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| Trade names | Oxandrin, Anavar, others[1] |
| Other names | Var; CB-8075; NSC-67068; SC-11585; Protivar; 17α-Methyl-2-oxa-4,5α-dihydrotestosterone; 17α-Methyl-2-oxa-DHT; 17α-Methyl-2-oxa-5α-androstan-17β-ol-3-one |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a604024 |
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| Routes of administration | By mouth |
| Drug class | Androgen;Anabolic steroid |
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| Pharmacokinetic data | |
| Bioavailability | 97%[3] |
| Protein binding | 94–97%[3] |
| Metabolism | Kidneys (primarily),liver[5][3] |
| Eliminationhalf-life | Adults: 9.4–10.4 hours[3][4] Elderly: 13.3 hours[4] |
| Excretion | Urine: 28% (unchanged)[4] Feces: 3%[4] |
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| ECHA InfoCard | 100.000.158 |
| Chemical and physical data | |
| Formula | C19H30O3 |
| Molar mass | 306.446 g·mol−1 |
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Oxandrolone is anandrogen and syntheticanabolic steroid (AAS) medication to help promoteweight gain in various situations, to help offsetprotein catabolism caused by long-termcorticosteroid therapy, to support recovery from severeburns, to treatbone pain associated withosteoporosis, to aid in the development of girls withTurner syndrome, and for other indications.[6][7][8] It is takenby mouth.[6] It was sold under the brand names Oxandrin and Anavar, among others.[1]
The drug is asynthetic androgen and anabolic steroid, hence is anagonist of theandrogen receptor (AR), thebiological target of androgens such astestosterone anddihydrotestosterone.[6][9]Side effects of oxandrolone include severe cases ofpeliosis hepatis, sometimes associated withliver failure and intra-abdominal hemorrhage;liver tumors, sometimes fatal; andblood lipid changes associated with increased risk ofatherosclerosis. Additional warnings include the risks associated withcholestatic hepatitis, hypercalcemia in patients with breast cancer, and increased risk for the development ofprostatic hypertrophy andprostatic carcinoma in older patients.[10] It has stronganabolic effects and weakandrogenic effects, which gave it a mild side effect profile in that regard and made it especially suitable for use in women.[6] Milder side effects in women were increasedsexual desire, symptoms of hyperandrogenism such asacne, andsymptoms ofmasculinization such asincreased hair growth andvoice changes.[6]
Oxandrolone was first described in 1962 and introduced for medical use in 1964.[6] The drug is acontrolled substance in many countries, so non-medical use for purposes such asimproving physique and performance has been generally illicit.[6][11][12][13][14]
In the United States, theFDA's Endocrinologic and Metabolic Drugs Advisory Committee unanimously concluded in 1984 that there was no evidence of efficacy for oxandrolone.[15] On March 26, 2019, Gemini asked FDA to withdraw approval for all doses of the drug, stating that they were no longer marketing it.[10][15] FDA notified Gemini and other license holders on December 16, 2022, that it believed that the potential problems with the drug that the drug were sufficiently serious that it should be removed from the market, citing the 1984 finding of lack of efficacy and the extensive safety warnings and precautions listed on theprescribing information, "includingpeliosis hepatis, sometimes associated withliver failure andintra-abdominal hemorrhage;liver cell tumors, sometimes fatal; andblood lipid changes that are known to be associated with increased risk ofatherosclerosis" as well as "cholestatic hepatitis,hypercalcemia in patients withbreast cancer, and increased risk for the development ofprostatic hypertrophy andprostatic carcinoma ingeriatric patients."[15] Gemini andSandoz requested that the FDA completely withdraw approval for the drug.[15]
Oxandrolone has been researched and prescribed as a treatment for a wide variety of conditions. It was FDA-approved for treatingbone pain associated withosteoporosis, aidingweight gain following surgery orphysical trauma, duringchronic infection, or in the context of unexplainedweight loss, and counteracting thecatabolic effect of long-termcorticosteroid therapy.[16][17] Oxandrolone is used to quicken recovery from severe burns.[7][18][19]
