Normethandrone

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Normethandrone
Methylestrenolone.svg
Clinical data
Trade namesMetalutin, others
SynonymsNormetandrone; Methylestrenolone; Methyloestrenolone; Methylnortestosterone; Normethyltestosterone; Normethandrolone; Normethisterone; Methylnandrolone; NMT; 17α-Methyl-19-nortestosterone; 17α-Methylestr-4-en-17β-ol-3-one; P-6051; RU-598; NSC-10039
Routes of
administration
By mouth
Drug classProgestin; Progestogen; Androgen; Anabolic steroid
ATC code
Identifiers
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.007.440 Edit this at Wikidata
Chemical and physical data
FormulaC19H28O2
Molar mass288.42 g/mol g·mol−1
3D model (JSmol)

Normethandrone, also known as methylestrenolone or methylnortestosterone and sold under the brand name Metalutin among others, is a progestin and androgen/anabolic steroid (AAS) medication which is used in combination with an estrogen in the treatment of amenorrhea and menopausal symptoms in women.[1][2][3][4] It is taken by mouth.[5]

Side effects of normethandrone include symptoms of masculinization like acne, increased hair growth, voice changes, and increased sexual desire.[6] It can also cause liver damage.[7] Normethandrone is a progestin, or a synthetic progestogen, and hence is an agonist of the progesterone receptor, the biological target of progestogens like progesterone.[5] It is also a synthetic AAS and hence is an agonist of the androgen receptor, the biological target of androgens like testosterone and dihydrotestosterone (DHT).[4][8] It has some estrogenic activity as well and no other important hormonal activity.[9][1][3]

Normethandrone was introduced for medical use by 1957.[10] It is available only in a few countries, including Brazil, Indonesia, and Venezuela, and is available only in combination with methylestradiol or estradiol valerate.[2][1]

Medical uses[edit]

Normethandrone is used in combination with an estrogen, either methylestradiol or estradiol valerate, in the treatment of amenorrhea and menopausal symptoms in women.[1][2][11] It has also been used to treat dysmenorrhea in women.[12] Normethandrone has been used successfully to inhibit libido in men with sexual deviance.[13] Although normethandrone can be classified as an AAS and has strong such effects at sufficiently high doses, it is not typically used as such and is instead used medically only as a progestin.[3][1][4] This is because it is so highly progestogenic in comparison.[4]

Androgen replacement therapy formulations and dosages used in women

Route Medication Form(s) Major brand name(s) Dosage
Oral Testosterone undecanoatea Capsule Andriol, Jatenzo 40–80 mg 1x/1–2 days
Methyltestosteroneb Tablet Metandren; Estratest 0.5–10 mg/day
Normethandronea,b Tablet Ginecoside 5 mg/day
Tibolonea Tablet Livial 1.25–2.5 mg/day
Prasterone (DHEA)c Tablet N/A 25–100 mg/day
Sublingual Testosteroned Tablet N/A 0.25–0.5 mg/day
Methyltestosterone Tablet Metandren 0.25 mg/day
Transdermal Testosteronea Patch Intrinsa 150–300 μg/day
Testosterone Cream; Gel AndroGel 5–10 mg/day
Vaginal Testosteroned Cream; Gel N/A ? mg 1x/1–3 days
Testosteroned Suppository N/A 1 mg 1x/2 days
Prasterone (DHEA) Insert Intrarosa 6.5 mg/day
Intramuscular Testosterone enanthateb Oil Delatestryl; Primodian Depot 25–100 mg 1x/4–6 weeks
Testosterone cypionateb Oil Depo-Testost.; Depo-Testadiol 25–100 mg 1x/4–6 weeks
Testosterone isobutyratea,b Water Femandren M, Folivirin 25–50 mg 1x/4–6 weeks
Testosterone EBHb,e Oil Climacteron 150 mg 1x/4–8 weeks
Nandrolone decanoate Oil Deca-Durabolin 25–50 mg 1x/6–12 weeks
Prasterone enanthatea,b Oil Gynodian Depot 200 mg 1x/4–6 weeks
Subcutaneous Testosterone Implant Testopel 50–100 mg 1x/3–6 months
Footnotes: a = Not available or no longer available in the United States. b = Alone and/or in combination with an estrogen. c = Over-the-counter. d = Compounded only. e = Discontinued. Sources: See template.

Androgen/anabolic steroid dosages for breast cancer

Route/form Androgen Dosage
Oral Methyltestosterone 30–200 mg/day
Fluoxymesterone 10–40 mg 3x/day
Calusterone 40 mg 4x/day
Normethandrone 40 mg/day
IM injection Testosterone propionate 50–100 mg 3x/week
Testosterone enanthate 200–400 mg 1x/2–4 weeks
Testosterone cypionate 200–400 mg 1x/2–4 weeks
Methandriol (aq. susp.) 100 mg 3x/week
Androstanolone (aq. susp.) 300 mg 3x/week
Drostanolone propionate 100 mg 3x/week
Nandrolone decanoate 50–100 mg 1x/1–3 weeks
Nandrolone phenylpropionate 50–100 mg/week
Notes: Dosages are not necessarily equivalent. Sources: See template.

