Chemical compound
Pharmaceutical compound
Estradiol acetate Clinical data Pronunciation /ˌ ɛ s t r ə ˈ d aɪ oʊ l ˈ æ s ə t eɪ t ES -trə-DY -ohlASS -ə-tayt[ 1] Trade names Femtrace, Femring, Menoring Other names EA; E2A; E3A; Estradiol 3-acetate Routes of By mouth ,vaginal (ring )[ 2] Drug class Estrogen ;Estrogen ester ATC code Legal status Legal status In general: ℞ (Prescription only) Identifiers [(8R ,9S ,13S ,14S ,17S )-17-hydroxy-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a ]phenanthren-3-yl] acetate
CAS Number PubChem CID DrugBank ChemSpider UNII KEGG ChEMBL CompTox Dashboard (EPA) ECHA InfoCard 100.167.088 Chemical and physical data Formula C 20 H 26 O 3 Molar mass −1 3D model (JSmol ) InChI=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
Key:FHXBMXJMKMWVRG-SLHNCBLASA-N
Estradiol acetate (EA ), sold under the brand namesFemtrace ,Femring , andMenoring , is anestrogen medication which is used inhormone therapy for the treatment ofmenopausal symptoms in women.[ 3] [ 4] [ 5] [ 6] by mouth once daily or given as avaginal ring once every three months.[ 2]
Side effects of estradiol acetate includebreast tenderness ,breast enlargement ,nausea ,headache , andfluid retention .[ 7] [ 5] [ 6] estrogen and hence is anagonist of theestrogen receptor , thebiological target ofestrogens likeestradiol .[ 8] [ 9] estrogen ester and aprodrug ofestradiol in the body.[ 9] [ 8] natural andbioidentical form of estrogen.[ 9] [ 10]
Estradiol acetate was introduced for medical use in 2001.[ 11] United States and theUnited Kingdom .[ 11] [ 3] [ 12]
Estradiol acetate is used as a component ofmenopausal hormone therapy to treat and preventmenopausal symptoms such ashot flashes andosteoporosis in women.[ 13] [ 14] [ 15] [ 16]
TheWomen's Health Initiative studies report increased health risks for menopausal women when using unopposed estrogens.[ 6] [ 6]
Estradiol acetate comes in the form of 0.45, 0.9, and 1.8 mgoral tablets (Femtrace) and in the form of 12.4 or 24.8 mgvaginal rings that release 50 or 100 μg/day estradiol for 3 months (Femring, Menoring).[ 5] [ 6] [ 17] United States .[ 12]
Contraindications of estrogens includecoagulation problems,cardiovascular diseases ,liver disease , and certainhormone-sensitive cancers such asbreast cancer andendometrial cancer , among others.[ 18] [ 19] [ 20] [ 21]
Theside effects of estradiol acetate are the same as those of estradiol. Examples of such side effects includebreast tenderness andenlargement ,nausea ,bloating ,edema ,headache , andmelasma .[ 7]
Symptoms of estrogenoverdosage may includenausea ,vomiting ,bloating ,increased weight ,water retention ,breast tenderness ,vaginal discharge ,heavy legs , andleg cramps .[ 18] [ 18]
Inhibitors andinducers ofcytochrome P450 may influence themetabolism of estradiol and by extension circulating estradiol levels.[ 22]
Estradiol , theactive form of estradiol acetate.Estradiol acetate is anestradiol ester , or aprodrug ofestradiol .[ 9] [ 8] estrogen , or anagonist of theestrogen receptors .[ 8] [ 9] molecular weight than estradiol due to the presence of its C3acetate ester.[ 3] natural andbioidentical form of estrogen.[ 9] [ 10]
Estradiol acetate is converted into estradiol in the body.[ 9] [ 8]
