Chemical compound
This article is about estrone sulfate as a medication. For its role as a hormone, see
Estrone sulfate .
Estrone sulfate (medication)
Other names E1S; Oestrone sulfate; Estrone 3-sulfate; Estra-1,3,5(10)-trien-17-one 3-sulfate
Routes of administration
By mouth , others
[1]
[2]
[3]
Drug class
Estrogen ;
Estrogen ester
Protein binding 90%, to
albumin , and not to
SHBG Tooltip sex hormone-binding globulin
[4]
Metabolism
Desulfation (via
STS Tooltip steroid sulfatase )
[6]
Metabolites •
Estrone
[1] •
Estradiol
[1]
Elimination half-life 12 hours
[5]
[(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
Formula C 18 H 22 O 5 S
Molar mass 350.43 g·mol−1 3D model (
JSmol )
O=S(=O)(O)Oc1cc4c(cc1)[C@H]3CC[C@@]2(C(=O)CC[C@H]2[C@@H]3CC4)C
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
Y Key:JKKFKPJIXZFSSB-CBZIJGRNSA-N
Y
(verify)
Estrone sulfate (E1S ) is an
estrogen medication and naturally occurring
steroid hormone .
[1] It is used in
menopausal hormone therapy among other indications.
[1]
[2] As the
sodium
salt (sodium estrone sulfate), it is the major estrogen component of
conjugated estrogens (Premarin) and
esterified estrogens (Estratab, Menest).
[1]
[3] In addition, E1S is used on its own as the
piperazine salt
estropipate (piperazine estrone sulfate; Ogen).
[1]
[3] The compound also occurs as a major and important
metabolite of
estradiol and
estrone .
[1] E1S is most commonly taken
by mouth , but in the form of Premarin can also be taken by
parenteral routes such as
transdermal ,
vaginal , and
injection .
[1]
[2]
Medical uses
E1S is used in
menopausal hormone therapy among other indications.
[1]
[2]
Pharmacology
Pharmacodynamics
E1S itself is essentially
biologically inactive , with less than 1% of the
relative binding affinity of
estradiol for the
estrogen receptors (ERs),
ERα and
ERβ .
[7] The compound acts as a
prodrug of
estrone and more importantly of estradiol, the latter of which is a
potent
agonist of the ERs.
[1] Hence, E1S is an
estrogen .
[1]
Pharmacokinetics
E1S is
cleaved by
steroid sulfatase (also called estrogen sulfatase) into
estrone .
[6] Simultaneously,
estrogen sulfotransferases transform estrone back into E1S, which results in an
equilibrium between the two steroids in various tissues.
[6] 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.
[1]
[8]
[9]
When estradiol is administered
orally , it is subject to extensive
first-pass metabolism (95%) in the
intestines and
liver .
[10]
[11] A single administered dose of estradiol is
absorbed 15% as estrone, 25% as E1S, 25% as
estradiol glucuronide , and 25% as
estrone glucuronide .
[10] 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.
[10] 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.
[10]
[11] To demonstrate the importance of first-pass metabolism and the estrogen conjugate reservoir in the
pharmacokinetics of estradiol,
[10] the terminal half-life of oral estradiol is 13 to 20 hours
[12] whereas with
intravenous injection its terminal half-life is only about 1 to 2 hours.
[13]
Estrogen sulfates like estrone sulfate are about twice as
potent as the corresponding free estrogens in terms of
estrogenic effect when given
orally to rodents.
[14] This in part led to the introduction of
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
Sources and footnotes
Notes: Values are ratios, with estradiol as standard (i.e., 1.0).
Abbreviations:
HF = Clinical relief of
hot flashes .
VE = Increased
proliferation of
vaginal epithelium .
UCa = Decrease in
UCa Tooltip urinary calcium .
FSH = Suppression of
FSH Tooltip follicle-stimulating hormone levels.
LH = Suppression of
LH Tooltip luteinizing hormone levels.
HDL -
C ,
SHBG ,
CBG , and
AGT = Increase in the serum levels of these
liver proteins . Liver = Ratio of liver estrogenic effects to general/systemic estrogenic effects (hot flashes/
gonadotropins ).
Sources: See template.
unidentified
unidentified
Chemistry
E1S, also known as estrone 3-sulfate or as estra-1,3,5(10)-trien-17-one 3-sulfate, is a
naturally occurring
estrane
steroid and a
derivative of
estrone .
[15] It is an
estrogen conjugate or
ester , and is specifically the C3
sulfate
ester of estrone.
[15]
Salts of E1S include
sodium estrone sulfate and
estropipate (piperazine estrone sulfate).
[15]
[1]
[3]
The
logP of E1S is 1.4.
[16]
References
^
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. Retrieved 19 February 2018 .
^
a
b
c
d Brucker MC, King TL (8 September 2015).
Pharmacology for Women's Health . Jones & Bartlett Publishers. pp. 361–.
ISBN
978-1-284-05748-5 .
^ Buchsbaum HJ (6 December 2012).
The Menopause . Springer Science & Business Media. pp. 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 . Elsevier Health Sciences. pp. 456–.
ISBN
978-0-323-07575-6 .
^
a
b
c Falcone T, Hurd WW (22 May 2013).
Clinical Reproductive Medicine and Surgery: A Practical Guide . Springer Science & Business Media. pp. 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 (13th ed.). Elsevier Health Sciences. pp. 607–.
ISBN
978-0-323-34157-8 .
^ Greenblatt JM,
Brogan K (27 April 2016).
Integrative Therapies for Depression: Redefining Models for Assessment, Treatment and Prevention . CRC Press. pp. 198–.
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 . Springer Science & Business Media. pp. 268–.
ISBN
978-3-642-60107-1 .
^
a
b Lauritzen C, Studd JW (22 June 2005).
Current Management of the Menopause . CRC Press. pp. 364–.
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 . Springer. pp. 900–.
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 .
Further reading
Estrogens
ER Tooltip Estrogen receptor agonists
Steroidal:
Alfatradiol
Certain
androgens /
anabolic steroids (e.g.,
testosterone ,
testosterone esters ,
methyltestosterone ,
metandienone ,
nandrolone esters ) (via estrogenic metabolites)
Certain
progestins (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
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Nilestriol
Prasterone (dehydroepiandrosterone; DHEA)
Promestriene
Quinestradol
Quinestrol
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Antiestrogens
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SERMs Tooltip selective estrogen receptor modulators /
SERDs Tooltip selective estrogen receptor downregulators )
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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 ,
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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 and
esters ,
methyltestosterone ,
metandienone (methandrostenolone) ,
nandrolone and
esters , many others; via estrogenic metabolites)
Atrimustine
Bolandiol
Bolandiol dipropionate
Butolame
Clomestrone
Cloxestradiol
Conjugated estriol
Conjugated estrogens
Cyclodiol
Cyclotriol
DHEA
DHEA-S
ent -Estradiol
Epiestriol (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.,
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Pesticides (e.g.,
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dieldrin ,
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HPTE ,
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methoxychlor ,
triclocarban ,
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Phytosteroids (e.g.,
digitoxin (
digitalis ),
diosgenin ,
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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 )
Mixed (
SERMs Tooltip Selective estrogen receptor modulators ) Antagonists
Coregulator-binding modulators:
ERX-11
GPER Tooltip G protein-coupled estrogen receptor
Agonists Antagonists Unknown