Estradiol acetate

{{Short description|Chemical compound}} {{Use dmy dates|date=April 2023}} {{Drugbox | Verifiedfields = | Watchedfields = | verifiedrevid = | IUPAC_name = [(8''R'',9''S'',13''S'',14''S'',17''S'')-17-hydroxy-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[''a'']phenanthren-3-yl] acetate | image = Estradiol 3-acetate.svg | image_class = skin-invert-image | width = 250px | image2 = Estradiol acetate molecule ball.png | image_class2 = bg-transparent | width2 = 250px

| pronounce = {{IPAc-en|ˌ|ɛ|s|t|r|ə|ˈ|d|aɪ|oʊ|l|_|ˈ|æ|s|ə|t|eɪ|t}}<br />{{respell|ES|trə|DY|ohl|_|ASS|ə|tayt}}<ref name="Drugs.com-2">{{Cite web|url=https://www.drugs.com/estradiol.html|title=Estradiol: Uses, Dosage & Side Effects|website=Drugs.com|access-date=21 April 2023}}</ref> | tradename = Femtrace, Femring, Menoring | pregnancy_AU =  | pregnancy_US =  | pregnancy_category = | legal_AU =  | legal_CA = | legal_UK = | legal_US = | legal_status = Rx-only | routes_of_administration = By mouth, vaginal (ring)<ref name="pmid17506242" /> | class = Estrogen; Estrogen ester

| C=20 | H=26 | O=3 | SMILES = CC(=O)OC1=CC2=C(C=C1)[C@H]3CC[C@]4([C@H]([C@@H]3CC2)CC[C@@H]4O)C | StdInChI_Ref = | StdInChI = 1S/C20H26O3/c1-12(21)23-14-4-6-15-13(11-14)3-5-17-16(15)9-10-20(2)18(17)7-8-19(20)22/h4,6,11,16-19,22H,3,5,7-10H2,1-2H3/t16-,17-,18+,19+,20+/m1/s1 | StdInChIKey_Ref = | StdInChIKey = FHXBMXJMKMWVRG-SLHNCBLASA-N }}  '''Estradiol acetate''' ('''EA'''), sold under the brand names '''Femtrace''', '''Femring''', and '''Menoring''', is an estrogen medication which is used in hormone therapy for the treatment of menopausal symptoms in women.<ref name="Drugs.com4">{{Cite web|url=https://www.drugs.com/international/estradiol-acetate.html|title = Estradiol Monograph for Professionals}}</ref><ref name="pmid12892687">{{cite journal | vauthors = Buckler H, Al-Azzawi F | title = The effect of a novel vaginal ring delivering oestradiol acetate on climacteric symptoms in postmenopausal women | journal = BJOG | volume = 110 | issue = 8 | pages = 753–759 | date = August 2003 | pmid = 12892687 | doi = 10.1016/s1470-0328(03)02908-2 | doi-access = }}</ref><ref name=FemtraceLabel>{{cite web |url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021633s005lbl.pdf|archive-url=https://web.archive.org/web/20160804054615/http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021633s005lbl.pdf|url-status=dead|archive-date=4 August 2016|access-date=21 April 2023|website=accessdata.fda.gov |title=Highlights of prescribing information|year=2014}}</ref><ref name="FemringLabel">{{cite web|title=FEMRING |url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=86b90d68-bfb6-47f6-aa5b-a6642391ff13#i4i_clinical_studies_id_2a230567-d4b8-4161-9dd0-fb082cd301e5|website=DailyMed|publisher=U.S. National Library of Medicine}}</ref> It is taken by mouth once daily or given as a vaginal ring once every three months.<ref name="pmid17506242" />

