Anavar – Oxandrolone

Oxandrolone is an androgen and synthetic anabolic steroid (AAS) medication. It helps promote weight gain in various situations. It helps offset protein catabolism caused by long-term corticosteroid therapy. It supports recovery from severe burns. It treats bone pain linked to osteoporosis. It aids in the development of girls with Turner syndrome. It is used for other indications. It is taken by mouth. It was sold under the brand names Oxandrin and Anavar, among others.

The drug is a synthetic androgen and anabolic steroid. Hence, it is an agonist of the androgen receptor (AR). This receptor is the biological target of androgen such as testosterone and dihydrotestosterone. Side effects of oxandrolone include severe cases of peliosis hepatis. This is sometimes associated with liver failure and intra-abdominal hemorrhage. It can also cause liver tumors, which can sometimes be fatal. Additionally, it causes blood lipid changes associated with increased risk of atherosclerosis. Additional warnings include the risks associated with cholestatic hepatitis. Hypercalcemia can occur in patients with breast cancer. There is an increased risk for the development of prostatic hypertrophy and prostatic carcinoma in older patients. It has strong anabolic effects and weak androgenic effects. This combination gave it a mild side effect profile in that regard. It also made it especially suitable for use in women. Milder side effects in women were increased sexual desire. Symptoms of hyperandrogenism such as acne can occur. They can also experience symptoms of masculinization such as increased hair growth and voice changes.

Oxandrolone was first described in 1962 and introduced for medical use in 1964. The drug was a controlled substance in many countries. Non-medical use for purposes such as improving physique and performance has generally been illicit. In the United States, the FDA withdrew in 2023 the approval for the drug. This decision was for reasons of safety or effectiveness. The withdrawal followed a 2019 letter from Gemini, a drug manufacturer, stating that the product was no longer being marketed.

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. It aids weight gain following surgery or physical trauma. It is also used during chronic infection, or in the context of unexplained weight loss. Additionally, it counteracts the catabolic effect of long-term corticosteroid therapy. Oxandrolone is used to quicken recovery from severe burns.

Numerous clinical trials have demonstrated the therapeutic advantages of oxandrolone in the management of severe burn injuries. 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. They include a reduction in catabolic weight loss. They also include augmentation of lean body mass. Furthermore, there is an enhancement of donor-site wound healing. Lastly, there is 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. They do not seem to cause hyperglycemia or hepatic dysfunction either. This underscores the safety profile of oxandrolone in the severe burn patient population. Data analysis confirms oxandrolone’s significant advantage in promoting skin healing as an adjunct therapy for adult burn patients. Oxandrolone improves weight regain, bone mineral density, lean body mass, and accelerates wound healing for donor graft sites. Oxandrolone is recommended as an adjunctive therapy. This is alongside insulin, metformin, and closely monitored propranolol. It is intended for severe burn patients for metabolic and nutritional support. Oxandrolone improves both short-term and long-term outcomes in people recovering from severe burns. It is well-established as a safe treatment for this indication. One of the underlying mechanisms in burn management is that oxandrolone helps reduce hypermetabolic response. This response is characterized by increased energy expenditure. It includes elevated stress hormones levels such as cortisol. Additionally, it includes insulin resistance, muscle wasting, and impaired wound healing. This response is reduced by improving whole-body nitrogen balance. It also helps in preserving lean body mass during recovery.

As of 2019, oxandrolone was prescribed off-label for the development of girls with Turner syndrome. It was also used to counteract wasting of diverse origin.

As of 2012, oxandrolone was used in the treatment of idiopathic short stature, anemia, hereditary angioedema, hypogonadism and alcoholic hepatitis.

