Stanozolol

Stanozolol

Systematic (IUPAC) name
(1S,3aS,3bR,5aS,10aS,10bS,12aS)-1,10a,12a-trimethyl-1,2,3,3a,3b,4,5,5a,6,7,10,10a,10b,11,12,12a-hexadecahydrocyclopenta[5,6]naphtho[1,2-f]indazol-1-ol
Clinical data
AHFS/Drugs.com	Multum Consumer Information
Pregnancy category	X
Routes of administration	Oral, Intramuscular
Legal status
Legal status	CA: Schedule IV US: POM
Pharmacokinetic data
Bioavailability	?
Metabolism	Hepatic
Biological half-life	1 day
Excretion	Renal: 84%
Identifiers
CAS Number	10418-03-8
ATC code	A14AA02 (WHO)
PubChem	CID 25249
DrugBank	DB06718
ChemSpider	23582
UNII	4R1VB9P8V3
KEGG	D00444
ChEBI	CHEBI:9249
ChEMBL	CHEMBL1200324
Chemical data
Formula	C21H32N2O
Molar mass	328.49
SMILES O[C@@]5(C)CC[C@H]4[C@H]3[C@@H]([C@]2(Cc1c(nnc1)C[C@@H]2CC3)C)CC[C@@]45C
InChI InChI=1S/C21H32N2O/c1-19-11-13-12-22-23-18(13)10-14(19)4-5-15-16(19)6-8-20(2)17(15)7-9-21(20,3)24/h12,14-17,24H,4-11H2,1-3H3,(H,22,23)/t14-,15+,16-,17-,19-,20-,21-/m0/s1 Key:LKAJKIOFIWVMDJ-IYRCEVNGSA-N
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Stanozolol, commonly sold under the name Winstrol (oral) and Winstrol Depot (intramuscular), is a synthetic anabolic steroid derived from dihydrotestosterone. It was developed by Winthrop Laboratories (Sterling Drug) in 1962, and has been approved by the FDA ^[1]for human use.

Unlike most injectable anabolic steroids, stanozolol is not esterified and is sold as an aqueous suspension, or in oral tablet form. The drug has a high oral bioavailability, due to a C17 α-alkylation which allows the hormone to survive first-pass liver metabolism when ingested. It is because of this that stanozolol is also sold in tablet form.

Stanozolol has been used in both animal and human patients for a number of conditions. In humans, it has been demonstrated to be successful in treating anaemia and hereditary angioedema. Veterinarians may prescribe the drug to improve muscle growth, red blood cell production, increase bone density and stimulate the appetite of debilitated or weakened animals.

Stanozolol is one of the anabolic steroids commonly used as performance-enhancing drugs and is banned from use in sports competition under the auspices of the International Association of Athletics Federations (IAAF) and many other sporting bodies. Additionally, stanozolol has been used in US horse racing.^[2]

Use in bodybuilding

Stanozolol 50mg tablets

Stanozolol is subject to non-medically supervised off-label use by some athletes for its anabolic properties frequently presenting with concomitant reduction of body fat. Stanozolol is a modified derivative of dihydrotestosterone (DHT) and thus not aromatized to oestrogens via the aromatase class of enzymes (see chemical structure to right). Bodybuilders frequently misuse the term "dry" in describing their joint pain while using stanozolol either orally or via IM injection of an aqueous suspension; a reference to their perceived reason for an increase in joint pain. Rather, stanozolol as a DHT derivative can selectively compete with progesterone and other natural and synthetic progestins (nandrolone) for progestin receptors; yielding a reduction in progesterone mediated anti-inflammatory processes and presenting patients with a perception of increased joint discomfort.

Commonly used by athletes and bodybuilders alike to lose fat while retaining lean body mass.^[3] It is usually used in a "cutting or leaning out" cycle, to help preserve lean body mass while metabolizing adipose,^[4] although it has not been proven conclusively that it has any special fat-burning properties.^[5]

It is presented most commonly as a 50 mg/mL injection. However, recently 75 mg/ml 100 mg/mL versions have become available.

