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Trade names | Ovulen, Demulen, others |
Other names | Ethynodiol diacetate; Norethindrol diacetate; 3β-Hydroxynorethisterone 3β,17β-diacetate;[1] 17α-Ethynylestr-4-ene-3β,17β-diyl diacetate; CB-8080; SC-11800 |
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Routes of administration | By mouth |
Drug class | Progestogen; Progestin; Progestogen ester |
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ECHA InfoCard | 100.005.496 |
Chemical and physical data | |
Formula | C24H32O4 |
Molar mass | 384.516 g·mol−1 |
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Etynodiol diacetate, or ethynodiol diacetate, sold under the brand name Ovulen among others, is a progestin medication which is used in birth control pills.[4][5][6] The medication is available only in combination with an estrogen.[7] It is taken by mouth.[8]
Etynodiol diacetate is a progestin, or a synthetic progestogen, and hence is an agonist of the progesterone receptor, the biological target of progestogens like progesterone.[9][10] It has weak androgenic and estrogenic activity and no other important hormonal activity.[11][12][13] The medication is a prodrug of norethisterone in the body, with etynodiol occurring as an intermediate.[9][10][14]
Etynodiol, a related compound, was discovered in 1954, and etynodiol diacetate was introduced for medical use in 1965.[15][16] The combination ethynodiol with mestranol (Ovulen) was approved for medical use in the United States in 1966.[17] The combination ethinylestradiol with ethynodiol (Demulen) was approved for medical use in the United States in 1970.[18]
In 2021, the combination with ethinylestradiol was the 276th most commonly prescribed medication in the United States, with more than 800,000 prescriptions.[19][20]
Etynodiol diacetate is used in combination with an estrogen such as ethinylestradiol or mestranol in combined oral contraceptives for women for the prevention of pregnancy.[8]
See also: Norethisterone § Side effects, and Progestin § Side effects |
Etynodiol diacetate is virtually inactive in terms of affinity for the progesterone and androgen receptors and acts as a rapidly converted prodrug of norethisterone, with etynodiol occurring as an intermediate.[9][10][14] Upon oral administration and during first-pass metabolism in the liver, etynodiol diacetate is rapidly converted by esterases into etynodiol,[14] which is followed by oxygenation of the C3 hydroxyl group to produce norethisterone.[10] In addition to its progestogenic activity, etynodiol diacetate has weak androgenic activity,[11][12] and, unlike most progestins but similarly to norethisterone and noretynodrel,[21] also has some estrogenic activity.[12][13]
The pharmacokinetics of etynodiol diacetate have been reviewed.[22]
Compound | Typea | PR | AR | ER | GR | MR | SHBG | CBG |
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Norethisterone | – | 67–75 | 15 | 0 | 0–1 | 0–3 | 16 | 0 |
5α-Dihydronorethisterone | Metabolite | 25 | 27 | 0 | 0 | ? | ? | ? |
3α,5α-Tetrahydronorethisterone | Metabolite | 1 | 0 | 0–1 | 0 | ? | ? | ? |
3α,5β-Tetrahydronorethisterone | Metabolite | ? | 0 | 0 | ? | ? | ? | ? |
3β,5α-Tetrahydronorethisterone | Metabolite | 1 | 0 | 0–8 | 0 | ? | ? | ? |
Ethinylestradiol | Metabolite | 15–25 | 1–3 | 112 | 1–3 | 0 | 0.18 | 0 |
Norethisterone acetate | Prodrug | 20 | 5 | 1 | 0 | 0 | ? | ? |
Norethisterone enanthate | Prodrug | ? | ? | ? | ? | ? | ? | ? |
Noretynodrel | Prodrug | 6 | 0 | 2 | 0 | 0 | 0 | 0 |
Etynodiol | Prodrug | 1 | 0 | 11–18 | 0 | ? | ? | ? |
Etynodiol diacetate | Prodrug | 1 | 0 | 0 | 0 | 0 | ? | ? |
Lynestrenol | Prodrug | 1 | 1 | 3 | 0 | 0 | ? | ? |
Notes: Values are percentages (%). Reference ligands (100%) were promegestone for the PR , metribolone for the AR , estradiol for the ER , dexamethasone for the GR , aldosterone for the MR , dihydrotestosterone for SHBG , and cortisol for CBG . Footnotes: a = Active or inactive metabolite, prodrug, or neither of norethisterone. Sources: See template. |
See also: List of progestogens, Progestogen ester, and List of progestogen esters |
Etynodiol diacetate, also known as 3β-hydroxy-17α-ethynyl-19-nortestosterone 3β,17β-diaceate, 3β-hydroxynorethisterone 3β,17β-diacetate, or 17α-ethynylestr-4-ene-3β,17β-diol 3β,17β-diacetate, is a synthetic estrane steroid and a derivative of testosterone.[1][5][6] It is specifically a derivative of 19-nortestosterone and 17α-ethynyltestosterone, or of norethisterone (17α-ethynyl-19-nortestosterone), in which the C3 ketone group has been dehydrogenated into a C3β hydroxyl group and acetate esters have been attached at the C3β and C17β positions.[5][6] Etynodiol diacetate is the 3β,17β-diacetate ester of etynodiol (17α-ethynylestr-4-ene-3β,17β-diol).[5][6]
Chemical syntheses of etynodiol diacetate have been published.[22]
Reduction of norethisterone (1) affords the 3,17-diol. The 3β-hydroxy compound is the desired product; since reactions at C3 do not show nearly the stereoselectivity as those at C17 by virtue of the relative lack of stereo-directing proximate substituents, the formation of the desired isomer is engendered by use of a bulky reducing agent, lithium tri-tert-butoxyaluminum hydride. Acetylation of the 3β,17β-diol affords etynodiol diacetate (3).[23]
Etynodiol was first synthesized in 1954, via reduction of norethisterone, and etynodiol diacetate was introduced for medical use in 1965.[15][16]
Etynodiol diacetate is the generic name of the drug (the INN of its free alcohol form is etynodiol), while ethynodiol diacetate is its USAN , BAN , and JAN .[5][6][7] It is also known by its former developmental code names CB-8080 and SC-11800.[5][6][7]
Etynodiol diacetate is or has been marketed under brand names including Conova, Continuin, Demulen,[18][25] Femulen, Kelnor,[3][25] Lo-Malmorede,[26] Luteonorm, Luto-Metrodiol, Malmorede,[27] Metrodiol, Ovulen,[17][25] Soluna, Zovia,[2] and others.[5][6][7]
Etynodiol diacetate is marketed in only a few countries, including the United States, Canada, Argentina, and Oman.[7]