Oxandrolone

Source: Wikipedia, the free encyclopedia.
Oxandrolone
Clinical data
Trade namesOxandrin, Anavar, others[1]
Other namesVar; 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.comMonograph
MedlinePlusa604024
Pregnancy
category
  • X
Routes of
administration		By mouth
Drug classAndrogen; Anabolic steroid
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability97%[4]
Protein binding94–97%[4]
MetabolismKidneys (primarily), liver[6][4]
Elimination half-lifeAdults: 9.4–10.4 hours[4][5]
Elderly: 13.3 hours[5]
ExcretionUrine: 28% (unchanged)[5]
Feces: 3%[5]
Identifiers
  • (1S,3aS,3bR,5aS,9aS,9bS,11aS)-1-hydroxy-1,9a,11a-trimethyl-2,3,3a,3b,4,5,5a,6,9,9b,10,11-dodecahydroindeno[4,5-h]isoch
JSmol)
  • C[C@]12CC[C@H]3[C@H]([C@@H]1CC[C@]2(C)O)CC[C@@H]4[C@@]3(COC(=O)C4)C
  • InChI=1S/C19H30O3/c1-17-11-22-16(20)10-12(17)4-5-13-14(17)6-8-18(2)15(13)7-9-19(18,3)21/h12-15,21H,4-11H2,1-3H3/t12-,13+,14-,15-,17-,18-,19-/m0/s1 checkY
  • Key:QSLJIVKCVHQPLV-PEMPUTJUSA-N checkY
  (verify)

Oxandrolone is an androgen and synthetic anabolic steroid (AAS) medication 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.[7][8][9] It is taken by mouth.[7] It was sold under the brand names Oxandrin and Anavar, among others.[1]

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.[7][10]
voice changes.[7]

Oxandrolone was first described in 1962 and introduced for medical use in 1964.

FDA withdrew in 2023 the approval for the drug for reasons of safety or effectiveness, following a 2019 letter from Gemini, a drug manufacturer, stating that the product was no longer being marketed.[11]

Medical uses

Oxandrolone has been researched and prescribed as a treatment for a wide variety of conditions. It was FDA-approved for treating

chronic infection, or in the context of unexplained weight loss, and counteracting the catabolic effect of long-term corticosteroid therapy.[16][17] Oxandrolone is used to quicken recovery from severe burns.[8][18]

In the management of severe burn injuries, numerous 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 significant advantage in promoting skin healing as an adjunct therapy for adult burn patients.[19] Oxandrolone improves weight regain, bone mineral density, lean body mass, and accelerates wound healing for donor graft sites.[20] Oxandrolone is recommended as an adjunctive therapy, alongside insulin, metformin, and closely monitored propranolol, in severe burn patients, for metabolic and nutritional support.[21][22] 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.[8][9] One of the underlying mechanisms in burn management is that oxandrolone helps reduce hypermetabolic response, which is characterized by increased energy expenditure, elevated stress hormones levels such as cortisol, 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.[23]

As of 2016,[needs update] oxandrolone was prescribed off-label for the development of girls with Turner syndrome,[medical citation needed] and counteract HIV/AIDS-induced wasting.[medical citation needed]

As of 2012, oxandrolone was used in the treatment of idiopathic short stature, anemia, hereditary angioedema,[24] hypogonadism and alcoholic hepatitis.[25][needs update]

Medical research established the effectiveness of oxandrolone in aiding the development of girls with

Cochrane 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 with Turner syndrome, and low-quality evidence showed no increase in adverse effects.[27] 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.[27] Children with idiopathic short stature or Turner syndrome were given doses of oxandrolone far smaller than those given to people with burns to minimize the likelihood of virilization and premature maturation.[26][28][incomprehensible
]

Oxandrolone shows positive effects on cardiometabolic health and visual, motor, and psychosocial functions in adolescent males with preserved testosterone production, such as those with Klinefelter syndrome.[22]

Non-medical uses

See also:
List of doping in sport cases § Oxandrolone

Oxandrolone has been used illicitly by bodybuilders and athletes for its muscle-building effects as

doping agent in sports. Cases of doping with oxandrolone by professional athletes have been reported.[7] Because it is more anabolic than androgenic, so women and those seeking less intense steroid regimens used it particularly often.[7] In the past[when?] many[who?] valued oxandrolone's supposed[clarification needed] low hepatotoxicity relative to most other orally active AASs.[7]

Contraindications

Like other AASs, oxandrolone may worsen

masculinization on the fetus.[16]

Side effects

See also: Anabolic steroid § Adverse effects

As of 2004 it was thought that "uniquely" among 17α-alkylated AASs, oxandrolone showed little to no

prostatic carcinoma in older patients.[11]

Women who are administered oxandrolone may experience

gonadotropic activity.[16]

Unlike some AASs, oxandrolone does not generally cause

aromatized into estrogenic metabolites.[31] 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.[32][33] 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.[32][33] 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.[32][33] 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.[32][33]

Interactions

As of 2004 it was known that oxandrolone greatly increases

hypoglycemic agents.[16] It may worsen edema when taken alongside corticosteroids or adrenocorticotropic hormone.[16]