In the management of severe burn injuries, clinical trials have demonstrated the therapeutic advantages of oxandrolone, and it was widely adopted as a standard treatment protocol in burn centers globally. Meta-analyses of clinical trials substantiate the efficacy of oxandrolone in severe burn cases: the benefits are manifold and significant, and include a reduction in catabolic weight loss, augmentation of lean body mass, enhancement of donor-site wound healing, and a decrease in the duration of both intensive care unit (ICU) and overall hospital stay. These benefits do not appear to be accompanied by an increased risk of infection, hyperglycemia, or hepatic dysfunction, which underscores the safety profile of oxandrolone in severe burn patient population.[18] Data analysis confirms oxandrolone's advantage in promoting skin healing as an adjunct therapy for adult burn patients.[20] Oxandrolone improves weight regain, bone mineral density, lean body mass, and accelerates wound healing for donor graft sites.[21] Oxandrolone was recommended as an adjunctive therapy, alongside insulin, metformin, and closely monitored propranolol, in severe burn patients, for metabolic and nutritional support.[22][23] Oxandrolone improves both short-term and long-term outcomes in people recovering from severe burns and was well-established as a safe treatment for this indication.[7][8] One of the underlying mechanisms in burn management is that oxandrolone helps reducehypermetabolic response, which is characterized by increased energy expenditure, elevated stress hormones levels such ascortisol,insulin resistance, muscle wasting, and impaired wound healing; this response is reduced by improving whole-body nitrogen balance as well as preserving lean body mass during recovery.[24]
As of 2019, oxandrolone was prescribedoff-label for the development of girls withTurner syndrome,[25] and counteractwasting of diverse origin.[25]
As of 2012, oxandrolone was used in the treatment ofidiopathic short stature,anemia,hereditary angioedema,[26]hypogonadism andalcoholic hepatitis.[27][needs update]
Medical research established the effectiveness of oxandrolone in aiding the development of girls withTurner syndrome. Although oxandrolone had 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;[citation needed] as such, as of 2015, oxandrolone has largely been replaced bygrowth hormone for this use.[28][needs update] However, a 2019Cochrane review comparing effects of adding oxandrolone to growth hormone treatment to growth hormone alone found moderate-quality evidence that the addition of oxandrolone led to an increase in final adult height of girls withTurner syndrome, and low-quality evidence showed no increase in adverse effects.[25] When the same review assessed the effects of adding oxandrolone to growth hormone treatment on speech, cognition and psychological status, the results were inconclusive due to very-low quality evidence.[25] Children withidiopathic short stature orTurner syndrome were given doses of oxandrolone far smaller than those given to people with burns to minimize the likelihood of virilization and premature maturation.[28][29][incomprehensible]
Oxandrolone shows positive effects on cardiometabolic health and visual, motor, and psychosocial functions in adolescent males with preserved testosterone production, such as those withKlinefelter syndrome.[23]
Oxandrolone has been used illicitly by bodybuilders and athletes for its muscle-building effects as adoping agent in sports. Cases of doping with oxandrolone by professional athletes have been reported.[6] Because it is moreanabolic than androgenic, women and those seeking less intense steroid regimens used it particularly often.[6] In the past[when?] many[who?] valued oxandrolone's supposed[clarification needed] low hepatotoxicity relative to most other orally active AASs.[6]
Like other AASs, oxandrolone may worsenhypercalcemia by increasingosteolytic bone resorption.[16] When taken by pregnant women, oxandrolone may have unintended effects such asmasculinization on the fetus.[16]
As of 2004, it was thought that "uniquely" among 17α-alkylated AASs, oxandrolone showed little to nohepatotoxicity, even at high doses.[30] However,elevated liver enzymes have been observed in some people, particularly with high doses and/or prolonged treatment, although sometimes returning to normal ranges following discontinuation.[30] However, there have been documented severe cases ofpeliosis hepatis, sometimes associated withliver failure and intra-abdominal hemorrhage;liver tumors, sometimes fatal; andblood lipid changes associated with increased risk ofatherosclerosis. This led the FDA to remove approval in June 2023. Additional warnings include the risks associated withcholestatic hepatitis, hypercalcemia in patients with breast cancer, and increased risk for the development ofprostatic hypertrophy andprostatic carcinoma in older patients.[10]
Women who are administered oxandrolone may experiencevirilization, irreversible development of masculine features such asvoice deepening,hirsutism,menstruation abnormalities,male-pattern hair loss, andclitoral enlargement.[28][16][29] Because of these side effects, doses given to women and children are minimized and people are usually monitored for virilization and growth abnormalities.[28][29] Like other androgens, oxandrolone can cause or worsen acne andpriapism (unwanted or prolonged erections).[16][31] Oxandrolone can also reduce males' fertility, another side effect common among androgens.[31] In an attempt to compensate for the exogenous increase in androgens, the body may reduce testosterone production viatesticular atrophy and inhibition ofgonadotropic activity.[16]
