Oxandrolone was first described in 1962 and was introduced for medical use in 1964.[6] The drug is a controlled substance in many countries, so non-medical use for purposes such as improving physique and performance is generally illicit.[6][10][11][12][13] Although primarily used in the United States, the FDA announced on June 28th, 2023 that the drug would no longer be approved for medical use. As of August 2023, neither the brand nor generic versions of oxandrolone are legally marketed in the US.[6][14][15]
Medical uses
Oxandrolone has been researched and prescribed as a treatment for a wide variety of conditions. It was 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.[16][17]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.[7][8] 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.[18]
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[citation needed]. Oxandrolone has, therefore, largely been replaced by growth hormone for this use.[21] However, a 2019 systematic review comparing effects of adding oxandrolone to growth hormone treatment to growth hormone alone has found moderate-quality evidence that the addition of oxandrolone leads to an increase in final adult height of girls with Turner syndrome, and low-quality evidence showed no increase in adverse effects.[22] 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.[22] 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.[21][23]
A 2021 study found that administration of oxandrolone in transgender adolescents resulted in an increase in adult height.[24]
Non-medical uses
Many bodybuilders and athletes use oxandrolone illicitly for its muscle-building effects.[6] It is much more anabolic than androgenic, so women and those seeking less intense steroid regimens use it particularly often.[6] Many also value oxandrolone's low hepatotoxicity relative to most other orally active AASs.[6]
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.[21][16][23] Because of these side effects, doses given to women and children are minimized and people are usually monitored for virilization and growth abnormalities.[21][23] Like other androgens, oxandrolone can cause or worsen acne and priapism (unwanted or prolonged erections).[16][25] Oxandrolone can also reduce males' fertility, another side effect common among androgens.[25] 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.[16]
Unlike some AASs, oxandrolone does not generally cause gynecomastia because it is not aromatized into estrogenic metabolites.[26] 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.[27][28] 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.[27][28] 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.[27][28] 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.[27][28]
Uniquely among 17α-alkylated AASs, oxandrolone shows little to no hepatotoxicity, even at high doses.[29] No cases of severe hepatotoxicity have been singularly attributed to oxandrolone.[29] 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.[29]
Interactions
Oxandrolone greatly increases warfarin's blood-thinning effect, sometimes dangerously so.[30] In April 2004, Savient Pharmaceuticals published a safety alert through the FDA warning healthcare professionals of this.[31] Oxandrolone can also inhibit the metabolism of oral hypoglycemic agents.[16] It may worsen edema when taken alongside corticosteroids or adrenocorticotropic hormone.[16]
Compared to testosterone and many other AASs, oxandrolone is less androgenic relative to its strength as an anabolic.[6][33] Oxandrolone has about 322 to 633% of the anabolic potency and 24% of the androgenic potency of methyltestosterone.[6] Similarly, oxandrolone has as much as 6 times the anabolic potency of testosterone and has significantly reduced androgenic potency in comparison.[6] 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.[6] The bodybuilding community also considers this fact when choosing between AASs.[6]
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.[6] This is involved in its reduced ratio of anabolic to androgenic activity.[6] 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.[6] This is in contrast to DHT, and is thought to underlie the preserved anabolic potency with oxandrolone.[6] Because it is 5α-reduced, oxandrolone is not a substrate for aromatase, hence cannot be aromatized into metabolites with estrogenic activity.[6] Oxandrolone similarly possesses no progestogenic activity.[6]
Oxandrolone is, uniquely, far less hepatotoxic than other 17α-alkylated AASs, which may be due to differences in metabolism.[29][6][5][4]
Pharmacokinetics
The oral bioavailability of oxandrolone is 97%.[3] Its plasma protein binding is 94 to 97%.[3] The drug is metabolized primarily by the kidneys and to a lesser extent by the liver.[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 diminished hepatotoxicity relative to other AASs.[5][4] Its elimination 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 is eliminated unchanged in the urine and 3% is excreted in the feces.[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.[6][36][37] They were immediately interested in oxandrolone's very weak androgenic effects relative to its anabolic effects.[36][6] It was introduced as a pharmaceutical drug in the United States in 1964.[6]
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.[6] It had also been shown to be partially successful in treating cases of osteoporosis.[6] However, in part due to bad publicity from its illicit use by bodybuilders, production of Anavar was discontinued by Searle Laboratories in 1989.[6] 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.[6] 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.[6] It is also indicated as an offset to protein catabolism caused by long-term administration of corticosteroids.[6]
Society and culture
Generic names
Oxandrolone is the generic name of the drug and its 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.[34][35][38][15][39]
Brand names
The original brand name of oxandrolone was Anavar, which was marketed in the United States and the Netherlands.[6][40] 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.[6][41] 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.[6][35][40][42] Additional brand names exist for products that are manufactured for the steroid black market.[6]
Among those using oxandrolone for nonmedical purposes, it is often referred to colloquially as "Var", a shortened form of the brand name Anavar.[43][44]
On June 28th, 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 U.S. market. As of August 2023, neither the brand nor generic versions of oxandrolone are marketed.[45]
Other countries
Outside of the United States, the availability of oxandrolone is quite limited.[6][15] With the exception of Moldova, it is no longer available in Europe.[6] Oxandrolone is available in some less-regulated markets in Asia such as Malaysia.[6] It is also available in Mexico.[6] 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.[6][35][40][15]
^ abLi H, Guo Y, Yang Z, Roy M, Guo Q (June 2016). "The efficacy and safety of oxandrolone treatment for patients with severe burns: A systematic review and meta-analysis". Burns. 42 (4): 717–727. doi:10.1016/j.burns.2015.08.023. PMID26454425. S2CID24139354.
^Korkia P, Stimson GV (October 1997). "Indications of prevalence, practice and effects of anabolic steroid use in Great Britain". International Journal of Sports Medicine. 18 (7): 557–562. doi:10.1055/s-2007-972681. PMID9414081. S2CID260169851. Low dose 28 +/- 18; High dose 80 +/- 13
^Grimstad FW, Knoll MM, Jacobson JD (2021). "Oxandrolone Use in Trans-Masculine Youth Appears to Increase Adult Height: Preliminary Evidence". LGBT Health. 8 (4): 300–306. doi:10.1089/lgbt.2020.0355. PMID33819432. S2CID233036343.
^ ab"Oxandrolone". MedlinePlus. The American Society of Health-System Pharmacists, Inc. 15 May 2016. Retrieved 21 June 2016.
^Corona G, Rastrelli G, Vignozzi L, Maggi M (June 2012). "Emerging medication for the treatment of male hypogonadism". Expert Opinion on Emerging Drugs. 17 (2): 239–259. doi:10.1517/14728214.2012.683411. PMID22612692. S2CID22068249.
^ abcdOrr R, Fiatarone Singh M (2004). "The anabolic androgenic steroid oxandrolone in the treatment of wasting and catabolic disorders: review of efficacy and safety". Drugs. 64 (7): 725–750. doi:10.2165/00003495-200464070-00004. PMID15025546. S2CID32262454.
^Chrousos GP (2012). "The Gonadal Hormones & Inhibitors". In Katzung BG (ed.). Basic & Clinical Pharmacology. New York London: McGraw-Hill Medical McGraw-Hill distributor. p. 735. ISBN978-0071764018.
^Fox M, Minot AS, Liddle GW (September 1962). "Oxandrolone: a potent anabolic steroid of novel chemical configuration". The Journal of Clinical Endocrinology and Metabolism. 22 (9): 921–924. doi:10.1210/jcem-22-9-921. PMID13894381.
