Norgestrel

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Norgestrel
Levonorgestrel.svg
Dextronorgestrel.svg
Top, levonorgestrel (CAS 797-63-7 );
Bottom: dextronorgestrel (CAS 797-64-8 ).
Clinical data
Trade names Ovral, 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.com Micromedex Detailed Consumer Information
MedlinePlus a602008
License data
Routes of
administration 		By mouth
Drug class Progestogen; 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 InfoCard 100.026.758 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C21H28O2
Molar mass 312.453 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 Yes check.svgY
  • Key:WWYNJERNGUHSAO-CULCCENASA-N Yes check.svgY
   (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. [2] [3] [4] [5] [6] It is taken by mouth. [4] [5]

Contents

Side effects of norgestrel include menstrual irregularities, headaches, nausea, and breast tenderness. [7] The most common side effects of the progestin-only Opill include irregular bleeding, headaches, dizziness, nausea, increased appetite, abdominal pain, cramps, or bloating. [1] Norgestrel 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 has weak androgenic activity and no other important hormonal activity. [5]

Norgestrel was patented in 1961 and came into medical use, specifically in birth control pills, in 1966. [8] [9] [10] It was subsequently introduced for use in menopausal hormone therapy as well. [6] Norgestrel is sometimes referred to as a "second-generation" progestin. [11] It is marketed widely throughout the world. [6] [3] Norgestrel is available as a generic medication. [12] In 2020, the version with ethinylestradiol was the 316th most commonly prescribed medication in the United States, with more than 900 thousand prescriptions. [13] [14] In July 2023, the US Food and Drug Administration (FDA) approved norgestrel for over-the-counter sale. [1] The FDA granted the approval to Laboratoire HRA Pharma which was acquired by Perrigo Company plc. [1]


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. [6] It has also been used as an emergency contraceptive in the Yuzpe regimen. [15]

Side effects

Pharmacology

Pharmacodynamics

Norgestrel is a progestogen, or an agonist of the progesterone receptor. [5] The biological activity of norgestrel lies in the levo enantiomer, levonorgestrel, whereas the dextro isomer is inactive. [5] As such, norgestrel is identical in its hormonal activity to levonorgestrel except that it is half as potent by weight. [5] Levonorgestrel, and by extension norgestrel, have some androgenic activity, but no estrogenic, antimineralocorticoid, or glucocorticoid activity. [5]

Relative affinities (%) of levonorgestrel and metabolites
Compound PR Tooltip Progesterone receptor AR Tooltip Androgen receptor ER Tooltip Estrogen receptor GR Tooltip Glucocorticoid receptor MR Tooltip Mineralocorticoid receptor SHBG Tooltip Sex hormone-binding globulin CBG Tooltip Corticosteroid binding globulin
Levonorgestrel 150–16234a, 4501–817–75500
5α-Dihydrolevonorgestrel 5038a0 ? ? ? ?
3α,5α-Tetrahydrolevonorgestrel ? ?0.4 ? ? ? ?
3β,5α-Tetrahydrolevonorgestrel ? ?2.4 ? ? ? ?
Notes: Values are percentages (%). Reference ligands (100%) were promegestone for the PR Tooltip progesterone receptor, metribolone (a = mibolerone) for the AR Tooltip androgen receptor, E2 for the ER Tooltip estrogen receptor, DEXA Tooltip dexamethasone for the GR Tooltip glucocorticoid receptor, aldosterone for the MR Tooltip mineralocorticoid receptor, DHT Tooltip dihydrotestosterone for SHBG Tooltip sex hormone-binding globulin, and cortisol for CBG Tooltip 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. [16] The ovulation-inhibiting dosage of levonorgestrel, which is twice as potent as norgestrel, is approximately 50 to 60 μg/day. [5] [17] [16] One review lists the ovulation-inhibiting dose of norgestrel as 100 μg/day. [18] 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. [18] [19]

Pharmacokinetics

The pharmacokinetics of norgestrel have been reviewed. [20]

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. [2] [3] 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). [21] [22] 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. [23]

Synthesis

Chemical syntheses of norgestrel have been published. [20]

History

Norgestrel was first introduced, as a birth control pill in combination with ethinylestradiol, under the brand name Eugynon in Germany in 1966. [8] [9] 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. [24] [25] [6]

The contraceptive efficacy of norgestrel was established in the US with the original approval for prescription use in 1973. [1] Opill has now been approved for non-presciption use as well.

