Estrone sulfate (medication)のソースを表示

{{Short description|Chemical compound}}
{{Use dmy dates|date=August 2018}}
{{About|estrone sulfate as a medication|its role as a hormone|Estrone sulfate}}
{{Drugbox
| Verifiedfields = verified
| Watchedfields = verified
| verifiedrevid = 443736791
| IUPAC_name = [(8''R'',9''S'',13''S'',14''S'')-13-methyl-17-oxo-7,8,9,11,12,14,15,16-octahydro-6''H''-cyclopenta[''a'']phenanthren-3-yl] hydrogen sulfate
| image = Estrone sulfate.svg
| width = 250px
| image2 = Estrone sulfate 3D ball.png
| width2 = 250px

<!--Clinical data-->
| tradename = 
| 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 = 
| legal_UK = 
| legal_US = 
| legal_status = 
| routes_of_administration = [[Oral administration|By mouth]], others<ref name="pmid16112947" /><ref name="Drugs@FDA" /><ref name="BruckerKing2015" />
| class = [[Estrogen (medication)|Estrogen]]; [[Estrogen ester]]

<!--Pharmacokinetic data-->
| bioavailability = 
| protein_bound = 90%, to [[human serum albumin|albumin]], and not to {{abbrlink|SHBG|sex hormone-binding globulin}}<ref name="Buchsbaum2012">{{cite book| vauthors = Buchsbaum HJ |title=The Menopause|url=https://books.google.com/books?id=z0LuBwAAQBAJ&pg=PA64|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-1-4612-5525-3|pages=63–64}}</ref>
| metabolism = [[Desulfation]] (via {{abbrlink|STS|steroid sulfatase}})<ref name="FalconeHurd2013" />
| metabolites = • [[Estrone (medication)|Estrone]]<ref name="pmid16112947" /><br />• [[Estradiol (medication)|Estradiol]]<ref name="pmid16112947" />
| elimination_half-life = 12 hours<ref name="WeckerWatts2009">{{cite book | vauthors = Wecker L, Watts S, Faingold C, Dunaway G, Crespo L |title=Brody's Human Pharmacology |url=https://books.google.com/books?id=kfsrz_-OrMQC&pg=PA456 |date=1 April 2009 |publisher=Elsevier Health Sciences |isbn=978-0-323-07575-6 |pages=456–}}</ref>
| excretion =

<!--Identifiers-->
| CAS_number_Ref = {{cascite|correct|CAS}}
| CAS_number = 481-97-0
| CAS_supplemental = <br />438-67-5 ([[sodium]])<br />7280-37-7 ([[piperazine]])
| ATC_prefix = 
| ATC_suffix = 
| PubChem = 3001028
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB04574
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 2272513
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = QTL48N278K
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 494753
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 17474
| IUPHAR_ligand = 4749
| synonyms = E1S; Oestrone sulfate; Estrone 3-sulfate; Estra-1,3,5(10)-trien-17-one 3-sulfate

<!--Chemical data-->
| C=18 | H=22 | O=5 | S=1
| SMILES = O=S(=O)(O)Oc1cc4c(cc1)[C@H]3CC[C@@]2(C(=O)CC[C@H]2[C@@H]3CC4)C
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 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
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = JKKFKPJIXZFSSB-CBZIJGRNSA-N
}}

'''Estrone sulfate''' ('''E1S''') is an [[estrogen (medication)|estrogen]] medication and naturally occurring [[steroid hormone]].<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> It is used in [[menopausal hormone therapy]] among other indications.<ref name="pmid16112947" /><ref name="Drugs@FDA" /> As the [[sodium]] [[salt (chemistry)|salt]] (sodium estrone sulfate), it is the major estrogen component of [[conjugated estrogens]] (Premarin) and [[esterified estrogens]] (Estratab, Menest).<ref name="pmid16112947" /><ref name="BruckerKing2015">{{cite book| vauthors = Brucker MC, King TL |title=Pharmacology for Women's Health|url=https://books.google.com/books?id=AniUCgAAQBAJ&pg=PA361|date=8 September 2015|publisher=Jones & Bartlett Publishers|isbn=978-1-284-05748-5|pages=361–}}</ref> In addition, E1S is used on its own as the [[piperazine]] salt [[estropipate]] (piperazine estrone sulfate; Ogen).<ref name="pmid16112947" /><ref name="BruckerKing2015" /> The compound also occurs as a major and important [[metabolite]] of [[estradiol (medication)|estradiol]] and [[estrone (medication)|estrone]].<ref name="pmid16112947" /> E1S is most commonly taken [[oral administration|by mouth]], but in the form of Premarin can also be taken by [[parenteral]] routes such as [[transdermal administration|transdermal]], [[vaginal administration|vaginal]], and [[injection (medicine)|injection]].<ref name="pmid16112947" /><ref name="Drugs@FDA">{{cite web | title = Drugs@FDA: FDA Approved Drug Products | publisher = United States Food and Drug Administration | access-date = 19 February 2018 | url = http://www.accessdata.fda.gov/scripts/cder/daf/}}</ref>

