increase protein within cells, especially in skeletal muscles, and also have varying degrees of androgenic and 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.
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 only increased when, as they often do, 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.
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.
قرص oxandrolone چیست
Most steroid users are not athletes.[51] In the United States, between 1 million and 3 million people (1% of the population) are thought to have used AAS.[52] Studies in the United States have shown that AAS users tend to be mostly middle-class heterosexual men with a median age of about 25 who are noncompetitive bodybuilders and non-athletes and use the drugs for cosmetic purposes.[53] “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%.[54] 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,[55] though a 2007 study found that sharing of needles was extremely uncommon among individuals using AAS for non-medical purposes, less than 1%.[56] 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.[56] 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.[56] AAS users tend to research the drugs they are taking more than other controlled-substance users; 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.[57]
AAS users tend to be unhappy with the portrayal of AAS as deadly in the media and in politics.[58] According to one study, AAS users also distrust their physicians and in the sample 56% had not disclosed their AAS use to their physicians.[59] 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.[56] 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.[60] A recent study in the Journal of Health Psychology showed that many users believed that steroids used in moderation were safe.[61]
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%.[62] Male students used AAS more frequently than female students and, on average, those that participated in sports used steroids more often than those that did not.
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),[63] 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.[64] 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.[65] Examples of notable designer steroids include 1-testosterone (dihydroboldenone), methasterone, trenbolone enanthate, desoxymethyltestosterone, tetrahydrogestrinone, and methylstenbolone.[65]
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.[66] 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 himself or herself; children and women are highly sensitive to testosterone and can suffer unintended masculinization and health effects, even from small doses. Injection is the most common method used by individuals administering AAS for non-medical purposes.[56]
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][67]
Known possible side effects of AAS include:[7][68][69][70][71]
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.[78] 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.[79] AAS such as testosterone also increase the risk of cardiovascular disease[3] or coronary artery disease.[80][81] Acne is fairly common among AAS users, mostly due to stimulation of the sebaceous glands by increased testosterone levels.[8][82] Conversion of testosterone to DHT can accelerate the rate of premature baldness for males genetically predisposed, but testosterone itself can produce baldness in females.[83]
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.[84]
WHO organization International Agency for Research on Cancer (IARC) list AAS under Group 2A: Probably carcinogenic to humans.[85]
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.[86] These changes are also seen in non-drug-using athletes, but steroid use may accelerate this process.[87][88] 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.[89][90]
AAS use can cause harmful changes in cholesterol levels: Some steroids cause an increase in LDL “bad” cholesterol and a decrease in HDL “good” cholesterol.[91] In addition, steroids provoke a rapid increase in body weight and an accompanying rise in blood pressure, both of which leave users more vulnerable to a cardiovascular event.[citation needed]
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.[92]
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.[93] Reduced sexual function and temporary infertility can also occur in males.[94][95][96] 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.[97]
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.[98] 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.[99]
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.[100]
High doses of oral AAS compounds can cause liver damage.[4] Peliosis hepatis has been increasingly recognised with the use of AAS.
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”.[73] 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.[102] 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.[103] 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.[102] 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.[104] 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.[105]
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.[106]
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.[110] Of 53 bodybuilders who used AAS, 27 (51%) reported unspecified mood disturbance.[111]
From the mid-1980s onward, the media reported “roid rage” as a side effect of AAS.[112]:23
قرص oxandrolone چیست
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.[113] 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.[114] 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.[115]
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.[116][117] 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.[118]
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.[119] A small-scale study of 10 AAS users found that cluster B personality disorders were confounding factors for aggression.[120]
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.[124] AAS are testosterone derivatives designed to maximize the anabolic effects of testosterone.[125] AAS are consumed by elite athletes competing in sports like weightlifting, bodybuilding, and track and field.[126] Male recreational athletes take AAS to achieve an “enhanced” physical appearance.[127]
AAS consumption disrupts the hypothalamic–pituitary–gonadal axis (HPG axis) in males.[124] 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).[128] In adult males, LH stimulates the Leydig cells in the testes to produce testosterone which is required to form new sperm through spermatogenesis.[124] 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.[124]
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[130] or activates processes that send signals to other parts of the cell.[131] Different types of AAS bind to the AAR with different affinities, depending on their chemical structure.[8] Some AAS such as metandienone bind weakly to this receptor in vitro, but still exhibit AR-mediated effects in vivo.[citation needed] The reason for this discrepancy is not known.[132]
The effect of AAS on muscle mass is caused in at least two ways:[133] 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.[134] AAS also affect the number of cells that develop into fat-storage cells, by favouring cellular differentiation into muscle cells instead.[135] AAS can also decrease fat by increasing basal metabolic rate (BMR), since an increase in muscle mass increases BMR.[citation needed]
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.[136][137][138]
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.[139] 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.[140]
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.[66]
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).[132][141] In the early 2000s, this procedure was standardized and generalized throughout OECD in what is now known as the Hershberger assay.
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.[142][143] 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][116] This dose is sufficient to significantly improve lean muscle mass relative to placebo even in subjects that did not exercise at all.[116] The anabolic effects of testosterone enanthate were highly dose dependent.[8][144]
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 is observed in rat bioassays with various AAS relative to the ratio observed with testosterone.[1] Explanations for the dissociation include differences in intracellular metabolism, functional selectivity (recruitment of coactivators), and non-genomic mechanisms (i.e., signaling through non-AR membrane androgen receptors, or mARs).[1] Support for the latter two explanations is limited and more hypothetical, but there is a good deal of support for the intracellular metabolism explanation.[1]
The measurement of the dissociation between anabolic and androgenic effects among AAS is based largely on a simple although arguably unsophisticated and outdated model involving rat tissue bioassays.[1] It is referred to as the myotrophic–androgenic index.[1] In this model, anabolic (myotrophic) 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] Then, the measurements are compared and used to form a ratio.[1]
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, beard-area of the face, pubic area, and genital area (penis and scrotum)), 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.[64]
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.[64]
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.[145][146] Males with this condition are born with ambiguous genitalia and a severely underdeveloped or even absent prostate gland.[145][146] 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.[146][147][148][149][150] They also notably do not develop gynecomastia as a consequence of their condition.[148]
An animal study found that two different kinds of androgen response elements could differentially respond to testosterone and DHT upon activation of the AR.[151][152] Whether this is involved in the differences in the ratios of anabolic-to-myotrophic effect of different AAS is unknown however.[151][152][1]
Testosterone signals not only through the nuclear AR, but also through mARs, including ZIP9 and GPRC6A.[153][154] 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.[154] This indicates that AAS do show differential interactions with the AR and mARs.[154] 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.[155] 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.[155] These women have little or no sebum production, incidence of acne, or body hair growth (including in the pubic and axillary areas).[155] Moreover, CAIS women have lean body mass that is normal for females but is of course greatly reduced relative to males.[156] These observations suggest that the AR is mainly or exclusively responsible for masculinization and myotrophy caused by androgens.[155][156] 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.[154][157]
Changes in endogenous testosterone levels may also contribute to differences in myotrophic–androgenic ratio between testosterone and synthetic AAS.[64] AR agonists are antigonadotropic – that is, they dose-dependently suppress gonadal testosterone production and hence reduce systemic testosterone concentrations.[64] 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.[64] 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.[64] 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%).[50][158] As such, combined progestogenic activity may serve to further increase the myotrophic–androgenic ratio for a given AAS.[64]
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][159][160][161][162][163][164]
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.[64][1][165]
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.[166] Conversely, certain 17α-alkylated AAS like methyltestosterone are 5α-reduced and potentiated in androgenic tissues similarly to testosterone.[1][64] 17α-Alkylated DHT derivatives cannot be potentiated via 5α-reductase however, as they are already 4,5α-reduced.[1][64]
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,[167] voice deepening, and changes in sex drive show no difference.[1][168]
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.[169] 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][170] 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.[170] 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][64] 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,[169] and for this reason, 17α-alkylated AAS can actually have high estrogenicity and comparatively greater estrogenic effects than testosterone.[169][64]
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.[171]
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 (AR) and hence are progestogens in addition to AAS.[1][172] Similarly to the case of estrogenic activity, the progestogenic activity of these drugs serves to augment their antigonadotropic activity.[172] 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).[172]
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).[173][174] 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%).[175] 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%),[176][177] with hepatotoxicity.[1][178][179] In contrast, testosterone esters have only extremely rarely or never been associated with hepatotoxicity,[177] 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).[176][180][63][additional citation(s) needed] In accordance, D-ring glucuronides of testosterone and DHT have been found to be cholestatic.[181]
Aside from prohormones and testosterone undecanoate, almost all orally active AAS are 17α-alkylated.[182] 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][63] 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][172] As these AAS are not 17α-alkylated, they show minimal potential for hepatotoxicity.[1]
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][159][160][161][162][163][164]
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][183][64]
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][183][64]
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.[184][185][186][187]
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.[139] 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.[188]
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.[188][189] 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).”[190] 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.”[191] 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).”[192] 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.[188][189]
Clinical trials on humans, involving either oral doses of methyltestosterone or injections of testosterone propionate, began as early as 1937.[188] Testosterone propionate is mentioned in a letter to the editor of Strength and Health magazine in 1938; this is the earliest known reference to an AAS in a U.S. weightlifting or bodybuilding magazine.[188] 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.[112]:6 Adolf Hitler himself, according to his physician, was injected with testosterone derivatives to treat various ailments.[193] AAS were used in experiments conducted by the Nazis on concentration camp inmates,[193] and later by the allies attempting to treat the malnourished victims that survived Nazi camps.[112]:6 President John F. Kennedy was administered steroids both before and during his presidency.[194]
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.[195] 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 suffered from enlarged prostates and atrophied testes.[196] 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 orally 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 oral and parenteral agents to seeking to obtain different anabolic-to-androgenic effect ratios.[8]
Androgens were discovered in the 1930s and were characterized as having effects described as androgenic (i.e., virilizing) and anabolic (e.g., myotrophic, renotrophic).[64][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.[197] 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.[197]
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.[64][1][198] 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.[64][1][198] (Likewise, all “androgens” are inherently anabolic.)[64][1][198] 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).[64][1][198]
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.[204] 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.[205] 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.[206] AAS are also illegal without prescription in Australia,[207] 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.
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.[208]
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.[209]
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.[210]
AAS are banned by all major sports bodies including Association of Tennis Professionals, Major League Baseball, Fédération Internationale de Football Association[211] the Olympics,[212] the National Basketball Association,[213] the National Hockey League,[214] World Wrestling Entertainment and the National Football League.[215] 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.[216][217] Spain has passed an anti-doping law creating a national anti-doping agency.[218] Italy passed a law in 2000 where penalties range up to three years in prison if an athlete has tested positive for banned substances.[219] In 2006, Russian President Vladimir Putin signed into law ratification of the International Convention Against Doping in Sport which would encourage cooperation with WADA. Many other countries have similar legislation prohibiting AAS in sports including Denmark,[220] France,[221] the Netherlands[222] and Sweden.[223]
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.[224] 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”.[225] 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.
Following the murder-suicide of Chris Benoit in 2007, the Oversight and Government Reform Committee investigated steroid usage in the wrestling industry.[226] The Committee investigated WWE and Total Nonstop Action Wrestling (TNA), 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.[227][228]
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.[229] In these countries, the majority of steroids are obtained illegally through black market trade.[230][231] 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.[232]
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.[233]
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.[234] 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.[235]
AAS, alone and in combination with progestogens, have been studied as potential male hormonal contraceptives.[50] 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.[236][172][237]
Topical androgens have been used and studied in the treatment of cellulite in women.[238] 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.[238] 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.[239]
The kidneys are two bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about 11 centimetres (4.3 in) in length. They receive blood from the paired renal arteries; blood exits into the paired renal veins. Each kidney is attached to a ureter, a tube that carries excreted urine to the bladder.
The nephron is the structural and functional unit of the kidney. Each human adult kidney contains around 1 million nephrons, while a mouse kidney contains only about 12,500 nephrons. The kidney participates in the control of the volume of various body fluid compartments, fluid osmolality, acid-base balance, various electrolyte concentrations, and removal of toxins. Filtration occurs in the glomerulus: one-fifth of the blood volume that enters the kidneys is filtered. Examples of substances reabsorbed are solute-free water, sodium, bicarbonate, glucose, and amino acids. Examples of substances secreted are hydrogen, ammonium, potassium and uric acid. The kidneys also carry out functions independent of the nephron. For example, they convert a precursor of vitamin D to its active form, calcitriol; and synthesize the hormones erythropoietin and renin.
Renal physiology is the study of kidney function. Nephrology is the medical specialty which addresses diseases of kidney function: these include chronic kidney disease, nephritic and nephrotic syndromes, acute kidney injury, and pyelonephritis. Urology addresses diseases of kidney (and urinary tract) anatomy: these include cancer, renal cysts, kidney stones and ureteral stones, and urinary tract obstruction.[1]
Procedures used in the management of kidney disease include chemical and microscopic examination of the urine (urinalysis), measurement of kidney function by calculating the estimated glomerular filtration rate (eGFR) using the serum creatinine; and kidney biopsy and CT scan to evaluate for abnormal anatomy. Dialysis and kidney transplantation are used to treat kidney failure; one (or both sequentially) of these are almost always used when renal function drops below 15%. Nephrectomy is frequently used to cure renal cell carcinoma.
