Chemical compound
This article is about estrone sulfate as a medication. For its role as a hormone, see
Estrone sulfate .
Pharmaceutical compound
Estrone sulfate (medication) Clinical data Other names E1S; Oestrone sulfate; Estrone 3-sulfate; Estra-1,3,5(10)-trien-17-one 3-sulfate Routes of By mouth , others[ 1] [ 2] [ 3] Drug class Estrogen ;Estrogen ester Pharmacokinetic dataProtein binding 90%, toalbumin , and not toSHBG Tooltip sex hormone-binding globulin [ 4] Metabolism Desulfation (viaSTS Tooltip steroid sulfatase )[ 6] Metabolites •Estrone [ 1] Estradiol [ 1] Eliminationhalf-life 12 hours[ 5] Identifiers [(8R ,9S ,13S ,14S )-13-methyl-17-oxo-7,8,9,11,12,14,15,16-octahydro-6H -cyclopenta[a ]phenanthren-3-yl] hydrogen sulfate
CAS Number PubChem CID IUPHAR/BPS DrugBank ChemSpider UNII ChEBI ChEMBL Chemical and physical data Formula C 18 H 22 O 5 S Molar mass −1 3D model (JSmol ) InChI=1S/C18H22O5S/c1-18-9-8-14-13-5-3-12(23-24(20,21)22)10-11(13)2-4-15(14)16(18)6-7-17(18)19/h3,5,10,14-16H,2,4,6-9H2,1H3,(H,20,21,22)/t14-,15-,16+,18+/m1/s1
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Estrone sulfate (E1S ) is anestrogen medication and naturally occurringsteroid hormone .[ 1] menopausal hormone therapy among other indications.[ 1] [ 2] sodium salt (sodium estrone sulfate), it is the major estrogen component ofconjugated estrogens (Premarin) andesterified estrogens (Estratab, Menest).[ 1] [ 3] piperazine saltestropipate (piperazine estrone sulfate; Ogen).[ 1] [ 3] metabolite ofestradiol andestrone .[ 1] by mouth , but in the form of Premarin can also be taken byparenteral routes such astransdermal ,vaginal , andinjection .[ 1] [ 2]
E1S is used inmenopausal hormone therapy among other indications.[ 1] [ 2]
E1S itself is essentiallybiologically inactive , with less than 1% of therelative binding affinity ofestradiol for theestrogen receptors (ERs),ERα andERβ .[ 7] prodrug ofestrone and more importantly of estradiol, the latter of which is apotent agonist of the ERs.[ 1] estrogen .[ 1]
E1S iscleaved bysteroid sulfatase (also called estrogen sulfatase) intoestrone .[ 6] estrogen sulfotransferases transform estrone back into E1S, which results in anequilibrium between the two steroids in various tissues.[ 6] [ 1] [ 8] [ 9]
When estradiol is administeredorally , it is subject to extensivefirst-pass metabolism (95%) in theintestines andliver .[ 10] [ 11] absorbed 15% as estrone, 25% as E1S, 25% asestradiol glucuronide , and 25% asestrone glucuronide .[ 10] parenteral estradiol.[ 10] terminal half-life of oral estradiol.[ 10] [ 11] pharmacokinetics of estradiol,[ 10] [ 12] intravenous injection its terminal half-life is only about 1 to 2 hours.[ 13]
Estrogen sulfates like estrone sulfate are about twice aspotent as the corresponding free estrogens in terms ofestrogenic effect when givenorally to rodents.[ 14] conjugated estrogens (Premarin), which are primarily estrone sulfate, in 1941.[ 14]
