Diethylstilbestrolのソースを表示

{{Short description|Chemical compound}}
{{Infobox drug
| Verifiedfields = verified
| Watchedfields = verified
| verifiedrevid = 464188812
| IUPAC_name = 4,4'-[(3''E'')-Hex-3-ene-3,4-diyl]diphenol
| image = Diethylstilbestrol.svg
| width = 250px
| image2 = Diethylstilbestrol molecule ball.png
| width2 = 250px

<!--Clinical data-->
| Drugs.com = {{drugs.com|CONS|diethylstilbestrol}}
| pregnancy_category = X
| routes_of_administration = [[Oral administration|By mouth]], [[vaginal administration|vaginal]], [[topical medication|topical]], [[intravenous injection|intravenous]], [[intramuscular injection]] (as an [[ester]])
| class = [[Nonsteroidal estrogen]]

<!--Pharmacokinetic data-->
| bioavailability = Well-absorbed<ref name="ChabnerLongo1996"/>
| protein_bound = >95%<ref name="OelschlägerRothley1988"/>
| metabolism = [[Hydroxylation]], [[oxidation]], [[glucuronidation]]<ref name="ChabnerLongo1996"/><ref name="OelschlägerRothley1988"/><ref name="pmid8428334"/>
| metabolites = • [[Dienestrol|(''Z'',''Z'')-Dienestrol]]<ref name="ChabnerLongo1996"/><br />• [[Paroxypropione]]<ref name="ChabnerLongo1996"/><br />• [[Glucuronide]]s<ref name="OelschlägerRothley1988"/><ref name="pmid8428334"/>
| elimination_half-life = 24 hours<ref name="ChabnerLongo1996"/><ref name="pmid7154205" />
| excretion = [[Urine]], [[feces]]<ref name="OelschlägerRothley1988"/><ref name="pmid8428334"/>

<!--Identifiers-->
| CAS_number_Ref = {{cascite|correct|CAS}}
| CAS_number = 56-53-1
| ATC_prefix = G03
| ATC_suffix = CB02
| ATC_supplemental = {{ATC|G03|CC05}}, {{ATC|L02|AA01}}
| PubChem = 448537
| IUPHAR_ligand = 2801
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00255
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 395306
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 731DCA35BT
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D00577
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 41922
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 411
| synonyms = DES; Stilboestrol; Stilbestrol; (''E'')-11,12-Diethyl-4,13-stilbenediol

<!--Chemical data-->
| C=18 | H=20 | O=2
| SMILES = Oc2ccc(/C(=C(/c1ccc(O)cc1)CC)CC)cc2
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C18H20O2/c1-3-17(13-5-9-15(19)10-6-13)18(4-2)14-7-11-16(20)12-8-14/h5-12,19-20H,3-4H2,1-2H3/b18-17+
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = RGLYKWWBQGJZGM-ISLYRVAYSA-N
}}
<!-- Definition and medical uses -->
'''Diethylstilbestrol''' ('''DES'''), also known as '''stilbestrol''' or '''stilboestrol''', is a [[nonsteroidal estrogen]] medication, which is presently rarely used.<ref name="pmid4276416" /><ref name="Elks2014">{{Cite book |url=https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA396 |title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies |vauthors=Elks J |date=14 November 2014 |publisher=Springer |isbn=978-1-4757-2085-3 |pages=396–}}</ref><ref name="Kuhl2005">{{cite journal |vauthors= Kuhl H |title= Pharmacology of estrogens and progestogens: influence of different routes of administration |journal= Climacteric |volume= 8 |issue= Suppl 1 |pages= 3–63 |date= August 2005 |pmid= 16112947 |doi= 10.1080/13697130500148875 |s2cid= 24616324 |url= http://hormonebalance.org/images/documents/Kuhl%2005%20%20Pharm%20Estro%20Progest%20Climacteric_1313155660.pdf |access-date= 2018-02-24 |archive-date= 2016-08-22 |archive-url= https://web.archive.org/web/20160822055012/http://hormonebalance.org/images/documents/Kuhl%2005%20%20Pharm%20Estro%20Progest%20Climacteric_1313155660.pdf |url-status= live }}</ref> In the past, it was widely used for a variety of indications, including [[pregnancy]] support for those with a history of [[recurrent miscarriage]], [[hormone therapy]] for [[menopausal symptoms]] and [[estrogen deficiency]], treatment of [[prostate cancer]] and [[breast cancer]], and other uses.<ref name="pmid4276416" /> By 2007, it was only used in the treatment of prostate cancer and breast cancer.<ref name="Watkins2007">{{cite book |vauthors=Watkins ES |title=The Estrogen Elixir: A History of Hormone Replacement Therapy in America |url=https://books.google.com/books?id=-tz4J4_hgdIC&pg=PA26 |date=16 April 2007 |publisher=JHU Press |isbn=978-0-8018-8602-7 |pages=26– |access-date=3 September 2020 |archive-date=12 May 2024 |archive-url=https://web.archive.org/web/20240512211905/https://books.google.com/books?id=-tz4J4_hgdIC&pg=PA26#v=onepage&q&f=false |url-status=live }}</ref> In 2011, Hoover and colleagues reported adverse reproductive health outcomes linked to DES including [[infertility]], [[miscarriage]], [[ectopic pregnancy]], [[preeclampsia]], [[preterm birth]], [[stillbirth]], [[infant death]], [[menopause]] prior to age 45, breast cancer, [[cervical cancer]], and [[vaginal cancer]].<ref>{{cite web | title = Effects of Diethylstilbestrol (DES), a Trans-placental Carcinogen | url = https://dceg.cancer.gov/research/public-health-impact/des | website = dceg.cancer.gov | date = 20 November 2012 | access-date = 3 September 2020 | archive-date = 8 February 2023 | archive-url = https://web.archive.org/web/20230208075515/https://dceg.cancer.gov/research/public-health-impact/des | url-status = live }}</ref> While most commonly taken [[oral administration|by mouth]], DES was available for use by other [[routes of administration|routes]] as well, for instance, [[vaginal administration|vaginal]], [[topical medication|topical]], and by [[injection (medicine)|injection]].

