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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/01/16 01:21:25」(JST)

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Ethinyl estradiol (EE) /ˌɛθɨnɨlˌiːstrəˈdaɪ.əl/, also sometimes written as ethinylestradiol, ethynyl estradiol, or ethinyl œstradiol, is a derivative of 17β-estradiol (E2), the major endogenous estrogen in humans. EE is an orally bioactive estrogen used in many formulations of combined oral contraceptive pills. It is one of the most commonly used medications for this purpose.

Transdermal ethinyl estradiol carries a greater risk of clot formation and venous thromboembolism than 17 beta estradiol, which some have theorized to be related to different amounts of hepatic metabolism after absorption. The same contraindications and precautions apply for EE as with other estrogen medications.

Estinyl was a preparation of EE alone that was used for the management of menopausal symptoms and female hypogonadism.^[1]

EE is released into the environment as a xenoestrogen from the urine and feces of people who take it as a medication.

The major concern with unopposed estrogen is of endometrial cancer. As such, the medication is generally prescribed with progesterone in the setting of birth control.

History[edit]

The first orally active semisynthetic steroidal estrogen, EE (17α-ethynylestradiol), the 17α-ethynyl analog of E2, was synthesized in 1938 by Hans Herloff Inhoffen and Walter Hohlweg at Schering AG in Berlin.^[2]^[3]^[4]^[5]^[6]

EE was approved by the FDA in the U.S. on June 25, 1943 and marketed by Schering as Estinyl.^[7]

The FDA withdrew approval of Estinyl effective June 4, 2004 at the request of Schering, who had discontinued marketing Estinyl.^[8]

Pharmacology[edit]

While E2 is readily absorbed when taken orally, it is also quickly inactivated by the liver. Substitution at C17 of the estrane steroid with an ethinyl group served to provide an estrogen that is much more resistant to degradation and paved the way for the development of oral contraceptives.

EE is absorbed in the small intestine and reaches a serum peak about 2 hours later. It undergoes extensive metabolism in the liver involving the cytochrome P450 3A4 isoenzyme. EE and its metabolites are excreted with the bile. Due to the effect of enterohepatic circulation a second peak is seen several hours later. Individually, wide variations exist in the overall absorption process, and can be further modified by drugs (i.e. antibiotics) that affect the enterohepatic circulation or liver enzymes. In circulation EE is almost fully bound to plasma albumin. It is metabolized by hydroxylation of the aromatic ring and excreted in both feces and urine, in part as glucuronide and sulfate conjugate.

EE is hormonally effective by activating the estrogen receptor and thus is an estrogen. It finds its most common use in the estrogen-progestin combination preparations of oral contraceptives. Over time, formulations have decreased the EE dose from as high as 100 μg to as low as 10 μg in LoLoestrin Fe.^[9]

Chemistry[edit]

EE is prepared from estron in one step by ethinylation with ethyne, sodium and sodium amide.^[10]

References[edit]

^ RxList.com - Estinyl (ethynyl estradiol)
^ Inhoffen, H. H.; Hohlweg, W. (1938). "Neue per os-wirksame weibliche Keimdrüsenhormon-Derivate: 17-Aethinyl-oestradiol und Pregnen-in-on-3-ol-17 (New female glandular derivatives active per os: 17α-ethynyl-estradiol and pregnen-in-on-3-ol-17)". Naturwissenschaften 26 (6): 96. doi:10.1007/BF01681040.
^ Maisel, Albert Q. (1965). The Hormone Quest. New York: Random House. OCLC 543168.
^ Petrow, Vladimir (December 1970). "The contraceptive progestagens". Chem Rev 70 (6): 713–26. doi:10.1021/cr60268a004. PMID 4098492. Cite uses deprecated parameters (help)
^ Sneader, Walter (2005). "Hormone analogues". Drug discovery : a history. Hoboken, NJ: John Wiley & Sons. pp. 188–225. ISBN 0-471-89980-1.
^ Djerassi, Carl (January 2006). "Chemical birth of the pill". American Journal of Obstetrics and Gynecology 194 (1): 290–8. doi:10.1016/j.ajog.2005.06.010. PMID 16389046. Cite uses deprecated parameters (help)
^ FDA (2007). "Drug details: Estinyl (ethinyl estradiol) NDA 005292". search: Estinyl
^ FDA (May 5, 2004). "Schering Corp. et al.; Withdrawal of Approval of 92 New Drug Applications and 49 Abbreviated New Drug Applications. Notice". Federal Register 69 (87): 25124–30. Cite uses deprecated parameters (help)
^ "LoLoestrin Fe website". Warner Chilcott. Retrieved 15 October 2011.
^ Kleemann, Axel; Engel, Jürgen; Kutscher, Bernd; Reichert, Dieter (2009). Pharmaceutical Substances (5 ed.). Thieme-Verlag Stuttgart. ISBN 978-3-13-558405-8.