Unlike some AASs, oxandrolone does not generally causegynecomastia because it is notaromatized intoestrogenic metabolites.[32] 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.[33][34] 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 necessitatedmastectomy.[33][34] 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.[33][34] 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.[33][34]
As of 2004 it was known that oxandrolone greatly increaseswarfarin's blood-thinning effect, sometimes dangerously so.[35] In April 2004, Savient Pharmaceuticals published a safety alert through the FDA warning healthcare professionals of this.[36] Oxandrolone also inhibits the metabolism of oralhypoglycemic agents.[16] It may worsenedema when taken alongsidecorticosteroids oradrenocorticotropic hormone.[16]
| Medication | Ratioa |
|---|---|
| Testosterone | ~1:1 |
| Androstanolone (DHT) | ~1:1 |
| Methyltestosterone | ~1:1 |
| Methandriol | ~1:1 |
| Fluoxymesterone | 1:1–1:15 |
| Metandienone | 1:1–1:8 |
| Drostanolone | 1:3–1:4 |
| Metenolone | 1:2–1:3 |
| Oxymetholone | 1:2–1:9 |
| Oxandrolone | 1:13–1:3 |
| Stanozolol | 1:1–1:3 |
| Nandrolone | 1:3–1:16 |
| Ethylestrenol | 1:2–1:19 |
| Norethandrolone | 1:1–1:2 |
| Notes: In rodents.Footnotes:a = Ratio of androgenic to anabolic activity.Sources: See template. | |
Like other AASs, oxandrolone is an agonist of the androgen receptor, similar to androgens such as testosterone and DHT.[6] Therelative binding affinity of oxandrolone for the androgen receptor is about 0.3% of that ofmetribolone.[37] Activation of the androgen receptor stimulatesprotein synthesis, which increasesmuscle growth,lean body mass, andbone mineral density.[8]
Compared totestosterone and many other AASs, oxandrolone is less androgenic relative to its strength as an anabolic.[6][38] Oxandrolone has as much as six times the anabolic potency of testosterone[6] and has significantly reduced androgenic potency in comparison:[6] oxandrolone exhibits significantly lower virilizing androgenic properties compared to testosterone, with a relative androgenic potency of only 5%.[39]
Compared tomethyltestosterone, oxandrolone has about 322 to 633% of the anabolic potency and 24% of the androgenic potency.[6]
The reduced ratio of anabolic to androgenic activity of oxandrolone motivated its medical use in children and women because less androgenic effect implies less risk of virilization.[6] The bodybuilding community also considers this fact when choosing between AASs.[6]
As of 2003 and 2011 Oxandrolone was thought to be "uniquely" far less hepatotoxic than other 17α-alkylated AASs, which was thought to be due to differences in metabolism.[30][6][5][4] This turned out not to be the case in the long run, which is why it was taken off the US market in 2023.[10][improper synthesis?][speculation?]
Oxandrolone is based on the tetracyclic steroid framework, which consists of three cyclohexane rings (A, B, and C) and one cyclopentane ring (D). This is a common structure shared by all steroids.[40]
The oxygen atom in the lactone bridge replaces a carbon atom at position 2 of the steroid nucleus, classifying oxandrolone as a 2-oxa-steroid. There is a hydroxyl group (-OH) attached at stereo-direction β to carbon 17, which is a characteristic of 17β-hydroxy-steroids.[41]
The overall structure of oxandrolone is distinguished by these modifications to the standard steroid nucleus, which contribute to its unique properties as an anabolic steroid. The presence of the lactone bridge, i.e., the 2-oxa-steroid classification, is particularly noteworthy, as it is not commonly found in the steroid family. This structural element is what gives oxandrolone its distinctive chemical identity within the class of anabolic steroids.[42][41] Due to its lactone bridge, oxandrolone is resistant toinactivation by3α-hydroxysteroid dehydrogenase inskeletal muscle.[6] This resistance, in contrast to DHT, is believed to underlie oxandrolone's preserved anabolic potency[6]
As oxandrolone is already a 5α-reduced steroid (has a single bond between carbons 4 and 5), it is not asubstrate for the5α-reductase enzyme, hence is not potentiated in androgenic tissues such as the skin,hair follicles, andprostate gland.[6] In addition, the 5α-reduced state preserves oxandrolone from being a substrate for thearomatase enzyme; therefore, oxandrolone cannot be aromatized intometabolites with estrogenic activity.[6] Oxandrolone similarly possesses noprogestogenic activity.[6]