==Medical uses==
E1S is used in [[menopausal hormone therapy]] among other indications.<ref name="pmid16112947" /><ref name="Drugs@FDA" />

==Pharmacology==

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

E1S itself is essentially [[biological activity|biologically inactive]], with less than 1% of the [[relative binding affinity]] of [[estradiol (medication)|estradiol]] for the [[estrogen receptor]]s (ERs), [[ERα]] and [[ERβ]].<ref name="pmid9048584">{{cite journal | vauthors = Kuiper GG, Carlsson B, Grandien K, Enmark E, Häggblad J, Nilsson S, Gustafsson JA | title = Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta | journal = Endocrinology | volume = 138 | issue = 3 | pages = 863–870 | date = March 1997 | pmid = 9048584 | doi = 10.1210/endo.138.3.4979 | doi-access = free }}</ref> The compound acts as a [[prodrug]] of [[estrone (medication)|estrone]] and more importantly of estradiol, the latter of which is a [[potency (pharmacology)|potent]] [[agonist]] of the ERs.<ref name="pmid16112947" /> Hence, E1S is an [[estrogen (medication)|estrogen]].<ref name="pmid16112947" />

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

E1S is [[bond cleavage|cleaved]] by [[steroid sulfatase]] (also called estrogen sulfatase) into [[estrone (medication)|estrone]].<ref name="FalconeHurd2013">{{cite book| vauthors = Falcone T, Hurd WW |title=Clinical Reproductive Medicine and Surgery: A Practical Guide|url=https://books.google.com/books?id=TAYnR1b8jRkC&pg=PA5|date=22 May 2013|publisher=Springer Science & Business Media|isbn=978-1-4614-6837-0|pages=5–6}}</ref> Simultaneously, [[estrogen sulfotransferase]]s transform estrone back into E1S, which results in an [[chemical equilibrium|equilibrium]] between the two steroids in various tissues.<ref name="FalconeHurd2013" /> E1S is thought to serve both as a rapidly-acting prodrug of estradiol and also as a long-lasting reservoir of estradiol in the body, which serves to greatly extend the duration of estradiol when used as a medication.<ref name="pmid16112947" /><ref name="MelmedPolonsky2015">{{cite book | vauthors = Melmed S, Polonsky KS, Larsen PR, Kronenberg HM  |title=Williams Textbook of Endocrinology |edition=13th |url=https://books.google.com/books?id=iPIACwAAQBAJ&pg=PA607 |date=11 November 2015 |publisher=Elsevier Health Sciences |isbn=978-0-323-34157-8 |pages=607–}}</ref><ref name="GreenblattBrogan2016">{{cite book| vauthors = Greenblatt JM, Brogan K |author-link2=Kelly Brogan|title=Integrative Therapies for Depression: Redefining Models for Assessment, Treatment and Prevention|url=https://books.google.com/books?id=GpHwCgAAQBAJ&pg=PA198|date=27 April 2016|publisher=CRC Press|isbn=978-1-4987-0230-0|pages=198–}}</ref>