Estradiol acetate is asynthetic estrane steroid and the C3acetate ester ofestradiol .[ 3] [ 3] estradiol valerate , which is a C17β ester of estradiol.[ 8] [ 23]
The experimentaloctanol/water partition coefficient (logP) of estradiol acetate is 4.2.[ 24]
Structural properties of selected estradiol esters Estrogen Structure Ester(s) Relativemol. weight RelativeE2 contentb log Pc Position(s) Moiet(ies) Type Lengtha Estradiol – – – – 1.00 1.00 4.0 Estradiol acetate C3 Ethanoic acid Straight-chain fatty acid 2 1.15 0.87 4.2 Estradiol benzoate C3 Benzoic acid Aromatic fatty acid – (~4–5) 1.38 0.72 4.7 Estradiol dipropionate C3, C17β Propanoic acid (×2)Straight-chain fatty acid 3 (×2) 1.41 0.71 4.9 Estradiol valerate C17β Pentanoic acid Straight-chain fatty acid 5 1.31 0.76 5.6–6.3 Estradiol benzoate butyrate C3, C17β Benzoic acid ,butyric acid Mixed fatty acid – (~6, 2) 1.64 0.61 6.3 Estradiol cypionate C17β Cyclopentylpropanoic acid Cyclic fatty acid – (~6) 1.46 0.69 6.9 Estradiol enanthate C17β Heptanoic acid Straight-chain fatty acid 7 1.41 0.71 6.7–7.3 Estradiol dienanthate C3, C17β Heptanoic acid (×2)Straight-chain fatty acid 7 (×2) 1.82 0.55 8.1–10.4 Estradiol undecylate C17β Undecanoic acid Straight-chain fatty acid 11 1.62 0.62 9.2–9.8 Estradiol stearate C17β Octadecanoic acid Straight-chain fatty acid 18 1.98 0.51 12.2–12.4 Estradiol distearate C3, C17β Octadecanoic acid (×2)Straight-chain fatty acid 18 (×2) 2.96 0.34 20.2 Estradiol sulfate C3 Sulfuric acid Water-soluble conjugate – 1.29 0.77 0.3–3.8 Estradiol glucuronide C17β Glucuronic acid Water-soluble conjugate – 1.65 0.61 2.1–2.7 Estramustine phosphate d C3, C17β Normustine ,phosphoric acid Water-soluble conjugate – 1.91 0.52 2.9–5.0 Polyestradiol phosphate e C3–C17β Phosphoric acid Water-soluble conjugate – 1.23f 0.81f 2.9g Footnotes: a = Length ofester incarbon atoms forstraight-chain fatty acids or approximate length of ester in carbon atoms foraromatic orcyclic fatty acids.b = Relative estradiol content by weight (i.e., relativeestrogenic exposure).c = Experimental or predictedoctanol/water partition coefficient (i.e.,lipophilicity /hydrophobicity ). Retrieved fromPubChem ,ChemSpider , andDrugBank .d = Also known asestradiol normustine phosphate .e =Polymer ofestradiol phosphate (~13repeat units ).f = Relative molecular weight or estradiol content per repeat unit.g = log P of repeat unit (i.e., estradiol phosphate).Sources: See individual articles.
Estradiol acetate is relatively recent to the market, having been first approved in avaginal ring formulation as Menoring in theUnited Kingdom in 2001,[ 13] United States in 2002,[ 2] oral preparation as Femtrace in the United States in 2004.[ 2] [ 11]
Society and culture [ edit ] Estradiol acetate is thegeneric name of the drug and itsUSAN Tooltip United States Adopted Name .[ 3]
Estradiol acetate is marketed under the brand names Femtrace, Femring, and Menoring.[ 3] [ 25] [ 26]
Estradiol acetate is available in theUnited States and theUnited Kingdom .[ 11] [ 3]