Society and culture

Generic names

Norgestrel is the generic name of the drug and its INN Tooltip International Nonproprietary Name, USAN Tooltip United States Adopted Name, USP Tooltip United States Pharmacopeia, BAN Tooltip British Approved Name, DCF Tooltip Dénomination Commune Française, DCIT Tooltip Denominazione Comune Italiana, and JAN Tooltip Japanese Accepted Name. [2] [3] [4] [6] It is also known as dl-norgestrel, DL-norgestrel, or (±)-norgestrel. [2] [3] [4] [6]

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. [2] [3] [6] [24]

See also

Related Research Articles

<span class="mw-page-title-main">Progestogen (medication)</span> Medication producing effects similar to progesterone

A progestogen, also referred to as a progestagen, gestagen, or gestogen, is a type of medication which produces effects similar to those of the natural female sex hormone progesterone in the body. A progestin is a synthetic progestogen. Progestogens are used most commonly in hormonal birth control and menopausal hormone therapy. They can also be used in the treatment of gynecological conditions, to support fertility and pregnancy, to lower sex hormone levels for various purposes, and for other indications. Progestogens are used alone or in combination with estrogens. They are available in a wide variety of formulations and for use by many different routes of administration. Examples of progestogens include natural or bioidentical progesterone as well as progestins such as medroxyprogesterone acetate and norethisterone.

<span class="mw-page-title-main">Levonorgestrel</span> Hormonal medication used for birth control

Levonorgestrel is a hormonal medication which is used in a number of birth control methods. It is combined with an estrogen to make combination birth control pills. As an emergency birth control, sold under the brand names Plan B One-Step and Julie, among others, it is useful within 72 hours of unprotected sex. The more time that has passed since sex, the less effective the medication becomes, and it does not work after pregnancy (implantation) has occurred. Levonorgestrel works by preventing ovulation or fertilization from occurring. It decreases the chances of pregnancy by 57–93%. In an intrauterine device (IUD), such as Mirena among others, it is effective for the long-term prevention of pregnancy. A levonorgestrel-releasing implant is also available in some countries.

Progestogen-only pills (POPs), colloquially known as "mini pills", are a type of oral contraceptive that contain synthetic progestogens (progestins) and do not contain estrogens. They are primarily used for the prevention of undesired pregnancy, although additional medical uses also exist.

<span class="mw-page-title-main">Ethinylestradiol</span> Estrogen medication

Ethinylestradiol (EE) is an estrogen medication which is used widely in birth control pills in combination with progestins. In the past, EE was widely used for various indications such as the treatment of menopausal symptoms, gynecological disorders, and certain hormone-sensitive cancers. It is usually taken by mouth but is also used as a patch and vaginal ring.

<span class="mw-page-title-main">Desogestrel</span> Medication

Desogestrel is a progestin medication which is used in birth control pills for women. It is also used in the treatment of menopausal symptoms in women. The medication is available and used alone or in combination with an estrogen. It is taken by mouth.

<span class="mw-page-title-main">Drospirenone</span> Medication drug

Drospirenone is a progestin and antiandrogen medication which is used in birth control pills to prevent pregnancy and in menopausal hormone therapy, among other uses. It is available both alone under the brand name Slynd and in combination with an estrogen under the brand name Yasmin among others. The medication is an analog of the drug spironolactone. Drospirenone is taken by mouth.

<span class="mw-page-title-main">Norethisterone acetate</span> Chemical compound

Norethisterone acetate (NETA), also known as norethindrone acetate and sold under the brand name Primolut-Nor among others, is a progestin medication which is used in birth control pills, menopausal hormone therapy, and for the treatment of gynecological disorders. The medication available in low-dose and high-dose formulations and is used alone or in combination with an estrogen. It is ingested orally.

<span class="mw-page-title-main">Norelgestromin</span> Pharmaceutical drug

Norelgestromin, or norelgestromine, sold under the brand names Evra and Ortho Evra among others, is a progestin medication which is used as a method of birth control for women. The medication is available in combination with an estrogen and is not available alone. It is used as a patch that is applied to the skin.

<span class="mw-page-title-main">Norgestimate</span> Chemical compound

Norgestimate, sold under the brand names Ortho Tri-Cyclen and Previfem among others, is a progestin medication which is used in birth control pills for women and in menopausal hormone therapy. The medication is available in combination with an estrogen and is not available alone. It is taken by mouth.