<!-- Side effects and mechanism -->
DES is an [[estrogen (medication)|estrogen]], or an [[agonist]] of the [[estrogen receptor]]s, the [[biological target]] of estrogens like [[estradiol]].<ref name="Kuhl2005" /> It is a [[synthetic compound|synthetic]] and [[nonsteroidal estrogen]] of the [[stilbestrol]] group, and differs from the [[natural product|natural]] estrogen [[estradiol (medication)|estradiol]].<ref name="Kuhl2005" /> Compared to estradiol, DES has greatly improved [[bioavailability]] when taken by mouth, is more resistant to [[metabolism]], and shows relatively increased effects in certain parts of the body like the [[liver]] and [[uterus]].<ref name="Kuhl2005"/> These differences result in DES having an increased risk of [[blood clot]]s, [[cardiovascular disease|cardiovascular issues]], and certain other adverse effects.<ref name="Kuhl2005"/>

<!-- History, society, and culture -->
DES was discovered in 1938 and introduced for medical use in 1939.<ref name="pmid16096877">{{cite journal |vauthors= Veurink M, Koster M, Berg LT |title= The history of DES, lessons to be learned |journal= Pharm World Sci |volume= 27 |issue= 3 |pages= 139–43 |date= June 2005 |pmid= 16096877 |doi= 10.1007/s11096-005-3663-z |s2cid= 12630813 }}</ref><ref name="FeldbergLadd-Taylor2003">{{cite book|vauthors=Feldberg GD, Ladd-Taylor M, Li A|title=Women, Health and Nation: Canada and the United States Since 1945|url=https://books.google.com/books?id=CRjtHlq1INcC&pg=PA103|year=2003|publisher=McGill-Queen's Press - MQUP|isbn=978-0-7735-2501-6|pages=103–|access-date=2020-09-03|archive-date=2023-01-14|archive-url=https://web.archive.org/web/20230114183724/https://books.google.com/books?id=CRjtHlq1INcC&pg=PA103|url-status=live}}</ref> From about 1940 to 1971, the medication was given to pregnant women in the incorrect belief that it would reduce the risk of pregnancy complications and losses.<ref name="pmid16096877"/> In 1971, DES was shown to cause [[clear-cell adenocarcinoma of the vagina|clear-cell carcinoma]], a rare [[vaginal tumor]], in those who had been exposed to this medication ''[[Uterus|in utero]]''.<ref name="pmid16096877"/><ref name="pmid4276416" /> The [[United States]] [[Food and Drug Administration]] subsequently withdrew approval of DES as a treatment for pregnant women.<ref name="pmid16096877"/><ref name="pmid4276416" /> Follow-up studies have indicated that DES also has the potential to cause a variety of significant adverse medical complications during the lifetimes of those exposed including infertility.<ref name="pmid16096877"/><ref name="urlDES Update: For Consumers. Centers for Disease Control and Prevention">{{cite web |url= https://www.cdc.gov/des/consumers/ |title= DES Update: For Consumers |publisher= United States Department of Health and Human Services: Centers for Disease Control and Prevention |access-date= 2011-06-30 |archive-date= 2020-12-11 |archive-url= https://web.archive.org/web/20201211201613/https://www.cdc.gov/des/consumers/ |url-status= live }}</ref>

The United States [[National Cancer Institute]] recommends<ref>{{cite web |url= https://www.cancer.gov/about-cancer/causes-prevention/risk/hormones/des-fact-sheet |title= Diethylstilbestrol (DES) and Cancer |publisher= National Cancer Institute |access-date= 2011-06-30 |archive-date= 2015-02-23 |archive-url= https://web.archive.org/web/20150223031713/http://www.cancer.gov/cancertopics/factsheet/Risk/DES |url-status= live }}</ref> children born to mothers who took DES to undergo special medical exams on a regular basis to screen for complications as a result of the medication. Individuals who were exposed to DES during their mothers' pregnancies are commonly referred to as "DES daughters" and "DES sons".<ref name="pmid16096877"/><ref name=Broadly-DES-Daughters-2017>{{cite news |vauthors=Arnold A |title=The Devastating Effects of a 1940s 'Wonder Pill' Haunt Women Generations Later |url=https://www.vice.com/en_us/article/zmbvp9/des-daughters-the-devastating-effects-of-a-1940s-wonder-pill-haunt-women-generations-later |work=[[Broadly]] |date=January 5, 2017 |access-date=July 27, 2019 |archive-date=August 14, 2020 |archive-url=https://web.archive.org/web/20200814152808/https://www.vice.com/en_us/article/zmbvp9/des-daughters-the-devastating-effects-of-a-1940s-wonder-pill-haunt-women-generations-later |url-status=live }}</ref> Since the discovery of the [[toxicity|toxic]] effects of DES, it has largely been discontinued and is now mostly no longer marketed for human treatment.<ref name="pmid16096877"/><ref name="pmid15063479">{{cite journal |vauthors= Coelingh Bennink HJ |title= Are all estrogens the same? |journal= Maturitas |volume= 47 |issue= 4 |pages= 269–275 |date= April 2004 |pmid= 15063479 |doi= 10.1016/j.maturitas.2003.11.009 }}</ref>

{{TOC limit|3}}