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In humans, the kidneys are located high in the abdominal cavity, one on each side of the spine, and lie in a retroperitoneal position at a slightly oblique angle.[2] The asymmetry within the abdominal cavity, caused by the position of the liver, typically results in the right kidney being slightly lower and smaller than the left, and being placed slightly more to the middle than the left kidney.[3][4][5] The left kidney is approximately at the vertebral level T12 to L3,[6] and the right is slightly lower. The right kidney sits just below the diaphragm and posterior to the liver. The left sits below the diaphragm and posterior to the spleen. On top of each kidney is an adrenal gland. The upper parts of the kidneys are partially protected by the 11th and 12th ribs. Each kidney, with its adrenal gland is surrounded by two layers of fat: the perirenal fat present between renal fascia and renal capsule and pararenal fat superior to the renal fascia.
The kidney is a bean-shaped structure with a convex and a concave border. A recessed area on the concave border is the renal hilum, where the renal artery enters the kidney and the renal vein and ureter leave. The kidney is surrounded by tough fibrous tissue, the renal capsule, which is itself surrounded by perirenal fat, renal fascia, and pararenal fat. The anterior (front) surface of these tissues is the peritoneum, while the posterior (rear) surface is the transversalis fascia.
The superior pole of the right kidney is adjacent to the liver. For the left kidney, it is next to the spleen. Both, therefore, move down upon inhalation.
In adult males, the kidney weighs between 125 and 170 grams. In females the weight of the kidney is between 115 and 155 grams.[7] A Danish study measured the median renal length to be 11.2 cm (4.4 in) on the left side and 10.9 cm (4.3 in) on the right side in adults. Median renal volumes were 146 cm3 on the left and 134 cm3 on the right.[8]
The substance, or parenchyma, of the kidney is divided into two major structures: the outer renal cortex and the inner renal medulla. Grossly, these structures take the shape of eight to 18 cone-shaped renal lobes, each containing renal cortex surrounding a portion of medulla called a renal pyramid.[7] Between the renal pyramids are projections of cortex called renal columns. Nephrons, the urine-producing functional structures of the kidney, span the cortex and medulla. The initial filtering portion of a nephron is the renal corpuscle, which is located in the cortex. This is followed by a renal tubule that passes from the cortex deep into the medullary pyramids. Part of the renal cortex, a medullary ray is a collection of renal tubules that drain into a single collecting duct.
The tip, or papilla, of each pyramid empties urine into a minor calyx; minor calyces empty into major calyces, and major calyces empty into the renal pelvis. This becomes the ureter. At the hilum, the ureter and renal vein exit the kidney and the renal artery enters. Hilar fat and lymphatic tissue with lymph nodes surrounds these structures. The hilar fat is contiguous with a fat-filled cavity called the renal sinus. The renal sinus collectively contains the renal pelvis and calyces and separates these structures from the renal medullary tissue.[9]
The kidneys possess no overtly moving structures.
A CT scan of the abdomen showing the position of the kidneys. The left cross-section in the uper abdomen shows the liver on the left side of scan (right side of body). Center: cross-section showing the kidneys below the liver and spleen. Right: further cross-section through the left kidney.
Image showing the structures that the kidney lies near.
Cross-section through a cadaveric specimen showing the position of the kidneys.
The kidneys receive blood from the renal arteries, left and right, which branch directly from the abdominal aorta. Despite their relatively small size, the kidneys receive approximately 20% of the cardiac output.[7] Each renal artery branches into segmental arteries, dividing further into interlobar arteries, which penetrate the renal capsule and extend through the renal columns between the renal pyramids. The interlobar arteries then supply blood to the arcuate arteries that run through the boundary of the cortex and the medulla. Each arcuate artery supplies several interlobular arteries that feed into the afferent arterioles that supply the glomeruli.
Blood drains from the kidneys, ultimately into the inferior vena cava. After filtration occurs, the blood moves through a small network of small veins (venules) that converge into interlobular veins. As with the arteriole distribution, the veins follow the same pattern: the interlobular provide blood to the arcuate veins then back to the interlobar veins, which come to form the renal veins which exiting the kidney .
The kidney and nervous system communicate via the renal plexus, whose fibers course along the renal arteries to reach each kidney.[10] Input from the sympathetic nervous system triggers vasoconstriction in the kidney, thereby reducing renal blood flow.[10] The kidney also receives input from the parasympathetic nervous system, by way of the renal branches of the vagus nerve; the function of this is yet unclear.[10][11] Sensory input from the kidney travels to the T10-11 levels of the spinal cord and is sensed in the corresponding dermatome.[10] Thus, pain in the flank region may be referred from corresponding kidney.[10]
Renal histology is the study of the microscopic structure of the kidney. Distinct cell types include:
About 20,000 protein coding genes are expressed in human cells and almost 70% of these genes are expressed in normal, adult kidneys.[12][13] Just over 300 genes are more specifically expressed in the kidney, with only some 50 genes being highly specific for the kidney. Many of the corresponding kidney specific proteins are expressed in the cell membrane and function as transporter proteins. The highest expressed kidney specific protein is uromodulin, the most abundant protein in urine with functions that prevent calcification and growth of bacteria. Specific proteins are expressed in the different compartments of the kidney with podocin and nephrin expressed in glomeruli, Solute carrier family protein SLC22A8 expressed in proximal tubules, calbindin expressed in distal tubules and aquaporin 2 expressed in the collecting duct cells.[14]
The mammalian kidney develops from intermediate mesoderm. Kidney development, also called nephrogenesis, proceeds through a series of three successive developmental phases: the pronephros, mesonephros, and metanephros. The metanephros are primordia of the permanent kidney.[15]
The kidneys excrete a variety of waste products produced by metabolism into the urine. The microscopic structural and functional unit of the kidney is the nephron. It processes the blood supplied to it via filtration, reabsorption, secretion and excretion; the consequence of those processes is the production of urine. These include the nitrogenous wastes urea, from protein catabolism, and uric acid, from nucleic acid metabolism. The ability of mammals and some birds to concentrate wastes into a volume of urine much smaller than the volume of blood from which the wastes were extracted is dependent on an elaborate countercurrent multiplication mechanism. This requires several independent nephron characteristics to operate: a tight hairpin configuration of the tubules, water and ion permeability in the descending limb of the loop, water impermeability in the ascending loop, and active ion transport out of most of the ascending limb. In addition, passive countercurrent exchange by the vessels carrying the blood supply to the nephron is essential for enabling this function.
The kidney participates in whole-body homeostasis, regulating acid-base balance, electrolyte concentrations, extracellular fluid volume, and blood pressure. The kidney accomplishes these homeostatic functions both independently and in concert with other organs, particularly those of the endocrine system. Various endocrine hormones coordinate these endocrine functions; these include renin, angiotensin II, aldosterone, antidiuretic hormone, and atrial natriuretic peptide, among others.
Filtration, which takes place at the renal corpuscle, is the process by which cells and large proteins are retained while materials of smaller molecular weights are[16] filtered from the blood to make an ultrafiltrate that eventually becomes urine. The kidney generates 180 liters of filtrate a day. The process is also known as hydrostatic filtration due to the hydrostatic pressure exerted on the capillary walls.
Reabsorption is the transport of molecules from this ultrafiltrate and into the peritubular capillary. It is accomplished via selective receptors on the luminal cell membrane. Water is 55% reabsorbed in the proximal tubule. Glucose at normal plasma levels is completely reabsorbed in the proximal tubule. The mechanism for this is the Na+/glucose cotransporter. A plasma level of 350 mg/dL will fully saturate the transporters and glucose will be lost in the urine. A plasma glucose level of approximately 160 is sufficient to allow glucosuria, which is an important clinical clue to diabetes mellitus.
Amino acids are reabsorbed by sodium dependent transporters in the proximal tubule. Hartnup disease is a deficiency of the tryptophan amino acid transporter, which results in pellagra.[17]
Secretion is the reverse of reabsorption: molecules are transported from the peritubular capillary through the interstitial fluid, then through the renal tubular cell and into the ultrafiltrate.
The last step in the processing of the ultrafiltrate is excretion: the ultrafiltrate passes out of the nephron and travels through a tube called the collecting duct, which is part of the collecting duct system, and then to the ureters where it is renamed urine. In addition to transporting the ultrafiltrate, the collecting duct also takes part in reabsorption.
The kidneys secrete a variety of hormones, including erythropoietin, calcitriol, and renin. Erythropoietin is released in response to hypoxia (low levels of oxygen at tissue level) in the renal circulation. It stimulates erythropoiesis (production of red blood cells) in the bone marrow. Calcitriol, the activated form of vitamin D, promotes intestinal absorption of calcium and the renal reabsorption of phosphate. Renin is an enzyme which regulates angiotensin and aldosterone levels.
Although the kidney cannot directly sense blood, long-term regulation of blood pressure predominantly depends upon the kidney. This primarily occurs through maintenance of the extracellular fluid compartment, the size of which depends on the plasma sodium concentration. Renin is the first in a series of important chemical messengers that make up the renin–angiotensin system. Changes in renin ultimately alter the output of this system, principally the hormones angiotensin II and aldosterone. Each hormone acts via multiple mechanisms, but both increase the kidney’s absorption of sodium chloride, thereby expanding the extracellular fluid compartment and raising blood pressure. When renin levels are elevated, the concentrations of angiotensin II and aldosterone increase, leading to increased sodium chloride reabsorption, expansion of the extracellular fluid compartment, and an increase in blood pressure. Conversely, when renin levels are low, angiotensin II and aldosterone levels decrease, contracting the extracellular fluid compartment, and decreasing blood pressure.
Two organ systems, the kidneys and lungs, maintain acid-base homeostasis, which is the maintenance of pH around a relatively stable value. The lungs contribute to acid-base homeostasis by regulating carbon dioxide (CO2) concentration. The kidneys have two very important roles in maintaining the acid-base balance: to reabsorb and regenerate bicarbonate from urine, and to excrete hydrogen ions and fixed acids (anions of acids) into urine.
The kidneys help maintain the water and salt level of the body. Any significant rise in plasma osmolality is detected by the hypothalamus, which communicates directly with the posterior pituitary gland. An increase in osmolality causes the gland to secrete antidiuretic hormone (ADH), resulting in water reabsorption by the kidney and an increase in urine concentration. The two factors work together to return the plasma osmolality to its normal levels.
Various calculations and methods are used to try and measure kidney function. Renal clearance is the volume of plasma from which the substance is completely cleared from the blood per unit time. The filtration fraction is the amount of plasma that is actually filtered through the kidney. This can be defined using the equation. The kidney is a very complex organ and mathematical modelling has been used to better understand kidney function at several scales, including fluid uptake and secretion.[18][19]
Nephrology is the subspeciality under Internal Medicine that deals with kidney function and disease states related to renal malfunction and their management including dialysis and kidney transplantation. Urology is the specialty under Surgery that deals with kidney structure abnormalities such as kidney cancer and cysts and problems with urinary tract. Nephrologists are internists, and urologists are surgeons, whereas both are often called “kidney doctors”. There are overlapping areas that both nephrologists and urologists can provide care such as kidney stones and kidney related infections.
There are many causes of kidney disease. Some causes are acquired over the course of life, such as diabetic nephropathy whereas others are congenital, such as polycystic kidney disease.
Medical terms related to the kidneys commonly use terms such as renal and the prefix nephro-. The adjective renal, meaning related to the kidney, is from the Latin rēnēs, meaning kidneys; the prefix nephro- is from the Ancient Greek word for kidney, nephros (νεφρός).[20] For example, surgical removal of the kidney is a nephrectomy, while a reduction in kidney function is called renal dysfunction.
Generally, humans can live normally with just one kidney, as one has more functioning renal tissue than is needed to survive. Only when the amount of functioning kidney tissue is greatly diminished does one develop chronic kidney disease. Renal replacement therapy, in the form of dialysis or kidney transplantation, is indicated when the glomerular filtration rate has fallen very low or if the renal dysfunction leads to severe symptoms.
Dialysis is a treatment that substitutes for the function of normal kidneys. Dialysis may be instituted when approximately 85%-90% of kidney function is lost, as indicated by a glomerular filtration rate (GFR) of less than 15. Dialysis removes metabolic waste products as well as excess water and sodium (thereby contributing to regulating blood pressure); and maintains many chemical levels within the body. Life expectancy is 5–10 years for those on dialysis; some live up to 30 years. Dialysis can occur via the blood (through a catheter or arteriovenous fistula), or through the peritoneum (peritoneal dialysis) Dialysis is typically administered three times a week for several hours at free-standing dialysis centers, allowing recipients to lead an otherwise essentially normal life.[21]
Many renal diseases are diagnosed on the basis of a detailed medical history, and physical examination.[citation needed] The medical history takes into account present and past symptoms, especially those of kidney disease; recent infections; exposure to substances toxic to the kidney; and family history of kidney disease.
Kidney function is tested for using blood tests and urine tests. A usual blood test is for urea and electrolytes, known as a U and E. Creatinine is also tested for. Urine tests such as urinalysis can evaluate for pH, protein, glucose, and the presence of blood. Microscopic analysis can also identify the presence of urinary casts and crystals.[25] The glomerular filtration rate (GFR) can be calculated.[25]
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Renal ultrasonography is essential in the diagnosis and management of kidney-related diseases.[26] Other modalities, such as CT and MRI, should always be considered as supplementary imaging modalities in the assessment of renal disease.[26]
The role of the renal biopsy is to diagnose renal disease in which the etiology is not clear based upon noninvasive means (clinical history, past medical history, medication history, physical exam, laboratory studies, imaging studies). In general, a renal pathologist will perform a detailed morphological evaluation and integrate the morphologic findings with the clinical history and laboratory data, ultimately arriving at a pathological diagnosis. A renal pathologist is a physician who has undergone general training in anatomic pathology and additional specially training in the interpretation of renal biopsy specimens.