Available forms[edit]

Normethandrone is marketed in combination with methylestradiol in the form of oral tablets containing 5 mg normethandrone and 0.3 mg methylestradiol.[11][14]

Side effects[edit]

Normethandrone has been associated with symptoms of masculinization and hepatotoxicity.[6][7][15]

Pharmacology[edit]

Pharmacodynamics[edit]

Normethandrone shows high progestogenic activity.[5] With sublingual administration in women, it has at least 150 times the potency of sublingual progesterone and 50 times the potency of sublingual ethisterone.[5] It also has 10 times the potency of injected progesterone via this route.[5] The oral potency of normethandrone in terms of endometrial transformation is similar to that of norethisterone.[16] In addition to its progestogenic activity, normethandrone has anabolic and androgenic activity and can produce effects associated with this activity.[1][4] It has a high ratio of anabolic to androgenic activity.[17] The anabolic potency of normethandrone is similar to that of norethandrolone and is much greater than that of nandrolone or metandienone.[8] It is also greater than that of ethylestrenol.[8] In addition to its progestogenic and androgenic/anabolic activity, normethandrone has estrogenic activity via aromatization into methylestradiol.[3]

Analogously to nandrolone and norethandrolone, 5α-dihydronormethandrone, the 5α-reduced metabolite of normethandrone, shows reduced affinity for the androgen receptor relative to normethandrone.[18][19] Its affinity for the androgen receptor is specifically about 33 to 60% of that of normethandrone.[18]

Relative affinities (%) of normethandrone and metabolites

Compound PR AR ER GR MR SHBG CBG
Normethandrone 75–125 125–150 <1 1–5 <1 ? ?
5α-Dihydronormethandrone 15–25 50–75 ? <1 ? ? ?
Notes: Values are percentages (%). Reference ligands (100%) were progesterone for the PR, testosterone for the AR, estradiol for the ER, dexamethasone for the GR, and aldosterone for the MR. Sources: See template.

Pharmacokinetics[edit]

Normethandrone is metabolized by aromatase into methylestradiol in small quantities, similarly to methyltestosterone and metandienone.[3][20][21] The metabolites of normethandrone have not been well-studied, but 5α-dihydronormethandrone is a likely metabolite formed by 5α-reductase.[22][23]

The pharmacokinetics of normethandrone have been reviewed.[24]

Chemistry[edit]

Normethandrone, also known as 17α-methyl-19-nortestosterone or as 17α-methylestr-4-en-17β-ol-3-one, is a synthetic estrane steroid and a 17α-alkylated derivative of nandrolone (19-nortestosterone; 19-NT). It is specifically the 17α-methyl derivative of nandrolone as well as the 17α-methyl variant of norethandrolone (17α-ethyl-19-NT) and norethisterone (17α-ethynyl-19-NT).[25]

Synthesis[edit]

Chemical syntheses of normethandrone have been published.[24]

History[edit]

Normethandrone has been marketed for medical use since 1957.[10] The combination of normethandrone and methylestradiol was introduced by at least 1966.[14]

Society and culture[edit]

Generic names[edit]

Normethandrone has not been assigned an INN or other formal name designations.[25][26][2] It is also known as methylestrenolone, methylnortestosterone, normethandrolone, and normethisterone.[25][26][2]

Brand names[edit]

Brand names of normethandrone include Batynid, Ginecosid, Ginecoside, Gynomin, Lutenin, Matronal, Mediol, Metalutin, Methalutin, Orgasteron, Orosteron, and Renodiol.[25][26][2][1][27][11]

Availability[edit]

Normethandrone is marketed in Brazil, Indonesia, and Venezuela in combination with methylestradiol or estradiol valerate.[2][1]

References[edit]

