Quinestrolのソースを表示

{{Short description|Pharmaceutical drug}}
{{Drugbox
| Verifiedfields = verified
| Watchedfields = verified
| verifiedrevid = 464378599
| IUPAC_name = (8''R'',9''S'',13''S'',14''S'',17''R'')-3-cyclopentyloxy-17-ethynyl-13-methyl-7,8,9,11,12,14,15,16-octahydro-6''H''-cyclopenta[''a'']phenanthren-17-ol
| image = Quinestrol.svg
| width = 250px
| image2 = Quinestrol molecule ball.png
| width2 = 250px

<!--Clinical data-->
| tradename = Estrovis, others
| Drugs.com = {{drugs.com|CONS|quinestrol}}
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_US = <!-- A / B / C / D / X -->
| pregnancy_category = 
| legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 -->
| legal_CA = <!-- / Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_UK = <!-- GSL / P / POM / CD / Class A, B, C -->
| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V -->
| legal_status = 
| routes_of_administration = [[Oral administration|By mouth]]
| class = [[Estrogen (medication)|Estrogen]]; [[Estrogen ether]]

<!--Pharmacokinetic data-->
| bioavailability = 
| protein_bound = 
| metabolism = 
| elimination_half-life = >120 hours (>5 days)<ref name="Sitruk-Ware_2012" />
| excretion = 

<!--Identifiers-->
| CAS_number_Ref = {{cascite|correct|CAS}}
| CAS_number = 152-43-2
| ATC_prefix = None
| ATC_suffix = 
| PubChem = 9046
| IUPHAR_ligand = 7097
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB04575
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 8694
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = JR0N7XD5GZ
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D00576
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 8716
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 1201165
| synonyms = Quinoestrol; Quinestrenol; Quinoestrenol; Ethinylestradiol 3-cyclopentyl ether; EECPE; EE2CPE; W-3566; 3-(Cyclopentyloxy)-17α-ethynylestra-1,3,5(10)-trien-17β-ol

<!--Chemical data-->
| C=25 | H=32 | O=2
| SMILES = O(c1ccc2c(c1)CC[C@H]3[C@@H]4CC[C@](C#C)(O)[C@@]4(C)CC[C@H]23)C5CCCC5
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C25H32O2/c1-3-25(26)15-13-23-22-10-8-17-16-19(27-18-6-4-5-7-18)9-11-20(17)21(22)12-14-24(23,25)2/h1,9,11,16,18,21-23,26H,4-8,10,12-15H2,2H3/t21-,22-,23+,24+,25+/m1/s1
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = PWZUUYSISTUNDW-VAFBSOEGSA-N
}}

'''Quinestrol''', also known as '''ethinylestradiol cyclopentyl ether''' ('''EECPE'''), sold under the brand name '''Estrovis''' among others, is an [[estrogen (medication)|estrogen]] medication which has been used in [[menopausal hormone therapy]], [[hormonal birth control]], and to treat [[breast cancer]] and [[prostate cancer]].<ref name="Zink_1988">{{cite book| vauthors = Zink C | chapter = Quinestrol |title=Dictionary of Obstetrics and Gynecology| chapter-url=https://books.google.com/books?id=EQlvzV9V7xIC&pg=PA204|date=1 January 1988|publisher=Walter de Gruyter|isbn=978-3-11-085727-6|pages=204–}}</ref><ref name="Peterson_1999" /> It is taken once per week to once per month [[oral administration|by mouth]].<ref name="Quirk_2012" /><ref name="HorskyPresl2012" /><ref name="HawkinsElder2013" /><ref name="Bennett_1974" />