Side effects of estradiol acetate include breast tenderness, breast enlargement, nausea, headache, and fluid retention.<ref name="Ghosh2010" /><ref name="FemtraceLabel" /><ref name="FemringLabel" /> Estradiol acetate is an estrogen and hence is an agonist of the estrogen receptor, the biological target of estrogens like estradiol.<ref name="pmid16112947">{{cite journal | vauthors = Kuhl H | title = Pharmacology of estrogens and progestogens: influence of different routes of administration | journal = Climacteric | volume = 8 | pages = 3–63 | date = August 2005 | issue = Suppl 1 | pmid = 16112947 | doi = 10.1080/13697130500148875 | s2cid = 24616324 }}</ref><ref name="OettelSchillinger2012" /> It is an estrogen ester and a prodrug of estradiol in the body.<ref name="OettelSchillinger2012" /><ref name="pmid16112947" /> Because of this, it is considered to be a natural and bioidentical form of estrogen.<ref name="OettelSchillinger2012">{{cite book| vauthors = Kuhnz W, Blode H, Zimmermann H | series = Handbook of Experimental Pharmacology | chapter = Pharmacokinetics of Exogenous Natural and Synthetic Estrogens and Antiestrogens | veditors = Oettel M, Schillinger E |title=Estrogens and Antiestrogens II: Pharmacology and Clinical Application of Estrogens and Antiestrogen| chapter-url=https://books.google.com/books?id=wBvyCAAAQBAJ&pg=PA261|date=6 December 2012| volume = 135 / 2 |publisher=Springer Science & Business Media|isbn=978-3-642-60107-1 | doi = 10.1007/978-3-642-60107-1_15 |page=261|quote=Natural estrogens considered here include: [...] Esters of 17β-estradiol, such as estradiol valerate, estradiol benzoate and estradiol cypionate. Esterification aims at either better absorption after oral administration or a sustained release from the depot after intramuscular administration. During absorption, the esters are cleaved by endogenous esterases and the pharmacologically active 17β-estradiol is released; therefore, the esters are considered as natural estrogens.}}</ref><ref name="pmid17627398">{{cite journal | vauthors = Cirigliano M | title = Bioidentical hormone therapy: a review of the evidence | journal = Journal of Women's Health | volume = 16 | issue = 5 | pages = 600–631 | date = June 2007 | pmid = 17627398 | doi = 10.1089/jwh.2006.0311 }}</ref>

Estradiol acetate was introduced for medical use in 2001.<ref name="pmid15382956" /> It is available in the United States and the United Kingdom.<ref name="pmid15382956" /><ref name="Drugs.com4" /> The formulation for use by mouth has been discontinued in the United States.<ref name="Femtrace-FDA" />

==Medical uses== {{See also|Estradiol (medication)#Medical uses}}

Estradiol acetate is used as a component of menopausal hormone therapy to treat and prevent menopausal symptoms such as hot flashes and osteoporosis in women.<ref name="pmid14551014" /><ref name="pmid15879923">{{cite journal | vauthors = Al-Azzawi F, Lees B, Thompson J, Stevenson JC | title = Bone mineral density in postmenopausal women treated with a vaginal ring delivering systemic doses of estradiol acetate | journal = Menopause | volume = 12 | issue = 3 | pages = 331–339 | year = 2005 | pmid = 15879923 | doi = 10.1097/01.gme.0000163870.03388.4d | s2cid = 22295565 | hdl = 2381/16795 | hdl-access = free }}</ref><ref name="pmid16278614">{{cite journal | vauthors = Utian WH, Speroff L, Ellman H, Dart C | title = Comparative controlled trial of a novel oral estrogen therapy, estradiol acetate, for relief of menopause symptoms | journal = Menopause | volume = 12 | issue = 6 | pages = 708–715 | year = 2005 | pmid = 16278614 | doi = 10.1097/01.gme.0000184220.63459.a8 | s2cid = 28927438 }}</ref><ref name="pmid16735941">{{cite journal | vauthors = Speroff L, Haney AF, Gilbert RD, Ellman H | title = Efficacy of a new, oral estradiol acetate formulation for relief of menopause symptoms | journal = Menopause | volume = 13 | issue = 3 | pages = 442–450 | year = 2006 | pmid = 16735941 | doi = 10.1097/01.gme.0000182802.06762.b2 | s2cid = 19563197 }}</ref>

The Women's Health Initiative studies report increased health risks for menopausal women when using unopposed estrogens.<ref name="FemringLabel" /> Estrogens with or without progestins should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman.<ref name="FemringLabel" />

===Available forms=== Estradiol acetate comes in the form of 0.45, 0.9, and 1.8 mg oral tablets (Femtrace) and in the form of 12.4 or 24.8 mg vaginal rings that release 50 or 100 μg/day estradiol for 3 months (Femring, Menoring).<ref name="FemtraceLabel" /><ref name="FemringLabel" /><ref name="LowdermilkPerry2014">{{cite book| vauthors = Lowdermilk DL, Perry SE, Cashion MC, Alden KR | chapter = Reproductive System Concerns |title=Maternity and Women's Health Care - E-Book| chapter-url = https://books.google.com/books?id=urzuBQAAQBAJ&pg=PA137|date=18 December 2014|publisher=Elsevier Health Sciences|isbn=978-0-323-39019-4|pages=137–}}</ref> However, the Femtrace product was discontinued in the United States.<ref name="Femtrace-FDA">{{Cite web|url=https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=021633|archive-url=https://web.archive.org/web/20170217120050/http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=021633|url-status=dead|archive-date=17 February 2017|title = Drugs@FDA: FDA-Approved Drugs}}</ref>