Medical research established the effectiveness of oxandrolone in aiding the development of girls with Turner syndrome. Oxandrolone had long been used to accelerate growth in children with idiopathic short stature. It is unlikely to increase adult height. In some cases, it may even decrease it. As of 2015, oxandrolone has largely been replaced by growth hormone for this use. However, a 2019 Cochrane review compared the effects of adding oxandrolone to growth hormone treatment to growth hormone alone. It found moderate-quality evidence. The addition of oxandrolone led to an increase in the final adult height of girls with Turner syndrome. Low-quality evidence showed no increase in adverse effects. When the same review assessed the effects of adding oxandrolone to growth hormone treatment on speech, cognition, and psychological status, the results were inconclusive. The review found the results to be inconclusive. The evidence was of very low-quality. 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.

Oxandrolone shows positive effects on cardiometabolic health and visual, motor, and psychosocial functions in adolescent males with preserved testosterone production. This is seen in those with Klinefelter syndrome.

Non-medical uses

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. Because it is more anabolic than androgenic, women and those seeking less intense steroid regimens used it particularly often. 

Contraindications

Like other AASs, oxandrolone may worsen hypercalcemia by increasing osteolytic bone resorption. When taken by pregnant women, oxandrolone may have unintended effects such as masculinization on the fetus.

Side effects

As of 2004 it was thought that “uniquely” among 17α-alkylated AASs, oxandrolone showed little to no hepatotoxicity. This was believed to be true even at high doses. However, elevated liver enzymes have been observed in some people. This is particularly true with high doses and/or prolonged treatment. The enzymes sometimes return to normal ranges following discontinuation. The lack of hepatotoxicity turned out not to be true in the long run. There were severe cases of peliosis hepatis, sometimes associated with liver failure and intra-abdominal hemorrhage. There were also instances of liver tumors, sometimes fatal. Changes in blood lipid profiles associated with increased risk of atherosclerosis led the FDA to remove approval in June 2023. Additional warnings include the risks associated with cholestatic hepatitis. There is also the risk of hypercalcemia in patients with breast cancer. Additionally, there is increased risk for the development of prostatic hypertrophy and prostatic carcinoma in older patients.

Women who are administered oxandrolone may experience virilization. This includes the irreversible development of masculine features such as voice deepening, hirsutism, menstruation abnormalities, male-pattern hair loss, and clitoral enlargement. Because of these side effects, doses given to women and children are minimized. People are usually monitored for virilization and growth abnormalities. Like other androgens, oxandrolone can cause or worsen acne and priapism (unwanted or prolonged erections). Oxandrolone can also reduce males’ fertility, another side effect common among androgens. 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.

Unlike some AASs, oxandrolone does not generally cause gynecomastia because it is not aromatized into estrogenic metabolites. However, although no reports of gynecomastia were made in spite of widespread use, oxandrolone was reported in a publication in 1991. It was associated with 33 cases of gynecomastia in adolescent boys treated with it for short stature. The gynecomastia developed during oxandrolone therapy in 19 of the boys. It developed after the therapy was completed in 14 of the boys. Ten of the boys had transient gynecomastia. Twenty-three had persistent gynecomastia that necessitated mastectomy. Though transient gynecomastia is a natural and common occurrence in pubertal boys. The gynecomastia associated with oxandrolone was of a late/delayed onset. It was persistent in a high percentage of the cases. 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.

Interactions

As of 2004 it was known that oxandrolone greatly increases warfarin’s blood-thinning effect, sometimes dangerously so. In April 2004, Savient Pharmaceuticals published a safety alert through the FDA warning healthcare professionals of this. Oxandrolone also inhibits the metabolism of oral hypoglycemic agents. It may worsen edema when taken alongside corticosteroids or adrenocorticotropic hormone.

Pharmacology

Pharmacodynamics

Like other AASs, oxandrolone is an agonist of the androgen receptor, similar to androgens such as testosterone and DHT. The relative binding affinity of oxandrolone for the androgen receptor is about 0.3% of that of metribolone. Activation of the androgen receptor stimulates protein synthesis, which increases muscle growth, lean body mass, and bone mineral density.