^ "Estradiol: Uses, Dosage & Side Effects" .Drugs.com . Retrieved21 April 2023 .^a b c d Sivanandy MS, Masimasi N, Thacker HL (May 2007). "Newer hormonal therapies: lower doses; oral, transdermal, and vaginal formulations".Cleveland Clinic Journal of Medicine .74 (5):369– 375.doi :10.3949/ccjm.74.5.369 .PMID 17506242 .S2CID 35423126 . ^a b c d e f g h "Estradiol Monograph for Professionals" .^ Buckler H, Al-Azzawi F (August 2003). "The effect of a novel vaginal ring delivering oestradiol acetate on climacteric symptoms in postmenopausal women".BJOG .110 (8):753– 759.doi :10.1016/s1470-0328(03)02908-2 .PMID 12892687 . ^a b c "Highlights of prescribing information" (PDF) .accessdata.fda.gov . 2014. Archived fromthe original (PDF) on 4 August 2016. Retrieved21 April 2023 .^a b c d e "FEMRING" .DailyMed . U.S. National Library of Medicine.^a b McIver B, Tebben PJ (23 September 2010)."Endocrinology" . In Ghosh AK (ed.).Mayo Clinic Internal Medicine Board Review . OUP USA. pp. 222–.ISBN 978-0-19-975569-1 ^a b c d e f Kuhl H (August 2005). "Pharmacology of estrogens and progestogens: influence of different routes of administration".Climacteric .8 (Suppl 1):3– 63.doi :10.1080/13697130500148875 .PMID 16112947 .S2CID 24616324 . ^a b c d e f g Kuhnz W, Blode H, Zimmermann H (6 December 2012)."Pharmacokinetics of Exogenous Natural and Synthetic Estrogens and Antiestrogens" . In Oettel M, Schillinger E (eds.).Estrogens and Antiestrogens II: Pharmacology and Clinical Application of Estrogens and Antiestrogen . Handbook of Experimental Pharmacology. Vol. 135 / 2. Springer Science & Business Media. p. 261.doi :10.1007/978-3-642-60107-1_15 .ISBN 978-3-642-60107-1 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. ^a b Cirigliano M (June 2007). "Bioidentical hormone therapy: a review of the evidence".Journal of Women's Health .16 (5):600– 631.doi :10.1089/jwh.2006.0311 .PMID 17627398 . ^a b c d Ballagh SA (2004). "Vaginal rings for menopausal symptom relief".Drugs & Aging .21 (12):757– 766.doi :10.2165/00002512-200421120-00001 .PMID 15382956 .S2CID 20717960 . ^a b "Drugs@FDA: FDA-Approved Drugs" . Archived fromthe original on 17 February 2017.^a b Speroff L (October 2003). "Efficacy and tolerability of a novel estradiol vaginal ring for relief of menopausal symptoms".Obstetrics and Gynecology .102 (4):823– 834.doi :10.1016/s0029-7844(03)00764-6 .PMID 14551014 .S2CID 10289535 . ^ Al-Azzawi F, Lees B, Thompson J, Stevenson JC (2005). "Bone mineral density in postmenopausal women treated with a vaginal ring delivering systemic doses of estradiol acetate".Menopause .12 (3):331– 339.doi :10.1097/01.gme.0000163870.03388.4d .PMID 15879923 .S2CID 22295565 . ^ Utian WH, Speroff L, Ellman H, Dart C (2005). "Comparative controlled trial of a novel oral estrogen therapy, estradiol acetate, for relief of menopause symptoms".Menopause .12 (6):708– 715.doi :10.1097/01.gme.0000184220.63459.a8 .PMID 16278614 .S2CID 28927438 . ^ Speroff L, Haney AF, Gilbert RD, Ellman H (2006). "Efficacy of a new, oral estradiol acetate formulation for relief of menopause symptoms".Menopause .13 (3):442– 450.doi :10.1097/01.gme.0000182802.06762.b2 .PMID 16735941 .S2CID 19563197 . ^ Lowdermilk DL, Perry SE, Cashion MC, Alden KR (18 December 2014)."Reproductive System Concerns" .Maternity and Women's Health Care - E-Book . Elsevier Health Sciences. pp. 137–.ISBN 978-0-323-39019-4 ^a b c Lauritzen C (September 1990). "Clinical use of oestrogens and progestogens".Maturitas .12 (3):199– 214.doi :10.1016/0378-5122(90)90004-P .PMID 2215269 . ^ Lauritzen C, Studd JW (22 June 2005).Current Management of the Menopause 95– 98, 488.ISBN 978-0-203-48612-2 ^ Laurtizen C (2001)."Hormone Substitution Before, During and After Menopause" (PDF) . In Fisch FH (ed.).Menopause – Andropause: Hormone Replacement Therapy Through the Ages . Krause & Pachernegg: Gablitz. pp. 67– 88.ISBN 978-3-901299-34-6 ^ Midwinter A (1976). "Contraindications to estrogen therapy and management of the menopausal syndrome in these cases". In Campbell S (ed.).