ESTRIOL SUCCINATE

Possibly Marketed Outside US

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C26H32O9
Molecular Weight	488.5269
Optical Activity	UNSPECIFIED
Defined Stereocenters	6 / 6
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

C[C@]12CC[C@H]3[C@@H](CCC4=C3C=CC(O)=C4)[C@@H]1C[C@@H](OC(=O)CCC(O)=O)[C@@H]2OC(=O)CCC(O)=O

InChI

InChIKey=VBRVDDFOBZNCPF-BRSFZVHSSA-N

InChI=1S/C26H32O9/c1-26-11-10-17-16-5-3-15(27)12-14(16)2-4-18(17)19(26)13-20(34-23(32)8-6-21(28)29)25(26)35-24(33)9-7-22(30)31/h3,5,12,17-20,25,27H,2,4,6-11,13H2,1H3,(H,28,29)(H,30,31)/t17-,18-,19+,20-,25+,26+/m1/s1

HIDE SMILES / InChI

Molecular Formula	C26H32O9
Molecular Weight	488.5269
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	6 / 6
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.drugs.com/pro/estradiol.html
Curator's Comment: The description was created based on several sources, including https://clinicaltrials.gov/ct2/show/NCT02906111 | https://www.ncbi.nlm.nih.gov/pubmed/27838536 | https://clinicaltrials.gov/ct2/show/NCT02419729 | https://www.ncbi.nlm.nih.gov/pubmed/26786399 |

Estriol (E3), also spelled oestriol, is a steroid, a weak agonist of the estrogen receptors ERα and ERβ., and a minor female sex hormone. According to in vitro study, the relative binding affinity (RBA) of estriol for the human ERα and ERβ was 11.3% and 17.6% of that estradiol, respectively, and the relative transactivational capacity of estrone at the ERα and ERβ was 10.6% and 16.6% of that of estradiol, respectively. Estriol is marketed widely in Europe and elsewhere throughout the world under the brand names Ovestin, Ortho-Gynest, and a variety of others. It is available in oral tablet, vaginal cream, and vaginal suppository form, and is used in menopausal hormone therapy for the treatment of menopausal symptoms. Estriol is also available in some countries as estriol succinate (brand name Synapause), a dosage-equivalent ester prodrug of estriol. Estriol and estriol succinate are not approved for use in the United States and Canada, although they have been produced and sold by compounding pharmacies in North America for use as a component of bioidentical hormone therapy. Estriol can be measured in maternal blood or urine and can be used as a marker of fetal health and well-being. If levels of unconjugated estriol (uE3 or free estriol) are abnormally low in a pregnant woman, this may indicate chromosomal or congenital anomalies like Down syndrome or Edward's syndrome. It is included as part of the triple test and quadruple test for antenatal screening for fetal anomalies.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Estrogen receptor 72 Target ID: CHEMBL2093866 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9357533	Agonist 2752
Testis-specific androgen-binding protein 6 Target ID: CHEMBL3305 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18330978	Binding Agent 1076	234.42 nM [Kd]
Corticosteroid binding globulin 4 Target ID: CHEMBL2421 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15139751	Binding Agent 1076

Conditions

Condition	Modality	Highest Phase	Product
Genital prolapse 3 Sources: https://clinicaltrials.gov/ct2/show/NCT02906111	Primary	Phase IV 63	Ovestin Approved Use Unknown
Urinary tract infections 207 Sources: https://clinicaltrials.gov/ct2/show/NCT00900653	Primary	Phase IV 63	Ovestin Approved Use Unknown
Atrophic vaginitis 13 Sources: https://clinicaltrials.gov/ct2/show/NCT00816556	Primary	Phase III 665	Ovestin Approved Use Unknown