Ideally, multiple core sections are obtained and evaluated for adequacy (presence of glomeruli) intraoperatively. A pathologist/pathology assistant divides the specimen(s) for submission for light microscopy, immunofluorescence microscopy and electron microscopy.
In the majority of vertebrates, the mesonephros persists into the adult, albeit usually fused with the more advanced metanephros; only in amniotes is the mesonephros restricted to the embryo. The kidneys of fish and amphibians are typically narrow, elongated organs, occupying a significant portion of the trunk. The collecting ducts from each cluster of nephrons usually drain into an archinephric duct, which is homologous with the vas deferens of amniotes. However, the situation is not always so simple; in cartilaginous fish and some amphibians, there is also a shorter duct, similar to the amniote ureter, which drains the posterior (metanephric) parts of the kidney, and joins with the archinephric duct at the bladder or cloaca. Indeed, in many cartilaginous fish, the anterior portion of the kidney may degenerate or cease to function altogether in the adult.[27]
In the most primitive vertebrates, the hagfish and lampreys, the kidney is unusually simple: it consists of a row of nephrons, each emptying directly into the archinephric duct. Invertebrates may possess excretory organs that are sometimes referred to as “kidneys”, but, even in Amphioxus, these are never homologous with the kidneys of vertebrates, and are more accurately referred to by other names, such as nephridia.[27] In amphibians, kidneys and the urinary bladder harbour specialized parasites, monogeneans of the family Polystomatidae.[28]
The kidneys of reptiles consist of a number of lobules arranged in a broadly linear pattern. Each lobule contains a single branch of the ureter in its centre, into which the collecting ducts empty. Reptiles have relatively few nephrons compared with other amniotes of a similar size, possibly because of their lower metabolic rate.[27]
Birds have relatively large, elongated kidneys, each of which is divided into three or more distinct lobes. The lobes consists of several small, irregularly arranged, lobules, each centred on a branch of the ureter. Birds have small glomeruli, but about twice as many nephrons as similarly sized mammals.[27]
The human kidney is fairly typical of that of mammals. Distinctive features of the mammalian kidney, in comparison with that of other vertebrates, include the presence of the renal pelvis and renal pyramids and a clearly distinguishable cortex and medulla. The latter feature is due to the presence of elongated loops of Henle; these are much shorter in birds, and not truly present in other vertebrates (although the nephron often has a short intermediate segment between the convoluted tubules). It is only in mammals that the kidney takes on its classical “kidney” shape, although there are some exceptions, such as the multilobed reniculate kidneys of pinnipeds and cetaceans.[27]
Kidneys of various animals show evidence of evolutionary adaptation and have long been studied in ecophysiology and comparative physiology. Kidney morphology, often indexed as the relative medullary thickness, is associated with habitat aridity among species of mammals[29] and diet (e.g., carnivores have only long loops of Henle).[19]
In ancient Egypt, the kidneys, like the heart, were left inside the mummified bodies, unlike other organs which were removed. Comparing this to the biblical statements, and to drawings of human body with the heart and two kidneys portraying a set of scales for weighing justice, it seems that the Egyptian beliefs had also connected the kidneys with judgement and perhaps with moral decisions.[30]
According to studies in modern and ancient Hebrew, various body organs in humans and animals served also an emotional or logical role, today mostly attributed to the brain and the endocrine system. The kidney is mentioned in several biblical verses in conjunction with the heart, much as the bowels were understood to be the “seat” of emotion – grief, joy and pain.[31] Similarly, the Talmud (Berakhoth 61.a) states that one of the two kidneys counsels what is good, and the other evil.
In the sacrifices offered at the biblical Tabernacle and later on at the temple in Jerusalem, the priests were instructed[32] to remove the kidneys and the adrenal gland covering the kidneys of the sheep, goat and cattle offerings, and to burn them on the altar, as the holy part of the “offering for God” never to be eaten.[33]
In ancient India, according to the Ayurvedic medical systems, the kidneys were considered the beginning of the excursion channels system, the ‘head’ of the Mutra Srotas, receiving from all other systems, and therefore important in determining a person’s health balance and temperament by the balance and mixture of the three ‘Dosha’s – the three health elements: Vatha (or Vata) – air, Pitta – bile, and Kapha – mucus. The temperament and health of a person can then be seen in the resulting color of the urine.[34]
Modern Ayurveda practitioners, a practice which is characterized as pseudoscience,[35] have attempted to revive these methods in medical procedures as part of Ayurveda Urine therapy.[36] These procedures have been called “nonsensical” by skeptics.[37]
The Latin term renes is related to the English word “reins”, a synonym for the kidneys in Shakespearean English (e.g. Merry Wives of Windsor 3.5), which was also the time when the King James Version of the Bible was translated. Kidneys were once popularly regarded as the seat of the conscience and reflection,[38][39] and a number of verses in the Bible (e.g. Ps. 7:9, Rev. 2:23) state that God searches out and inspects the kidneys, or “reins”, of humans, together with the heart.
The kidneys, like other offal, can be cooked and eaten.
Kidneys are usually grilled or sautéed, but in more complex dishes they are stewed with a sauce that will improve their flavor. In many preparations, kidneys are combined with pieces of meat or liver, as in mixed grill. Dishes include the British steak and kidney pie, the Swedish hökarpanna (pork and kidney stew), the French rognons de veau sauce moutarde (veal kidneys in mustard sauce) and the Spanish riñones al Jerez (kidneys stewed in sherry sauce) .[40]
Right Kidney
Kidney
Right Kidney
Right kidney
Left kidney
Kidneys
Left kidney
The liver is an organ only found in vertebrates which detoxifies various metabolites, synthesizes proteins and produces biochemicals necessary for digestion.[2][3][4] In humans, it is located in the right upper quadrant of the abdomen, below the diaphragm. Its other roles in metabolism include the regulation of glycogen storage, decomposition of red blood cells and the production of hormones.[4]
The liver is an accessory digestive gland that produces bile, an alkaline compound which helps the breakdown of fat. Bile aids in digestion via the emulsification of lipids. The gallbladder, a small pouch that sits just under the liver, stores bile produced by the liver which is afterwards moved to the small intestine to complete digestion.[5] The liver’s highly specialized tissue consisting of mostly hepatocytes regulates a wide variety of high-volume biochemical reactions, including the synthesis and breakdown of small and complex molecules, many of which are necessary for normal vital functions.[6] Estimates regarding the organ’s total number of functions vary, but textbooks generally cite it being around 500.[7]
Terminology related to the liver often starts in hepat- from ἡπατο-, from the Greek word for liver.[8]
No way is yet known to compensate for the absence of liver function in the long term, although liver dialysis techniques can be used in the short term. Artificial livers are yet to be developed to promote long-term replacement in the absence of the liver. As of 2018[update],[9] liver transplantation is the only option for complete liver failure.
The liver is a reddish-brown, wedge-shaped organ with four lobes of unequal size and shape. A human liver normally weighs approximately 1.5 kg (3.3 lb),[10] and has a width of about 15 cm (6 in).[11] It is both the heaviest internal organ and the largest gland in the human body.
Located in the right upper quadrant of the abdominal cavity, it rests just below the diaphragm, to the right of the stomach and overlies the gallbladder.[5]
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The liver is connected to two large blood vessels: the hepatic artery and the portal vein and common hepatic duct. The hepatic artery carries oxygen-rich blood from the aorta via the celiac plexus, whereas the portal vein carries blood rich in digested nutrients from the entire gastrointestinal tract and also from the spleen and pancreas.[9] These blood vessels subdivide into small capillaries known as liver sinusoids, which then lead to lobules.
Lobules are the functional units of the liver. Each lobule is made up of millions of hepatic cells (hepatocytes), which are the basic metabolic cells. The lobules are held together by a fine, dense, irregular, fibroelastic connective tissue layer which extends from the fibrous capsule covering the entire liver known as Glisson’s capsule.[4] This extends into the structure of the liver, by accompanying the blood vessels (veins and arteries), ducts, and nerves at the hepatic hilum. The whole surface of the liver except for the bare area, is covered in a serous coat derived from the peritoneum, and this firmly adheres to the inner Glisson’s capsule.
The liver is grossly divided into two parts when viewed from above – a right and a left lobe, and four parts when viewed from below (left, right, caudate, and quadrate lobes).[12]
The falciform ligament divides the liver into a left and right lobe. From below, the two additional lobes are located between the right and left lobes, one in front of the other. A line can be imagined running from the left of the vena cava and all the way forward to divide the liver and gallbladder into two halves.[13] This line is called “Cantlie’s line”.[14]
Other anatomical landmarks include the ligamentum venosum and the round ligament of the liver (ligamentum teres), which further divide the left side of the liver in two sections. An important anatomical landmark, the porta hepatis, divides this left portion into four segments, which can be numbered starting at the caudate lobe as I in an anticlockwise manner. From this parietal view, seven segments can be seen, because the eighth segment is only visible in the visceral view.[15]
On the diaphragmatic surface, apart from a triangular bare area where it connects to the diaphragm, the liver is covered by a thin, double-layered membrane, the peritoneum, that helps to reduce friction against other organs.[16] This surface covers the convex shape of the two lobes where it accommodates the shape of the diaphragm. The peritoneum folds back on itself to form the falciform ligament and the right and left triangular ligaments.[17]
These peritoneal ligaments are not related to the anatomic ligaments in joints, and the right and left triangular ligaments have no known functional importance, though they serve as surface landmarks.[17] The falciform ligament functions to attach the liver to the posterior portion of the anterior body wall.
The visceral surface or inferior surface, is uneven and concave. It is covered in peritoneum apart from where it attaches the gallbladder and the porta hepatis.[16] The fossa of gall bladder lies to the right of the quadrate lobe,occupied by the gallbladder with its cystic duct close to the right end of porta hepatis.
Several impressions on the surface of the liver accommodate the various adjacent structures and organs. Underneath the right lobe and to the right of the gallbladder fossa are two impressions, one behind the other and separated by a ridge. The one in front is a shallow colic impression, formed by the hepatic flexure and the one behind is a deeper renal impression accommodating part of the right kidney and part of the suprarenal gland.[18]
The suprarenal impression is a small, triangular, depressed area on the liver. It is located close to the right of the fossa, between the bare area and the caudate lobe, and immediately above the renal impression. The greater part of the suprarenal impression is devoid of peritoneum and it lodges the right suprarenal gland.[19]
Medial to the renal impression is a third and slightly marked impression, lying between it and the neck of the gall bladder. This is caused by the descending portion of the duodenum, and is known as the duodenal impression.[19]
The inferior surface of the left lobe of the liver presents behind and to the left the gastric impression.[19] This is moulded over the upper front surface of the stomach, and to the right of this is a rounded eminence, the tuber omentale, which fits into the concavity of the lesser curvature of the stomach and lies in front of the anterior layer of the lesser omentum.
Microscopically, each liver lobe is seen to be made up of hepatic lobules. The lobules are roughly hexagonal, and consist of plates of hepatocytes radiating from a central vein.[20][page needed]The central vein joins to the hepatic vein to carry blood out from the liver. A distinctive component of a lobule is the portal triad, which can be found running along each of the lobule’s corners. The portal triad, misleadingly named, consists of five structures: a branch of the hepatic artery, a branch of the hepatic portal vein, and a bile duct, as well as lymphatic vessels and a branch of the vagus nerve.[21] Between the hepatocyte plates are liver sinusoids, which are enlarged capillaries through which blood from the hepatic portal vein and hepatic artery enters via the portal triads, then drains to the central vein.[20][page needed]
Histology, the study of microscopic anatomy, shows two major types of liver cell: parenchymal cells and nonparenchymal cells. About 70–85% of the liver volume is occupied by parenchymal hepatocytes. Nonparenchymal cells constitute 40% of the total number of liver cells but only 6.5% of its volume.[22] The liver sinusoids are lined with two types of cell, sinusoidal endothelial cells, and phagocytic Kupffer cells.[23] Hepatic stellate cells are nonparenchymal cells found in the perisinusoidal space, between a sinusoid and a hepatocyte.[22]
Additionally, intrahepatic lymphocytes are often present in the sinusoidal lumen.[22]
The central area or hepatic hilum, includes the opening known as the porta hepatis which carries the common bile duct and common hepatic artery, and the opening for the portal vein. The duct, vein, and artery divide into left and right branches, and the areas of the liver supplied by these branches constitute the functional left and right lobes. The functional lobes are separated by the imaginary plane, Cantlie’s line, joining the gallbladder fossa to the inferior vena cava. The plane separates the liver into the true right and left lobes. The middle hepatic vein also demarcates the true right and left lobes. The right lobe is further divided into an anterior and posterior segment by the right hepatic vein. The left lobe is divided into the medial and lateral segments by the left hepatic vein.