  1. ^ a b c d e f g h https://www.medicinescomplete.com/about/
  2. ^ a b c d e f g https://www.drugs.com/international/normethandrone.html
  3. ^ a b c d e Friedl KE (1990). "Reappraisal of the health risks associated with the use of high doses of oral and injectable androgenic steroids". NIDA Res. Monogr. 102: 142–77. PMID 1964199.
  4. ^ a b c d e H.-L. Krüskemper (22 October 2013). Anabolic Steroids. Elsevier. pp. 10–. ISBN 978-1-4832-6504-9.
  5. ^ a b c d e Ferin J (1956). "A new substance with progestational activity; comparative assays in ovariectomized women; clinical results". Acta Endocrinol. 22 (4): 303–17. doi:10.1530/acta.0.0220303. PMID 13354223.
  6. ^ a b Lundberg, P O (1962). "Migraine Prophylaxis with Progestogens". European Journal of Endocrinology. 40 (4 Suppl): S5–S22. doi:10.1530/acta.0.040S0005. ISSN 0804-4643.
  7. ^ a b Delorimier AA, Gordan GS, Lowe RC, Carbone JV (1965). "Methyltestosterone, Related Steroids, and Liver Function". Arch. Intern. Med. 116: 289–94. doi:10.1001/archinte.1965.03870020129023. PMID 14315662.
  8. ^ a b c Brueggemeier, Robert W. (2006). "Sex Hormones (Male): Analogs and Antagonists": 42. doi:10.1002/3527600906.mcb.200500066. Cite journal requires |journal= (help)
  9. ^ Erich Heftmann (1970). Steroid Biochemistry. Academic Press. p. 72. Normethandrone (Fig. 49) is a 19-nortestosterone derivative having progestational as well as androgenic and anabolic activity.
  10. ^ a b United States. Patent Office (1957). Official Gazette of the United States Patent Office. U.S. Patent Office.
  11. ^ a b c Unlisted Drugs. Pharmaceutical Section, Special Libraries Association. 1982. Batynid. C. Each dragee contains: normethandrone, 5 mg.; and methylestradiol, 0.3 mg. E. (Formerly) Gynaekosid. M. Boehringer Biochemia, Florence. A. Estrogenic; Rx of secondary amenorrhea. R. Notiz Med Farm 32;295, Nov-Dec 81.
  12. ^ Begni-Calvet, D. (1959). "Two properties of methylestrenolone (17-alpha-methyl-19-nortestosterone): Its effectiveness in the treatment of dysmenorrhea, its anabolic action". Gynecologie pratique. 10: 261–272. PMID 13798272.
  13. ^ Servais, J. (1973). "A clinical study of cases of psychosexual disturbances in men treated by a libido inhibitor: Methylestrenolone". Archives of Sexual Behavior. 2 (4): 387–390. doi:10.1007/BF01541012. ISSN 0004-0002.
  14. ^ a b Akingba JB, Ayodeji EA (February 1966). "Amenorrhea as a leading symptom of choriocarcinoma". J Obstet Gynaecol Br Commonw. 73 (1): 153–5. doi:10.1111/j.1471-0528.1966.tb05137.x. PMID 5948541.
  15. ^ Feldman, Elaine Bossak; Carter, Anne C.; Kossa, Jane L.; Mccarrick, James F.; Schwartz, Harold L. (1960). "Endocrinologic and metabolic effects of 17α-methyl-19-nortestosterone in women". The Journal of Clinical Endocrinology & Metabolism. 20 (6): 842–857. doi:10.1210/jcem-20-6-842. ISSN 0021-972X.
  16. ^ Horský, Jan; Presl, Jiří (1981). "Hormonal Treatment of Disorders of the Menstrual Cycle". In J. Horsky; J. Presl (eds.). Ovarian Function and its Disorders: Diagnosis and Therapy. Springer Science & Business Media. pp. 309–332. doi:10.1007/978-94-009-8195-9_11. ISBN 978-94-009-8195-9.
  17. ^ Charles D. Kochakian (6 December 2012). Anabolic-Androgenic Steroids. Springer Science & Business Media. pp. 379–. ISBN 978-3-642-66353-6.
  18. ^ a b Ojasoo T, Delettré J, Mornon JP, Turpin-VanDycke C, Raynaud JP (1987). "Towards the mapping of the progesterone and androgen receptors". J. Steroid Biochem. 27 (1–3): 255–69. doi:10.1016/0022-4731(87)90317-7. PMID 3695484.
  19. ^ Behre HM, Kliesch S, Lemcke B, von Eckardstein S, Nieschlag E (December 2001). "Suppression of spermatogenesis to azoospermia by combined administration of GnRH antagonist and 19-nortestosterone cannot be maintained by this non-aromatizable androgen alone". Hum. Reprod. 16 (12): 2570–7. PMID 11726576.
  20. ^ Detlef Thieme; Peter Hemmersbach (18 December 2009). Doping in Sports. Springer Science & Business Media. pp. 470–. ISBN 978-3-540-79088-4.
  21. ^ William Llewellyn (2011). Anabolics. Molecular Nutrition Llc. pp. 444–454, 533. ISBN 978-0-9828280-1-4.
  22. ^ Fragkaki AG, Angelis YS, Tsantili-Kakoulidou A, Koupparis M, Georgakopoulos C (May 2009). "Schemes of metabolic patterns of anabolic androgenic steroids for the estimation of metabolites of designer steroids in human urine". J. Steroid Biochem. Mol. Biol. 115 (1–2): 44–61. doi:10.1016/j.jsbmb.2009.02.016. PMID 19429460.
  23. ^ Schjølberg, T. H. (2013). In Vitro Synthesis of Metabolites of three Anabolic Androgenic Steroids, by Human Liver Microsomes (Master's thesis, Institutt for bioteknologi). https://brage.bibsys.no/xmlui/handle/11250/246018
  24. ^ a b Die Gestagene. Springer-Verlag. 27 November 2013. pp. 12–13, 282. ISBN 978-3-642-99941-3.
  25. ^ a b c d J. Elks (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 888–. ISBN 978-1-4757-2085-3.
  26. ^ a b c I.K. Morton; Judith M. Hall (6 December 2012). Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Science & Business Media. pp. 202–. ISBN 978-94-011-4439-1.
  27. ^ Martin Negwer; Hans-Georg Scharnow (2001). Organic-chemical drugs and their synonyms: (an international survey). Wiley-VCH. p. 1831. ISBN 978-3-527-30247-5.