Mestranol

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Mestranol
Mestranol.svg
Clinical data
AHFS/Drugs.com International Drug Names
MedlinePlus a601050
Routes of
administration
Oral
ATC code none
Legal status
Legal status
  • ℞ (Prescription only)
Identifiers
Synonyms CB-8027, EE3ME, L-33355, RS-1044; 17α-Ethynyl-3-(methyloxy)estra-1,3,5(10)-trien-17β-ol
CAS Number 72-33-3 YesY
PubChem (CID) 6291
IUPHAR/BPS 7087
DrugBank DB01357 YesY
ChemSpider 6054 YesY
UNII B2V233XGE7 YesY
KEGG D00575 YesY
ChEBI CHEBI:6784 YesY
ChEMBL CHEMBL1201151 N
Chemical and physical data
Formula C21H26O2
Molar mass 310.43 g/mol
3D model (Jmol) Interactive image
 NYesY (what is this?)  (verify)

Mestranol (INN, USAN, BAN, JAN) (brand names Devocin, Ovastol, Tranel), also known as ethinyl estradiol 3-methyl ether (EEME),[1] is a synthetic, steroidal estrogen that has been widely used medically.[2][3] It was employed as the estrogen component in many of the first oral contraceptives, such as mestranol/noretynodrel (brand names Enovid, Enavid),[4] and is still in use today. It was also a component of Ortho-Novum, Ortho-Novin, Femigen, and Norbiogest.[2][5] In addition to its use as an oral contraceptive, mestranol has been used as a component of hormone replacement therapy.[3]

Pharmacology[edit]

Mestranol is the 3-methyl ether of ethinyl estradiol,[2] and is a biologically inactive prodrug of ethinyl estradiol to which it is demethylated in the liver with a conversion efficiency of 70% (50 µg of mestranol is pharmacokinetically bioequivalent to 35 µg of ethinyl estradiol, or ethinyl estradiol being about 1.7 times as orally potent by weight as mestranol).[6][7][8]

History[edit]

In April 1956, noretynodrel was investigated, in Puerto Rico, in the first large-scale clinical trial of a progestogen as an oral contraceptive.[9][10] The trial was conducted in Puerto Rico due to the high birth rate in the country and concerns of moral censure in the United States.[11] It was discovered early into the study that the initial chemical syntheses of noretynodrel had been contaminated with small amounts (1–2%) of the 3-methyl ether of ethinyl estradiol (noretynodrel having been synthesized from ethinyl estradiol).[9][10] When this impurity was removed, higher rates of breakthrough bleeding occurred.[9][10] As a result, mestranol, that same year (1956),[12] was developed and serendipitously identified as a very potent synthetic estrogen (and eventually as a prodrug of ethinyl estradiol), given its name, and added back to the formulation.[9][10] This resulted in Enovid by G. D. Searle & Company, the first oral contraceptive and a combination of 9.85 mg noretynodrel and 150 μg mestranol per pill.[9][10]

Around 1969, mestranol was replaced by ethinyl estradiol in most or all combined oral contraceptives due to widespread panic about the recently uncovered increased risk of venous thromboembolism with estrogen-containing oral contraceptives.[13] The rationale was that ethinyl estradiol was approximately twice as potent by weight as mestranol and hence that the dose could be halved, which it was thought might result in a lower incidence of venous thromboembolism.[13] Whether this actually did result in a lower incidence of venous thromboembolism has never been assessed.[13]

See also[edit]

References[edit]

  1. ^ A. Labhart (6 December 2012). Clinical Endocrinology: Theory and Practice. Springer Science & Business Media. pp. 575–. ISBN 978-3-642-96158-8. 
  2. ^ a b c J. Elks (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 775–. ISBN 978-1-4757-2085-3. 
  3. ^ a b I.K. Morton; Judith M. Hall (6 December 2012). Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Science & Business Media. pp. 177–. ISBN 978-94-011-4439-1. 
  4. ^ Lara Marks (2010). Sexual Chemistry: A History of the Contraceptive Pill. Yale University Press. pp. 75–. ISBN 978-0-300-16791-7. 
  5. ^ William Andrew Publishing (22 October 2013). Pharmaceutical Manufacturing Encyclopedia, 3rd Edition. Elsevier. pp. 2109–. ISBN 978-0-8155-1856-3. 
  6. ^ Faigle, Johann W.; Schenkel, Lotte (1998). "Pharmacokinetics of estrogens and progestogens". In in Fraser; Ian S. Estrogens and Progestogens in Clinical Practice. London: Churchill Livingstone. pp. 273–294. ISBN 0-443-04706-5. 
  7. ^ Tommaso Falcone; William W. Hurd (2007). Clinical Reproductive Medicine and Surgery. Elsevier Health Sciences. pp. 388–. ISBN 0-323-03309-1. 
  8. ^ Donna Shoupe (7 November 2007). The Handbook of Contraception: A Guide for Practical Management. Springer Science & Business Media. pp. 23–. ISBN 978-1-59745-150-5. EE is about 1.7 times as potent as the same weight of mestranol. 
  9. ^ a b c d e Walter Sneader (23 June 2005). Drug Discovery: A History. John Wiley & Sons. pp. 202–. ISBN 978-0-471-89979-2. 
  10. ^ a b c d e Gretchen M. Lentz; Rogerio A. Lobo; David M. Gershenson; Vern L. Katz (2012). Comprehensive Gynecology. Elsevier Health Sciences. pp. 224–. ISBN 0-323-06986-X.  Cite uses deprecated parameter |coauthors= (help)
  11. ^ Marcus Filshie; John Guillebaud (22 October 2013). Contraception: Science and Practice. Elsevier Science. pp. 12–. ISBN 978-1-4831-6366-6. 
  12. ^ Billingsley FS (1969). "Lactation suppression utilizing norethynodrel with mestranol". J Fla Med Assoc. 56 (2): 95–7. PMID 4884828. 
  13. ^ a b c Jeffrey K. Aronson (21 February 2009). Meyler's Side Effects of Endocrine and Metabolic Drugs. Elsevier. pp. 224–. ISBN 978-0-08-093292-7.