Stanozolol

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Stanozolol
Stanozolol.png
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 cat.
  • X
Legal status
  • Prescription only
    (US)
Routes Oral, Intramuscular
Pharmacokinetic data
Bioavailability ?
Metabolism Hepatic
Half-life 1 day
Excretion Renal: 84%
Identifiers
CAS number 10418-03-8 N
ATC code A14AA02
PubChem CID 25249
DrugBank DB06718
ChemSpider 23582 YesY
UNII 4R1VB9P8V3 YesY
KEGG D00444 YesY
ChEBI CHEBI:9249 N
ChEMBL CHEMBL1200324 N
Chemical data
Formula C21H32N2O 
Mol. mass 328.49
 N (what is this?)  (verify)

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 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.[1]

Use in bodybuilding[edit]

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.[citation needed] It is usually used in a "cutting or leaning out" cycle, to help preserve lean body mass while metabolizing adipose,[citation needed] although it has not been proven conclusively that it has any special fat-burning properties.[citation needed]

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

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

According to one source,[2]

Detection of use[edit]

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.[3][4][5]

History[edit]

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."[6]

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 and safety of their drugs before approval.[7] 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 either effective, ineffective, or needing further study.[8] The FDA enlisted the National Academy of Sciences/National Research Council to evaluate publications on relevant drugs under the DESI program.[9]

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 dis ease, malnourished adults, and chronic illness; pediatric nutritional problems; prostatic carcinoma; and endocrine deficiencies."[10] The FDA gave Sterling 6 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.[10]

In August and September of 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.[11]

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.[12] 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.[11]

In April of 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.[11][13]

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[14][15]

Sanofi had stanzolol manufactured in the US by Searle, which stopped making the drug in October 2002.[16] Even with no drug in production, Sanofi sold the stanozolol business to Ovation Pharmaceuticals in 2003, along with the two other drugs.[17] At that time, the drug had not been discontinued and was considered a treatment for hereditary angioedema.[17] In March 2009, Lundbeck purchased Ovation[18]

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.[19][20][21][22]

Pfizer had marketed stanozolol as a veterinary drug; in 2013 Pfizer spun off its veterinary business to Zoetis[23] and in 2014 Pfizer transferred the authorizations to market injectable and tablet forms of stanozolol as a veterinary drug to Zoetis.[24][25]

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.[26]: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.[21][22] Stanozolol is still used for long-term reduction in the frequency of severity of attacks.[27]

Society and culture[edit]

Regulation[edit]

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.[28]: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.[29]:716

Publicized abuse cases[edit]

See also[edit]

References[edit]