The hilum of the liver is described in terms of three plates that contain the bile ducts and blood vessels. The contents of the whole plate system are surrounded by a sheath.[24] The three plates are the hilar plate, the cystic plate and the umbilical plate and the plate system is the site of the many anatomical variations to be found in the liver.[24]
In the widely used Couinaud system, the functional lobes are further divided into a total of eight subsegments based on a transverse plane through the bifurcation of the main portal vein.[25] The caudate lobe is a separate structure that receives blood flow from both the right- and left-sided vascular branches.[26][27] The Couinaud classification of liver anatomy divides the liver into eight functionally independent liver segments. Each segment has its own vascular inflow, outflow and biliary drainage. In the centre of each segment are branches of the portal vein, hepatic artery, and bile duct. In the periphery of each segment is vascular outflow through the hepatic veins.[28] The classification system uses the vascular supply in the liver to separate the functional units (numbered I to VIII), with unit 1, the caudate lobe, receiving its supply from both the right and the left branches of portal vein. It contains one or more hepatic veins which drain directly into the inferior vena cava.[25] The remainder of the units (II to VIII) are numbered in a clockwise fashion:[28]
About 20,000 protein coding genes are expressed in human cells and 60% of these genes are expressed in a normal, adult liver.[29][30] Over 400 genes are more specifically expressed in the liver, with some 150 genes highly specific for liver tissue. A large fraction of the corresponding liver specific proteins are mainly expressed in hepatocytes and secreted into the blood and constitute plasma proteins. Other liver specific proteins are certain liver enzymes such as HAO1 and RDH16, proteins involved in bile synthesis such as BAAT and SLC27A5, and transporter proteins involved in the metabolism of drugs, such as ABCB11 and SLC2A2. Examples of highly liver-specific proteins include apolipoprotein A II, coagulation factors F2 and F9, complement factor related proteins, and the fibrinogen beta chain protein.[31]
Organogenesis, the development of the organs takes place from the third to the eighth week during embryogenesis. The origins of the liver lie in both the ventral portion of the foregut endoderm (endoderm being one of the three embryonic germ layers) and the constituents of the adjacent septum transversum mesenchyme. In the human embryo, the hepatic diverticulum is the tube of endoderm that extends out from the foregut into the surrounding mesenchyme. The mesenchyme of septum transversum induces this endoderm to proliferate, to branch, and to form the glandular epithelium of the liver. A portion of the hepatic diverticulum (that region closest to the digestive tube) continues to function as the drainage duct of the liver, and a branch from this duct produces the gallbladder.[32] Besides signals from the septum transversum mesenchyme, fibroblast growth factor from the developing heart also contributes to hepatic competence, along with retinoic acid emanating from the lateral plate mesoderm. The hepatic endodermal cells undergo a morphological transition from columnar to pseudostratified resulting in thickening into the early liver bud. Their expansion forms a population of the bipotential hepatoblasts.[33] Hepatic stellate cells are derived from mesenchyme.[34]
After migration of hepatoblasts into the septum transversum mesenchyme, the hepatic architecture begins to be established, with liver sinusoids and bile canaliculi appearing. The liver bud separates into the lobes. The left umbilical vein becomes the ductus venosus and the right vitelline vein becomes the portal vein. The expanding liver bud is colonized by hematopoietic cells. The bipotential hepatoblasts begin differentiating into biliary epithelial cells and hepatocytes. The biliary epithelial cells differentiate from hepatoblasts around portal veins, first producing a monolayer, and then a bilayer of cuboidal cells. In ductal plate, focal dilations emerge at points in the bilayer, become surrounded by portal mesenchyme, and undergo tubulogenesis into intrahepatic bile ducts. Hepatoblasts not adjacent to portal veins instead differentiate into hepatocytes and arrange into cords lined by sinudoidal epithelial cells and bile canaliculi. Once hepatoblasts are specified into hepatocytes and undergo further expansion, they begin acquiring the functions of a mature hepatocyte, and eventually mature hepatocytes appear as highly polarized epithelial cells with abundant glycogen accumulation. In the adult liver, hepatocytes are not equivalent, with position along the portocentrovenular axis within a liver lobule dictating expression of metabolic genes involved in drug metabolism, carbohydrate metabolism, ammonia detoxification, and bile production and secretion. WNT/β-catenin has now been identified to be playing a key role in this phenomenon.[33]
At birth, the liver comprises roughly 4% of body weight and weighs on average about 120 g (4 oz). Over the course of further development, it will increase to 1.4–1.6 kg (3.1–3.5 lb) but will only take up 2.5–3.5% of body weight.[35]
In the growing fetus, a major source of blood to the liver is the umbilical vein, which supplies nutrients to the growing fetus. The umbilical vein enters the abdomen at the umbilicus and passes upward along the free margin of the falciform ligament of the liver to the inferior surface of the liver. There, it joins with the left branch of the portal vein. The ductus venosus carries blood from the left portal vein to the left hepatic vein and then to the inferior vena cava, allowing placental blood to bypass the liver.
In the fetus, the liver does not perform the normal digestive processes and filtration of the infant liver because nutrients are received directly from the mother via the placenta. The fetal liver releases some blood stem cells that migrate to the fetal thymus, creating the T-cells or T-lymphocytes. After birth, the formation of blood stem cells shifts to the red bone marrow.
After 2–5 days, the umbilical vein and ductus venosus are completely obliterated; the former becomes the round ligament of liver and the latter becomes the ligamentum venosum. In the disorders of cirrhosis and portal hypertension, the umbilical vein can open up again.
The various functions of the liver are carried out by the liver cells or hepatocytes. The liver is thought to be responsible for up to 500 separate functions, usually in combination with other systems and organs. Currently, no artificial organ or device is capable of reproducing all the functions of the liver. Some functions can be carried out by liver dialysis, an experimental treatment for liver failure. The liver also accounts for about 20% of resting total body oxygen consumption.
The liver receives a dual blood supply from the hepatic portal vein and hepatic arteries. The hepatic portal vein delivers around 75% of the liver’s blood supply, and carries venous blood drained from the spleen, gastrointestinal tract, and its associated organs. The hepatic arteries supply arterial blood to the liver, accounting for the remaining quarter of its blood flow. Oxygen is provided from both sources; about half of the liver’s oxygen demand is met by the hepatic portal vein, and half is met by the hepatic arteries.[36] The hepatic artery also has both alpha- and beta-adrenergic receptors; therefore, flow through the artery is controlled, in part, by the splanchnic nerves of the autonomic nervous system.
Blood flows through the liver sinusoids and empties into the central vein of each lobule. The central veins coalesce into hepatic veins, which leave the liver and drain into the inferior vena cava.[21]
The biliary tract is derived from the branches of the bile ducts. The biliary tract, also known as the biliary tree, is the path by which bile is secreted by the liver then transported to the first part of the small intestine, the duodenum. The bile produced in the liver is collected in bile canaliculi, small grooves between the faces of adjacent hepatocytes. The canaliculi radiate to the edge of the liver lobule, where they merge to form bile ducts. Within the liver, these ducts are termed intrahepatic bile ducts, and once they exit the liver, they are considered extrahepatic. The intrahepatic ducts eventually drain into the right and left hepatic ducts, which exit the liver at the transverse fissure, and merge to form the common hepatic duct. The cystic duct from the gallbladder joins with the common hepatic duct to form the common bile duct.[21] The biliary system and connective tissue is supplied by the hepatic artery alone
Bile either drains directly into the duodenum via the common bile duct, or is temporarily stored in the gallbladder via the cystic duct. The common bile duct and the pancreatic duct enter the second part of the duodenum together at the hepatopancreatic ampulla, also known as the ampulla of Vater.
The liver plays a major role in carbohydrate, protein, amino acid, and lipid metabolism.
The liver performs several roles in carbohydrate metabolism: The liver synthesizes and stores around 100 g of glycogen via glycogenesis, the formation of glycogen from glucose. When needed, the liver releases glucose into the blood by performing glycogenolysis, the breakdown of glycogen into glucose.[37] The liver is also responsible for gluconeogenesis, which is the synthesis of glucose from certain amino acids, lactate, or glycerol. Adipose and liver cells produce glycerol by breakdown of fat, which the liver uses for gluconeogenesis.[37]
The liver is responsible for the mainstay of protein metabolism, synthesis as well as degradation. It is also responsible for a large part of amino acid synthesis. The liver plays a role in the production of clotting factors, as well as red blood cell production. Some of the proteins synthesized by the liver include coagulation factors I (fibrinogen), II (prothrombin), V, VII, VIII, IX, X, XI, factor XII|[XII]], XIII, as well as protein C, protein S and antithrombin. In the first trimester fetus, the liver is the main site of red blood cell production. By the 32nd week of gestation, the bone marrow has almost completely taken over that task. The liver is a major site of production for thrombopoietin, a glycoprotein hormone that regulates the production of platelets by the bone marrow.[38]
The liver plays several roles in lipid metabolism: it performs cholesterol synthesis, lipogenesis, and the production of triglycerides, and a bulk of the body’s lipoproteins are synthesized in the liver.
The liver plays a key role in digestion, as it produces and excretes bile (a yellowish liquid) required for emulsifying fats and help the absorption of vitamin K from the diet. Some of the bile drains directly into the duodenum, and some is stored in the gallbladder.
The liver also produces insulin-like growth factor 1, a polypeptide protein hormone that plays an important role in childhood growth and continues to have anabolic effects in adults.
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The liver is responsible for the breakdown of insulin and other hormones. The liver breaks down bilirubin via glucuronidation, facilitating its excretion into bile.
The liver is responsible for the breakdown and excretion of many waste products. It plays a key role in breaking down or modifying toxic substances (e.g., methylation) and most medicinal products in a process called drug metabolism. This sometimes results in toxication, when the metabolite is more toxic than its precursor. Preferably, the toxins are conjugated to avail excretion in bile or urine. The liver breaks down ammonia into urea as part of the urea cycle, and the urea is excreted in the urine.[20]
The oxidative capacity of the liver decreases with aging and therefore any medications that require oxidation (for instance, benzodiazepines) are more likely to accumulate to toxic levels. However, medications with shorter half-lives, such as lorazepam and oxazepam, are preferred in most cases when benzodiazepines are required in regard to geriatric medicine.
The liver is a vital organ and supports almost every other organ in the body. Because of its strategic location and multidimensional functions, the liver is also prone to many diseases.[40] The bare area of the liver is a site that is vulnerable to the passing of infection from the abdominal cavity to the thoracic cavity.
Hepatitis is a common condition of inflammation of the liver. The most usual cause of this is viral, and the most common of these infections are hepatitis A, B, C, D, and E. Some of these infections are sexually transmitted. Inflammation can also be caused by other viruses in the family Herpesviridae such as the herpes simplex virus. Chronic (rather than acute) infection with hepatitis B virus or hepatitis C virus is the main cause of liver cancer.[41] Globally, about 248 million individuals are chronically infected with HBV (with 843,724 in the U.S.)[42] and 142 million are chronically infected with HCV[43] (with 2.7 million in the U.S.[44]). Globally there are about 114 million and 20 million cases of hepatitis A[43] and hepatitis E[45] respectively, but these generally resolve, and do not become chronic. Hepatitis D virus is a “satellite” of hepatitis B virus (can only infect in the presence of hepatitis B), and co-infects nearly 20 million people with hepatitis B, globally.[46]
Hepatic encephalopathy is caused by an accumulation of toxins in the bloodstream that are normally removed by the liver. This condition can result in coma and can prove fatal.
Other disorders caused by excessive alcohol consumption are grouped under alcoholic liver diseases and these include alcoholic hepatitis, fatty liver, and cirrhosis. Factors contributing to the development of alcoholic liver diseases are not only the quantity and frequency of alcohol consumption, but can also include gender, genetics, and liver insult.
Liver damage can also be caused by drugs, particularly paracetamol and drugs used to treat cancer. A rupture of the liver can be caused by a liver shot used in combat sports.
Budd–Chiari syndrome is a condition caused by blockage of the hepatic veins (including thrombosis) that drain the liver. It presents with the classical triad of abdominal pain, ascites and liver enlargement.[47]
Primary biliary cholangitis is an autoimmune disease of the liver.[48][49] It is marked by slow progressive destruction of the small bile ducts of the liver, with the intralobular ducts (Canals of Hering) affected early in the disease.[50] When these ducts are damaged, bile and other toxins build up in the liver (cholestasis) and over time damages the liver tissue in combination with ongoing immune related damage. This can lead to scarring (fibrosis) and cirrhosis. Cirrhosis increases the resistance to blood flow in the liver, and can result in portal hypertension. Congested anastomoses between the portal venous system and the systemic circulation, can be a subsequent condition.
Many diseases of the liver are accompanied by jaundice caused by increased levels of bilirubin in the system. The bilirubin results from the breakup of the hemoglobin of dead red blood cells; normally, the liver removes bilirubin from the blood and excretes it through bile.
There are also many pediatric liver diseases, including biliary atresia, alpha-1 antitrypsin deficiency, alagille syndrome, progressive familial intrahepatic cholestasis, Langerhans cell histiocytosis and hepatic hemangioma a benign tumour the most common type of liver tumour, thought to be congenital. A genetic disorder causing multiple cysts to form in the liver tissue, usually in later life, and usually asymptomatic, is polycystic liver disease. Diseases that interfere with liver function will lead to derangement of these processes. However, the liver has a great capacity to regenerate and has a large reserve capacity. In most cases, the liver only produces symptoms after extensive damage.
