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{{Drugbox|
{{Drugbox
|IUPAC_name =17-ethynyl-13-methyl- 7,8,9,11,12,13,14,15,16,17- decahydro-6H-cyclopenta[a] phenanthrene-
| verifiedrevid = 458286647
3,17-diol  
| IUPAC_name = 19-nor-17α-pregna-1,3,5(10)-trien-20-yne-3,17-diol
| image=Ethinylestradiol-2D-skeletal.png
| image = Ethinylestradiol-2D-skeletal.svg
| width=200px
| image2 = Etinilestradiol3D.png
| CAS_number=57-63-6
| width = 220px
| ATC_prefix=G03
| width2 = 220px
| ATC_suffix=CA01
 
| ATC_supplemental={{ATC|L02|AA03}}
<!--Clinical data-->
| PubChem=5991
| tradename =
| DrugBank=APRD00691
| Drugs.com = {{drugs.com|international|ethinylestradiol}}
| C=20 | H=24 | O=2
| MedlinePlus = a604032
| molecular_weight = 296.403
| bioavailability= 97% is bound
| metabolism = [[Liver]]
| elimination_half-life=36±13 hours
| excretion =  Urine
| pregnancy_category = X ([[United States|USA]])
| pregnancy_category = X ([[United States|USA]])
| legal_status = Rx-only <small>(U.S.)</small>
| legal_status = Rx-only <small>(U.S.)</small>
| routes_of_administration=Oral, transdermal  
| routes_of_administration = Oral, [[transdermal]]
 
<!--Pharmacokinetic data-->
| bioavailability = 97% is bound
| metabolism = [[Liver]]
| elimination_half-life = 36 ± 13 hours
| excretion = Feces and Urine
 
<!--Identifiers-->
| CASNo_Ref = {{cascite|correct|CAS}}
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 57-63-6
| ATC_prefix = G03
| ATC_suffix = CA01
| ATC_supplemental = {{ATC|L02|AA03}}
| PubChem = 5991
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00977
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 5770
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 423D2T571U
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D00554
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 4903
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 691
 
<!--Chemical data-->
| C = 20 | H = 24 | O = 2
| molecular_weight = 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 = 1/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
| InChIKey = BFPYWIDHMRZLRN-SLHNCBLABF
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 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
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = BFPYWIDHMRZLRN-SLHNCBLASA-N
}}
}}
{{SI}}


'''Ethinyl estradiol''' (EE2) {{IPAc-en|ˌ|ɛ|θ|ɨ|n|ɨ|l|ˌ|iː|s|t|r|ə|ˈ|d|aɪ|.|əl}}, also sometimes written as '''17α-ethinyl estradiol''', '''ethinylestradiol''', '''ethynyl estradiol''', or '''ethinyl œstradiol''', is a [[derivative (chemistry)|derivative]] of [[17β-estradiol]] (E2), the major [[endogenous]] [[estrogen]] in humans. EE2 is an orally [[biological activity|bioactive]] estrogen used in many [[oral contraceptive formulations|formulations]] of [[combined oral contraceptive pill]]s. It is one of the most commonly used [[medication]]s for this purpose.


==Overview==
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 [[contraindication]]s and precautions apply for EE2 as with other estrogen medications.


'''Ethinylestradiol''', also '''ethinyl estradiol''' (EE), is a synthetic [[derivative]] of [[estradiol]]. Ethinyl estradiol is orally bio-active and the [[estrogen]] in almost all modern [[oral contraceptive formulations|formulations]] of [[combined oral contraceptive pill]]s (the Pill). It is one of the most commonly used [[medication]]s.
''Estinyl'' was a preparation of EE2 alone that was used for the management of menopausal symptoms and female [[hypogonadism]].<ref>[http://www.rxlist.com/cgi/generic3/estinyl_ids.htm RxList.com] - Estinyl (ethynyl estradiol)</ref>


The first orally active synthetic steroidal estrogen, ethinylestradiol (17α-ethynylestradiol), the 17α-[[ethynyl radical|ethynyl]] analog of [[estradiol]], was [[chemical synthesis|synthesized]] in 1938 by Hans Herloff Inhoffen and Walter Hohlweg at [[Schering|Schering AG]] in Berlin.<!--
EE2 is released into the environment as a [[xenoestrogen]] from the [[urine]] and [[feces]] of people who take it as a medication.
--><ref name="Inhoffen 1938">{{cite journal |author=Inhoffen HH, Hohlweg W |month=February 11, |year=1938 |title=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) |journal=[[Naturwissenschaften |volume=26 |issue=6 |pages=96 |url=http://www.springerlink.com/content/h016u5tg61l00022/?p=6ced2951d3f04b188a3c302670b43768&pi=5}}</ref><!--
--><ref name="Maisel 1965">{{cite book |author=Maisel, Albert Q. |year=1965 |title=The Hormone Quest |location=New York |publisher=Random House |oclc=543168 }}</ref><!--
--><ref name="Petrow 1970">{{cite journal |author=Petrow V |year=1970 |title=The contraceptive progestagens |journal=Chem Rev |volume=70 |issue=6 |pages=713-26 |id=PMID 4098492}}</ref><!--
--><ref name="Sneader 2005">{{cite book |author=Sneader, Walter |year=2005 |title=Drug discovery : a history |location=Hoboken, NJ |publisher=John Wiley & Sons |isbn=0471899801 |chapter=Hormone analogues |pages=pp. 188-225}}</ref><!--
--><ref name="Djerassi 2006">{{cite journal |author=Djerassi C |year=2006 |title=Chemical birth of the pill |journal=Am J Obstet Gynecol |volume=194 |issue=1 |pages=290-8 |id=PMID 16389046}}</ref>


