Norgestrel

Norgestrel, sold under the brand name Ovral among others, is a progestin medication which is used in birth control pills and in menopausal hormone therapy.[1][2][3][4] It is available both in combination with an estrogen and alone.[5] It is taken by mouth.[3][4]

Not to be confused with Levonorgestrel.
Norgestrel
Top, levonorgestrel (CAS 797-63-7 );
Bottom: dextronorgestrel (CAS 797-64-8 ).
Clinical data
Trade namesOvral, others
Other namesdl-Norgestrel; DL-Norgestrel; (±)-Norgestrel; WY-3707; SH-70850; SH-850; FH 122-A; rac-13-Ethyl-17α-ethynyl-19-nortestosterone; rac-13-Ethyl-17α-ethynylestr-4-en-17β-ol-3-one
AHFS/Drugs.comMicromedex Detailed Consumer Information
MedlinePlusa602008
Routes of
administration		By mouth
Drug classProgestogen; Progestin
ATC code
Legal status
Legal status
Identifiers
IUPAC name
  • (8R,9S,10R,13S,14S)-13-ethyl-17-ethynyl-17-hydroxy-1,2,6,7,8,9,10,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-3-one
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.026.758
Chemical and physical data
FormulaC21H28O2
Molar mass312.453 g·mol−1
3D model (JSmol)
SMILES
  • O=C\1CC[C@H]4C(=C/1)/CC[C@@H]3[C@@H]4CC[C@@]2(CC)[C@H]3CCC2(O)C#C
InChI
  • InChI=1S/C21H28O2/c1-3-20-11-9-17-16-8-6-15(22)13-14(16)5-7-18(17)19(20)10-12-21(20,23)4-2/h2,13,16-19,23H,3,5-12H2,1H3/t16-,17+,18+,19-,20-,21?/m0/s1 Y
  • Key:WWYNJERNGUHSAO-CULCCENASA-N Y
  (verify)

Side effects of norgestrel include menstrual irregularities, headaches, nausea, breast tenderness, mood changes, acne, increased hair growth, and others. Norgestrel is a progestin, or a synthetic progestogen, and hence is an agonist of the progesterone receptor, the biological target of progestogens like progesterone.[4] It has weak androgenic activity and no other important hormonal activity.[4]

Norgestrel was patented in 1961 and came into medical use, specifically in birth control pills, in 1966.[6][7][8] It was subsequently introduced for use in menopausal hormone therapy as well.[5] Norgestrel is sometimes referred to as a "second-generation" progestin.[9] It is marketed widely throughout the world.[5][2] Norgestrel is available as a generic medication.[10] In 2017, the version with ethinylestradiol was the 284th most commonly prescribed medication in the United States, with more than one million prescriptions.[11][12]

Medical uses

Norgestrel is used in combination with ethinylestradiol or quinestrol in combined birth control pills, alone in progestogen-only birth control pills, and in combination with estradiol or conjugated estrogens in menopausal hormone therapy.[5] It has also been used as an emergency contraceptive in the Yuzpe regimen.[13]

Side effects
See also: Levonorgestrel § Side effects, and Progestin § Side effects

Pharmacology

Pharmacodynamics
See also: Levonorgestrel § Pharmacodynamics

Norgestrel is a progestogen, or an agonist of the progesterone receptor.[4] The biological activity of norgestrel lies in the levo enantiomer, levonorgestrel, whereas the dextro isomer is inactive.[4] As such, norgestrel is identical in its hormonal activity to levonorgestrel except that it is half as potent by weight.[4] Levonorgestrel, and by extension norgestrel, have some androgenic activity, but no estrogenic, antimineralocorticoid, or glucocorticoid activity.[4]

Relative affinities (%) of levonorgestrel and metabolites
CompoundPRARERGRMRSHBGCBG
Levonorgestrel150–16234a, 4501–817–75500
5α-Dihydrolevonorgestrel5038a0 ? ? ? ?
3α,5α-Tetrahydrolevonorgestrel ? ?0.4 ? ? ? ?
3β,5α-Tetrahydrolevonorgestrel ? ?2.4 ? ? ? ?
Notes: Values are percentages (%). Reference ligands (100%) were promegestone for the PR, metribolone (a = mibolerone) for the AR, E2 for the ER, DEXA for the GR, aldosterone for the MR, DHT for SHBG, and cortisol for CBG. Sources: See template.