Hepatomegaly refers to an enlarged liver and can be due to many causes. It can be palpated in a liver span measurement.
Liver diseases may be diagnosed by liver function tests–blood tests that can identify various markers. For example, acute-phase reactants are produced by the liver in response to injury or inflammation.
The classic symptoms of liver damage include the following:
The diagnosis of liver disease is made by liver function tests, groups of blood tests, that can readily show the extent of liver damage. If infection is suspected, then other serological tests will be carried out. A physical examination of the liver can only reveal its size and any tenderness, and some form of imaging such as an ultrasound or CT scan may also be needed.[52]
Sometimes a liver biopsy will be necessary, and a tissue sample is taken through a needle inserted into the skin just below the rib cage. This procedure may be helped by a sonographer providing ultrasound guidance to an interventional radiologist.[53]
Axial CT image showing anomalous hepatic veins coursing on the subcapsular anterior surface of the liver.[54]
Maximum intensity projection (MIP) CT image as viewed anteriorly showing the anomalous hepatic veins coursing on the anterior surface of the liver
Lateral MIP view in the same patient
A CT scan in which the liver and portal vein are shown.
The liver is the only human internal organ capable of natural regeneration of lost tissue; as little as 25% of a liver can regenerate into a whole liver.[55] This is, however, not true regeneration but rather compensatory growth in mammals.[56] The lobes that are removed do not regrow and the growth of the liver is a restoration of function, not original form. This contrasts with true regeneration where both original function and form are restored. In some other species, such as fish, the liver undergoes true regeneration by restoring both shape and size of the organ.[57] In the liver, large areas of the tissues are formed but for the formation of new cells there must be sufficient amount of material so the circulation of the blood becomes more active.[58]
This is predominantly due to the hepatocytes re-entering the cell cycle. That is, the hepatocytes go from the quiescent G0 phase to the G1 phase and undergo mitosis. This process is activated by the p75 receptors.[59] There is also some evidence of bipotential stem cells, called hepatic oval cells or ovalocytes (not to be confused with oval red blood cells of ovalocytosis), which are thought to reside in the canals of Hering. These cells can differentiate into either hepatocytes or cholangiocytes. Cholangiocytes are the epithelial lining cells of the bile ducts.[60] They are cuboidal epithelium in the small interlobular bile ducts, but become columnar and mucus secreting in larger bile ducts approaching the porta hepatis and the extrahepatic ducts. Research is being carried out on the use of stem cells for the generation of an artificial liver.
Scientific and medical works about liver regeneration often refer to the Greek Titan Prometheus who was chained to a rock in the Caucasus where, each day, his liver was devoured by an eagle, only to grow back each night. The myth suggests the ancient Greeks may have known about the liver’s remarkable capacity for self-repair.[61]
Human liver transplants were first performed by Thomas Starzl in the United States and Roy Calne in Cambridge, England in 1963 and 1967, respectively.
Liver transplantation is the only option for those with irreversible liver failure. Most transplants are done for chronic liver diseases leading to cirrhosis, such as chronic hepatitis C, alcoholism, and autoimmune hepatitis. Less commonly, liver transplantation is done for fulminant hepatic failure, in which liver failure occurs over days to weeks.
Liver allografts for transplant usually come from donors who have died from fatal brain injury. Living donor liver transplantation is a technique in which a portion of a living person’s liver is removed (hepatectomy) and used to replace the entire liver of the recipient. This was first performed in 1989 for pediatric liver transplantation. Only 20 percent of an adult’s liver (Couinaud segments 2 and 3) is needed to serve as a liver allograft for an infant or small child.
More recently,[when?] adult-to-adult liver transplantation has been done using the donor’s right hepatic lobe, which amounts to 60 percent of the liver. Due to the ability of the liver to regenerate, both the donor and recipient end up with normal liver function if all goes well. This procedure is more controversial, as it entails performing a much larger operation on the donor, and indeed there have been at least two donor deaths out of the first several hundred cases. A recent publication has addressed the problem of donor mortality, and at least 14 cases have been found.[62] The risk of postoperative complications (and death) is far greater in right-sided operations than that in left-sided operations.
With the recent advances of noninvasive imaging, living liver donors usually have to undergo imaging examinations for liver anatomy to decide if the anatomy is feasible for donation. The evaluation is usually performed by multidetector row computed tomography (MDCT) and magnetic resonance imaging (MRI). MDCT is good in vascular anatomy and volumetry. MRI is used for biliary tree anatomy. Donors with very unusual vascular anatomy, which makes them unsuitable for donation, could be screened out to avoid unnecessary operations.
MDCT image. Arterial anatomy contraindicated for liver donation
MDCT image. Portal venous anatomy contraindicated for liver donation
MDCT image. 3D image created by MDCT can clearly visualize the liver, measure the liver volume, and plan the dissection plane to facilitate the liver transplantation procedure.
Phase contrast CT image. Contrast is perfusing the right liver but not the left due to a left portal vein thrombus.
Some cultures regard the liver as the seat of the soul.[63]
In Greek mythology, the gods punished Prometheus for revealing fire to humans by chaining him to a rock where a vulture (or an eagle) would peck out his liver, which would regenerate overnight. (The liver is the only human internal organ that actually can regenerate itself to a significant extent.) Many ancient peoples of the Near East and Mediterranean areas practiced a type of divination called haruspicy or hepatomancy, where they tried to obtain information by examining the livers of sheep and other animals.
In Plato, and in later physiology, the liver was thought to be the seat of the darkest emotions (specifically wrath, jealousy and greed) which drive men to action.[64] The Talmud (tractate Berakhot 61b) refers to the liver as the seat of anger, with the gallbladder counteracting this.
The Persian, Urdu, and Hindi languages (جگر or जिगर or jigar) refer to the liver figurative speech to indicate courage and strong feelings, or “their best”; e.g., “This Mecca has thrown to you the pieces of its liver!”.[65] The term jan e jigar, literally “the strength (power) of my liver”, is a term of endearment in Urdu. In Persian slang, jigar is used as an adjective for any object which is desirable, especially women. In the Zulu language, the word for liver (isibindi) is the same as the word for courage.
Humans commonly eat the livers of mammals, fowl, and fish as food. Domestic pig, ox, lamb, calf, chicken, and goose livers are widely available from butchers and supermarkets. In the Romance languages, the anatomical word for “liver” (French foie, Spanish hígado, etc.) derives not from the Latin anatomical term, jecur, but from the culinary term ficatum, literally “stuffed with figs,” referring to the livers of geese that had been fattened on figs.[66]
Liver can be baked, boiled, broiled, fried, stir-fried, or eaten raw (asbeh nayeh or sawda naye in Lebanese cuisine, or liver sashimi in Japanese cuisine). In many preparations, pieces of liver are combined with pieces of meat or kidneys, as in the various forms of Middle Eastern mixed grill (e.g. meurav Yerushalmi). Well-known examples include liver pâté, foie gras, chopped liver, and leverpastej. Liver sausages such as Braunschweiger and liverwurst are also a valued meal. Liver sausages may also be used as spreads. A traditional South African delicacy, skilpadjies, is made of minced lamb’s liver wrapped in netvet (caul fat), and grilled over an open fire.
Animal livers are rich in iron, vitamin A and vitamin B12; and cod liver oil is commonly used as a dietary supplement. Traditionally, some fish livers were valued as food, especially the stingray liver. It was used to prepare delicacies, such as poached skate liver on toast in England, as well as the beignets de foie de raie and foie de raie en croute in French cuisine.[67]
The Humr, one of the tribes in the Baggara ethnic grouping, native to southwestern Kordofan in Sudan and speakers of Shuwa or Chadian Arabic, prepare a ( non-alcoholic ) drink from the liver and bone marrow of the giraffe which they call umm nyolokh, and which they claim is intoxicating ( Arabic سكران sakran ), causing dreams and even waking hallucinations.[68] Anthropologist Ian Cunnison, who accompanied the Humr on one of their giraffe-hunting expeditions in the late 1950s, notes that:
It is said that a person, once he has drunk umm nyolokh, will return to giraffe again and again. Humr, being Mahdists, are strict abstainers [ from alcohol ] and a Humrawi is never drunk ( sakran ) on liquor or beer. But he uses this word to describe the effects which umm nyolokh has upon him.[69]
Cunnison’s remarkable account of an apparently psychoactive mammal found its way from a somewhat obscure scientific paper into more mainstream literature through a conversation between Dr. Wendy James of the Institute of Social and Cultural Anthropology at the University of Oxford and specialist on the use of hallucinogens and intoxicants in society Richard Rudgley, who considered its implications in his popular work The Encyclopedia of Psychoactive Substances. Rudgley hypothesises that the presence of the hallucinogenic compound DMT might account for the putative intoxicating properties of umm nyolokh. [68]
Cunnison himself, on the other hand, had found it hard fully to believe in the literal truth of the Humr’s assertion that their drink was intoxicating:
I can only assume that there is no intoxicating substance in the drink and that the effect it produces is simply a matter of convention, although it may be brought about subconsciously.[69]
The study of entheogens in general – including entheogens of animal origin ( e.g. hallucinogenic fish and toad venom ) – has, however made considerable progress in the sixty-odd years since Cunnison’s report and the idea that some intoxicating principle might reside in giraffe liver no longer seems as far-fetched as it was in Cunnison’s day, although conclusive proof ( or disproof ) will have to await detailed analyses of the animal organ in question and the drink prepared therefrom.[68]
Certain Tungusic peoples formerly prepared a type of arrow poison from rotting animal livers, which was, in later times, also applied to bullets. Russian anthropologist Sergei Mikhailovich Shirokogorov, revered as one of the greatest scholars of Tungusic studies, notes that :
Formerly the using of poisoned arrows was common. For instance, among the Kumarčen, [ a subgroup of the Oroqen ] even in recent times a poison was used which was prepared from decaying liver. * ( Note ) This has been confirmed by the Kumarčen. I am not competent to judge as to the chemical conditions of production of poison which is not destroyed by the heat of explosion. However, the Tungus themselves compare this method [ of poisoning ammunition ] with the poisoning of arrows.[70]
The liver is found in all vertebrates, and is typically the largest visceral (internal) organ. Its form varies considerably in different species, and is largely determined by the shape and arrangement of the surrounding organs. Nonetheless, in most species it is divided into right and left lobes; exceptions to this general rule include snakes, where the shape of the body necessitates a simple cigar-like form. The internal structure of the liver is broadly similar in all vertebrates.[71]
An organ sometimes referred to as a liver is found associated with the digestive tract of the primitive chordate Amphioxus. Although it performs many functions of a liver, it is not considered a true liver but a homolog of the vertebrate liver.[72][73][74] The amphioxus hepatic caecum produces the liver-specific proteins vitellogenin, antithrombin, plasminogen, alanine aminotransferase, and insulin/Insulin-like growth factor (IGF)[75]
نسبت اثر آنابولیک به آندروژنیک آن ۲۴:۶۳۰–۳۲۲
مدت زمان مؤثر ۱۲–۸ ساعت (Active Time)
اکساندرولون (به انگلیسی: Oxandrolone)
نامهای تجارتی: Anavar- Oxandrin
قرص oxandrolone چیست
رده درمانی: درمان کمکی جهت افزایش وزن.
رده فارماکولوژیک: استروئید آنابولیک
اشکال دارویی: قرص ۲٫۵ میلیگرمی
اکساندرولون از مشتقات صناعی تستوسترون و جزو آندروژنهای سنتتیک است و دارای خواص آندروژنیک میباشد. این دارو باعث تحریک آنابولیسم پروتئینها و تحریک اشتها میشود.
۱- درمان کمکی جهت افزایش وزن، به دنبال کاهش وزن ناشی از:
۲- تسکین دردهای استخوانی ناشی از پوکی استخوان
۳-جبران کاتابولیسم پروتئینها به دنبال تجویز طولانی کورتیکواستروئیدها [بیان دیگری برای کاربرد نخست]
۴- درمان هیپرتری گلیسریدمی در مردان.
نکته از کتاب کاتزونگ: یکی از کاربردهای آندروژنها، از جمله آندروژنهای سنتتیک مثل اگزاندرولون و استانوزولول، افزایش وزن در سندرمهای تحلیل برنده (نظیر ایدز) میباشد.
۵-ترمیم تسریع زخمهای پوستی وبهبودعملکردریوی درورزشکاران
دورهٔ درمانی ۲ تا ۴ هفتهاست و در صورت لزوم میتوان این دوره را تکرار نمود.
دوز مؤثر Anavar در ورزشکاران مذکر ۲۰ تا ۱۰۰ میلیگرم در روز و در ورزشکاران مؤنث ۵/۲ تا ۲۰ میلیگرم در روزمیباشد.
توجه: از اکساندرولوندر افراد مسن، نوجوانان، اختلال عملکردکلیه و سابقه آنفارکتوس میوکارد، باید با احتیاط استفاده کرد.
نسبت اثر آنابولیک به آندروژنیک آن ۲۴:۶۳۰–۳۲۲
مدت زمان مؤثر ۱۲–۸ ساعت (Active Time)
اکساندرولون (به انگلیسی: Oxandrolone)
نامهای تجارتی: Anavar- Oxandrin
قرص oxandrolone چیست
رده درمانی: درمان کمکی جهت افزایش وزن.