==Medical uses==
Quinestrol has been used as the estrogen component in [[menopausal hormone therapy]] and in [[combined hormonal birth control]].<ref name="Zink_1988" /><ref name="Peterson_1999" /> It has also occasionally been used in the treatment of [[breast cancer]] and [[prostate cancer]], as well as to suppress [[lactation]].<ref name="Zink_1988" /><ref name="Peterson_1999" /><ref name="Vorherr_2012">{{cite book| vauthors = Vorherr H |title=The Breast: Morphology, Physiology, and Lactation|url=https://books.google.com/books?id=wYxirvD2X2IC&pg=PA201|date=2 December 2012|publisher=Elsevier Science|isbn=978-0-323-15726-1|pages=201–203}}</ref> On its own as an estrogen, quinestrol was taken once per week [[oral administration|by mouth]].<ref name="Quirk_2012">{{cite book | vauthors = Quirk Jr JG, Wendel Jr GD | chapter = Biologic effects of natural and synthetic estrogens. | veditors = Buchsbaum HJ |title=The Menopause| chapter-url= https://books.google.com/books?id=z0LuBwAAQBAJ&pg=PA60 |date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-1-4612-5525-3|pages=60–}}</ref> As a [[combined birth control pill]], it was used together with [[quingestanol acetate]] and was taken once per month by mouth.<ref name="HorskyPresl2012">{{cite book | vauthors = Horsky | chapter = Contraception | veditors = Horsky J, Presl J |title=Ovarian Function and its Disorders: Diagnosis and Therapy| chapter-url=https://books.google.com/books?id=7IrpCAAAQBAJ&pg=PA367|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-94-009-8195-9|pages=85,358,367}}</ref><ref name="HawkinsElder2013">{{cite book| vauthors = Hawkins DF, Elder MG | chapter = Other Hormal Contraception Procedures |title=Human Fertility Control: Theory and Practice| chapter-url = https://books.google.com/books?id=1lL0AgAAQBAJ&pg=PA92|date=22 October 2013|publisher=Elsevier Science|isbn=978-1-4831-6361-1|pages=92–94}}</ref><ref name="Bennett_1974">{{cite book | vauthors = Bennett JP |title=Chemical Contraception|url=https://books.google.com/books?id=4FVdDwAAQBAJ&pg=PA61|date=18 June 1974|publisher=Macmillan International Higher Education|isbn=978-1-349-02287-8|pages=61–}}</ref>

==Pharmacology==
[[File:Ethinylestradiol.svg|thumb|right|225px|[[Ethinylestradiol]] (EE), the [[active metabolite|active form]] of quinestrol.]]

Quinestrol is a [[prodrug]] of [[ethinylestradiol]] (EE), with no estrogenic activity of its own.<ref name="Peterson_1999" /><ref name="pmid6033895">{{cite journal | vauthors = Epstein JA | title = Prolonged menstrual response of patients with gonadal failure following quinestrol administration | journal = International Journal of Fertility | volume = 12 | issue = 2 | pages = 181–186 | date = 1967 | pmid = 6033895 }}</ref><ref name="pmid4390151">{{cite journal | vauthors = Giannina T, Meli A | title = Prolonged oestrogenic activity in rats after single oral administration of ethinyloestradiol-3-cyclopentyl ether | journal = The Journal of Pharmacy and Pharmacology | volume = 21 | issue = 4 | pages = 271–272 | date = April 1969 | pmid = 4390151 | doi = 10.1111/j.2042-7158.1969.tb08247.x | s2cid = 19407816 }}</ref> It is taken [[oral administration|orally]] and has prolonged activity following a single dose,<ref name="pmid6033895" /><ref name="pmid4390151" /> with a very long [[biological half-life]] of more than 120&nbsp;hours (5&nbsp;days) due to enhanced [[lipophilicity]] and storage in [[fat]].<ref name="Peterson_1999" /><ref name="Sitruk-Ware_2012">{{cite book| vauthors =  Sitruk-Ware R | chapter = Pharmacology of Different Administration Routes-Oral vs Transdermal. | veditors = Oettel M, Schillinger E |title=Estrogens and Antiestrogens II: Pharmacology and Clinical Application of Estrogens and Antiestrogen| series = Handbook of Experimental Pharmacology | chapter-url= https://books.google.com/books?id=wBvyCAAAQBAJ&pg=PA248 |date=6 December 2012| volume = 135 / 2 |publisher=Springer Science & Business Media|isbn=978-3-642-60107-1|pages=248– | doi = 10.1007/978-3-642-60107-1_14 }}</ref> Because of its much longer half-life, quinestrol is two to three times as potent as EE.<ref name="Peterson_1999">{{cite book | vauthors = Peterson CM, Udoff LC | chapter = Primary and secondary hypogonadism in women. | veditors = Meikle AW |title=Hormone Replacement Therapy| chapter-url = https://books.google.com/books?id=ja2nBgAAQBAJ&pg=PA381|date=1 June 1999|publisher=Springer Science & Business Media|isbn=978-1-59259-700-0|pages=381–}}</ref> Also because of its long half-life, quinestrol can be taken once a week or once a month.<ref name="Peterson_1999" /><ref name="Quirk_2012" /><ref name="HorskyPresl2012" /><ref name="HawkinsElder2013" /><ref name="Bennett_1974" />