Relative oral potencies of estrogens Estrogen HF Tooltip Hot flashes VE Tooltip Vaginal epithelium UCa Tooltip Urinary calcium FSH Tooltip Follicle-stimulating hormone LH Tooltip Luteinizing hormone HDL Tooltip High-density lipoprotein -C Tooltip Cholesterol SHBG Tooltip Sex hormone-binding globulin CBG Tooltip Corticosteroid-binding globulin AGT Tooltip Angiotensinogen Liver Estradiol 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 Estrone ? ? ? 0.3 0.3 ? ? ? ? ? Estriol 0.3 0.3 0.1 0.3 0.3 0.2 ? ? ? 0.67 Estrone sulfate ? 0.9 0.9 0.8–0.9 0.9 0.5 0.9 0.5–0.7 1.4–1.5 0.56–1.7 Conjugated estrogens 1.2 1.5 2.0 1.1–1.3 1.0 1.5 3.0–3.2 1.3–1.5 5.0 1.3–4.5 Equilin sulfate ? ? 1.0 ? ? 6.0 7.5 6.0 7.5 ? Ethinylestradiol 120 150 400 60–150 100 400 500–600 500–600 350 2.9–5.0 Diethylstilbestrol ? ? ? 2.9–3.4 ? ? 26–28 25–37 20 5.7–7.5
E1S, also known as estrone 3-sulfate or as estra-1,3,5(10)-trien-17-one 3-sulfate, is anaturally occurring estrane steroid and aderivative ofestrone .[ 15] estrogen conjugate orester , and is specifically the C3sulfate ester of estrone.[ 15] Salts of E1S includesodium estrone sulfate andestropipate (piperazine estrone sulfate).[ 15] [ 1] [ 3]
ThelogP of E1S is 1.4.[ 16]
^a b c d e f g h i j k l m n 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 "Drugs@FDA: FDA Approved Drug Products" . United States Food and Drug Administration. Retrieved19 February 2018 .^a b c d Brucker MC, King TL (8 September 2015).Pharmacology for Women's Health ISBN 978-1-284-05748-5 ^ Buchsbaum HJ (6 December 2012).The Menopause 63– 64.ISBN 978-1-4612-5525-3 ^ Wecker L, Watts S, Faingold C, Dunaway G, Crespo L (1 April 2009).Brody's Human Pharmacology ISBN 978-0-323-07575-6 ^a b c Falcone T, Hurd WW (22 May 2013).Clinical Reproductive Medicine and Surgery: A Practical Guide 5– 6.ISBN 978-1-4614-6837-0 ^ Kuiper GG, Carlsson B, Grandien K, Enmark E, Häggblad J, Nilsson S, Gustafsson JA (March 1997)."Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta" .Endocrinology .138 (3):863– 870.doi :10.1210/endo.138.3.4979 PMID 9048584 . ^ Melmed S, Polonsky KS, Larsen PR, Kronenberg HM (11 November 2015).Williams Textbook of Endocrinology ISBN 978-0-323-34157-8 ^ Greenblatt JM,Brogan K (27 April 2016).Integrative Therapies for Depression: Redefining Models for Assessment, Treatment and Prevention ISBN 978-1-4987-0230-0 ^a b c d e Oettel M, Schillinger E (6 December 2012).Estrogens and Antiestrogens II: Pharmacology and Clinical Application of Estrogens and Antiestrogen ISBN 978-3-642-60107-1 ^a b Lauritzen C, Studd JW (22 June 2005).Current Management of the Menopause ISBN 978-0-203-48612-2 ^ Stanczyk FZ, Archer DF, Bhavnani BR (June 2013). "Ethinyl estradiol and 17β-estradiol in combined oral contraceptives: pharmacokinetics, pharmacodynamics and risk assessment".Contraception .87 (6):706– 727.doi :10.1016/j.contraception.2012.12.011 .PMID 23375353 . ^ 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 . ^a b Herr F, Revesz C, Manson AJ, Jewell JB (1970). "Biological Properties of Estrogen Sulfates".Chemical and Biological Aspects of Steroid Conjugation . Springer. pp. 368– 408.doi :10.1007/978-3-642-95177-0_8 .ISBN 978-3-642-95179-4 ^a b c Elks J (14 November 2014).The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies ISBN 978-1-4757-2085-3 ^ Banerjee N, Fonge H, Mikhail A, Reilly RM, Bendayan R, Allen C (2013)."Estrone-3-sulphate, a potential novel ligand for targeting breast cancers" .PLOS ONE .8 (5) e64069.Bibcode :2013PLoSO...864069B .doi :10.1371/journal.pone.0064069 PMC 3661587 PMID 23717534 .
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