10 mg is the lowest strength tablets, but 50 mg tablets are also available.

According to one source,^[6]

“

injectable Winstrol carries with it a half-life of approximately 24 hours while the oral Winny form as it is commonly known carries with it a half-life of approximately 9 hours.

”

Stanozolol is thirty-five times more potent than methyltestosterone as an anabolic agent. On the other hand, it is only one-fourth as androgenic as methyltestosterone.^[7]

Detection of use

Stanozolol is subject to extensive hepatic biotransformation by a variety of enzymatic pathways. The primary metabolites are unique to stanozolol and are detectable in the urine for up to 10 days after a single 5–10 mg oral dose. Methods for detection in urine specimens usually involve gas chromatography-mass spectrometry or liquid chromatography-mass spectrometry.^[8][9][10]

History

In 1962, Stanozolol was brought to market in the US by Winthrop under the tradename "Winstrol" and in Europe by Winthrop's partner, Bayer, under the name "Stromba".^[11]

Also in 1962, the Kefauver Harris Amendment was passed, amending the Federal Food, Drug, and Cosmetic Act to require drug manufacturers to provide proof of the effectiveness of their drugs before approval.^[12] The FDA implemented its Drug Efficacy Study Implementation (DESI) program to study and regulate drugs, including stanozolol, that had been introduced prior to the amendment. The DESI program was intended to classify all pre-1962 drugs that were already on the market as effective, ineffective, or needing further study.^[13] The FDA enlisted the National Research Council of the National Academy of Sciences to evaluate publications on relevant drugs under the DESI program.^[14]

In June 1970 the FDA announced its conclusions on the effectiveness of certain anabolic steroid drugs, including stanozolol, based on the NAS/NRC reports made under DESI. The drugs were classified as probably effective as adjunctive therapy in the treatment of senile and postmenopausal osteoporosis but only as an adjunct, and in pituitary dwarfism (with a specific caveat for dwarfism, "until growth hormone is more available"), and as lacking substantial evidence of effectiveness for several other indications. Specifically, the FDA found a lack of efficacy for stanozolol as "an adjunct to promote body tissue-building processes and to reverse tissue-depleting processes in such conditions as malignant diseases and chronic nonmalignant diseases; debility in elderly patients, and other emaciating diseases; gastrointestinal disorders resulting in alterations of normal metabolism; use during pre-operative and postoperative periods in undernourished patients and poor-risk surgical cases due to traumatism; use in infants, children, and adolescents who do not reach an adequate weight; supportive treatment to help restore or maintain a favorable metabolic balance, as in postsurgical, postinfectious, and convalescent patients; of value in pre- operative patients who have lost tissue from a disease process or who have associated symptoms, such as anorexia; retention and utilization of calcium; surgical applications; gastrointestinal disease, malnourished adults, and chronic illness; pediatric nutritional problems; prostatic carcinoma; and endocrine deficiencies."^[15] The FDA gave Sterling six months to stop marketing stanozolol for the indications for which there was no evidence for efficacy, and one year to submit further data for the two indications for which it found probable efficacy.^[15]

In August and September 1970, Sterling submitted more data; the data was not sufficient but the FDA allowed the drug to be continued to be marketed, since there was an unmet need for drugs for osteoporosis and pituitary dwarfism, but Sterling was required to submit more data.^[16]

In 1980 the FDA removed the dwarfism indication from the label for stanozolol since human growth hormone drugs had come on the market, and mandated that the label for stanozolol and other steroids say: "As adjunctive therapy in senile and postmenopausal osteoporosis. Anabolic steroids are without value as primary therapy but may be of value as adjunctive therapy. Equal or greater consideration should be given to diet, calcium balance, physiotherapy, and good general health promoting measures." and gave Sterling a timeline to submit further data for other indications it wanted for the drug.^[17] Sterling submitted data to the FDA intended to support the effectiveness of Winstrol for postmenopausal osteoporosis and aplastic anemia in December, 1980 and August 1983 respectively. The FDA's Endocrinologic and Metabolic Drugs Advisory Committee considered the data submitted for osteoporosis in two meetings held 1981 and the data for aplastic anemia in 1983.^[16]