C_max

Value	Dose	Analyte	Population
60.57 pg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26786399/	20 μg single, vaginal dose: 20 μg route of administration: Vaginal experiment type: SINGLE co-administered:	ESTRIOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
106.4 pg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26786399/	50 μg single, vaginal dose: 50 μg route of administration: Vaginal experiment type: SINGLE co-administered:	ESTRIOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
13.77 pg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26786399/	20 μg 1 times / day steady-state, vaginal dose: 20 μg route of administration: Vaginal experiment type: STEADY-STATE co-administered:	ESTRIOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
22.8 pg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26786399/	50 μg 1 times / day steady-state, vaginal dose: 50 μg route of administration: Vaginal experiment type: STEADY-STATE co-administered:	ESTRIOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
0.546 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33129232/	0.5 mg single, vaginal dose: 0.5 mg route of administration: Vaginal experiment type: SINGLE co-administered:	ESTRIOL serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
68 pg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30480330/	0.125 mg 1 times / day multiple, vaginal dose: 0.125 mg route of administration: Vaginal experiment type: MULTIPLE co-administered:	ESTRIOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
155 pg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30480330/	0.5 mg 1 times / day multiple, vaginal dose: 0.5 mg route of administration: Vaginal experiment type: MULTIPLE co-administered:	ESTRIOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
171.65 pg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26786399/	20 μg single, vaginal dose: 20 μg route of administration: Vaginal experiment type: SINGLE co-administered:	ESTRIOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
406.75 pg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26786399/	50 μg single, vaginal dose: 50 μg route of administration: Vaginal experiment type: SINGLE co-administered:	ESTRIOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
36.33 pg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26786399/	20 μg 1 times / day steady-state, vaginal dose: 20 μg route of administration: Vaginal experiment type: STEADY-STATE co-administered:	ESTRIOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
73.71 pg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26786399/	50 μg 1 times / day steady-state, vaginal dose: 50 μg route of administration: Vaginal experiment type: STEADY-STATE co-administered:	ESTRIOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
2.145 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33129232/	0.5 mg single, vaginal dose: 0.5 mg route of administration: Vaginal experiment type: SINGLE co-administered:	ESTRIOL serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
5643 pg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30480330/	0.125 mg 1 times / day multiple, vaginal dose: 0.125 mg route of administration: Vaginal experiment type: MULTIPLE co-administered:	ESTRIOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
18323 pg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30480330/	0.5 mg 1 times / day multiple, vaginal dose: 0.5 mg route of administration: Vaginal experiment type: MULTIPLE co-administered:	ESTRIOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
1.59 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26786399/	20 μg single, vaginal dose: 20 μg route of administration: Vaginal experiment type: SINGLE co-administered:	ESTRIOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
1.65 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26786399/	50 μg single, vaginal dose: 50 μg route of administration: Vaginal experiment type: SINGLE co-administered:	ESTRIOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
2.72 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33129232/	0.5 mg single, vaginal dose: 0.5 mg route of administration: Vaginal experiment type: SINGLE co-administered:	ESTRIOL serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
10% OTHER https://www.medicines.org.uk/emc/product/10400/smpc#PHARMACOKINETIC_PROPS			ESTRIOL serum	Homo sapiens

Doses

Dose	Population	Adverse events
0.2 mg 1 times / day steady-state, vaginal Highest studied dose Dose: 0.2 mg, 1 times / day Route: vaginal Route: steady-state Dose: 0.2 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/22285095/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/22285095/	Other AEs: Vulvovaginal burning sensation, vulvovaginal burning sensation... Other AEs: Vulvovaginal burning sensation (9 patients) vulvovaginal burning sensation (5 patients) Vulvovaginal pruritus (2 patients) Vaginal discharge (1 pt) Vaginal haemorrhage (2 patients) Genital burning sensation (2 patients) Genital swelling (2 patients) Nasopharyngitis (2 patients) Application site pain (3 patients) Nausea (1 pt) Abdominal pain lower (2 patients) Diarrhea (2 patients) Nervous system disorders (1 pt) Skin and subcutaneous tissue disorders (4 patients) Renal and urinary disorders (2 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/22285095/
0.5 mg 1 times / day steady-state, vaginal Recommended Dose: 0.5 mg, 1 times / day Route: vaginal Route: steady-state Dose: 0.5 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/7493689/	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/7493689/	Sources: https://pubmed.ncbi.nlm.nih.gov/7493689/