رده فارماکولوژیک: استروئید آنابولیک
اشکال دارویی: قرص ۲٫۵ میلیگرمی
اکساندرولون از مشتقات صناعی تستوسترون و جزو آندروژنهای سنتتیک است و دارای خواص آندروژنیک میباشد. این دارو باعث تحریک آنابولیسم پروتئینها و تحریک اشتها میشود.
۱- درمان کمکی جهت افزایش وزن، به دنبال کاهش وزن ناشی از:
۲- تسکین دردهای استخوانی ناشی از پوکی استخوان
۳-جبران کاتابولیسم پروتئینها به دنبال تجویز طولانی کورتیکواستروئیدها [بیان دیگری برای کاربرد نخست]
۴- درمان هیپرتری گلیسریدمی در مردان.
نکته از کتاب کاتزونگ: یکی از کاربردهای آندروژنها، از جمله آندروژنهای سنتتیک مثل اگزاندرولون و استانوزولول، افزایش وزن در سندرمهای تحلیل برنده (نظیر ایدز) میباشد.
۵-ترمیم تسریع زخمهای پوستی وبهبودعملکردریوی درورزشکاران
دورهٔ درمانی ۲ تا ۴ هفتهاست و در صورت لزوم میتوان این دوره را تکرار نمود.
دوز مؤثر Anavar در ورزشکاران مذکر ۲۰ تا ۱۰۰ میلیگرم در روز و در ورزشکاران مؤنث ۵/۲ تا ۲۰ میلیگرم در روزمیباشد.
توجه: از اکساندرولوندر افراد مسن، نوجوانان، اختلال عملکردکلیه و سابقه آنفارکتوس میوکارد، باید با احتیاط استفاده کرد.
نسبت اثر آنابولیک به آندروژنیک آن ۲۴:۶۳۰–۳۲۲
مدت زمان مؤثر ۱۲–۸ ساعت (Active Time)
اکساندرولون (به انگلیسی: Oxandrolone)
نامهای تجارتی: Anavar- Oxandrin
قرص oxandrolone چیست
رده درمانی: درمان کمکی جهت افزایش وزن.
رده فارماکولوژیک: استروئید آنابولیک
اشکال دارویی: قرص ۲٫۵ میلیگرمی
اکساندرولون از مشتقات صناعی تستوسترون و جزو آندروژنهای سنتتیک است و دارای خواص آندروژنیک میباشد. این دارو باعث تحریک آنابولیسم پروتئینها و تحریک اشتها میشود.
۱- درمان کمکی جهت افزایش وزن، به دنبال کاهش وزن ناشی از:
۲- تسکین دردهای استخوانی ناشی از پوکی استخوان
۳-جبران کاتابولیسم پروتئینها به دنبال تجویز طولانی کورتیکواستروئیدها [بیان دیگری برای کاربرد نخست]
۴- درمان هیپرتری گلیسریدمی در مردان.
نکته از کتاب کاتزونگ: یکی از کاربردهای آندروژنها، از جمله آندروژنهای سنتتیک مثل اگزاندرولون و استانوزولول، افزایش وزن در سندرمهای تحلیل برنده (نظیر ایدز) میباشد.
۵-ترمیم تسریع زخمهای پوستی وبهبودعملکردریوی درورزشکاران
دورهٔ درمانی ۲ تا ۴ هفتهاست و در صورت لزوم میتوان این دوره را تکرار نمود.
دوز مؤثر Anavar در ورزشکاران مذکر ۲۰ تا ۱۰۰ میلیگرم در روز و در ورزشکاران مؤنث ۵/۲ تا ۲۰ میلیگرم در روزمیباشد.
توجه: از اکساندرولوندر افراد مسن، نوجوانان، اختلال عملکردکلیه و سابقه آنفارکتوس میوکارد، باید با احتیاط استفاده کرد.
Anavar- Oxandrin
درمان کمکی جهت افزایش وزن
استروئید آنابولیک
قرص oxandrolone چیست
قرص ۵/۲ میلی گرمی
اکس آندرلون یک استروئید خوراکی ضعیف با عوارض استروژنی میباشد که وقتی در دوزهای کم استفاده گردد عوارض جانبی برای آن گزارش نشده است. اکس آندرلون از معدود استروئیدهایی است که میتوان برای کودکان و خانمها مورد استفاده قرار داد، زیرا عوارض هورمون مردانه در بدن خانمها ایجاد نمیکند و همچنین در کودکان نیز باعث توقف رشد استخوانها و بسته شدن اپوفیز استخوانها نمیگردد.اکس آندرلون بیشتر در دورههای خشک و کات کردن بدن استفاده میگردد،یعنی به عبارتی بدن ورزشکار با مصرف اوکس آندرلون عضلانی تر به نظر میرسد و عضلات نیز سفت تر و قویتر میگردند.
اکساندرولون از مشتقات صناعی تستوسترون و جزو آندروژنهای سنتتیک است و دارای خواص آندروژنیک میباشد. این دارو باعث تحریک آنابولیسم پروتئینها و تحریک اشتها میشود.
مقالات ارائه شده در بخش استروئیدها و داروهای نیروزا،صرفا جهت افزایش اطلاعات شما در زمینه این داروها میباشد.ضمنا مقادیر گفته شده در این مقالات جنبه تئوری دارند و استفاده از این داروها به هیچ وجه توصیه نمیشود.
دربالغین: ابتدا ، روزانه ۵/۲ میلی گرم از راه خوراکی ، ۲ تا ۴ بار در روز تجویز میشود و سپس دوزهای بعدی بر مبنای پاسخ بالینی بیمار تعیین و بین ۵/۲ تا ۲۰ میلی گرم در روز تنظیم و تجویز میگردد.دور درمانی ۲ تا ۴ هفتهاست و در صورت لزوم میتوان این دوره را تکرار نمود.
در کودکان روزانه ۱/۰ میلی گرم به ازای هر کیلوگرم وزن بدن از راه خوراکی تجویز میشود.در صورت لزوم میتوان این دوره را تکرار نمود.
برای آن که بدانیم اکساندرولون چیست ، ابتدا لازم است بدانیم که استروئید چیست . حتما تا به حال اسم استروئید آنابولیک به گوش شما خورده است ؛ مخصوصا اگر ورزشکار باشید ! استروئید آنابولیک در واقع نوعی لیپید یا چربی هستند که ساختار شیمیایی دارند و ساختار آن ها به گونه ای می باشد که هورمون جنسی مردانه (آندروژن) را در خود جای داده اند . استروئیدها در ابتدا تنها برای درمان های غدد جنسی مردان مورد استفاده قرار می گرفتند . اما با گذشت زمان دانشمندان دریافتند که این دارو قابلیت این را دارد که باعث رشد ماهیچه های اسکلتی (اثرات آنابولیکی) بشود و پس از آن مورد استفاده ورزشکاران قرار گرفت . استروئیدها در حال حاضر مورد استفاده عده ای زیادی از مردم و ورزشکاران قرار گرفته اند . این بدان معنا نیست که استروئیدها کاملا بدون ضرر می باشند . امروزه صد نوع استروئید به بازار عرضه شده است که یکی از انواع آن ، اکساندرولون می باشد . در ادامه قصد داریم به معرفی اکساندرولون بپردازیم .
توجه داشته باشید که در سال 1995 این هورمون توسط شخصی دیگر با نام تجاری الکساندرولون به بازار عرضه شد و هزینه تولید آن بسیار زیاد بود تا جایی که در حال حاضر برخی از داروخانه های آمریکا مانند واتسون هزینه تولید این محصول را بر عهده گرفته اند . اما این مسئله بر گران قیمت بودن الکساندرولون تاثیری نذاشته و این محصول هم چنان با قیمتی بالا در بازار به فروش می رسد . تا به این جا فهمیدیم که آناوار یا همان الکساندرولون چیست و چه تاریخچه ای را پشت سر دارد . حال می خواهیم درباره اثرات این محصول به شما توضیح دهیم .
1-رشد عضلانی :
هر حجمی که توسط الکساندرولون به دست می آید ، یک توده عضلانی عاری از چربی است . برای استفاده از این استروئید ، خوردن آب کافی بسیار مهم است . اما باید بدانید که فرد در حین به دست آوردن وزن و توده عضلانی باید مقداری چربی جامد نیز به دست آورد تا مقدار حجمی که به دست آورده ثابت باقی بماند . در حالی که آناوار، استروئیدی بسیار مناسب برای مردان به شمار نمی رود ، زمانی که برای زنان مورد استفاده قرار می گیرد ، باید استثنائی قائل شویم ؛ چرا که بانوان نسبت به این هورمون حساس تر می باشند . به هر حال بانوان به اندازه مردان انتظار رشد عضلانی ندارند و اغلب به دنبال رشدی جزئی می باشند .صرف نظر از جنسیت ، همه کسانی که از این استروئید استفاده می کنند ، برای افزایش متابولیسم قدردان آن هستند . افرادی که از هورمون الکساندرولون استفاده می کنند ، چربی کمتری نسبت به دیگر افراد به دست می آورند و به علت افزایش سطح تستسترون آزاد ، افراد قوی تر می شوند ؛ ممکن است زیاد نباشد ، اما به هر حال کمکی به بدن تان خواهد کرد .
2-از دست دادن چربی :
بدون شک ، بهترین زمان استفاده از آناوار برای مردان و زنان در زمانی است که در دوره چربی سوزی قرار دارند . این مسئله یکی از شایع ترین دلایل استفاده از این استروئید در ورزشکاران به شمار می رود . یکی از بهترین ویژگی های این محصول ، حفظ بافت چربی در طی مرحله رژیم می باشد . هنگامی که بدن ما چربی می سوزاند ، باید کالری بیشتری مصرف و جایگزین کنیم . رمز یک رژیم غذایی موفق این است که در طول رژیم چربی مناسبی از دست بدهیم ؛ به طوری که در بافت ها چربی باقی بماند . اما مهم نیست که شما در این راه چه قدر تلاش می کنید ، به هر حال عدم وجود آنابولیک قوی سبب می شود که خودبخود تعدادی از عضلات از بین برود . کسانی که در دوره رژیم خود از آنابولیک استفاده کنند ، چربی بیشتر و کارامدتری را می سوزانند .
3-قدرت ورزشی :
یکی از اصلی ترین دلایلی که ورزشکاران از آناوار قدردانی می کنند این است که به آن ها قدرت بسیاری می دهد . استحکام یکی از ویژگی های اصلی یک ورزشکار موفق است ؛ زیرا به سرعت و قدرت تبدیل می شود . در بعضی از شرایط افزایش حجم به ورزش نیز بستگی دارد . اما به هر حال آناوار به عنوان یکی از محبوب ترین استروئید ها در میان ورزشکاران باقی مانده است .
4-عملکرد پیشرفته :
صرف نظر از این که آناوار در حجیم کردن عضلات کمک بسیاری می کند ، کسانی که از این مکمل استفاده می کنند بدن خود را بهبود می بخشد و استقامت عضلانی خود را افزایش می دهد . جالب است بدانید که استروئید ها در درمان کم کاری غدد جنسی ، درمان به تاخیر افتادن بلوغ ، درمان برخی از انواع ناتوانی های جنسی ، درمان تحلیل رفتن بدن آلوده به ویروس ایدز و بهبود بیماری های دیگر مورد استفاده قرار می گیرد . پس استفاده از این استروئید سبب می شود که فرد استحکام و قدرت بیشتری داشته باشد و به همان نسبت بتواند فشار و سختی بیشتری را در تمرینات تحمل کند . البته این بدان معنا نیست که با استفاده از آناوار باید مدت زمان ورزش خود را در طی یک روز بیشتر کنیم و خود را خسته کنیم ؛ به هر حال استفاده از آناوار سبب می شود که بدن در هر جلسه بهتر عمل خواهد کرد و همه ی تمرینات با کیفیت بهتری انجام خواهد شد .
و اما پس از آن که به ویژگی های مثبت این استروئید پرداختیم ، حال می خواهیم شما را با عوارض جانبی این محصول آشنا کنیم . آناوار در بزرگسالان عوارض جانبی کمتری از خود نشان می دهد اما با این حال با استفاده درست و به جا از این محصول ، می توانیم از اثرات منفی آن جلوگیری کنیم . اثرات منفی آناوار را در دسته هایی جداگانه برای شما آورده ایم . با ما همراه باشید !
1-استروژن :
هورمون الکساندرولون عوارض جانبی هورمون استروژنی را ندارد . به دلیل افزایش سطح استروژن نمی تواند باعث بروز مشکلات سینوزیتی شود . هم چنین لازم است بدانید که این استروئید به دلیل نگه نداشتن آب زیاد ، خطر ابتلا به فشار خون بالا را کاهش می دهد . نگهداری آب زیاد سبب بالا رفتن فشار خون می شود . برخی از استروئید ها باعث افزایش فشار خون می شوند ، اما این مسئله در آناوار به ندرت مشاهده شده است .