In April 1984, the FDA announced that the data was not sufficient, and withdrew the marketing authority for stanozolol for senile and postmenopausal osteoporosis and for raising hemoglobin levels in aplastic anemia.^[16][18]

In 1988, Sterling was acquired by Eastman Kodak for $5.1 billion and in 1994 Kodak sold the drug business of Sterling to Sanofi for $1.675 billion.^[19][20]

Sanofi had stanzolol manufactured in the US by Searle, which stopped making the drug in October 2002.^[21] Even with no drug in production, Sanofi sold the stanozolol business to Ovation Pharmaceuticals in 2003, along with the two other drugs.^[22] At that time, the drug had not been discontinued and was considered a treatment for hereditary angioedema.^[22] In March 2009, Lundbeck purchased Ovation^[23]

In 2010, Lundbeck withdrew stanozolol from the market in the US; as of 2014 no other company is marketing stanozolol as a pharmaceutical drug in the US but it can be obtained via a compounding pharmacy.^{[24][25][26][27]}

Pfizer had marketed stanozolol as a veterinary drug; in 2013 Pfizer spun off its veterinary business to Zoetis^[28] and in 2014 Pfizer transferred the authorizations to market injectable and tablet forms of stanozolol as a veterinary drug to Zoetis.^[29][30]

It is used in veterinary medicine as an adjunct in the management of wasting diseases, to stimulate the formation of red blood cells, arouse appetite, and promote weight gain, but the evidence for these uses is weak. It is used as a performance-enhancing drug in race horses. Its side effects include weight gain, water retention, and difficulty eliminating nitrogen-based waste products and it is toxic to the liver, especially in cats. Because it may promote the growth of tumors, it is contraindicated in dogs with enlarged prostates.^[31]:730-371

Stanozolol and other anabolic steroids were commonly used to treat hereditary angioedema attacks, until several drugs were brought to market specifically for treatment of that disease, the first in 2009: Cinryze, Berinert, ecallantide (Kalbitor), icatibant (Firazyr) and Ruconest.^[26][27] Stanozolol is still used long-term to reduce the frequency of severity of attacks.^[32]

Society and culture

Regulation

In the United States, like other anabolic steroids, stanozolol is classified as a controlled substance under federal regulation; they were included as Schedule III controlled substances under the Anabolic Steroids Act, which was passed as part of the Crime Control Act of 1990.^[33]:30 In New York, the state legislature classifies anabolic steroids under DEA Schedule III.

Stanozolol and other synthetic steroids were first banned by the International Olympic Committee and the International Amateur Athletic Federation in 1974, after methods to detect them had been developed.^[34]:716

