Chemistry:Mesterolone

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Short description: Chemical compound
Mesterolone
Mesterolone.svg
Clinical data
Trade namesProviron, others
Other namesNSC-75054; SH-60723; SH-723; 1α-Methyl-4,5α-dihydrotestosterone; 1α-Methyl-DHT; 1α-Methyl-5α-androstan-17β-ol-3-one
AHFS/Drugs.comInternational Drug Names
Routes of
administration		By mouth
Drug classAndrogen; Anabolic steroid
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability3%
Protein binding98% (40% to Albumin, 58% to SHBG)
MetabolismLiver
Elimination half-life12-13 hours
ExcretionUrine
Identifiers
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEMBL
Chemical and physical data
FormulaC20H32O2
Molar mass304.474 g·mol−1
3D model (JSmol)
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Mesterolone, sold under the brand name Proviron among others, is an androgen and anabolic steroid (AAS) medication which is used mainly in the treatment of low testosterone levels.[1][2] It has also been used to treat male infertility, although this use is controversial.[1][3][4] It is taken by mouth.[1]

Side effects of mesterolone include symptoms of masculinization like acne, scalp hair loss, increased body hair growth, voice changes, and increased sexual desire.[1] It has no risk of liver damage.[1][2] The drug is a synthetic androgen and anabolic steroid and hence is an agonist of the androgen receptor (AR), the biological target of androgens like testosterone and dihydrotestosterone (DHT).[1][5] It has strong androgenic effects and weak anabolic effects, which make it useful for producing masculinization.[1] The drug has no estrogenic effects.[1][2]

Mesterolone was first described by 1966[6] and introduced for medical use by 1967.[7][8] In addition to its medical use, mesterolone has been used to improve physique and performance, although it is not commonly used for such purposes due to its weak anabolic effects.[1] The drug is a controlled substance in many countries and so non-medical use is generally illicit.[1][9]

Medical uses

Mesterolone is used in the treatment of androgen deficiency in male hypogonadism, anemia, and to support male fertility among other indications.[1][10][11] It has also been used to treat delayed puberty in boys.[12] Because it lacks estrogenic effects, mesterolone may be indicated for treating cases of androgen deficiency in which breast tenderness or gynecomastia is also present.[13] The drug is described as a relatively weak androgen with partial activity and is rarely used for the purpose of androgen replacement therapy, but is still widely used in medicine.[1][11][14][2]

Mesterolone is used in androgen replacement therapy at a dosage of 50 to 100 mg 2 to 3 times per day.[15]


Non-medical uses

Mesterolone has been used for physique- and performance-enhancing purposes by competitive athletes, bodybuilders, and powerlifters.[1]

Side effects

Side effects of mesterolone include virilization among others.[1]

Pharmacology

Pharmacodynamics

Like other AAS, mesterolone is an agonist of the androgen receptor (AR).[1] Mesterolone is described as a very poor anabolic agent due to inactivation by 3α-hydroxysteroid dehydrogenase (3α-HSD) in skeletal muscle tissue, similarly to DHT and mestanolone (17α-methyl-DHT).[1] In contrast, testosterone is a very poor substrate for 3α-HSD, and so is not similarly inactivated in skeletal muscle.[1] Because of its lack of potentiation by 5α-reductase in "androgenic" tissues and its inactivation by 3α-HSD in skeletal muscle, mesterolone is relatively low in both its androgenic potency and its anabolic potency.[1] However, it does still show a greater ratio of anabolic activity to androgenic activity relative to testosterone.[1]

Mesterolone is not a substrate for 5α-reductase, as it is already 5α-reduced, and hence is not potentiated in so-called "androgenic" tissues such as the skin, hair follicles, and prostate gland.[1]

Mesterolone is not a substrate for aromatase, and so cannot be converted into an estrogen.[1] As such, it has no propensity for producing estrogenic side effects such as gynecomastia and fluid retention.[1] It also has no progestogenic activity.[1]

Because mesterolone is not 17α-alkylated, it has little or no potential for hepatotoxicity.[1] However, its risk of deleterious effects on the cardiovascular system is comparable to that of several other oral AAS.[1]

Pharmacokinetics

The C1α methyl group of mesterolone inhibits its hepatic metabolism and thereby confers significant oral activity, although its oral bioavailability is still much lower than that of 17α-alkylated AAS.[1] In any case, mesterolone is one of the few non-17α-alkylated AAS that is active with oral ingestion.[1] Uniquely among AAS, mesterolone has very high affinity for human serum sex hormone-binding globulin (SHBG), about 440% that of DHT in one study and 82% of that of DHT in another study.[16][1][17] As a result, it may displace endogenous testosterone from SHBG and thereby increase free testosterone concentrations, which may in part be involved in its effects.[1]

Chemistry

Mesterolone, also known as 1α-methyl-4,5α-dihydrotestosterone (1α-methyl-DHT) or as 1α-methyl-5α-androstan-17β-ol-3-one, is a synthetic androstane steroid and derivative of DHT.[18][19][1] It is specifically DHT with a methyl group at the C1α position.[18][19][1] Closely related AAS include metenolone and its esters metenolone acetate and metenolone enanthate.[18][19][1] The antiandrogen rosterolone (17α-propylmesterolone) is also closely related to mesterolone.[20]