2-آندروژنی :
اکساندرولون استروئید آندروژنی قوی نیست ، اما در آن فعالیت آندروژنیک وجود دارد . چنین فعالیتی می تواند باعث ایجاد جوش و آکنه و هم چنین ریزش مو در افرادی که زمینه طاسی را دارند ، بشود . اما به دلیل این که وجود آندروژنیک بسیار کم است ، خطر ابتلا به این مشکل نیز بسیار کم است . اما طبیعت آندروژنیک ، هر چند کوچک ، می تواند خطر ابتلا به بیماری مردانه شدن در زنان را افزایش دهد . علائم این بیماری عبارتند از رشد مو در بدن ، کلفت شدن صدا و …
خوشبختانه امکان ابتلا به این بیماری بسیار کم است ؛ اکثر زنان می توانند بدون ابتلا به این بیماری ها ، به آن چه که می خواهند برسند . اما در نظر داشته باشید که همیشه مسئله واکنش فردی وجود دارد . هورمون اکساندرولون هم چنان به عنوان یک استروئید بسیار مطمئن برای زنان مورد استفاده قرار می گیرد . اگر علائم بیماری مردانه در بدن تان به هر دلیلی بروز داده شود ، شما موظف هستنید که مصرف آن را فورا قطع کنید تا علائم از بین بروند . ار علائم نادیده گرفته شوند ، ممکن است به طور دائمی در بدن تان باقی بمانند .
3-قلب و عروق :
عوارض جانبی آناوار بیشتر در حیطه کلسترول قرار دارد . هورمون اکساندرولون اغلب برای کاهش کلسترول HDL و افزیش کلسترول LDL شناخته شده است . دوزهای استانداردی که جهت درمان برای مردان مورد استفاده قرار می گیرد می تواند تا 30% کلسترول HDL را کاهش دهد و از طرفی میزان کارایی HDL را تا 50% افزایش دهد . هم چنین ممکن است کلسترل LDL را تا 30% افزایش دهد . با توجه به تاثیر منفی که اکساندرولون بر روی کلسترول می گذارد ، اگر از هر نوع بیماری کلسترولی رنج می برید ، هرگز نباید از این استروئید مصرف کنید . و در صورتی که به این بیماری مبتلا نیستید و زندگی سالمی دارید ، در استفاده از این استروئید باید رژیم غذایی بسیار مناسب و سالمی را برای خود در نظر بگیرید و ورزش های هوازی را در اولویت قرار دهید تا با سلامتی قلب و عروق خود نتیجه مثبتی به دست آورید .
4-تستسترون :
استفاده از استروئید آنابولیک تولید تستسترون طبیعی را مهار می کند ؛ آنوار یک استروئید کاهش دهنده تستسترون خفیف در بازار به شمار می رود و اگر شما قصد استفاده از استروئید دیگری را دارید باید به شما بگویم که کاهش تستسترون در آنوار از دیگر استروئید ها بسیار کم تر می باشد . اما به طور معمول اکثر مردان دوست دارند که یک تستسترون خارجی را به مکمل غذایی خود اضافه کنند . عدم انجام این کار سبب می شود که مقدار تستسترون کاهش یابد و علائم بدی را در بدن ایجاد کند . اما توجه داشته باشید که میزان کم و زیاد شدن تستسترون رابطه مستقیمی با بدن طبیعی فرد دارد . همانند دیگر استروئید ها ، اگر علائم بدی در بدن ظاهر شود ، با قطع سریع آن می توان تمام علائم را از بدن پاک کرد و از آن طرف تولید طبیعی تستسترون آغاز می شود .
5-سم کبد :
آنابولیک به عنوان یک استروئید برای کبد سمی است . به طور معمول استفاده از این استروئید میزان آنزیم های کبد را افزایش می دهد . اما توجه داشته باشید که استروئید آنابولیک اگر در جهت درمان و با دوزهای پزشکی و درمانی مورد استفاده قرار بگیرد ، میزان آنزیم های کبد را زیاد افزایش نمی دهد . توجه داشته باشید که افزایش آنزیم های کبد معادل با آسیب کبدی نیست ؛ بلکه وجود استرس هایی است که می تواند منجر به آسیب شود .
پس توجه داشته باشید که اگر شما از بیماری کبدی رنج می برید ، هرگز نباید از آناوار یا هر استروئید دیگری استفاده کنید .
در هنگام استفاده از استروئید آنابولیک هرگز نباید از نوشیدنی های الکلی استفاده کنید ؛ زیرا این امر باعث بروز مشکلات کبدی خواهد شد . هم چنین بهتر است که مصرف داروهای ضد مخدر را کنار بگذارید .
شما باید دوره مصرفی اکساندرولون را به 8 هفته محدود کنید تا با مشکلات کبدی و افزایش آنزیم ها مواجه نشوید .
دوزهای استاندارد استفاده از آناوار ، 5 تا 10 میلی گرم در روز بین 2 تا 4 هفته است که پس از 4 هفته باید میزان آن کمتر شود . برای کسانی که ورزشکار هستند ، روزانه بین 20 تا 30 میلی رم استفاده از این استروئید توصیه می شود . در بعضی از موارد استفاده از استروئید بین 40 تا 50 میلی گرم بسیار کارامد خواهد بود و اگر قصد افزایش استفاده بیشتر از 50 میلی گرم از این استروئید را دارید ، باید مشکلات و عوارض جانبی آن را در نظر بگیرید . دوره استفاده مردان بین 6 تا 8 هفته می باشد . برای ورزشکاران خانم ، استفاده روزانه بین 5 تا 10 میلی گرم توصیه می شود . اگر دوز را افزایش دهید ، امکان بروز عوارض جانبی بیشتر می شود .
به طور کلی نمی توان آناوار را یک استروئید آنابولیک بسیار قوی دانست ؛ اما می توانیم آن را بسیار مفید بدانیم . توجه داشته باشید که اگر در مدتی کوتاه انتظار معجزه و به دست آوردن حجم عظیمی از ماهیچه عضلانی هستید ، سخت در اشتباهید و ناامید خواهید شد . هیچ چیزی بدون تلاش به راحتی به دست نمی آید و اگر این اتفاق رخ دهد ، عوارض جانبی در پیش دارد و همیشگی نیست . اگر به دنبال به دست آوردن حجمی عظیم نیستید و می خواهید تنها تحولاتی در بدن خود ایجاد کنید ، باید به شما بگوییم که بهترین انتخاب برای شما می تواند آناوار باشد .
سایت باشگاهها مطالب منتشر شده را در جهت آگاهی ورزشکاران عزیز منتشر مینماید و توصیه مینماید برای مصرف هرگونه مکمل، دارو و یا خوراکی بایستی با متخصص مشورت نمایید .ما معتقدیم که نظرات و پیشنهادات شما دوستان و مخاطبین گرامی می تواند ما را در پیشبرد و تولید محتوای با کیفیت تر یاری نماید. پس اگر در این زمینه اطلاعات ارزشمندی دارید می توانید با ما درمیان بگذارید.
قرص oxandrolone چیست
اگر می خواهید آخرین اخبار ما را مستقیما به ایمیل خود دریافت کنید، لطفا آدرس ایمیل خود را پایین وارد کنید. اشتراک رایگان است و شما می توانید در هر زمان لغو کنید.
طراحی سایت نیودیتا
قرص اکساندرولون (Oxandrolone) از داروهای تحریک کننده اشتها است که به افزایش وزن کمک میکند. سردرد و بی خوابی از عوارض قرص اکساندرولون است.
اگرچه چاقی یکی از مشکلات جسمانی است که باید با تغذیه درست رفع گردد اما لاغری بیش از اندازه هم میتواند برای خیلیها ناخوشایند باشد. برای رفع لاغری داروهای مختلفی جهت افزایش اشتها تولید میشود که یکی از آنها قرص اکساندرولون میباشد. با”ستاره” همراه شوید تا درباره آن بیشتر بدانید.
قرص اکساندرولون (Oxandrolone) از مشتقات صناعی تستوسترون و جزو آندروژنهای سنتتیک است و دارای خواص آندروژنیک میباشد.
این دارو باعث تحریک آنابولیسم پروتئینها و تحریک اشتها میشود. اکس آندرلون از معدود استروئیدهایی است که میتوان برای کودکان و خانمها مورد استفاده قرار داد، زیرا عوارض هورمون مردانه در بدن خانمها ایجاد نمیکند. همچنین بدن ورزشکار با مصرف اوکساندرلون عضلانیتر به نظر میرسد و عضلات نیز سفتتر و قویتر میگردند.
این دار و به شکل قرصهای ۲.۵ میلیگرمی تولید شده و به سرعت از مجرای گوارش جذب میشود. دفع دارو عمدتا از طریق ادرار و به صورت متابولیت و داروی تغییر نیافته است.
قرص oxandrolone چیست
کمک به افزایش وزن
تسکین درد ناشی از پوکی استخوان
درمان هیپرتری گلیسریدمی در مردان
ترمیم تسریع زخمهای پوستی
بهبود عملکرد ریوی در ورزشکاران
سردرد، بیخوابی، افسردگی، اختلالات قاعدگی، آتروفی بیضهها، بزرگی پستانها، آکنه، رشد غیرطبیعی مو، تهوع، استفراغ، درد شکم، افزایش وزن، خشونت صدا و اقزایش کلسترول
داروهای محرک فعالیت آنزیمهای کبدی، داروهای ضد دیابت خوراکی، داروهای ضد انعقاد خوراکی
میزان مصرف این دارو در بزرگسالان و کودکان متفاوت است. بهتر است میزان دقیق مصرف توسط پزشک تعیین گردد:
بزرگسالان: ابتدا ، روزانه ۵/۲ میلیگرم از راه خوراکی ، ۲ تا ۴ بار در روز تجویز میشود و سپس دوزهای بعدی بر مبنای پاسخ بالینی بیمار تعیین و بین ۵/۲ تا ۲۰ میلیگرم در روز تنظیم و تجویز میگردد. دور درمانی ۲ تا ۴ هفته است و در صورت لزوم میتوان این دوره را تکرار نمود.
کودکان: روزانه ۱/۰ میلیگرم به ازای هر کیلوگرم وزن بدن از راه خوراکی تجویز میشود. در صورت لزوم میتوان این دوره را تکرار نمود.
توجه: کسانی که با مصرف این دارو دچار دردهای شکمی میشوند باید دارو را با چند ساعت فاصله از وعده غذایی مصرف کنند.
توجه: مصرف روزانه بیش از ۶ قرص از این دارو در زنان توصیه نمیشود و در صورت مصرف افراطی عوارض جانبی از قبیل آکنه، خشونت صدا، بزرگی کلیتوریس و افزایش رشد موهای زاید در بدن مشاهده میشود.
مصرف این دارو در دوران شیردهی توصیه نمیشود.
دارو را در دمای ۱۵ الی ۳۰ درجه سانتیگراد نگهداری کنید.
چنانچه سابقه حساسیت به دارو را دارید موضوع را با پزشک در میان بگذارید.
این دارو در اختلالات کبدی، زیادی قند خون، زیادی کلسیم خون، بارداری و در مردان مبتلا به سرطان سینه و پروستات نباید مصرف شود.
این دارو در مواردی که فرد مصرف کننده مبتلا به بیماری هایی همچون ناراحتیهای قلبی – عروقی، نارسایی کلیوی و کبدی، صرع، میگرن و یا دیابت میباشد باید با احتیاط مصرف شود.
در صورت پیدایش هیپرکلسمی در بیماران مبتلا به سرطان سینه مصرف قرص اکساندرولون را متوقف کرده و به پزشک اطلاع دهید.
وزن بیمار را در سرتاسر دوره درمان کنترل کنید. علایم و نشانههای یرقان و پیدایش ادم راکنترل کنید.
به زنان بیاموزید علایم پیدایش ویژگیهای مردانه شامل آکنه و تغییرات در دورههای قاعدگی را گزارش کنند.
به مردان بیاموزید تا نعوظهای بسیار مکرر یا طولانی و همچنین ظهور یا تشدید آکنه را گزارش کنند.
به افراد دیابتی که داروهای خوراکی مصرف میکنند توصیه کنید تا علایم و نشانههای هیپوگلیسمی را کنترل کنند.
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دیدگاه
وبسایت
0245-0271-11
Updated
July 10, 2017
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Rx only
قرص oxandrolone چیست
Oxandrolone Tablets, USP, oral tablets, contain 2.5 mg of the anabolic steroid oxandrolone. Oxandrolone is 17β-hydroxy-17α-methyl-2-oxa-5α-androstan-3-one with the following structural formula:
Inactive ingredients include anhydrous lactose, hypromellose, magnesium stearate, and pregelatinized starch.
Meets USP Dissolution Test 3.
Anabolic steroids are synthetic derivatives of testosterone. Certain clinical effects and adverse reactions demonstrate the androgenic properties of this class of drugs. Complete dissociation of anabolic and androgenic effects has not been achieved. The actions of anabolic steroids are therefore similar to those of male sex hormones with the possibility of causing serious disturbances of growth and sexual development if given to young children. Anabolic steroids suppress the gonadotropic functions of the pituitary and may exert a direct effect upon the testes.
During exogenous administration of anabolic androgens, endogenous testosterone release is inhibited through inhibition of pituitary luteinizing hormone (LH). At large doses, spermatogenesis may be suppressed through feedback inhibition of pituitary follicle-stimulating hormone (FSH).
Anabolic steroids have been reported to increase low-density lipoproteins and decrease high-density lipoproteins. These levels revert to normal on discontinuation of treatment.
In a single dose pharmacokinetic study of oxandrolone in elderly subjects, the mean elimination half-life was 13.3 hours. In a previous single dose pharmacokinetic study in younger volunteers, the mean elimination half-life was 10.4 hours. No significant differences between younger and elderly volunteers were found for time to peak, peak plasma concentration or AUC after a single dose of oxandrolone. The correlation between plasma level and therapeutic effect has not been defined.