Ethinylestradiol was approved by the [[Food and Drug Administration|FDA]] in the [[United States|U.S.]] on June 25, 1943 and marketed by [[Schering-Plough|Schering]] as ''Estinyl''.<!--
The major concern with unopposed estrogen (without [[progestogen]]) is of [[endometrial cancer]].{{citation needed|date=November 2014}} As such, the medication is generally prescribed with [[progesterone]] in the setting of birth control.
--><ref name="Estinyl 1943">{{cite web |author=[[Food and Drug Administration|FDA]] |year=2007 |title=Drug details: Estinyl (ethinyl estradiol) NDA 005292 |url=http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.DrugDetails}} search: Estinyl</ref>
The FDA withdrew approval of ''Estinyl'' effective June 4, 2004 at the request of Schering, who had discontinued marketing ''Estinyl''.<!--
--><ref name="Estinyl 2004">{{cite journal |author=[[Food and Drug Administration|FDA]] |month=May 5, |year=2004 |title=Schering Corp. et al.; Withdrawal of Approval of 92 New Drug Applications and 49 Abbreviated New Drug Applications. Notice |journal=Fed Regist |volume=69 |issue=87 |pages=25124-30 |url=http://a257.g.akamaitech.net/7/257/2422/14mar20010800/edocket.access.gpo.gov/2004/pdf/04-10194.pdf}}</ref>


While estradiol is readily absorbed when taken orally, it is also quickly inactivated by the [[liver]]. Substitution at C17 of the estrane steroid with an [[ethyne|ethinyl]] group proved to provide an estrogen that is much more resistant to degradation and paved the way for the development of oral contraceptives.  
==History==
The first orally active [[semisynthetic]] [[steroid]]al estrogen, EE2 (17α-ethynylestradiol), the 17α-[[ethynyl radical|ethynyl]] [[structural analog|analog]] of E2, was [[chemical synthesis|synthesized]] in 1938 by Hans Herloff Inhoffen and Walter Hohlweg at [[Schering|Schering AG]] in [[Berlin]].<ref name="Inhoffen 1938">{{Cite journal | last1 = Inhoffen | first1 = H. H. | last2 = Hohlweg | first2 = W. | doi = 10.1007/BF01681040 | title = 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) | journal = [[Die Naturwissenschaften|Naturwissenschaften]] | volume = 26 | issue = 6 | pages = 96| year = 1938 | pmid =  | pmc = }}</ref><ref name="Maisel 1965">{{cite book |author=Maisel, Albert Q. |year=1965 |title=The Hormone Quest |location=New York |publisher=Random House |oclc=543168 }}</ref><ref name="Petrow 1970">{{cite journal |last=Petrow |first=Vladimir |date=December 1970 |title=The contraceptive progestagens |journal=Chem Rev |volume=70 |issue=6 |pages=713–26 |pmid=4098492 |doi=10.1021/cr60268a004}}</ref><ref name="Sneader 2005">{{cite book |author=Sneader, Walter |year=2005 |title=Drug discovery : a history |location=Hoboken, NJ |publisher=John Wiley & Sons |isbn=0-471-89980-1 |chapter=Hormone analogues |pages=188–225}}</ref><ref name="Djerassi 2006">{{cite journal |last=Djerassi |first=Carl |date=January 2006 |title=Chemical birth of the pill |journal=American Journal of Obstetrics and Gynecology |volume=194 |issue=1 |pages=290–8 |pmid=16389046 |doi=10.1016/j.ajog.2005.06.010}}</ref>


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 in excreted with the bile.  Due to the effect of [[enterohepatic circulation]] as second peak is seen several hours later. Individually, wide variations exist in the overall absorption process, and can be further modified by drug (i.e. [[antibiotic]]s) that affect the enterohepatic circulation or [[liver enzyme]]s. In circulation EE is almost fully bound to [[human serum albumin|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 was approved by the [[Food and Drug Administration|FDA]] in the [[United States|U.S.]] on June 25, 1943 and marketed by [[Schering-Plough|Schering]] as ''Estinyl''.<ref name="Estinyl 1943">{{cite web |author=FDA |year=2007 |title=Drug details: Estinyl (ethinyl estradiol) NDA 005292 |url=http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.DrugDetails |authorlink=Food and Drug Administration}} search: Estinyl</ref>


EE is hormonally effective by activating the [[estrogen receptor]] and thus used as 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 20 μg.  
The FDA withdrew approval of ''Estinyl'' effective June 4, 2004 at the request of Schering, who had discontinued marketing ''Estinyl''.<ref name="Estinyl 2004">{{cite journal |author=FDA |date=May 5, 2004 |title=Schering Corp. et al.; Withdrawal of Approval of 92 New Drug Applications and 49 Abbreviated New Drug Applications. Notice |journal=[[Federal Register]] |volume=69 |issue=87 |pages=25124–30 |url=http://edocket.access.gpo.gov/2004/pdf/04-10194.pdf |authorlink=Food and Drug Administration}}</ref>


All the [[contraindication]] and precautions apply for EE as with other estrogen medications.
==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 [[ethyne|ethinyl]] group served to provide an estrogen that is much more resistant to degradation and paved the way for the development of oral contraceptives.