History

Mesterolone was developed in the 1960s[21] and was first described by 1966.[6][22][23][24] It was introduced for medical use by Schering under the brand name Proviron by 1967.[7][8] The well-established brand name Proviron had previously been used by Schering for testosterone propionate starting in 1936.[25] Following the introduction of mesterolone as Proviron, Schering continued to market testosterone propionate under the brand name Testoviron.[25] A number of sources incorrectly state that mesterolone was synthesized or introduced for medical use in 1934.[21][1][26][27]

Society and culture

Generic names

Mesterolone is the generic name of the drug and its INN, USAN, BAN, and DCIT, while mestérolone is its DCF.[18][19][28][29]

Brand names

Mesterolone is marketed mainly under the brand name Proviron.[18][19][29][1]

Availability

Mesterolone is available widely throughout the world, including in the United Kingdom , Australia , and South Africa , as well as many non-English-speaking countries.[19][29] It is not available in the United States , Canada , or New Zealand.[19][29] The drug has never been marketed in the United States.[26]

Legal status

Mesterolone, along with other AAS, is a schedule III controlled substance in the United States under the Controlled Substances Act and a schedule IV controlled substance in Canada under the Controlled Drugs and Substances Act.[9][30]

Research

In one small scale clinical trial of depressed patients, an improvement of symptoms which included anxiety, lack of drive and desire was observed.[31] In patients with dysthymia, unipolar, and bipolar depression significant improvement was observed.[31] In this series of studies, mesterolone lead to a significant decrease in luteinizing hormone and testosterone levels.[31] In another study, 100 mg mesterolone cipionate was administered twice monthly.[32] With regards to plasma testosterone levels, there was no difference between the treated versus untreated group, and baseline luteinizing hormone levels were minimally affected.[32]