<span class="mw-page-title-main">Etynodiol diacetate</span> Chemical compound

Etynodiol diacetate, or ethynodiol diacetate, sold under the brand name Ovulen among others, is a progestin medication which is used in birth control pills. The medication is available only in combination with an estrogen. It is taken by mouth.

<span class="mw-page-title-main">Norethisterone</span> Progestin medication

Norethisterone, also known as norethindrone and sold under many brand names, is a progestin medication used in birth control pills, menopausal hormone therapy, and for the treatment of gynecological disorders. The medication is available in both low-dose and high-dose formulations and both alone and in combination with an estrogen. It is used by mouth or, as norethisterone enanthate, by injection into muscle.

<span class="mw-page-title-main">Gestodene</span> Progestin medication

Gestodene, sold under the brand names Femodene and Minulet among others, is a progestin medication which is used in birth control pills for women. It is also used in menopausal hormone therapy. The medication is available almost exclusively in combination with an estrogen. It is taken by mouth.

<span class="mw-page-title-main">Norgestrienone</span> Chemical compound

Norgestrienone, sold under the brand names Ogyline, Planor, and Miniplanor, is a progestin medication which has been used in birth control pills, sometimes in combination with ethinylestradiol. It was developed by Roussel Uclaf and has been registered for use only in France. Under the brand name Planor, it has been marketed in France as 2 mg norgestrienone and 50 μg ethinylestradiol tablets. It is taken by mouth.

<span class="mw-page-title-main">Ethisterone</span> Chemical compound

Ethisterone, also known as ethinyltestosterone, pregneninolone, and anhydrohydroxyprogesterone and formerly sold under the brand names Proluton C and Pranone among others, is a progestin medication which was used in the treatment of gynecological disorders but is now no longer available. It was used alone and was not formulated in combination with an estrogen. The medication is taken by mouth.

<span class="mw-page-title-main">Mestranol</span> Chemical compound

Mestranol, sold under the brand names Enovid, Norinyl, and Ortho-Novum among others, is an estrogen medication which has been used in birth control pills, menopausal hormone therapy, and the treatment of menstrual disorders. It is formulated in combination with a progestin and is not available alone. It is taken by mouth.

Birth control pills come in a variety of formulations. The main division is between combined oral contraceptive pills, containing both estrogens and synthetic progestogens (progestins), and progestogen only pills. Combined oral contraceptive pills also come in varying types, including varying doses of estrogen, and whether the dose of estrogen or progestogen changes from week to week.

<span class="mw-page-title-main">Chlormadinone acetate</span> Chemical compound

Chlormadinone acetate (CMA), sold under the brand names Belara, Gynorelle, Lutéran, and Prostal among others, is a progestin and antiandrogen medication which is used in birth control pills to prevent pregnancy, as a component of menopausal hormone therapy, in the treatment of gynecological disorders, and in the treatment of androgen-dependent conditions like enlarged prostate and prostate cancer in men and acne and hirsutism in women. It is available both at a low dose in combination with an estrogen in birth control pills and, in a few countries like France and Japan, at low, moderate, and high doses alone for various indications. It is taken by mouth.

<span class="mw-page-title-main">Norethisterone enanthate</span> Chemical compound

Norethisterone enanthate (NETE), also known as norethindrone enanthate, is a form of hormonal birth control which is used to prevent pregnancy in women. It is used both as a form of progestogen-only injectable birth control and in combined injectable birth control formulations. It may be used following childbirth, miscarriage, or abortion. The failure rate per year in preventing pregnancy for the progestogen-only formulation is 2 per 100 women. Each dose of this form lasts two months with only up to two doses typically recommended.

<span class="mw-page-title-main">Segesterone acetate</span> Progestin medication

Segesterone acetate (SGA), sold under the brand names Nestorone, Elcometrine, and Annovera, is a progestin medication which is used in birth control and in the treatment of endometriosis in the United States, Brazil, and other South American countries. It is available both alone and in combination with an estrogen. It is not effective by mouth and must be given by other routes, most typically as a vaginal ring or implant that is placed into fat.

<span class="mw-page-title-main">Norgesterone</span> Chemical compound

Norgesterone, also known as norvinodrel or vinylestrenolone and sold under the brand name Vestalin, is a progestin medication which was formerly used in birth control pills for women but is now no longer marketed. It was used in combination with the estrogen ethinylestradiol. It is taken by mouth.

References

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