''Estinyl'' was a preparation of EE alone that was used for the management of menopausal symptoms and female [[hypogonadism]].<ref>[http://www.rxlist.com/cgi/generic3/estinyl_ids.htm RxList.com] - Estinyl (ethinyl estradiol)</ref>
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. [[antibiotic]]s) that affect the enterohepatic circulation or [[liver enzyme]]s. In circulation EE2 is almost fully bound to [[human serum albumin|plasma albumin]]. It is metabolized by [[hydroxylation]]  of the [[aromatic ring]] and excreted in both feces and urine, in part as [[glucuronide]] and [[sulfate]] [[Conjugation (biochemistry)|conjugate]].


EE is released into the environment as a [[xenoestrogen]].
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.<ref name="Warner Chilcott - LoLoestrin Fe">{{cite web | authorlink = Warner Chilcott | title = LoLoestrin Fe website | publisher = Warner Chilcott | url = http://www.loloestrin.com/index.jsp | accessdate = 15 October 2011}}</ref>


==See also==
==See also==
{{colbegin|2}}
*[[Mestranol]]
*[[Estrofurate]]<ref>{{cite doi|10.1530/jrf.0.0220027}}</ref>
* [[Estrogen]]
* [[Hormonal contraception]]
* [[Hormonal contraception]]
* [[Oral contraceptive formulations]]
* [[Oral contraceptive formulations]]
* [[Birth Control]]
* [[Hormone replacement therapy]]
* [[Diethylstilbestrol]]
* [[Diethylstilbestrol]]
* [[Estradiol]]
* [[Estrogen ester]]
{{colend}}


==References==
==References==
<div class="references-small">{{reflist|2}}</div>
{{Reflist|2}}


==External links==
==External links==
* [http://www.drugs.com/sfx/ethinyl-estradiol-side-effects.html Drugs.com - Ethinyl Estradiol Side Effects]


{{Sex hormones}}
{{Estrogens}}
{{Estrogenics}}


[[Category:Alkynes]]
[[Category:Diols]]
[[Category:Hormonal contraception]]
[[Category:Hormonal contraception]]
[[Category:Steroids]]
[[Category:Synthetic estrogens]]
[[Category:Synthetic estrogens]]
[[Category:Alcohols]]
[[Category:Endocrinology]]
[[da:Ethinyløstradiol]]
[[no:Etinyløstradiol]]
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Revision as of 15:53, 13 April 2015

Ethinylestradiol
File:Ethinylestradiol-2D-skeletal.svg
Clinical data
AHFS/Drugs.comInternational Drug Names
MedlinePlusa604032
Pregnancy
category
Routes of
administration		Oral, transdermal
ATC code
Legal status
Legal status
  • Rx-only (U.S.)
Pharmacokinetic data
Bioavailability97% is bound
MetabolismLiver
Elimination half-life36 ± 13 hours
ExcretionFeces and Urine
Identifiers
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
E number{{#property:P628}}
ECHA InfoCard{{#property:P2566}}Lua error in Module:EditAtWikidata at line 36: attempt to index field 'wikibase' (a nil value).
Chemical and physical data
FormulaC20H24O2
Molar mass296.403 g/mol
3D model (JSmol)
  (verify)

Ethinyl estradiol (EE2) /ˌɛθ[invalid input: 'ɨ']n[invalid input: 'ɨ']lˌiːstrəˈdaɪ.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]

See also

References

  1. ↑ RxList.com - Estinyl (ethynyl estradiol)
  2. ↑ 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.
  3. ↑ Maisel, Albert Q. (1965). The Hormone Quest. New York: Random House. OCLC 543168.
  4. ↑ Petrow, Vladimir (December 1970). "The contraceptive progestagens". Chem Rev. 70 (6): 713–26. doi:10.1021/cr60268a004. PMID 4098492.
  5. ↑ Sneader, Walter (2005). "Hormone analogues". Drug discovery : a history. Hoboken, NJ: John Wiley & Sons. pp. 188–225. ISBN 0-471-89980-1.
  6. ↑ 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.
  7. ↑ FDA (2007). "Drug details: Estinyl (ethinyl estradiol) NDA 005292". search: Estinyl
  8. ↑ 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.
  9. ↑ "LoLoestrin Fe website". Warner Chilcott. Retrieved 15 October 2011.
  10. ↑ Template:Cite doi

External links

Template:Estrogens

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