External links[edit]

Drugs.com - Ethinyl Estradiol Side Effects

UpToDate Contents

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English Journal

Drug-drug interaction profile of components of a fixed combination of netupitant and palonosetron: Review of clinical data.

Natale JJ1, Spinelli T2, Calcagnile S2, Lanzarotti C2, Rossi G2, Cox D3, Kashef K4.
Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners.J Oncol Pharm Pract.2016 Jun;22(3):485-95. doi: 10.1177/1078155215586824. Epub 2015 May 20.
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Simultaneous determination of estrogens (ethinylestradiol and norgestimate) concentrations in human and bovine serum albumin by use of fluorescence spectroscopy and multivariate regression analysis.

Hordge LN1, McDaniel KL1, Jones DD1, Fakayode SO2.
Talanta.Talanta.2016 May 15;152:401-9. doi: 10.1016/j.talanta.2016.02.034. Epub 2016 Feb 17.
The endocrine disruption property of estrogens necessitates the immediate need for effective monitoring and development of analytical protocols for their analyses in biological and human specimens. This study explores the first combined utility of a steady-state fluorescence spectroscopy and multiva
PMID 26992536

Activity of binary mixtures of drospirenone with progesterone and 17α-ethinylestradiol in vitro and in vivo.

Rossier NM1, Chew G2, Zhang K2, Riva F3, Fent K4.
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Despite potential exposure of aquatic organisms to mixtures of steroid hormones, very little is known on their joint activity in fish. Drospirenone (DRS) is a new synthetic progestin used in contraceptive pills in combination with 17α-ethinylestradiol (EE2). Here we systematically analyzed effects
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Japanese Journal

症例報告ドロスピレノン・エチニルエストラジオール内服中に生じた無症候肺血栓塞栓症の1例

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去勢抵抗性前立腺癌に対するエチニルエストラジオールの有用性

林拓自,関井洋輔,片山欽三 [他]
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NAID 40020045297

Molecular Cloning and Characterization of the Expression Profiles of Vitellogenin Transcripts in the Dojo Loach (Misgurnus anguillicaudatus) in Response to 17α-ethinylestradiol and 17β-estradiol Administration

Wu Meiqin,Nishimiya Osamu,Nakamori Misato [他],Soyano Kiyoshi,Todo Takashi,Hara Akihiko,Hiramatsu Naoshi
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… Males were administered (aqueous exposure) either 17 beta-estradiol (E2) or 17 alpha-ethinylestradiol (EE2), the results from which were used to determine that hepatic vtgAo1 expression was estrogen-sensitive. …
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「エチニルエストラジオール」

Ethinyl estradiol
Systematic (IUPAC) name
	19-nor-17α-pregna-1,3,5(10)-trien-20-yne-3,17-diol
Clinical data
AHFS/Drugs.com	International Drug Names
MedlinePlus	a604032
Pregnancy cat.	X (USA)
Legal status	Rx-only (U.S.)
Routes	Oral, transdermal
Pharmacokinetic data
Bioavailability	97% is bound
Metabolism	Liver
Half-life	36 ± 13 hours
Excretion	Feces and Urine
Identifiers
CAS number	57-63-6
ATC code	G03CA01 L02AA03
PubChem	CID 5991
DrugBank	DB00977
ChemSpider	5770
UNII	423D2T571U
KEGG	D00554
ChEBI	CHEBI:4903
ChEMBL	CHEMBL1078384
Chemical data
Formula	C20H24O2
Mol. mass	296.403 g/mol
	SMILES Oc1cc4c(cc1)[C@H]3CC[C@]2([C@@H](CC[C@]2(C#C)O)[C@@H]3CC4)C;
	InChI InChI=1S/C20H24O2/c1-3-20(22)11-9-18-17-6-4-13-12-14(21)5-7-15(13)16(17)8-10-19(18,20)2/h1,5,7,12,16-18,21-22H,4,6,8-11H2,2H3/t16-,17-,18+,19+,20+/m1/s1 ; Key:BFPYWIDHMRZLRN-SLHNCBLASA-N ;
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