The oralbioavailability of oxandrolone is 97%.[3] Itsplasma protein binding is 94 to 97%.[3] The drug ismetabolized primarily by thekidneys and to a lesser extent by theliver.[5][3] Oxandrolone is the only AAS that is not primarily or extensively metabolized by the liver, and this is thought to be related to its diminishedhepatotoxicity relative to other AASs.[5][4] Itselimination half-life is reported as 9.4 to 10.4 hours, but is extended to 13.3 hours in the elderly.[3][4] About 28% of an oral dose of oxandrolone iseliminated unchanged in the urine and 3% is excreted in the feces.[4]
Oxandrolone is asyntheticandrostanesteroid and a17α-alkylatedderivative of DHT.[43][44][6] 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 amethyl group at the C17α position and the C2carbon replaced with anoxygen atom.[43][44][6] Closely related AASs include the marketed AASmestanolone (17α-methyl-DHT),oxymetholone (2-hydroxymethylene-17α-methyl-DHT), andstanozolol (a 2,3-pyrazole Aring-fused derivative of 17α-methyl-DHT) and the never-marketed/designer AASdesoxymethyltestosterone (3-deketo-17α-methyl-δ2-DHT),methasterone (2α,17α-dimethyl-DHT),methyl-1-testosterone (17α-methyl-δ1-DHT), andmethylstenbolone (2,17α-dimethyl-δ1-DHT).[43][44][6]
Oxandrolone was first made by Raphael Pappo and Christopher J. Jung while atSearle Laboratories, now part ofPfizer and they first described the drug in 1962.[45][46] They were immediately interested in oxandrolone's very weak androgenic effects relative to its anabolic effects.[45] It was introduced as a pharmaceutical drug in the United States in 1964.[6]
It was prescribed to promote muscle regrowth in disorders which cause involuntary weight loss, and is used as part of treatment for HIV/AIDS.[6] It had also been shown to be partially successful in treating cases of osteoporosis.[6] However, in 1989, in part due to bad publicity from its illicit use bybodybuilders, production of Anavar was discontinued by Searle Laboratories.[6] It was picked up by Bio-Technology General Corporation, which changed its name toSavient Pharmaceuticals. In 1995, following successful clinical trials, Savient released it under the brand nameOxandrin.[6] As of 2011 BTG subsequently had won approvals fororphan drug status by theFood and Drug Administration for treatingalcoholic hepatitis, Turner syndrome, and HIV-induced weight loss and as an offset toprotein catabolism caused by long-term administration of corticosteroids.[6]
Oxandrolone is thegeneric name of the drug and itsINNTooltip International Nonproprietary Name,USANTooltip United States Adopted Name,USPTooltip United States Pharmacopeia,BANTooltip British Approved Name,DCFTooltip Dénomination Commune Française,DCITTooltip Denominazione Comune Italiana, andJANTooltip Japanese Accepted Name, whileossandrolone is or was formerly theDCITTooltip Denominazione Comune Italiana.[43][44][47][48][49]
The original brand name of oxandrolone wasAnavar, which was marketed in the United States and the Netherlands.[6][50] This product was eventually discontinued and replaced in the United States with a new name ofOxandrin, which as of 2011 was the sole remaining brand name for oxandrolone in the United States.[6][51] Oxandrolone has also been sold under the brand namesAntitriol (Spain),Anatrophill (France),Lipidex (Brazil),Lonavar (Argentina, Australia, Italy), Protivar, andVasorome (Japan), among others.[44][50][52][6]As of 2016, among those using oxandrolone for nonmedical purposes, it has been referred to colloquially as "Var", a shortened form of the old brand name Anavar.[53][54] Additional brand names existed for products that were manufactured for the steroid black market.[6]
As of 2017, Oxandrolone was one of the few AASs that remained available for medical use in the United States.[51]
In June 2023, the FDA formally withdrewapproval for oxandrolone for all indications, stating that possible adverse effects of the drug were sufficiently serious to warrant removal from the US market. The FDA decision was for reasons of safety or effectiveness, following a 2019 letter from Gemini, a drug manufacturer, stating that the product was no longer being marketed.[10]
As of August 2023, the AASs that remained available for medical use in the US weretestosterone,testosterone cypionate,testosterone enanthate,testosterone undecanoate,methyltestosterone,fluoxymesterone, andoxymetholone.[51]
Generally speaking, the availability of oxandrolone is quite limited.[6][48] It is no longer available in Europe.[6][55] Oxandrolone is available in some less-regulated markets in Asia such as Malaysia and in Mexico.[6]
Historically, oxandrolone has been marketed in Argentina, Australia, Brazil, France, Italy, Japan, and Spain,[6][44][50] but it appears to no longer be available in these countries.[48]
In the United States, oxandrolone was categorized as aSchedule III controlled substance under theControlled Substances Act along with many other AASs.[12] In 2017, it was aSchedule IV controlled substance in Canada,[13] and aSchedule 4 controlled drug in the United Kingdom.[14]
Oxandrolone (trade name Anavar or Oxandrin)
Low dose 28 +/- 18; High dose 80 +/- 13
