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Norgestrel

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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
  • (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 Edit this at Wikidata
Chemical and physical data
FormulaC21H28O2
Molar mass312.453 g·mol−1
3D model (JSmol)
  • 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=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 checkY
  • Key:WWYNJERNGUHSAO-CULCCENASA-N checkY
  (verify)

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]

Side effects of norgestrel include menstrual irregularities, headaches, nausea, breast tenderness, mood changes, acne, increased hair growth, and others.[citation needed] 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
Compound PRTooltip Progesterone receptor ARTooltip Androgen receptor ERTooltip Estrogen receptor GRTooltip Glucocorticoid receptor MRTooltip Mineralocorticoid receptor SHBGTooltip Sex hormone-binding globulin CBGTooltip Corticosteroid binding globulin
Levonorgestrel 150–162 34a, 45 0 1–8 17–75 50 0
5α-Dihydrolevonorgestrel 50 38a 0 ? ? ? ?
3α,5α-Tetrahydrolevonorgestrel ? ? 0.4 ? ? ? ?
3β,5α-Tetrahydrolevonorgestrel ? ? 2.4 ? ? ? ?
Notes: Values are percentages (%). Reference ligands (100%) were promegestone for the PRTooltip progesterone receptor, metribolone (a = mibolerone) for the ARTooltip androgen receptor, E2 for the ERTooltip estrogen receptor, DEXATooltip dexamethasone for the GRTooltip glucocorticoid receptor, aldosterone for the MRTooltip mineralocorticoid receptor, DHTTooltip dihydrotestosterone for SHBGTooltip sex hormone-binding globulin, and cortisol for CBGTooltip Corticosteroid-binding globulin. 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 INNTooltip International Nonproprietary Name, USANTooltip United States Adopted Name, USPTooltip United States Pharmacopeia, BANTooltip British Approved Name, DCFTooltip Dénomination Commune Française, DCITTooltip Denominazione Comune Italiana, and JANTooltip Japanese Accepted Name.[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

References

  1. ^ a b c d e 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. ^ a b c d e f Index Nominum 2000: International Drug Directory. Taylor & Francis. 2000. pp. 751–. ISBN 978-3-88763-075-1.
  3. ^ a b c d 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. ^ a b c d e f g h i 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. ^ a b c d e f g h "Norgestrel - brand name list from". Drugs.com. Retrieved 2022-09-17.
  6. ^ a b 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. ^ a b 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. ^ "A Multicenter Clinical Investigation Employing Ethinyl Estradiol Combined with dl-Norgestrel as Postcoital Contraceptive Agent". Fertility and Sterility. 37 (4): 508–513. 1982. doi:10.1016/s0015-0282(16)46157-1. PMID 7040117. {{cite journal}}: Unknown parameter |authors= ignored (help)
  14. ^ a b 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. ^ a b 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. ^ a b 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. ^ a b 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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