Norgestrel

Norgestrel
Top, levonorgestrel (CAS 797-63-7 );
Bottom: dextronorgestrel (CAS 797-64-8 ).
Clinical data
Trade namesOvral, Opill, 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
License data
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 is a progestin which is used in birth control pills sold under the brand name Ovral in combination with the estrogen ethinylestradiol and Opill by itself. It is also used in menopausal hormone therapy. It is taken by mouth.

Side effects of norgestrel include menstrual irregularities, headaches, nausea, and breast tenderness. The most common side effects of the progestin-only Opill include irregular bleeding, headaches, dizziness, nausea, increased appetite, abdominal pain, cramps, or bloating. Norgestrel is a progestin, or a synthetic progestogen, and hence is an agonist of the progesterone receptor, the biological target of progestogens like progesterone. It has weak androgenic activity and no other important hormonal activity.

Norgestrel was patented in 1961 and came into medical use, specifically in birth control pills, in 1966. It was subsequently introduced for use in menopausal hormone therapy as well. Norgestrel is sometimes referred to as a "second-generation" progestin. It is marketed widely throughout the world. Norgestrel is available as a generic medication. In 2020, the version with ethinylestradiol was the 316th most commonly prescribed medication in the United States, with more than 900thousand prescriptions. In July 2023, the US Food and Drug Administration (FDA) approved norgestrel for over-the-counter sale. The FDA granted the approval to Laboratoire HRA Pharma which was acquired by Perrigo Company plc.


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. It has also been used as an emergency contraceptive in the Yuzpe regimen.

Side effects

Pharmacology

Pharmacodynamics

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

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

Pharmacokinetics

The pharmacokinetics of norgestrel have been reviewed.

Chemistry

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. 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). 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.

Synthesis

Chemical syntheses of norgestrel have been published.

History

Norgestrel was first introduced, as a birth control pill in combination with ethinylestradiol, under the brand name Eugynon in Germany in 1966. 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.

The contraceptive efficacy of norgestrel was established in the US with the original approval for prescription use in 1973.

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. It is also known as dl-norgestrel, DL-norgestrel, or (±)-norgestrel.

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.

See also


This page was last updated at 2024-02-02 09:14 UTC. Update now. View original page.

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