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 . MTP Press Limited. pp. 377– 382.doi :10.1007/978-94-011-6165-7_33 .ISBN 978-94-011-6167-1 ^ Cheng ZN, Shu Y, Liu ZQ, Wang LS, Ou-Yang DS, Zhou HH (February 2001). "Role of cytochrome P450 in estradiol metabolism in vitro".Acta Pharmacologica Sinica .22 (2):148– 154.PMID 11741520 . ^ Düsterberg B, Nishino Y (December 1982). "Pharmacokinetic and pharmacological features of oestradiol valerate".Maturitas .4 (4):315– 324.doi :10.1016/0378-5122(82)90064-0 .PMID 7169965 . ^ "Estradiol acetate | C20H26O3 | ChemSpider" .www.chemspider.com . Retrieved21 April 2023 .^ U.S. Food and Drug Administration (2009).Menopause - Medicines to Help You ISBN 978-1-61221-026-1 ^ Fritz MA, Speroff L (28 March 2012)."Postmenopausal Hormone Therapy" .Clinical Gynecologic Endocrinology and Infertility . Lippincott Williams & Wilkins. pp. 757–.ISBN 978-1-4511-4847-3
Estrogens
ER Tooltip Estrogen receptor agonistsSteroidal: Alfatradiol Certainandrogens /anabolic steroids (e.g.,testosterone ,testosterone esters ,methyltestosterone ,metandienone ,nandrolone esters ) (via estrogenic metabolites) Certainprogestins (e.g.,norethisterone ,noretynodrel ,etynodiol diacetate ,tibolone ) Clomestrone Cloxestradiol acetate Conjugated estriol Conjugated estrogens Epiestriol Epimestrol Esterified estrogens Estetrol † Estradiol Estradiol esters (e.g.,estradiol acetate ,estradiol benzoate ,estradiol cypionate ,estradiol enanthate ,estradiol undecylate ,estradiol valerate ,polyestradiol phosphate ,estradiol ester mixtures (Climacteron ))Estramustine phosphate Estriol Estriol esters (e.g.,estriol succinate ,polyestriol phosphate )Estrogenic substances Estrone Estrone esters Ethinylestradiol # Hydroxyestrone diacetate Mestranol Methylestradiol Moxestrol Nilestriol Prasterone (dehydroepiandrosterone; DHEA) Promestriene Quinestradol Quinestrol Progonadotropins
Antiestrogens
ER Tooltip Estrogen receptor antagonistsSERMs Tooltip selective estrogen receptor modulators /SERDs Tooltip selective estrogen receptor downregulators )Aromatase inhibitors Antigonadotropins Androgens /anabolic steroids (e.g.,testosterone ,testosterone esters ,nandrolone esters ,oxandrolone ,fluoxymesterone )D2 receptor antagonists (prolactin releasers) (e.g.,domperidone ,metoclopramide ,risperidone ,haloperidol ,chlorpromazine ,sulpiride )GnRH agonists (e.g.,leuprorelin ,goserelin )GnRH antagonists (e.g.,cetrorelix ,elagolix )Progestogens (e.g.,chlormadinone acetate ,cyproterone acetate ,gestonorone caproate ,hydroxyprogesterone caproate ,medroxyprogesterone acetate ,megestrol acetate )Others
ER Tooltip Estrogen receptor
