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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/06/18 13:44:50」(JST)

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Ethinyl estradiol (EE2) /ˌɛθɨnɨlˌiːstrəˈdaɪ.əl/, also sometimes written as 17α-ethinyl estradiol, ethinylestradiol, ethynyl estradiol, or ethinyl œstradiol, is a derivative of 17β-estradiol (E2), the major endogenous estrogen in humans. EE2 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 naturally occurring 17β-estradiol, which some have theorized to be related to different amounts of hepatic metabolism after absorption. The same contraindications and precautions apply for EE2 as with other estrogen medications.

Estinyl was a preparation of EE2 alone that was used for the management of menopausal symptoms and female hypogonadism.^[1]

EE2 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 (without progestogen) is of endometrial cancer.^{[citation needed]} As such, the medication is generally prescribed with progesterone in the setting of birth control.

History

The first orally active semisynthetic steroidal estrogen, EE2 (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]

EE2 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

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.

EE2 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. EE2 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 EE2 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.

EE2 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 EE2 dose from as high as 100 μg to as low as 10 μg in LoLoestrin Fe.^[9]

References

^ 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.
^ 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.
^ 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" (PDF). Federal Register 69 (87): 25124–30.
^ "LoLoestrin Fe website". Warner Chilcott. Retrieved 15 October 2011.
^ Revesz, C.; Banik, U. K.; Lefebvre, Y. (1970). "Ay-11483, A New Type of Orally Active Oestrogen". Reproduction 22: 27. doi:10.1530/jrf.0.0220027. edit

External links

Drugs.com - Ethinyl Estradiol Side Effects

English Journal

Effects of exposure to 17-alpha-ethynylestradiol on sperm quality of tench (Tinca tinca).

Oropesa AL1, Martín-Hidalgo D2, Fallola C3, Gil MC4.
Ecotoxicology and environmental safety.Ecotoxicol Environ Saf.2015 Oct;120:318-25. doi: 10.1016/j.ecoenv.2015.06.016. Epub 2015 Jun 19.
Alterations of sperm quality were studied in tench (Tinca tinca) exposed to sub-lethal doses of 17-alpha-ethynylestradiol-EE2-(50, 100 and 500μg/kg t.w) under semi-static conditions for 30 days. Thus, different biomarkers of sperm quality were assessed: concentration and volume of ejaculate, total
PMID 26099462

Performance of metal-organic framework MIL-101 after surfactant modification in the extraction of endocrine disrupting chemicals from environmental water samples.

Huang Z1, Lee HK2.
Talanta.Talanta.2015 Oct 1;143:366-73. doi: 10.1016/j.talanta.2015.05.006. Epub 2015 May 9.
The research presented in this paper explored the modification and application of a metal-organic framework, MIL-101, with nonionic surfactant-Triton X-114 in dispersive solid-phase extraction for the preconcentration of four endocrine disrupting chemicals (estrone, 17α-ethynylestradiol, estriol an
PMID 26078172

Occurrence and risk assessment of pharmaceuticals and personal care products and endocrine disrupting chemicals in reclaimed water and receiving groundwater in China.

Li Z1, Xiang X1, Li M1, Ma Y1, Wang J2, Liu X3.
Ecotoxicology and environmental safety.Ecotoxicol Environ Saf.2015 Sep;119:74-80. doi: 10.1016/j.ecoenv.2015.04.031. Epub 2015 May 14.
Groundwater recharge using reclaimed water is considered a promising method to alleviate groundwater depletion. However, pollutants in reclaimed water could be recharged into groundwater during this process, thereby posing a risk to groundwater and human health. In this study, 12 cities in northern
PMID 25982733

Japanese Journal

Dose-dependent acceleration in the delayed effects of neonatal oral exposure to low-dose 17α-ethynylestradiol on reproductive functions in female Sprague-Dawley rats

The Journal of Toxicological Sciences 40(6), 727-738, 2015
NAID 130005108876

Early indicators of delayed adverse effects in female reproductive organs in rats receiving neonatal exposure to 17alpha-ethynylestradiol

The Journal of Toxicological Sciences 39(5), 775-784, 2014
NAID 130004690965

新生ラットへのエチニルエストラジオール曝露が幼若期の卵巣における卵胞発育関連遺伝子の発現に及ぼす影響

日本毒性学会学術年会 40.1(0), 2002108, 2013
NAID 130004676701

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★リンクテーブル★

リンク元	「エチニルエストラジオール」

「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; category	X (USA);
Legal status	Rx-only (U.S.);
Routes of; administration	Oral, transdermal
Pharmacokinetic data
Bioavailability	97% is bound
Metabolism	Liver
Half-life	36 ± 13 hours
Excretion	Feces and Urine
Identifiers
CAS Registry Number	57-63-6
ATC code	G03CA01 L02AA03
PubChem	CID: 5991
IUPHAR ligand	7071
DrugBank	DB00977
ChemSpider	5770
UNII	423D2T571U
KEGG	D00554
ChEBI	CHEBI:4903
ChEMBL	CHEMBL691
Chemical data
Formula	C20H24O2
Molecular 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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