The ovulation-inhibiting dose of norgestrel appears to be greater than 75 μg/day, as ovulation occurred in 50 to 75% of cycles with this dosage of norgestrel in studies.[14] The ovulation-inhibiting dosage of levonorgestrel, which is twice as potent as norgestrel, is approximately 50 to 60 μg/day.[4][15][14] One review lists the ovulation-inhibiting dose of norgestrel as 100 μg/day.[16] The endometrial transformation dose of norgestrel is listed as 12 mg per cycle and the menstrual delay test dose of norgestrel is listed as 0.5 to 2 mg/day.[16][17]

Pharmacokinetics
See also: Levonorgestrel § Pharmacokinetics

The pharmacokinetics of norgestrel have been reviewed.[18]

Chemistry
See also: List of progestogens, List of androgens/anabolic steroids, and Levonorgestrel

Norgestrel, also known as rac-13-ethyl-17α-ethynyl-19-nortestosterone or as rac-13-ethyl-17α-ethynylestr-4-en-17β-ol-3-one, is a synthetic estrane steroid and a derivative of testosterone.[1][2] It is a racemic mixture of stereoisomers dextronorgestrel (the C13α isomer; l-norgestrel, L-norgestrel, or (+)-norgestrel) and levonorgestrel (the C13β isomer; d-norgestrel, D-norgestrel, or (–)-norgestrel), the former of which is inactive (making norgestrel exactly half as potent as levonorgestrel).[19][20] Norgestrel is more specifically a derivative of norethisterone (17α-ethynyl-19-nortestosterone) and is a member of the gonane (18-methylestrane) subgroup of the 19-nortestosterone family of progestins.[21]

Synthesis

Chemical syntheses of norgestrel have been published.[18]

History

Norgestrel was first introduced, as a birth control pill in combination with ethinylestradiol, under the brand name Eugynon in Germany in 1966.[6][7] It was subsequently marketed as a combined birth control pill with ethinylestradiol in the United States under the brand name Ovral in 1968, and was marketed in many other countries as well.[22][23][5]

Society and culture

Generic names

Norgestrel is the generic name of the drug and its INN, USAN, USP, BAN, DCF, DCIT, and JAN.[1][2][3][5] It is also known as dl-norgestrel, DL-norgestrel, or (±)-norgestrel.[1][2][3][5]

Brand names

Norgestrel has been marketed under a variety of brand names including Cyclacur, Cryselle, Cyclo-Progynova, Duoluton, Elinest, Eugynon, Microgynon, Lo/Ovral, Low-Ogestrel, Logynon, Microlut, Minicon, Nordette, Neogest, Ogestrel, Ovral, Ovran, Ovranette, Ovrette, Planovar, Prempak, Progyluton, and Trinordiol among others.[1][2][5][22]