Following administration, quinestrol is absorbed via the [[lymphatic system]], is stored in [[adipose tissue]], and is gradually released from adipose tissue.<ref name="WallachHammond1982">{{cite journal | vauthors = Hammond CB, Maxson WS | title = Current status of estrogen therapy for the menopause | journal = Fertility and Sterility | volume = 37 | issue = 1 | pages = 5–25 | date = January 1982 | pmid = 6277697 | doi = 10.1016/S0015-0282(16)45970-4 | doi-access =  }}</ref>

{{Affinities and estrogenic potencies of estrogen esters and ethers at the estrogen receptors}}

{{Oral potencies of estrogens}}

==Chemistry==
{{See also|List of estrogens#Estradiol derivatives|List of estrogen esters#Ethers of steroidal estrogens}}

Quinestrol, also known as ethinylestradiol 3-cyclopentyl ether (EE2CPE), is a [[synthetic compound|synthetic]] [[estrane]] [[steroid]] and a [[chemical derivative|derivative]] of [[estradiol (medication)|estradiol]].<ref name="Elks_2014" /><ref name="IndexNominum2000" /> It is an [[estrogen ether]], specifically the C3 [[cyclopentane|cyclopentyl]] [[ether]] of [[ethinylestradiol]] (17α-ethynylestradiol).<ref name="Elks_2014" /><ref name="IndexNominum2000" /> Closely related estrogens include [[mestranol]] (ethinylestradiol 3-methyl ether) and [[ethinylestradiol sulfonate]] (EES; Turisteron; ethinylestradiol 3-isopropylsulfonate).<ref name="Elks_2014" /><ref name="IndexNominum2000" />

==History==
Quinestrol was developed and introduced for medical use in the 1960s.<ref name="MedicalScientificServices1967">{{cite book|title=Medical Gynaecology and Sociology|url=https://books.google.com/books?id=WfxxAAAAIAAJ|year=1967|publisher=Medical and Scientific Services Limited|quote=[...] J. Fertil., 1967, 12, 2) contains 23 papers presented at a symposium on QUINESTROL. Quinestrol is a newly-developed synthetic steroid, and is the cyclo-pentyl ether of a ethinyl oestradiol.}}</ref>

==Society and culture==

===Generic names===
''Quinestrol'' is the [[generic term|generic name]] of the drug and its {{abbrlink|INN|International Nonproprietary Name}}, {{abbrlink|USAN|United States Adopted Name}}, and {{abbrlink|BAN|British Approved Name}}.<ref name="Elks_2014">{{cite book| vauthors = Elks J |title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies|url=https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA522|date=14 November 2014|publisher=Springer|isbn=978-1-4757-2085-3|pages=522–}}</ref><ref name="IndexNominum2000">{{cite book | chapter = Quinestrol |title=Index Nominum 2000: International Drug Directory| chapter-url=https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA905|date=January 2000|publisher=Taylor & Francis|isbn=978-3-88763-075-1|pages=905–}}</ref><ref name="Morton_2012">{{cite book| vauthors = Morton IK, Hall JM |title=Concise Dictionary of Pharmacological Agents: Properties and Synonyms|url=https://books.google.com/books?id=tsjrCAAAQBAJ&pg=PA243|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-94-011-4439-1|pages=243–}}</ref><ref name="Drugs.com">{{cite web | title = Quinestrol | work = Drugs.com | url = https://www.drugs.com/international/quinestrol.html| archive-url = https://web.archive.org/web/20151020003656/https://www.drugs.com/international/quinestrol.html | archive-date = 20 October 2015}}</ref> It is also known by its former developmental code name ''W-3566''.<ref name="Elks_2014" /><ref name="IndexNominum2000" /><ref name="Morton_2012" /><ref name="Drugs.com" />