AEs

PubMed

Title	Date	PubMed
Biochemical markers for preterm labor and birth: what is their role in the care of pregnant women?	1999 Mar-Apr	10083784
Female sex steroids: effects upon microglial cell activation.	2000 Nov 1	11063824
Clinical validation of a new dimeric inhibin-A assay suitable for second trimester Down's syndrome screening.	2001	11373844
Effect of oral estriol on urogenital symptoms, vaginal cytology, and plasma hormone level in postmenopausal women.	2001 Apr	11460966
Triple marker screening for fetal chromosomal abnormalities in Korean women of advanced maternal age.	2001 Apr	11371107
First-trimester increased nuchal translucency and fetal hypokinesia associated with Zellweger syndrome.	2001 Apr	11339194
[Effect of estriol treatment per vaginam before Burch culposuspension].	2001 Apr	11319508
Randomized comparison between orally and transdermally administered hormone replacement therapy regimens of long-term effects on 24-hour ambulatory blood pressure in postmenopausal women.	2001 Apr	11303197
Postmenopausal women with recurrent UTI.	2001 Apr	11295406
Do urinary estrogen metabolites reflect the differences in breast cancer risk between Singapore Chinese and United States African-American and white women?	2001 Apr 15	11309288
Preterm birth risk assessment.	2001 Aug	11561909
Sequential first and second trimester screening tests: correlation of the markers' levels in normal versus Down syndrome affected pregnancies.	2001 Dec	11787048
Plasma prolactin/oestradiol ratio at 38 weeks gestation predicts the duration of lactational amenorrhoea.	2001 Dec	11726571
Treatment of bitches with acquired urinary incontinence with oestriol.	2001 Dec 22-29	11808663
Estrogenic potency of chemicals detected in sewage treatment plant effluents as determined by in vivo assays with Japanese medaka (Oryzias latipes).	2001 Feb	11351429
The physiological role of estriol during human fetal development is to act as antioxidant at lipophilic milieus of the central nervous system.	2001 Jan	11133265
Evaluation of an EIA method for measuring serum levels of the estrogen metabolite 2-hydroxyestrone in adults.	2001 Jan	11090660
In vivo regulation of syndecan-3 expression in the rat uterus by 17 beta-estradiol.	2001 Jan 5	11024013
Facilitated tissue expansion with topical estriol.	2001 Jun	11405361
Mammographic breast density during hormone replacement therapy: effects of continuous combination, unopposed transdermal and low-potency estrogen regimens.	2001 Mar	11379377
[Hormone replacement therapy].	2001 Mar	11347156
Estrogens act in rat hippocampus and frontal cortex to produce rapid, receptor-mediated decreases in serotonin 5-HT(1A) receptor function.	2001 Mar	11307035
Hormone replacement therapy plus pelvic floor muscle exercise for postmenopausal stress incontinence. A randomized, controlled trial.	2001 Mar	11304861
Repellent activity of estrogenic compounds toward zoospores of the phytopathogenic fungus Aphanomyces cochlioides.	2001 Mar-Apr	11371017
Estriol improves membrane fluidity of erythrocytes by the nitric oxide-dependent mechanism: an electron paramagnetic resonance study.	2001 May	11409649
Urinary excretion pattern of catecholestrogens in preovulatory LH surge during the 4-day estrous cycle of rats.	2001 May	11407653
Effect of incorrect gestational dating on Down's syndrome and neural tube risk assessment.	2001 May	11392497
Gas chromatography-mass spectrometric determination of activity of human placental aromatase using 16alpha-hydroxyandrostenedione as a substrate.	2001 May	11379781
Biochemical screening for chromosomal disorders and neural tube defects (NTD): is adjustment of maternal alpha-fetoprotein (AFP) still appropriate in insulin-dependent diabetes mellitus (IDDM)?	2001 May	11360279
[Indications of fetal chromosome abnormalities in 1st trimester ultrasound].	2001 May 3	11392281
Reduced 11beta-hydroxysteroid dehydrogenase type 2 activity is associated with decreased birth weight centile in pregnancies complicated by asthma.	2002 Apr	11932298
Topical estrogens combined with argon plasma coagulation in the management of epistaxis in hereditary hemorrhagic telangiectasia.	2002 Mar	11913682

Patents

Sample Use Guides

In Vivo Use Guide

1 g/daily of the vaginal gel containing 50 μg of estriol (0.005%) for 3 weeks and then twice weekly for 9 weeks, for a complete cycle of treatment of 12 weeks

Route of Administration: Vaginal

In Vitro Use Guide

TNBC cell lines HCC1806, HCC70 and MDA-MB-231 were used for activity evaluation. For stimulation of TNBC cells to analyze signal transduction of GPR30, 4×106 cells were plated in culture medium into 25 cm2 -culture flasks. After attachment, cells were serum starved for 24 hours to synchronize the 17β- estradiol-starved cells in G0-phase. Serum starved cells were treated for 30 minutes either with 10^−4 M estriol or solvent (0.1% ethanol) and subsequently stimulated with 10^−8 M 17β-estradiol in 0.1% ethanol for 10 min or 20 minutes. Cells were harvested and cell pellets lysed in 100 μl Cell lytic M (Sigma, Deisendorf, Germany), supplemented with protease-inhibitor (Sigma, Deisendorf, Germany) and phosphatase-inhibitor (Sigma, Deisendorf, Germany).

Substance Class	Chemical Created by `admin` on `Mon Mar 31 17:50:48 GMT 2025` Edited by `admin` on `Mon Mar 31 17:50:48 GMT 2025`
Record UNII	AS13K2DY03
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

estriol succinate [INN]

Preferred Name

English

ESTRIOL SUCCINATE

Official Name

English

Estriol succinate [WHO-DD]

Common Name

English

ESTRIOL SUCCINATE [MART.]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C2181