Pharmacology

Pharmacodynamics

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

Like other AASs, oxandrolone is an agonist of the androgen receptor, similar to androgens such as testosterone and DHT.

bone mineral density.[9]

Compared to testosterone and many other AASs, oxandrolone is less androgenic relative to its strength as an anabolic.[7][37] Oxandrolone has as much as 6 times the anabolic potency of testosterone.[7] Still, and has significantly reduced androgenic potency in comparison:[7] oxandrolone exhibits significantly lower virilizing androgenic properties compared to testosterone, with a relative potency of only 5%.[38]

Compared to methyltestosterone, oxandrolone has about 322 to 633% of the anabolic potency and 24% of the androgenic potency.[7]

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.[7] The bodybuilding community also considers this fact when choosing between AASs.[7]

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.[29][7][6][5] This turned out not to be the case in the long run, which is why it was taken off the US market in 2023.[11][improper synthesis?][speculation?]

Steroid configuration

See also: Steroid
Numbering of carbon atoms up to position 17 in a hypothetical steroid nucleus
Oxandrolone chimical formula structure

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.[39]

The oxygen atom in the lactone bridge replaces a carbon atom at position 2 of the steroid nucleus, classifying oxandrolone as an 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.[40]

The overall structure of oxandrolone is distinguished by these modifications to the standard steroid skeleton, 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.

3α-hydroxysteroid dehydrogenase in skeletal muscle.[7] This is in contrast to DHT, and is thought to underlie the preserved anabolic potency with oxandrolone.[7]

As oxandrolone is already 5α-reduced (have a single bond between carbons 4 and 5), it is not a

prostate gland.[7] This is involved in its reduced ratio of anabolic to androgenic activity.[7] Because it is 5α-reduced, oxandrolone is not a substrate for aromatase, hence cannot be aromatized into metabolites with estrogenic activity.[7] Oxandrolone similarly possesses no progestogenic activity.[7]

Pharmacokinetics

The oral

elimination half-life is reported as 9.4 to 10.4 hours, but is extended to 13.3 hours in the elderly.[4][5] About 28% of an oral dose of oxandrolone is eliminated unchanged in the urine and 3% is excreted in the feces.[5]

Chemistry

See also:
List of androgens/anabolic steroids

Oxandrolone is a

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).[42][43][7]

History

Oxandrolone was first made by Raphael Pappo and Christopher J. Jung while at

Searle Laboratories, now part of Pfizer and they first described the drug in 1962.[44][45] They were immediately interested in oxandrolone's very weak androgenic effects relative to its anabolic effects.[44] It was introduced as a pharmaceutical drug in the United States in 1964.[7]

It was prescribed to promote muscle regrowth in disorders which cause involuntary weight loss, and is used as part of treatment for HIV/AIDS.[7] It had also been shown to be partially successful in treating cases of osteoporosis.[7] However, in 1989, in part due to bad publicity from its illicit use by bodybuilders, production of Anavar was discontinued by Searle Laboratories.[7] It was picked up by Bio-Technology General Corporation, which changed its name to Savient Pharmaceuticals. In 1995, following successful clinical trials, Savient released it under the brand name Oxandrin.[7] As of 2011 BTG subsequently had won approvals for orphan drug status by the Food and Drug Administration for treating alcoholic hepatitis, Turner syndrome, and HIV-induced weight loss and as an offset to protein catabolism caused by long-term administration of corticosteroids.[7]

Society and culture

Generic names

Oxandrolone is the

INNTooltip International Nonproprietary Name, USANTooltip United States Adopted Name, USPTooltip United States Pharmacopeia, BANTooltip British Approved Name, DCFTooltip Dénomination Commune Française, DCITTooltip Denominazione Comune Italiana, and JANTooltip Japanese Accepted Name, while ossandrolone is or was formerly the DCITTooltip Denominazione Comune Italiana.[42][43][46][47][48]

Brand names

The original brand name of oxandrolone was Anavar, which was marketed in the United States and the Netherlands.[7][49] This product was eventually discontinued and replaced in the United States with a new name of Oxandrin, which as of 2011 was the sole remaining brand name for oxandrolone in the United States.[7][50] 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.[43][49][51][7] 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.[52][53] Additional brand names existed for products that were manufactured for the steroid black market.[7]

Availability

United States

See also: List of androgens/anabolic steroids available in the United States

As of 2017, Oxandrolone was one of the few AASs that remained available for medical use in the United States.[50]

In June 2023, the FDA formally withdrew approval 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.[11]

As of August 2023, the AASs that remained available for medical use in the US were testosterone, testosterone cypionate, testosterone enanthate, testosterone undecanoate, methyltestosterone, fluoxymesterone, and oxymetholone.[50]

Other countries

Outside of the United States, the availability of oxandrolone is also quite limited.[7][47] It is no longer available in Europe.[7][54] Oxandrolone is available in some less-regulated markets in Asia such as Malaysia and in Mexico.[7]

Historically, oxandrolone has been marketed in Argentina, Australia, Brazil, France, Italy, Japan, and Spain,[7][43][49] but it appears to no longer be available in these countries.[47]

Legal status

See also: Anabolic steroid § Legal status

In the United States, oxandrolone was categorized as a

Schedule 4 controlled drug in the United Kingdom.[15]

References

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External links

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