===Brand names===
Quinestrol has been marketed under brand names including Agalacto-Quilea, Basaquines, Eston, Estrovis, Estrovister, Plestrovis, Qui-Lea, Soluna, and Yueketing, among others.<ref name="Elks_2014" /><ref name="IndexNominum2000" /><ref name="Morton_2012" /><ref name="Drugs.com" />

===Availability===
Quinestrol was marketed as ''Estrovis'' in the [[United States]] by [[Parke-Davis]] and as ''Qui-Lea'' in [[Argentina]],<ref name="IndexNominum2000" /> but is reportedly not currently marketed.<ref name="Peterson_1999" /> However, it does appear to still be available as an [[oral contraceptive]] in combination with [[progestin]]s in Argentina and [[China]].<ref name="Drugs.com" />

One tablet form available in China consists of 6&nbsp;mg levonorgestrel and 3&nbsp;mg quinestrol; it is used as a prescription "long-term" oral contraceptive, with one dose taken each month.<ref name="Drugs.com"/><ref name="tmall_levono_quin_tab">{{cite web|url=https://detail.yao.95095.com/item.htm?id=528371420852|title=悦可婷 左炔诺孕酮炔雌醚片 6片/盒 | trans-title = Yueketing Levonorgestrel Ethinylestradiol Tablets 6 Pieces/Box |language = Chinese |website=Tmall|archive-url=https://archive.today/20180716053328/https://detail.yao.95095.com/item.htm?id=528371420852|archive-date=2018-07-16|access-date=2018-07-16|quote=When taking the medicine for the first time, take the medicine once after lunch on the fifth day counting from the day of menstrual cramps, and take the second medicine at an interval of 20 days. Afterwards, take the second medicine taking day as the monthly medicine taking date, and take one tablet every month. When changing from short-acting oral contraceptives to long-acting contraceptives, you can take one long-acting contraceptive the next day after taking 22 tablets, and then take one tablet every month on the same day you started taking long-acting contraceptives. }}</ref> It is sold under various brand names including Yuèkětíng ({{zh|悦可婷}}) and Àiyuè ({{zh|艾悦}}). A version with the racemic [[norgestrel]] in place of levonorgestrel also appears to be available.<ref name="Drugs.com"/>

==Veterinary use==

===Rodents===
The Chinese levonorgestrel/quinestrol 2:1 formula is known as EP-1 in veterinary practice. It is known to have some organ-specific effects on the [[Mongolian gerbil]] as measured by receptor mRNA expression.<ref>{{cite journal | vauthors = Lv X, Shi D | title = Combined effects of levonorgestrel and quinestrol on reproductive hormone levels and receptor expression in females of the Mongolian gerbil (Meriones unguiculatus) | journal = Zoological Science | volume = 29 | issue = 1 | pages = 37–42 | date = January 2012 | pmid = 22233494 | doi = 10.2108/zsj.29.37 | s2cid = 22347486 }}</ref> Incorporated into baits at a concentration of 50&nbsp;ppm, EP-1 has been used to control wild Mongolian gerbil populations with some success.<ref>{{cite journal | vauthors = Fu H, Zhang J, Shi D, Wu X | title = Effects of levonorgestrel-quinestrol (EP-1) treatment on Mongolian gerbil wild populations: a case study | journal = Integrative Zoology | volume = 8 | issue = 3 | pages = 277–284 | date = September 2013 | pmid = 24020466 | doi = 10.1111/1749-4877.12018 }}</ref>

== References ==
{{Reflist}}

{{Estrogens and antiestrogens}}
{{Estrogen receptor modulators}}

[[Category:Ethynyl compounds]]
[[Category:Antigonadotropins]]
[[Category:Cyclopentyl ethers]]
[[Category:Estranes]]
[[Category:Estrogen ethers]]
[[Category:Synthetic estrogens]]
[[Category:Tertiary alcohols]]