==Contraindications== {{See also|Estradiol (medication)#Contraindications}}

Contraindications of estrogens include coagulation problems, cardiovascular diseases, liver disease, and certain hormone-sensitive cancers such as breast cancer and endometrial cancer, among others.<ref name="pmid2215269" /><ref name="LauritzenStudd2005">{{cite book| vauthors = Lauritzen C, Studd JW |title=Current Management of the Menopause|url=https://books.google.com/books?id=WD7S7677xUUC&pg=PA95|date=22 June 2005|publisher=CRC Press|isbn=978-0-203-48612-2|pages=95–98,488}}</ref><ref name="Lauritzen2001">{{cite book | vauthors = Laurtizen C | chapter = Hormone Substitution Before, During and After Menopause | pages = 67–88 | chapter-url = https://www.kup.at/kup/pdf/4978.pdf | veditors = Fisch FH | title = Menopause – Andropause: Hormone Replacement Therapy Through the Ages | year = 2001 | publisher = Krause & Pachernegg: Gablitz | isbn = 978-3-901299-34-6}}</ref><ref name="Midwinter1976">{{cite book| vauthors = Midwinter A |chapter=Contraindications to estrogen therapy and management of the menopausal syndrome in these cases|pages=377–382|doi=10.1007/978-94-011-6165-7_33| veditors = Campbell S |title=The Management of the Menopause & Post-Menopausal Years: The Proceedings of the International Symposium held in London 24–26 November 1975 Arranged by the Institute of Obstetrics and Gynaecology, The University of London|year=1976|isbn=978-94-011-6167-1|publisher=MTP Press Limited}}</ref>

==Side effects== {{See also|Estradiol (medication)#Side effects}}

The side effects of estradiol acetate are the same as those of estradiol. Examples of such side effects include breast tenderness and enlargement, nausea, bloating, edema, headache, and melasma.<ref name="Ghosh2010">{{cite book| vauthors = McIver B, Tebben PJ | chapter = Endocrinology | veditors = Ghosh AK |title=Mayo Clinic Internal Medicine Board Review| chapter-url = https://books.google.com/books?id=LS65jBzoD40C&pg=PA222|date=23 September 2010|publisher=OUP USA|isbn=978-0-19-975569-1|pages=222–}}</ref>

==Overdose== {{See also|Estradiol (medication)#Overdose}}

Symptoms of estrogen overdosage may include nausea, vomiting, bloating, increased weight, water retention, breast tenderness, vaginal discharge, heavy legs, and leg cramps.<ref name="pmid2215269">{{cite journal | vauthors = Lauritzen C | title = Clinical use of oestrogens and progestogens | journal = Maturitas | volume = 12 | issue = 3 | pages = 199–214 | date = September 1990 | pmid = 2215269 | doi = 10.1016/0378-5122(90)90004-P }}</ref> These side effects can be diminished by reducing the estrogen dosage.<ref name="pmid2215269" />

== Interactions == {{See also|Estradiol (medication)#Interactions}}

Inhibitors and inducers of cytochrome P450 may influence the metabolism of estradiol and by extension circulating estradiol levels.<ref name="pmid11741520">{{cite journal | vauthors = Cheng ZN, Shu Y, Liu ZQ, Wang LS, Ou-Yang DS, Zhou HH | title = Role of cytochrome P450 in estradiol metabolism in vitro | journal = Acta Pharmacologica Sinica | volume = 22 | issue = 2 | pages = 148–154 | date = February 2001 | pmid = 11741520 }}</ref>

===Pharmacodynamics=== {{See also|Pharmacodynamics of estradiol}}

Estradiol acetate is an estradiol ester, or a prodrug of estradiol.<ref name="OettelSchillinger2012" /><ref name="pmid16112947" /> As such, it is an estrogen, or an agonist of the estrogen receptors.<ref name="pmid16112947" /><ref name="OettelSchillinger2012" /> Estradiol acetate is of about 15% higher molecular weight than estradiol due to the presence of its C3 acetate ester.<ref name="Drugs.com4" /> Because estradiol acetate is a prodrug of estradiol, it is considered to be a natural and bioidentical form of estrogen.<ref name="OettelSchillinger2012" /><ref name="pmid17627398" />