Agonists Steroidal: 2-Hydroxyestradiol 2-Hydroxyestrone 3-Methyl-19-methyleneandrosta-3,5-dien-17β-ol 3α-Androstanediol 3α,5α-Dihydrolevonorgestrel 3β,5α-Dihydrolevonorgestrel 3α-Hydroxytibolone 3β-Hydroxytibolone 3β-Androstanediol 4-Androstenediol 4-Androstenedione 4-Fluoroestradiol 4-Hydroxyestradiol 4-Hydroxyestrone 4-Methoxyestradiol 4-Methoxyestrone 5-Androstenediol 7-Oxo-DHEA 7α-Hydroxy-DHEA 7α-Methylestradiol 7β-Hydroxyepiandrosterone 8,9-Dehydroestradiol 8,9-Dehydroestrone 8β-VE2 10β,17β-Dihydroxyestra-1,4-dien-3-one (DHED) 11β-Chloromethylestradiol 11β-Methoxyestradiol 15α-Hydroxyestradiol 16-Ketoestradiol 16-Ketoestrone 16α-Fluoroestradiol 16α-Hydroxy-DHEA 16α-Hydroxyestrone 16α-Iodoestradiol 16α-LE2 16β-Hydroxyestrone 16β,17α-Epiestriol (16β-hydroxy-17α-estradiol) 17α-Estradiol (alfatradiol )17α-Dihydroequilenin 17α-Dihydroequilin 17α-Epiestriol (16α-hydroxy-17α-estradiol) 17α-Ethynyl-3α-androstanediol 17α-Ethynyl-3β-androstanediol 17β-Dihydroequilenin 17β-Dihydroequilin 17β-Methyl-17α-dihydroequilenin Abiraterone Abiraterone acetate Alestramustine Almestrone Anabolic steroids (e.g.,testosterone andesters ,methyltestosterone ,metandienone (methandrostenolone) ,nandrolone andesters , many others; via estrogenic metabolites)Atrimustine Bolandiol Bolandiol dipropionate Butolame Clomestrone Cloxestradiol Conjugated estriol Conjugated estrogens Cyclodiol Cyclotriol DHEA DHEA-S ent -EstradiolEpiestriol (16β-epiestriol, 16β-hydroxy-17β-estradiol) Epimestrol Equilenin Equilin ERA-63 (ORG-37663) Esterified estrogens Estetrol Estradiol Estramustine Estramustine phosphate Estrapronicate Estrazinol Estriol Estrofurate Estrogenic substances Estromustine Estrone Etamestrol (eptamestrol) Ethinylandrostenediol Ethinylestradiol Ethinylestriol Ethylestradiol Etynodiol Etynodiol diacetate Hexolame Hippulin Hydroxyestrone diacetate Lynestrenol Lynestrenol phenylpropionate Mestranol Methylestradiol Moxestrol Mytatrienediol Nilestriol Norethisterone Noretynodrel Orestrate Pentolame Prodiame Prolame Promestriene RU-16117 Quinestradol Quinestrol Tibolone Xenoestrogens: Anise -related (e.g.,anethole ,anol ,dianethole ,dianol ,photoanethole )Chalconoids (e.g.,isoliquiritigenin ,phloretin ,phlorizin (phloridzin) ,wedelolactone )Coumestans (e.g.,coumestrol ,psoralidin )Flavonoids (incl.7,8-DHF ,8-prenylnaringenin ,apigenin ,baicalein ,baicalin ,biochanin A ,calycosin ,catechin ,daidzein ,daidzin ,ECG ,EGCG ,epicatechin ,equol ,formononetin ,glabrene ,glabridin ,genistein ,genistin ,glycitein ,kaempferol ,liquiritigenin ,mirificin ,myricetin ,naringenin ,penduletin ,pinocembrin ,prunetin ,puerarin ,quercetin ,tectoridin ,tectorigenin )Lavender oil Lignans (e.g.,enterodiol ,enterolactone ,nyasol (cis -hinokiresinol) )Metalloestrogens (e.g.,cadmium )Pesticides (e.g.,alternariol ,dieldrin ,endosulfan ,fenarimol ,HPTE ,methiocarb ,methoxychlor ,triclocarban ,triclosan )Phytosteroids (e.g.,digitoxin (digitalis ),diosgenin ,guggulsterone )Phytosterols (e.g.,β-sitosterol ,campesterol ,stigmasterol )Resorcylic acid lactones (e.g.,zearalanone ,α-zearalenol ,β-zearalenol ,zearalenone ,zeranol (α-zearalanol) ,taleranol (teranol, β-zearalanol) )Steroid -like (e.g.,deoxymiroestrol ,miroestrol )Stilbenoids (e.g.,resveratrol ,rhaponticin )Synthetic xenoestrogens (e.g.,alkylphenols ,bisphenols (e.g.,BPA ,BPF ,BPS ),DDT ,parabens ,PBBs ,PHBA ,phthalates ,PCBs )Others (e.g.,agnuside ,rotundifuran ) MixedSERMs Tooltip Selective estrogen receptor modulators ) Antagonists Coregulator-binding modulators: ERX-11
GPER Tooltip G protein-coupled estrogen receptor
Agonists Antagonists Unknown