References

  1. ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 1.15 1.16 1.17 1.18 1.19 1.20 1.21 1.22 1.23 1.24 1.25 1.26 1.27 1.28 1.29 1.30 1.31 1.32 1.33 Anabolics. Molecular Nutrition Llc. 2011. pp. 641–. ISBN 978-0-9828280-1-4. https://books.google.com/books?id=afKLA-6wW0oC&pg=PT642. 
  2. ↑ 2.0 2.1 2.2 2.3 Testosterone: Action, Deficiency, Substitution. Cambridge University Press. 1 April 2004. pp. 411–. ISBN 978-1-139-45221-2. https://books.google.com/books?id=ZiZ7MWDqo5oC&pg=PA411. 
  3. ↑ Male Infertility. Springer Science & Business Media. 6 December 2012. pp. 398–399. ISBN 978-1-4471-1029-3. https://books.google.com/books?id=3m_rBwAAQBAJ&pg=PA398. 
  4. ↑ Infertility in the Male. Cambridge University Press. 24 September 2009. pp. 445–446. ISBN 978-0-521-87289-8. https://books.google.com/books?id=D89GbMA8lxkC&pg=PA445. 
  5. ↑ "Pharmacology of anabolic steroids". British Journal of Pharmacology 154 (3): 502–521. June 2008. doi:10.1038/bjp.2008.165. PMID 18500378. 
  6. ↑ 6.0 6.1 "Pharmacology of testosterone preparations". Testosterone. Cambridge University Press. 2004. pp. 405–444. doi:10.1017/CBO9780511545221.015. ISBN 9780521833806. 
  7. ↑ 7.0 7.1 "The influence of mesterolone on testicular function". Research on Steroids (Pergamon) 3: 181–184. 1967. https://books.google.com/books?id=zBVrAAAAMAAJ. 
  8. ↑ 8.0 8.1 "Practically Applicable Results of Twenty Years of Research in Endocrinology". Progress in Drug Research / Fortschritte der Arzneimittelforschung / Progrès des recherches pharmaceutiques. 12. 1968. 137–164. doi:10.1007/978-3-0348-7065-8_3. ISBN 978-3-0348-7067-2. 
  9. ↑ 9.0 9.1 Drug Abuse Handbook, Second Edition. CRC Press. 21 December 2006. pp. 30–. ISBN 978-1-4200-0346-8. https://books.google.com/books?id=ZjrMBQAAQBAJ&pg=PA30. 
  10. ↑ The Art and Science of Assisted Reproductive Techniques. CRC Press. 12 November 2004. pp. 824–. ISBN 978-0-203-64051-7. https://books.google.com/books?id=_ldpcClfnrgC&pg=PA824. 
  11. ↑ 11.0 11.1 Principles and Practice of Endocrinology and Metabolism. Lippincott Williams & Wilkins. 2001. pp. 1186–. ISBN 978-0-7817-1750-2. https://books.google.com/books?id=FVfzRvaucq8C&pg=PA1186. 
  12. ↑ Endocrinology. Springer Science & Business Media. 6 December 2012. pp. 119–. ISBN 978-94-010-9298-2. https://books.google.com/books?id=QbjUBgAAQBAJ&pg=PA119. 
  13. ↑ "Emerging medication for the treatment of male hypogonadism". Expert Opinion on Emerging Drugs 17 (2): 239–259. June 2012. doi:10.1517/14728214.2012.683411. PMID 22612692. 
  14. ↑ "Testosterone replacement therapy: current trends and future directions". Human Reproduction Update 10 (5): 409–419. 2004. doi:10.1093/humupd/dmh035. PMID 15297434. 
  15. ↑ "Testosterone Replacement Therapy". Sexual Medicine. Springer. 2019. pp. 79–93. doi:10.1007/978-981-13-1226-7_8. ISBN 978-981-13-1225-0. 
  16. ↑ "Relative binding affinity of anabolic-androgenic steroids: comparison of the binding to the androgen receptors in skeletal muscle and in prostate, as well as to sex hormone-binding globulin". Endocrinology 114 (6): 2100–2106. June 1984. doi:10.1210/endo-114-6-2100. PMID 6539197. 
  17. ↑ "Transport of steroid hormones: interaction of 70 drugs with testosterone-binding globulin and corticosteroid-binding globulin in human plasma". The Journal of Clinical Endocrinology and Metabolism 53 (1): 69–75. July 1981. doi:10.1210/jcem-53-1-69. PMID 7195405. 
  18. ↑ 18.0 18.1 18.2 18.3 18.4 The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. 14 November 2014. pp. 775–. ISBN 978-1-4757-2085-3. https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA775. 
  19. ↑ 19.0 19.1 19.2 19.3 19.4 19.5 19.6 Index Nominum 2000: International Drug Directory. Taylor & Francis. 2000. pp. 656–. ISBN 978-3-88763-075-1. https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA656. 
  20. ↑ "Topical anti-androgenicity of a new 4-azasteroid in the hamster". Steroids 56 (8): 428–433. August 1991. doi:10.1016/0039-128x(91)90031-p. PMID 1788861. 
  21. ↑ 21.0 21.1 Androgen Deficiency in the Adult Male: Causes, Diagnosis and Treatment. CRC Press. 2006. pp. 137–178. ISBN 978-0-367-80018-5. https://books.google.com/books?id=YFYgyAEACAAJ. 
  22. ↑ "[Experimental animal studies with a new androgen--mesterolone (1-alpha-methyl-5-alpha-androstan-17-beta-ol-one)]" (in de). Arzneimittel-Forschung 16 (4): 455–458. April 1966. PMID 6014248. 
  23. ↑ "Mesterolone, a potent oral active androgen without gonadotropin inhibition". Acta Endocrinologica 56 (1_Suppl): S55. 1967. doi:10.1530/acta.0.056S055. ISSN 0804-4643. 
  24. ↑ "Practically Applicable Results of Twenty Years of Research in Endocrinology". Progress in Drug Research / Fortschritte der Arzneimittelforschung / Progrès des recherches pharmaceutiques. 12. 1968. 137–164. doi:10.1007/978-3-0348-7065-8_3. ISBN 978-3-0348-7067-2. 
  25. ↑ 25.0 25.1 "The History of Testosterone and The Testes: From Antiquity to Modern Times". Testosterone. Springer. 2017. pp. 1–19. doi:10.1007/978-3-319-46086-4_1. ISBN 978-3-319-46084-0. 
  26. ↑ 26.0 26.1 Testosterone: From Basic to Clinical Aspects. Springer. 6 April 2017. pp. 204–. ISBN 978-3-319-46086-4. https://books.google.com/books?id=Et6TDgAAQBAJ&pg=PA204. 
  27. ↑ "Testosterone Therapy: Oral Androgens". Testosterone. Springer. 2017. pp. 203–224. doi:10.1007/978-3-319-46086-4_10. ISBN 978-3-319-46084-0. 
  28. ↑ Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Science & Business Media. 6 December 2012. pp. 176–177. ISBN 978-94-011-4439-1. https://books.google.com/books?id=tsjrCAAAQBAJ&pg=PA177. 
  29. ↑ 29.0 29.1 29.2 29.3 "Mesterolone". https://www.drugs.com/international/mesterolone.html. 
  30. ↑ Pharmacology for Canadian Health Care Practice. Elsevier Health Sciences. 5 August 2016. pp. 50–. ISBN 978-1-77172-066-3. https://books.google.com/books?id=dNgoDwAAQBAJ&pg=PA50. 
  31. ↑ 31.0 31.1 31.2 "The effects of mesterolone, a male sex hormone in depressed patients (a double blind controlled study)". Methods and Findings in Experimental and Clinical Pharmacology 6 (6): 331–337. June 1984. PMID 6431212. 
  32. ↑ 32.0 32.1 "Testosterone levels and gonadotrophins in Klinefelter's patients treated with injections of mesterolone cipionate". Archives for Dermatological Research 258 (3): 289–294. May 1977. doi:10.1007/bf00561132. PMID 883846. 

Further reading

External links


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