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

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

The reduced ratio of anabolic to androgenic activity of oxandrolone often motivates its medical use in children and women. Less androgenic effect implies less risk of virilization. The bodybuilding community also considers this fact when choosing between AASs.

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. This turned out not to be the case in the long run, which is why it was taken off the US market in 2023.

Steroid configuration

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.

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.

The overall structure of oxandrolone is distinguished by these modifications to the standard steroid skeleton. These modifications 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. Due to this lactone bridge, oxandrolone is resistant to inactivation by 3α-hydroxysteroid dehydrogenase in skeletal muscle. This is in contrast to DHT, and is thought to underlie the preserved anabolic potency with oxandrolone.

As oxandrolone is already 5α-reduced (have a single bond between carbons 4 and 5), it is not a substrate for the 5α-reductase enzyme. Because of this reduction, it is not a substrate for the enzyme. Hence, it is not potentiated in androgenic tissues such as the skin, hair follicles, and prostate gland. This is involved in its reduced ratio of anabolic to androgenic activity. Because it is 5α-reduced, oxandrolone is not a substrate for aromatase, hence cannot be aromatized into metabolites with estrogenic activity. Oxandrolone similarly possesses no progestogenic activity.

Pharmacokinetics

The oral bioavailability of oxandrolone is 97%. Its plasma protein binding is 94 to 97%. The drug is metabolized primarily by the kidneys and to a lesser extent by the liver. 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.^[6][5] Its elimination half-life is reported as 9.4 to 10.4 hours, but is extended to 13.3 hours in the elderly. About 28% of an oral dose of oxandrolone is eliminated unchanged in the urine. Additionally, 3% is excreted in the feces.

Chemistry

Oxandrolone is a synthetic androstane steroid and a 17α-alkylated derivative of DHT. 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. Closely related AASs include the marketed AAS mestanolone (17α-methyl-DHT). There is also oxymetholone (2-hydroxymethylene-17α-methyl-DHT) and stanozolol (a 2,3-pyrazole A ring-fused derivative of 17α-methyl-DHT). The never-marketed/designer AASs include 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).

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. They were immediately interested in oxandrolone’s very weak androgenic effects relative to its anabolic effects. It was introduced as a pharmaceutical drug in the United States in 1964.

It was prescribed to promote muscle regrowth in disorders which cause involuntary weight loss, and is used as part of treatment for HIV/AIDS. It had also been shown to be partially successful in treating cases of osteoporosis. However, in 1989, in part due to bad publicity from its illicit use by bodybuilders, production of Anavar was discontinued by Searle Laboratories. 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. 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.

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.

Brand names

The original brand name of oxandrolone was Anavar, which was marketed in the United States and the Netherlands. This product was eventually discontinued and replaced in the United States with a new name of Oxandrin. As of 2011, it was the sole remaining brand name for oxandrolone in the United States. Oxandrolone has also been sold under the brand names Antitriol (Spain), Anatrophill (France), Lipidex (Brazil), Lonavar (Argentina, Australia, Italy). Other names include Protivar and Vasorome (Japan). As of 2016, among those using oxandrolone for nonmedical purposes, it has been referred to colloquially as “Var”. This is a shortened form of the old brand name Anavar. Additional brand names existed for products that were manufactured for the steroid black market.

Availability

United States

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

In June 2023, the FDA formally withdrew approval for oxandrolone for all indications. The agency stated 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. This followed a 2019 letter from Gemini, a drug manufacturer. The letter stated that the product was no longer being marketed.

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

Other countries

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

Historically, oxandrolone has been marketed in Argentina, Australia, Brazil, France, Italy, Japan, and Spain. However, it appears to no longer be available in these countries.

Legal status

In the United States, oxandrolone was categorized as a Schedule III controlled substance. This was under the Controlled Substances Act along with many other AASs. In 2017, it was a Schedule IV controlled substance in Canada. It was also a Schedule 4 controlled drug in the United Kingdom.