Oxandrolone Tablets, USP are indicated as adjunctive therapy to promote weight gain after weight loss following extensive surgery, chronic infections, or severe trauma, and in some patients who without definite pathophysiologic reasons fail to gain or to maintain normal weight, to offset the protein catabolism associated with prolonged administration of corticosteroids, and for the relief of the bone pain frequently accompanying osteoporosis (see DOSAGE AND ADMINISTRATION).
Oxandrolone is classified as a controlled substance under the Anabolic Steroids Control Act of 1990 and has been assigned to Schedule III (non-narcotic).
PELIOSIS HEPATIS, A CONDITION IN WHICH LIVER AND SOMETIMES SPLENIC TISSUE IS REPLACED WITH BLOOD-FILLED CYSTS, HAS BEEN REPORTED IN PATIENTS RECEIVING ANDROGENIC ANABOLIC STEROID THERAPY. THESE CYSTS ARE SOMETIMES PRESENT WITH MINIMAL HEPATIC DYSFUNCTION, BUT AT OTHER TIMES THEY HAVE BEEN ASSOCIATED WITH LIVER FAILURE. THEY ARE OFTEN NOT RECOGNIZED UNTIL LIFE-THREATENING LIVER FAILURE OR INTRA-ABDOMINAL HEMORRHAGE DEVELOPS. WITHDRAWAL OF DRUG USUALLY RESULTS IN COMPLETE DISAPPEARANCE OF LESIONS.
LIVER CELL TUMORS ARE ALSO REPORTED. MOST OFTEN THESE TUMORS ARE BENIGN AND ANDROGEN-DEPENDENT, BUT FATAL MALIGNANT TUMORS HAVE BEEN REPORTED. WITHDRAWAL OF DRUG OFTEN RESULTS IN REGRESSION OR CESSATION OF PROGRESSION OF THE TUMOR. HOWEVER, HEPATIC TUMORS ASSOCIATED WITH ANDROGENS OR ANABOLIC STEROIDS ARE MUCH MORE VASCULAR THAN OTHER HEPATIC TUMORS AND MAY BE SILENT UNTIL LIFE-THREATENING INTRA-ABDOMINAL HEMORRHAGE DEVELOPS. BLOOD LIPID CHANGES THAT ARE KNOWN TO BE ASSOCIATED WITH INCREASED RISK OF ATHEROSCLEROSIS ARE SEEN IN PATIENTS TREATED WITH ANDROGENS OR ANABOLIC STEROIDS. THESE CHANGES INCLUDE DECREASED HIGH-DENSITY LIPOPROTEINS AND SOMETIMES INCREASED LOW-DENSITY LIPOPROTEINS. THE CHANGES MAY BE VERY MARKED AND COULD HAVE A SERIOUS IMPACT ON THE RISK OF ATHEROSCLEROSIS AND CORONARY ARTERY DISEASE.
Cholestatic hepatitis and jaundice may occur with 17-alpha-alkylated androgens at a relatively low dose. If cholestatic hepatitis with jaundice appears or if liver function tests become abnormal, oxandrolone should be discontinued and the etiology should be determined. Drug-induced jaundice is reversible when the medication is discontinued.
In patients with breast cancer, anabolic steroid therapy may cause hypercalcemia by stimulating osteolysis. Oxandrolone therapy should be discontinued if hypercalcemia occurs.
Edema with or without congestive heart failure may be a serious complication in patients with pre-existing cardiac, renal, or hepatic disease. Concomitant administration of adrenal cortical steroid or ACTH may increase the edema.
In children, androgen therapy may accelerate bone maturation without producing compensatory gain in linear growth. This adverse effect results in compromised adult height. The younger the child, the greater the risk of compromising final mature height. The effect on bone maturation should be monitored by assessing bone age of the left wrist and hand every 6 months (see PRECAUTIONS, Laboratory Tests).
Geriatric patients treated with androgenic anabolic steroids may be at an increased risk for the development of prostatic hypertrophy and prostatic carcinoma.
ANABOLIC STEROIDS HAVE NOT BEEN SHOWN TO ENHANCE ATHLETIC ABILITY.
Concurrent dosing of oxandrolone and warfarin may result in unexpectedly large increases in the International Normalized Ratio (INR) or prothrombin time (PT). When oxandrolone is prescribed to patients being treated with warfarin, doses of warfarin may need to be decreased significantly to maintain the desirable INR level and diminish the risk of potentially serious bleeding (see PRECAUTIONS, Drug Interactions).
Women should be observed for signs of virilization (deepening of the voice, hirsutism, acne, clitoromegaly). Discontinuation of drug therapy at the time of evidence of mild virilism is necessary to prevent irreversible virilization. Some virilizing changes in women are irreversible even after prompt discontinuance of therapy and are not prevented by concomitant use of estrogens. Menstrual irregularities may also occur.
Anabolic steroids may cause suppression of clotting factors II, V, VII, and X, and an increase in prothrombin time.
The physician should instruct patients to report immediately any use of warfarin and any bleeding.
The physician should instruct patients to report any of the following side effects of androgens:
Oxandrolone, at daily doses of 5 mg bid and 10 mg bid, was evaluated in four clinical trials involving a total of 339 patients with different underlying medical conditions. The maximum duration of treatment was 4 months with the average duration of treatment from 68.5 days to 94.7 days across the studies. A total of 172 elderly patients (≥ 65 years of age) received oxandrolone treatment. Mean weight gain was similar in those ≥ 65 and those < 65 years of age. No significant differences in efficacy were detected between the 5 mg bid and 10 mg bid daily doses. The adverse event profiles were similar between the two age groups although the elderly, particularly in women, had a greater sensitivity to fluid retention and increases in hepatic transaminases. A single dose pharmacokinetic study in elderly volunteers revealed an increased half-life when compared to younger volunteers (see CLINICAL PHARMACOLOGY). Based on greater sensitivity to drug-induced fluid retention and transaminase elevations, a lower dose is recommended in the elderly (see DOSAGE AND ADMINISTRATION).
قرص oxandrolone چیست
Women with disseminated breast carcinoma should have frequent determination of urine and serum calcium levels during the course of therapy (see WARNINGS).
Because of the hepatotoxicity associated with the use of 17-alpha-alkylated androgens, liver function tests should be obtained periodically.
Periodic (every 6 months) x-ray examinations of bone age should be made during treatment of children to determine the rate of bone maturation and the effects of androgen therapy on the epiphyseal centers.
Androgenic anabolic steroids have been reported to increase low-density lipoproteins and decrease high-density lipoproteins. Therefore, caution is required when administering these agents to patients with a history of cardiovascular disease or who are at risk for cardiovascular disease. Serum determination of lipid levels should be performed periodically and therapy adjusted accordingly.
Hemoglobin and hematocrit should be checked periodically for polycythemia in patients who are receiving high doses of anabolic steroids.
Anabolic steroids may increase sensitivity to oral anticoagulants. Dosage of the anticoagulant may have to be decreased in order to maintain desired prothrombin time. Patients receiving oral anticoagulant therapy require close monitoring, especially when anabolic steroids are started or stopped.
A multidose study of oxandrolone, given as 5 or 10 mg bid in 15 healthy subjects concurrently treated with warfarin, resulted in a mean increase in S-warfarin half-life from 26 to 48 hours and AUC from 4.55 to 12.08 ng∙hr/mL; similar increases in R-warfarin half-life and AUC were also detected. Microscopic hematuria (9/15) and gingival bleeding (1/15) were also observed. A 5.5-fold decrease in the mean warfarin dose from 6.13 mg/day to 1.13 mg/day (approximately 80 to 85% reduction of warfarin dose), was necessary to maintain a target INR of 1.5. When oxandrolone therapy is initiated in a patient already receiving treatment with warfarin, the INR or prothrombin time (PT) should be monitored closely and the dose of warfarin adjusted as necessary until a stable target INR or PT has been achieved.
Furthermore, in patients receiving both drugs, careful monitoring of the INR or PT, and adjustment of the warfarin dosage if indicated are recommended when the oxandrolone dose is changed or discontinued. Patients should be closely monitored for signs and symptoms of occult bleeding.
Oxandrolone may inhibit the metabolism of oral hypoglycemic agents.
In patients with edema, concomitant administration with adrenal cortical steroids or ACTH may increase the edema.
Anabolic steroids may decrease levels of thyroxine-binding globulin, resulting in decreased total T4 serum levels and increased resin uptake of T3 and T4. Free thyroid hormone levels remain unchanged. In addition, a decrease in PBI and radioactive iodine uptake may occur.
Oxandrolone has not been tested in laboratory animals for carcinogenic or mutagenic effects. In 2-year chronic oral rat studies, a dose-related reduction of spermatogenesis and decreased organ weights (testes, prostate, seminal vesicles, ovaries, uterus, adrenals, and pituitary) were shown.
Liver cell tumors have been reported in patients receiving long-term therapy with androgenic anabolic steroids in high doses (see WARNINGS). Withdrawal of the drugs did not lead to regression of the tumors in all cases.
Geriatric patients treated with androgenic anabolic steroids may be at an increased risk for the development of prostatic hypertrophy and prostatic carcinoma.
(see CONTRAINDICATIONS).
It is not known whether anabolic steroids are excreted in human milk. Because of the potential of serious adverse reactions in nursing infants from oxandrolone, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Anabolic agents may accelerate epiphyseal maturation more rapidly than linear growth in children and the effect may continue for 6 months after the drug has been stopped. Therefore, therapy should be monitored by x-ray studies at 6-month intervals in order to avoid the risk of compromising adult height. Androgenic anabolic steroid therapy should be used very cautiously in children and only by specialists who are aware of the effects on bone maturation (see WARNINGS).
Patients with moderate to severe COPD or COPD patients who are unresponsive to bronchodilators should be monitored closely for COPD exacerbation and fluid retention.
The following adverse reactions have been associated with use of anabolic steroids:
Hepatic: Cholestatic jaundice with, rarely, hepatic necrosis and death. Hepatocellular neoplasms and peliosis hepatis with long-term therapy (see WARNINGS). Reversible changes in liver function tests also occur including increased bromsulfophthalein (BSP) retention, changes in alkaline phosphatase and increases in serum bilirubin, aspartate aminotransferase (AST, SGOT) and alanine aminotransferase (ALT, SGPT).
In Males Prepubertal: Phallic enlargement and increased frequency or persistence of erections.
Postpubertal: Inhibition of testicular function, testicular atrophy and oligospermia, impotence, chronic priapism, epididymitis, and bladder irritability.
In Females Clitoral enlargement, menstrual irregularities.
CNS: Habituation, excitation, insomnia, depression, and changes in libido.
Hematologic: Bleeding in patients on concomitant oral anticoagulant therapy.
Breast: Gynecomastia.
Larynx: Deepening of the voice in females.
Hair: Hirsutism and male pattern baldness in females.
Skin: Acne (especially in females and prepubertal males).
Skeletal: Premature closure of epiphyses in children (see PRECAUTIONS, Pediatric Use).
Fluid and Electrolytes: Edema, retention of serum electrolytes (sodium chloride, potassium, phosphate, calcium).
Metabolic/Endocrine: Decreased glucose tolerance (see PRECAUTIONS, Laboratory Tests), increased creatinine excretion, increased serum levels of creatinine phosphokinase (CPK). Masculinization of the fetus. Inhibition of gonadotropin secretion.
No symptoms or signs associated with overdosage have been reported. It is possible that sodium and water retention may occur.
The oral LD50 of oxandrolone in mice and dogs is greater than 5,000 mg/kg. No specific antidote is known, but gastric lavage may be used.
Therapy with anabolic steroids is adjunctive to and not a replacement for conventional therapy. The duration of therapy with Oxandrolone Tablets will depend on the response of the patient and the possible appearance of adverse reactions. Therapy should be intermittent.
The response of individuals to anabolic steroids varies. The daily adult dosage is 2.5 mg to 20 mg given in 2 to 4 divided doses. The desired response may be achieved with as little as 2.5 mg or as much as 20 mg daily. A course of therapy of 2 to 4 weeks is usually adequate. This may be repeated intermittently as indicated.
For children the total daily dosage of Oxandrolone Tablets is ≤0.1 mg per kilogram body weight or ≤0.045 mg per pound of body weight. This may be repeated intermittently as indicated.
Recommended dose for geriatric patients is 5 mg bid.
Oxandrolone Tablets, USP 2.5 mg are oval, white, scored, uncoated tablets, debossed with “2.5” on one side and “U” to the left and “S” to the right of the score on the other side. Oxandrolone Tablets, USP are available in bottles of 100 tablets (NDC 0245-0271-11), bottles of 1000 tablets (NDC 0245-0271-10) and in unit dose cartons of 100 tablets (10 cards containing 10 tablets each) (NDC 0245-0271-01).
Store at 20° to 25°C (68° to 77°F). Excursions permitted to 15° to 30°C (59° to 86°F). [See USP Controlled Room Temperature.] Dispense in a tight, light-resistant container with a child-resistant closure as defined in the USP.
Keep out of reach of children.
Manufactured for UPSHER-SMITH LABORATORIES, LLC Maple Grove, MN 55369
by: Pharmaceutics International, Inc.Hunt Valley, MD 21031
Revised 0617
NDC 0245-0271-11
OxandroloneTablets, USP
2.5 mgCIII
100 Tablets Rx only
UPSHER-SMITH
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