===Pharmacokinetics=== {{See also|Pharmacokinetics of estradiol}}

Estradiol acetate is converted into estradiol in the body.<ref name="OettelSchillinger2012" /><ref name="pmid16112947" />

==Chemistry== {{See also|Estrogen ester|List of estrogen esters#Estradiol esters}}

Estradiol acetate is a synthetic estrane steroid and the C3 acetate ester of estradiol.<ref name="Drugs.com4" /> It is also known as estradiol 3-acetate or as estra-1,3,5(10)-triene-3,17β-diol 3-acetate.<ref name="Drugs.com4" /> Another common ester of estradiol in use for oral administration is estradiol valerate, which is a C17β ester of estradiol.<ref name="pmid16112947" /><ref name="pmid7169965">{{cite journal | vauthors = Düsterberg B, Nishino Y | title = Pharmacokinetic and pharmacological features of oestradiol valerate | journal = Maturitas | volume = 4 | issue = 4 | pages = 315–324 | date = December 1982 | pmid = 7169965 | doi = 10.1016/0378-5122(82)90064-0 }}</ref>

The experimental octanol/water partition coefficient (logP) of estradiol acetate is 4.2.<ref name="ChemSpider">{{Cite web|url=http://www.chemspider.com/Chemical-Structure.5254726.html|title=Estradiol acetate | C20H26O3 | ChemSpider|website=www.chemspider.com|access-date=21 April 2023}}</ref>

==History== Estradiol acetate is relatively recent to the market, having been first approved in a vaginal ring formulation as Menoring in the United Kingdom in 2001,<ref name="pmid14551014">{{cite journal | vauthors = Speroff L | title = Efficacy and tolerability of a novel estradiol vaginal ring for relief of menopausal symptoms | journal = Obstetrics and Gynecology | volume = 102 | issue = 4 | pages = 823–834 | date = October 2003 | pmid = 14551014 | doi = 10.1016/s0029-7844(03)00764-6 | s2cid = 10289535 }}</ref> followed by a vaginal ring formulation as Femring in the United States in 2002,<ref name="pmid17506242">{{cite journal | vauthors = Sivanandy MS, Masimasi N, Thacker HL | title = Newer hormonal therapies: lower doses; oral, transdermal, and vaginal formulations | journal = Cleveland Clinic Journal of Medicine | volume = 74 | issue = 5 | pages = 369–375 | date = May 2007 | pmid = 17506242 | doi = 10.3949/ccjm.74.5.369 | s2cid = 35423126 }}</ref> and finally as an oral preparation as Femtrace in the United States in 2004.<ref name="pmid17506242" /><ref name="pmid15382956">{{cite journal | vauthors = Ballagh SA | title = Vaginal rings for menopausal symptom relief | journal = Drugs & Aging | volume = 21 | issue = 12 | pages = 757–766 | date = 2004 | pmid = 15382956 | doi = 10.2165/00002512-200421120-00001 | s2cid = 20717960 }}</ref>

==Society and culture==

===Generic names=== ''Estradiol acetate'' is the generic name of the drug and its {{abbrlink|USAN|United States Adopted Name}}.<ref name="Drugs.com4" />

===Brand names=== Estradiol acetate is marketed under the brand names Femtrace, Femring, and Menoring.<ref name="Drugs.com4" /><ref name="Administration2009">{{cite book|author=U.S. Food and Drug Administration|title=Menopause - Medicines to Help You| url=https://books.google.com/books?id=LCajOxNaM_4C&pg=PA3|year=2009|publisher=GPO FCIC|isbn=978-1-61221-026-1|pages=3–}}</ref><ref name="FritzSperoff2012">{{cite book| vauthors = Fritz MA, Speroff L | chapter = Postmenopausal Hormone Therapy |title=Clinical Gynecologic Endocrinology and Infertility| chapter-url = https://books.google.com/books?id=KZLubBxJEwEC&pg=PA757|date=28 March 2012|publisher=Lippincott Williams & Wilkins|isbn=978-1-4511-4847-3|pages=757–}}</ref>

===Availability=== Estradiol acetate is available in the United States and the United Kingdom.<ref name="pmid15382956" /><ref name="Drugs.com4" />

== References == {{Reflist}}

Category:Acetate esters Category:Estradiol esters Category:Secondary alcohols Category:Synthetic estrogens