See also
  • Elsimar M. Coutinho
  • Herchel Smith

References
  1. J. Elks (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 887–. ISBN 978-1-4757-2085-3.
  2. Index Nominum 2000: International Drug Directory. Taylor & Francis. 2000. pp. 751–. ISBN 978-3-88763-075-1.
  3. 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.
  4. Kuhl H (2005). "Pharmacology of estrogens and progestogens: influence of different routes of administration" (PDF). Climacteric. 8 Suppl 1: 3–63. doi:10.1080/13697130500148875. PMID 16112947. S2CID 24616324.
  5. "Norgestrel - brand name list from". Drugs.com. Retrieved 2022-09-17.
  6. Teresa Ortiz-Gómez; María Jesús Santesmases (22 April 2016). Gendered Drugs and Medicine: Historical and Socio-Cultural Perspectives. Taylor & Francis. pp. 175–. ISBN 978-1-317-12981-3. The 1966 marketing campaign for Schering's second contraceptive, Eugynon, [...] (Schering AG Berline 1966, 11). [...] In 1970 [Schering] had already conducted an opinion poll among doctors in the run up to the marketing campaign for the newly introduced Neogynon. [...]
  7. W. Gerhard Pohl (2004). Die wissenschaftliche Welt von gestern: die Preisträger des Ignaz L. Lieben-Preises 1865-1937 und des Richard Lieben-Preises 1912-1928 : ein Kapitel österreichischer Wissenschaftsgeschichte in Kurzbiografien. Böhlau Verlag Wien. pp. 150–. ISBN 978-3-205-77303-0. [The contraceptive EUGYNON is launched in 1966. NEOGYNON follows in 1970.]
  8. Fischer, Jnos; Ganellin, C. Robin (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 479. ISBN 9783527607495.
  9. Howard J.A. Carp (9 April 2015). Progestogens in Obstetrics and Gynecology. Springer. p. 112. ISBN 978-3-319-14385-9.
  10. "Generic Lo/Ovral-28 Availability".
  11. "The Top 300 of 2020". ClinCalc. Retrieved 11 April 2020.
  12. "Ethinyl Estradiol; Norgestrel - Drug Usage Statistics". ClinCalc. Retrieved 11 April 2020.
  13. Yuzpe AA, Smith RP & Rademaker AW (1982). "A Multicenter Clinical Investigation Employing Ethinyl Estradiol Combined with dl-Norgestrel as Postcoital Contraceptive Agent". Fertility and Sterility. 37 (4): 508–513. doi:10.1016/s0015-0282(16)46157-1. PMID 7040117.{{cite journal}}: CS1 maint: uses authors parameter (link)
  14. Endrikat J, Gerlinger C, Richard S, Rosenbaum P, Düsterberg B (December 2011). "Ovulation inhibition doses of progestins: a systematic review of the available literature and of marketed preparations worldwide". Contraception. 84 (6): 549–57. doi:10.1016/j.contraception.2011.04.009. PMID 22078182.
  15. Schindler AE, Campagnoli C, Druckmann R, Huber J, Pasqualini JR, Schweppe KW, Thijssen JH (December 2003). "Classification and pharmacology of progestins". Maturitas. 46 Suppl 1: S7–S16. doi:10.1016/j.maturitas.2003.09.014. PMID 14670641.
  16. Knörr K, Knörr-Gärtner H, Beller FK, Lauritzen C (8 March 2013). Geburtshilfe und Gynäkologie: Physiologie und Pathologie der Reproduktion. Springer-Verlag. pp. 583–. ISBN 978-3-642-95583-9.
  17. Freimut A. Leidenberger; Thomas Strowitzki; Olaf Ortmann (29 August 2009). Klinische Endokrinologie für Frauenärzte. Springer-Verlag. pp. 225, 227. ISBN 978-3-540-89760-6.
  18. Die Gestagene. Springer-Verlag. 27 November 2013. pp. 16–17, 284–. ISBN 978-3-642-99941-3.
  19. Brian K. Alldredge; Robin L. Corelli; Michael E. Ernst (1 February 2012). Koda-Kimble and Young's Applied Therapeutics: The Clinical Use of Drugs. Lippincott Williams & Wilkins. pp. 1072–. ISBN 978-1-60913-713-7.
  20. J.P. Lavery; J.S. Sanfilippo (6 December 2012). Pediatric and Adolescent Obstetrics and Gynecology. Springer Science & Business Media. pp. 248–. ISBN 978-1-4612-5064-7.
  21. Stefan Offermanns; W. Rosenthal (14 August 2008). Encyclopedia of Molecular Pharmacology. Springer Science & Business Media. pp. 390–. ISBN 978-3-540-38916-3.
  22. William Andrew Publishing (22 October 2013). Pharmaceutical Manufacturing Encyclopedia, 3rd Edition. Elsevier. pp. 2935–. ISBN 978-0-8155-1856-3.
  23. Lara Marks (2010). Sexual Chemistry: A History of the Contraceptive Pill. Yale University Press. pp. 73–. ISBN 978-0-300-16791-7.
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