Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references
Chemical compound
Estrone glucuronide, or estrone-3-D-glucuronide, is a conjugated metabolite of estrone.[1] It is formed from estrone in the liver by UDP-glucuronyltransferase via attachment of glucuronic acid and is eventually excreted in the urine by the kidneys.[1] It has much higher water solubility than does estrone.[1] Glucuronides are the most abundant estrogen conjugates and estrone glucuronide is the dominant metabolite of estradiol.[1]
When exogenous estradiol is administered orally, it is subject to extensive first-pass metabolism (95%) in the intestines and liver.[2][3] A single administered dose of estradiol is absorbed 15% as estrone, 25% as estrone sulfate, 25% as estradiol glucuronide, and 25% as estrone glucuronide.[2] 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.[2] 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.[2][3] In demonstration of the importance of first-pass metabolism and the estrogen conjugate reservoir in the pharmacokinetics of estradiol,[2] the terminal half-life of oral estradiol is 13 to 20 hours[4] whereas with intravenous injection its terminal half-life is only about 1 to 2 hours.[5]
v
t
e
Affinities and estrogenic potencies of estrogen esters and ethers at the estrogen receptors
Estrogen
Other names
RBATooltip Relative binding affinity (%)a
REP (%)b
ER
ERα
ERβ
Estradiol
E2
100
100
100
Estradiol 3-sulfate
E2S; E2-3S
?
0.02
0.04
Estradiol 3-glucuronide
E2-3G
?
0.02
0.09
Estradiol 17β-glucuronide
E2-17G
?
0.002
0.0002
Estradiol benzoate
EB; Estradiol 3-benzoate
10
1.1
0.52
Estradiol 17β-acetate
E2-17A
31–45
24
?
Estradiol diacetate
EDA; Estradiol 3,17β-diacetate
?
0.79
?
Estradiol propionate
EP; Estradiol 17β-propionate
19–26
2.6
?
Estradiol valerate
EV; Estradiol 17β-valerate
2–11
0.04–21
?
Estradiol cypionate
EC; Estradiol 17β-cypionate
?c
4.0
?
Estradiol palmitate
Estradiol 17β-palmitate
0
?
?
Estradiol stearate
Estradiol 17β-stearate
0
?
?
Estrone
E1; 17-Ketoestradiol
11
5.3–38
14
Estrone sulfate
E1S; Estrone 3-sulfate
2
0.004
0.002
Estrone glucuronide
E1G; Estrone 3-glucuronide
?
<0.001
0.0006
Ethinylestradiol
EE; 17α-Ethynylestradiol
100
17–150
129
Mestranol
EE 3-methyl ether
1
1.3–8.2
0.16
Quinestrol
EE 3-cyclopentyl ether
?
0.37
?
Footnotes:a = Relative binding affinities (RBAs) were determined via in-vitro displacement of labeled estradiol from estrogen receptors (ERs) generally of rodent uterine cytosol. Estrogen esters are variably hydrolyzed into estrogens in these systems (shorter ester chain length -> greater rate of hydrolysis) and the ER RBAs of the esters decrease strongly when hydrolysis is prevented. b = Relative estrogenic potencies (REPs) were calculated from half-maximal effective concentrations (EC50) that were determined via in-vitro β‐galactosidase (β-gal) and green fluorescent protein (GFP) production assays in yeast expressing human ERα and human ERβ. Both mammalian cells and yeast have the capacity to hydrolyze estrogen esters. c = The affinities of estradiol cypionate for the ERs are similar to those of estradiol valerate and estradiol benzoate (figure). Sources: See template page.
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t
e
Metabolic pathways of estradiol in humans
Estradiol
Estrone sulfate
Estrone glucuronide
2-Hydroxyestrone
Estrone
4-Hydroxyestrone
2-Methoxyestrone
16α-Hydroxyestrone
4-Methoxyestrone
17-Epiestriol
Estriol
16-Epiestriol
17β-HSD
EST
STS
UGT1A3 UGT1A9
CYP450
CYP450
COMT
CYP450
COMT
unidentified
17β-HSD
unidentified
Description: The metabolic pathways involved in the metabolism of estradiol and other natural estrogens (e.g., estrone, estriol) in humans. In addition to the metabolic transformations shown in the diagram, conjugation (e.g., sulfation and glucuronidation) occurs in the case of estradiol and metabolites of estradiol that have one or more available hydroxyl (–OH) groups. Sources: See template page.
^ abcd"Human Metabolome Database: Showing metabocard for Estrone glucuronide (HMDB0004483)".
^ abcdeOettel 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.
^ abLauritzen 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): 706–27. 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): 315–24. doi:10.1016/0378-5122(82)90064-0. PMID 7169965.
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