  1. ^ Win, Place, and Dope Slate, May 1, 2009
  2. ^ http://www.steroidabuse.com/Profiles/winstrol.html
  3. ^ Mateus-Avois L, Mangin P, Saugy M. Use of ion trap gas chromatography-multiple mass spectrometry for the detection and confirmation of 3'hydroxystanozolol at trace levels in urine for doping control. J. Chromatogr. B 816: 193-201, 2005.
  4. ^ Pozo OJ, Van Eenoo P, Deventer K et al. Detection and structural investigation of metabolites of stanozolol in human urine by liquid chromatography tandem mass spectrometry. Steroids 74: 837-852, 2009.
  5. ^ R. Baselt, Disposition of Toxic Drugs and Chemicals in Man, 8th edition, Biomedical Publications, Foster City, CA, 2008, pp. 1442-1443.
  6. ^ Levin J, Trafford JA, Bishop PM. Stanozolol, a new anabolic steroid. J New Drugs. 1962 Jan-Feb;2:50-5. PMID 14464563
  7. ^ "Promoting Safe and Effective Drugs for 100 Years". The Kefauver-Harris Drug Amendments. U.S. Food and Drug Administration. 
  8. ^ Pharmacy Today. August 2008. FDA aims to remove unapproved drugs from market: Risk-based enforcement program focuses on removing potentially harmful products
  9. ^ National Academies of Sciences archives. The Drug Efficacy Study of the National Research Council’s Division of Medical Sciences, 1966-1969
  10. ^ a b Food and Drug Administration Notice. "DESI 7630. Certain Anabolic Steroids. Drugs for Human Use: Drug Efficacy Study Implementation" Federal Register Vol 35, No. 122. June 24, 1970. page 10327-28
  11. ^ a b c Food and Drug Admininistration Notice. Docket No 80N-0276; DESI 7630. Winstrol Tablets; Drugs for Human Use; Drug Efficacy Study Implementation, Revocation of Exemption; Followup Notice and Opportunity for Hearing on Proposal to Withdraw Approval of New Drug Federal Register, April 23, 1984. page 17094-99
  12. ^ Food and Drug Admininistration Notice. Docket No 80N-0276; Drugs for Human Use; Drug Efficacy Study Implementation; Conditions for Continued Marketing of Anabolic Steroids for Treatment Federal Register Vol 45 No. 213. October 31 1980. pages 72291-93
  13. ^ The Pink Sheet 30 April, 1984 Sterling Winstrol (Stanozolol) NDA Withdrawal Process Beginning, FDA
  14. ^ Joseph C. Collins And John R. Gwilt The Life Cycle of Sterling Drug, Inc. Bull. Hist. Chem., VOLUME 25, Number 1 (2000)
  15. ^ "Kodak to Sell Drug Unit for $1.68 Billion". Los Angeles Times. June 24, 1994. Retrieved 3 May 2013. 
  16. ^ Ovation Pharmaceuticals Products Archive of website captured January 10, 2004]
  17. ^ a b PRnewswire. 7 August 2003. [http://www.prnewswire.com/news-releases/ovation-pharmaceuticals-acquires-mebaralr-chemetr-and-winstrolr-from-sanofi-synthelabo-inc-70900312.html Press release: Ovation Pharmaceuticals Acquires Mebaral(R), Chemet(R), and Winstrol(R) From Sanofi-Synthelabo Inc.
  18. ^ Reuters. 19 Mar, 2009 Press Release: GTCR Completes the Sale of Ovation Pharmaceuticals to Lundbeck
  19. ^ Notice by the Food and Drug Administration n the US Federal Register. 21 July, 2010 [https://www.federalregister.gov/articles/2010/07/21/2010-17785/novartis-pharmaceuticals-corp-et-al-withdrawal-of-approval-of-27-new-drug-applications-and-58 Novartis Pharmaceuticals Corp. et al.; Withdrawal of Approval of 27 New Drug Applications and 58 Abbreviated New Drug Applications}
  20. ^ FDA Drugs@FDA: Stanozolol
  21. ^ a b The US Hereditary Angioedema Association Treatments
  22. ^ a b Timothy J. Craig and Neelu Kalra for MedScape Education. Contemporary Issues in Prophylactic Therapy of Hereditary Angioedema Released: 10/04/2010; Reviewed and Renewed: 07/30/2012.
  23. ^ Zoetis. 24 June, 2013 Zoetis Press Release: Zoetis Becomes Fully Independent With Acceptance of Pfizer Shares Tendered in Exchange Offer
  24. ^ A Rule by the Food and Drug Administration, published in the Federal Register 20 May, 2014 Implantation or Injectable Dosage Form New Animal Drugs; Change of Sponsor
  25. ^ A Rule by the Food and Drug Administration, published in the Federal Register 25 March, 2014 Oral Dosage Form New Animal Drugs; Change of Sponsor
  26. ^ Jim E. Riviere, Mark G. Papich. Veterinary Pharmacology and Therapeutics. John Wiley & Sons, 2013 ISBN 9781118685907
  27. ^ Merck Manual. http://www.merckmanuals.com/professional/immunology_allergic_disorders/allergic_autoimmune_and_other_hypersensitivity_disorders/hereditary_and_acquired_angioedema.html Hereditary and Acquired Angioedema] Last full review/revision March 2014 by Peter J. Delves, PhD
  28. ^ Steven B. Karch. Pathology, Toxicogenetics, and Criminalistics of Drug Abuse. CRC Press, 2007 ISBN 9781420054569
  29. ^ Shänzer, W. Abuse of Androgens and Detection of Illiegal Use. Chapter 24 in Testosterone: Action, Deficiency, Substitution, edited by E. Nieschlag, H. M. Behr. Cambridge University Press, 2004. ISBN 9781139452212
  30. ^ "The most corrupt race ever". Guardian Unlimited (London). August 1, 2004. Retrieved May 24, 2010. 
  31. ^ Ivanova Sets First Record in Helsinki The Moscow Times.com, 8-8-2005
  32. ^ Hooper, James (5 October 2006). "Webcke defends 'cover-up'". Fox Sports. Retrieved 13 August 2012. 
  33. ^ WOMEN'S SHOT-PUT CHAMPION BARRED FOR LIFE The New York Times, June 2, 2004
  34. ^ Blonska Thrown Out of Long Jump BBC Sport, August 21, 2008
  35. ^ Ukrainian Blonska Given Life Ban BBC Sport, August 29, 2008
  36. ^ Jenkins, Lee (August 3, 2005). "Popular Steroid Is at the Center of Palmeiro's Case". The New York Times. Retrieved May 24, 2010. 
  37. ^ Bonds exposed: Shadows details superstar slugger's steroid use, Sports Illustrated, March 7, 2006
  38. ^ "CAS 2006/A/1149 WADA v/ FMF & José Salvador Carmona Alvarez", May 16, 2007 Accessed May 17, 2007
  39. ^ Carson, Alan (June 30, 2009). "Ex-Celt ace Hedman faces Steroids rap". The Sun (London). Retrieved November 3, 2010. 
  40. ^ Ken Pishna (2007-07-03). "Breaking News: Phil Baroni Tests Positive". MMAWeekly.com. Retrieved 2007-07-03. 
  41. ^ "Two Positive at K-1 World GP Vegas". Nokaut. August 17, 2007. Retrieved 2007-08-17. 
  42. ^ All-Star Roster Shows Up on Mitchell Report washingtonpost.com, 12-13-2007
  43. ^ Bossert, Jerry; Red, Christian (May 16, 2008). "Big Brown's legal doping a concern". Daily News (New York). 
  44. ^ http://mma-live.com/chris-leben-fails-ufc-89-drug-test/
  45. ^ Sidelnikov Suspended for Steroid Use sherdog.com, 03-03-2009
  46. ^ Sylvia Comes Clean sherdog.com, 10-13-2003
  47. ^ http://lowkick.blitzcorner.com/Strikeforce/How-Does-Cyborgs-Failed-Drug-Test-Change-the-Landscape-of-WMMA-14823
  48. ^ Sky Sports http://www1.skysports.com/olympics/story/21822/7945311 |url= missing title (help). 
  49. ^ http://www.sport24.co.za/Rugby/VarsityCup/Tuks-star-banned-for-doping-20130306