When estradiol is administered [[oral administration|orally]], it is subject to extensive [[first-pass metabolism]] (95%) in the [[intestine]]s and [[liver]].<ref name="OettelSchillinger2012">{{cite book| vauthors = Oettel M, Schillinger E |title=Estrogens and Antiestrogens II: Pharmacology and Clinical Application of Estrogens and Antiestrogen|url=https://books.google.com/books?id=wBvyCAAAQBAJ&pg=PA268|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-3-642-60107-1|pages=268–}}</ref><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=PA364|date=22 June 2005|publisher=CRC Press|isbn=978-0-203-48612-2|pages=364–}}</ref> A single administered dose of estradiol is [[absorption (pharmacokinetics)|absorbed]] 15% as estrone, 25% as E1S, 25% as [[estradiol glucuronide]], and 25% as [[estrone glucuronide]].<ref name="OettelSchillinger2012" /> Formation of estrogen glucuronide conjugates is particularly important with oral estradiol as the percentage of estrogen glucuronide conjugates in circulation is much higher with oral ingestion than with [[parenteral]] estradiol.<ref name="OettelSchillinger2012" /> Estrone glucuronide can be reconverted back into estradiol, and a large circulating pool of estrogen glucuronide and sulfate conjugates serves as a long-lasting reservoir of estradiol that effectively extends its [[terminal half-life]] of oral estradiol.<ref name="OettelSchillinger2012" /><ref name="LauritzenStudd2005" /> To demonstrate the importance of first-pass metabolism and the estrogen conjugate reservoir in the [[pharmacokinetics]] of estradiol,<ref name="OettelSchillinger2012" /> the terminal half-life of oral estradiol is 13 to 20&nbsp;hours<ref name="StanczykArcher2013">{{cite journal | vauthors = Stanczyk FZ, Archer DF, Bhavnani BR | title = Ethinyl estradiol and 17β-estradiol in combined oral contraceptives: pharmacokinetics, pharmacodynamics and risk assessment | journal = Contraception | volume = 87 | issue = 6 | pages = 706–727 | date = June 2013 | pmid = 23375353 | doi = 10.1016/j.contraception.2012.12.011 }}</ref> whereas with [[intravenous injection]] its terminal half-life is only about 1 to 2&nbsp;hours.<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>

Estrogen sulfates like estrone sulfate are about twice as [[potency (pharmacology)|potent]] as the corresponding free estrogens in terms of [[estrogen (medication)|estrogen]]ic effect when given [[oral administration|orally]] to rodents.<ref name="HerrRevesz1970">{{cite book| vauthors = Herr F, Revesz C, Manson AJ, Jewell JB |title=Chemical and Biological Aspects of Steroid Conjugation|chapter=Biological Properties of Estrogen Sulfates|year=1970|pages=368–408|publisher=Springer |doi=10.1007/978-3-642-95177-0_8|isbn=978-3-642-95179-4}}</ref> This in part led to the introduction of [[conjugated estrogens]] (Premarin), which are primarily estrone sulfate, in 1941.<ref name="HerrRevesz1970" />

{{Relative oral potencies of estrogens}}
{{Estradiol metabolism}}

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

E1S, also known as estrone 3-sulfate or as estra-1,3,5(10)-trien-17-one 3-sulfate, is a [[natural product|naturally occurring]] [[estrane]] [[steroid]] and a [[chemical derivative|derivative]] of [[estrone]].<ref name="Elks2014">{{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=PA900|date=14 November 2014|publisher=Springer|isbn=978-1-4757-2085-3|pages=900–}}</ref> It is an [[estrogen conjugate]] or [[estrogen ester|ester]], and is specifically the C3 [[sulfate]] [[ester]] of estrone.<ref name="Elks2014" /> [[Salt (chemistry)|Salt]]s of E1S include [[sodium estrone sulfate]] and [[estropipate]] (piperazine estrone sulfate).<ref name="Elks2014" /><ref name="pmid16112947" /><ref name="BruckerKing2015" />

The [[partition coefficient|logP]] of E1S is 1.4.<ref name="pmid23717534">{{cite journal | vauthors = Banerjee N, Fonge H, Mikhail A, Reilly RM, Bendayan R, Allen C | title = Estrone-3-sulphate, a potential novel ligand for targeting breast cancers | journal = PLOS ONE | volume = 8 | issue = 5 | pages = e64069 | date = 2013 | pmid = 23717534 | pmc = 3661587 | doi = 10.1371/journal.pone.0064069 | doi-access = free | bibcode = 2013PLoSO...864069B }}</ref>

== References ==
{{Reflist}}

== Further reading ==
{{refbegin}}
* {{cite journal | vauthors = Rezvanpour A, Don-Wauchope AC | title = Clinical implications of estrone sulfate measurement in laboratory medicine | journal = Critical Reviews in Clinical Laboratory Sciences | volume = 54 | issue = 2 | pages = 73–86 | date = March 2017 | pmid = 27960570 | doi = 10.1080/10408363.2016.1252310 | s2cid = 1825531 }}
{{refend}}

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

[[Category:Estrogens]]
[[Category:Estrone esters]]
[[Category:Human drug metabolites]]
[[Category:Phenol esters]]
[[Category:Sex hormone esters and conjugates]]
[[Category:Sulfate esters]]