Publicized abuse cases

• Ben Johnson was stripped of his gold medal in the 100 meter sprint at the 1988 Summer Olympics when he tested positive for stanozolol after winning the final.^[35]
• Olimpiada Ivanova was stripped of her silver medal in the 10 kilometer walk at the 1997 World Championships in Athletics after she had tested positive for stanozolol, and she was banned for two years.^[36]
• Australian National Rugby League footballer Rodney Howe was banned for 22 matches in 1998 for using stanozolol.^[37]
• Vita Pavlysh was stripped of her gold medal in shot put at the 1999 IAAF World Indoor Championships after she had tested positive for stanozolol. 5 years later at the 2004 IAAF World Indoor Championships in Budapest, Hungary, she won the title again only to fail the drug test for the same reason. She was again stripped of her title and banned from athletics for life.^[38]
• Liudmyla Blonska, a Ukrainian heptathlete, tested positive for traces of stanozolol shortly after finishing thirteenth at the 2002 European Championships in Athletics and in June 2003 was handed a two-year ban, whereafter she returned to the sport.^[39] At the 2008 Beijing Games, she was stripped of a silver medal and given a lifetime ban after testing positive for stanozolol again.^[40]
• Rafael Palmeiro was suspended 10 days from Major League Baseball on August 1, 2005, after testing positive for steroids.^[41] According to the published report in The New York Times, stanozolol was the steroid detected in Palmeiro's system. This came not long after he testified before the United States House Committee on Oversight and Government Reform on steroid usage in baseball, and he denied ever using steroids.
• Barry Bonds is accused of using stanozolol in Game of Shadows, a book by Mark Fainaru-Wada and Lance Williams. The accusations were first aired on 7 March 2006 by Sports Illustrated, which published excerpts from the book.^[42]
• Salvador Carmona, footballer, tested positive for stanozolol in 2005 and 2006. He was banned for life by the Court of Arbitration for Sport (CAS) due to repeated drug offences. Tribunal Arbitral du Sport.^[43]
• Magnus Hedman, footballer, was charged and convicted by Swedish court in June 2009 when he tested positive for stanozolol. At the time he was a "ambassador" for Swedish anti-steroid organization Ren Idrott ("Clean Sports") and sports commentator for Swedish TV4. He lost both assignments as a consequence.^[44]
• Phil Baroni, former UFC and PRIDE Fighting Championship fighter, tested positive for stanozolol following his June 22, 2007 fight against Frank Shamrock at Strikeforce: Judgment Day.^[45]
• K-1's 2007 World Grand Prix in Las Vegas finalist Zabit Samedov tested positive for stanozolol following the August 11, 2007 event.^[46]
• Roger Clemens was reported to have been injected with stanozolol (Winstrol) by major league strength coach Brian McNamee during the 1998 baseball season.^[47]
• 2008 Triple Crown hopeful Big Brown was reported to have been injected with Winstrol, which is legal in some states in US horse racing, by trainer Richard E. Dutrow, Jr. ^[48]
• Chris Leben, mixed martial artist, tested positive for the substance after UFC 89 where he was defeated by Michael Bisping and was suspended for 9 months.^[49]
• Kirill Sidelnikov, mixed martial artist, tested positive for the substance after Affliction: Day of Reckoning where he was defeated by Paul Buentello and was suspended for 1 year and fined $2,500.^[50]
• Tim Sylvia, mixed martial artist, tested positive for the drug stanozolol after a Nevada State Athletic Commission test. As a result, Sylvia was stripped of his title, served a 6-month suspension, and was fined $10,000. Sylvia has stated that he used the drug to shed excess body fat and lose weight.^[51]
• Cristiane Justino tested positive for anabolic steroids and as a result of the banned substance, her fight against Hiroko Yamanaka result has been changed to a "No Contest" while Cristiane has had her license suspended and was fined $2500.^[52]
• Hysen Pulaku, an Albanian weightlifter, was expelled from the 2012 Olympics after testing positive for stanozolol.^[53]
• Zane Botha, a South African rugby player, was banned from competing in rugby for 2 years in January 2013 after testing positive for stanozolol.^[54]
• David Rollins, Seattle Mariners pitcher, was suspended for 80 games in 2015 after testing positive for stanozolol.^[55]
• Ervin Santana, Minnesota Twins pitcher, was suspended for 80 games without pay in 2015 after testing positive for stanozolol.^[56]
• Jenrry Mejía, New York Mets pitcher, was suspended for 80 games without pay early in 2015 after testing positive for stanozolol, and another 162 later in the season after a second positive test.^{[57] [58]}
• Sheila Ocasio, Puerto Rican volleyball player, tested positive^[59] before the bronze medal match lost 1-3 to by her national team to the Dominican Republic in the 2015 Pan American Games^[60] and could not play that game.^[61]
• Mauricio Fiol, Peruvian swimmer, tested positive for stanozolol after winning the silver medal in the 200-metre butterfly at the 2015 Pan American Games. He was stripped of his medal and disqualified from competing in the 2016 Olympics by FINA.^[62]

See also

• Dromostanolone

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