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Clinical data
Trade names Ovestin[1]
Routes of
Pharmacokinetic data
Biological half-life 5 hours[2]
CAS Number 50-27-1 YesY
ATC code G03CA04 (WHO)
G03CC06 (WHO)
PubChem CID 5756
DrugBank DB04573 YesY
ChemSpider 5553 YesY
UNII FB33469R8E YesY
KEGG C05141 YesY
ChEBI CHEBI:27974 YesY
Synonyms 16α-Hydroxyestradiol; Estra-1,3,5(10)-triene-3,16α,17β-triol
Chemical data
Formula C18H24O3
Molar mass 288.39 g·mol−1

Estriol (E3), or oestriol, also known as 16α-hydroxyestradiol or estra-1,3,5(10)-triene-3,16α,17β-triol, is one of the three main estrogens produced by the human body.


Human steroidogenesis, showing estriol at bottom right. In essence, it follows the pathway from dehydroepiandrosterone or DHEA (at left), but with a modified DHEA with an additional OH-group.

Estriol is only produced in significant amounts during pregnancy as it is made by the placenta from 16-hydroxydehydroepiandrosterone sulfate (16-OH DHEAS),[3] an androgen steroid made in the fetal liver and adrenal glands.

The human placenta produces pregnenolone and progesterone from circulating cholesterol. Pregnenolone is converted in the fetal adrenal gland into dehydroepiandrosterone (DHEA), a C19 steroid, then subsequently sulfonated to dehydroepiandrosterone sulfate (DHEAS). DHEAS is converted to 16-OH DHEAS in the fetal liver. The placenta converts 16-OH DHEAS to estriol, and is the predominant site of estriol synthesis.

Estetrol, which is the 15α-hydroxy derivative of estriol, is synthesized from estriol during pregnancy.[4]

Mechanism of action[edit]

Similarly to estradiol and estrone, estriol binds to and acts as an agonist of both of the estrogen receptors (ER), ERα and ERβ.[5] The affinities of estriol for the ERα and ERβ relative to those of estradiol are 14% and 21%, respectively.[6] As such, unlike estradiol (and estrone), estriol has preferential affinity for ERβ.[5] However, estriol is described as a relatively weak estrogen and has mixed agonist-antagonist activity at the ER; on its own, it is weakly estrogenic, but in the presence estradiol, it is antiestrogenic.[4][7] Relative to estradiol, estriol has 80-fold lower estrogenic potency while estrone has 12-fold lower estrogenic potency.[8] Estriol also acts as an antagonist of the GPER, where, conversely, estradiol acts as an agonist.[5][7][9] Estradiol increases breast cancer cell growth via activation of the GPER (in addition to the ER), and estriol has been found to inhibit estradiol-induced proliferation of triple-negative breast cancer cells through blockade of the GPER.[9]


Levels of estriol in non-pregnant women do not change much after menopause, and levels are not significantly different from levels in men. During pregnancy, estriol is the principle estrogen produced by the placenta.[7] Its levels increase 1000-fold during pregnancy,[7] while levels of estradiol and estrone each increase 100-fold.[8] Estriol circulates at levels 10 to 20 times those of other estrogens during pregnancy.[10][11] At term, the daily production of estriol by the placenta is 35 to 45 mg.[8] Postpartum women continue to produce higher levels of estriol relative to nulliparous women following pregnancy.[7]

Medical use[edit]

Estriol is marketed widely in Europe and elsewhere throughout the world under the brand names Ovestin, Ortho-Gynest, and a variety of others.[1] It is available in oral tablet, vaginal cream, and vaginal suppository form, and is used in hormone replacement therapy for menopausal symptoms.[12] Estriol is also available in some countries as estriol succinate (brand name Synapause), a dosage-equivalent ester of estriol.[1][13][14]


In pregnant women with multiple sclerosis, estriol reduces the symptoms of the disease noticeably,[15] according to researchers at UCLA's Geffen Medical School.

Estriol can be a weak or strong estrogen depending on if it is given acutely or chronically when given to immature animals, but is an antagonist when given in combination with estradiol.[16] Estriol may play a role in the development of breast cancer, but based on in vitro research, does appear to act as an antagonist to the GPER.[17] Though estriol is used as part of the primarily North American phenomenon of bioidentical hormone replacement therapy, it is not approved for use by the FDA or Health Canada. Though initial research in the 1970s suggested it could be used therapeutically as an estrogen, subsequent research failed to confirm this hypothesis.[18][19]

Use in screening[edit]

Estriol can be measured in maternal blood or urine and can be used as a marker of fetal health and wellbeing. DHEA-S is produced by the adrenal cortex of the fetus. This is converted to estriol by the placenta.

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 & quadruple test for antenatal screening for fetal anomalies.

Because many pathological conditions in a pregnant woman can cause deviations in estriol levels, these screenings are often seen as less definitive of fetal-placental health than a nonstress test. Conditions which can create false positives and false negatives in estriol testing for fetal distress include preeclampsia, anemia, and impaired kidney function.[20]

See also[edit]


  1. ^ a b c Index Nominum 2000: International Drug Directory. Taylor & Francis. January 2000. pp. 407–. ISBN 978-3-88763-075-1. 
  2. ^ Anne Colston Wentz (January 1988). Gynecologic endocrinology and infertility for the house officer. Williams & Wilkins. ISBN 978-0-683-08931-8. 
  3. ^ Raju U, Bradlow HL, Levitz M (1990). "Estriol-3-sulfate in human breast cyst fluid. Concentrations, possible origin, and physiologic implications". Ann. N. Y. Acad. Sci. 586: 83–7. doi:10.1111/j.1749-6632.1990.tb17793.x. PMID 2141460. 
  4. ^ a b Kenneth L. Becker (2001). Principles and Practice of Endocrinology and Metabolism. Lippincott Williams & Wilkins. pp. 932, 1061. ISBN 978-0-7817-1750-2. 
  5. ^ a b c Gérard Jaouen; Mich?le Salmain (20 April 2015). Bioorganometallic Chemistry: Applications in Drug Discovery, Biocatalysis, and Imaging. John Wiley & Sons. pp. 45–. ISBN 978-3-527-33527-5. 
  6. ^ Gabor M. Rubanyi; R Kauffman (2 September 2003). Estrogen and the Vessel Wall. CRC Press. pp. 8–. ISBN 978-0-203-30393-1. 
  7. ^ a b c d e Lappano, Rosamaria; Rosano, Camillo; De Marco, Paola; De Francesco, Ernestina Marianna; Pezzi, Vincenzo; Maggiolini, Marcello (2010). "Estriol acts as a GPR30 antagonist in estrogen receptor-negative breast cancer cells". Molecular and Cellular Endocrinology. 320 (1-2): 162–170. doi:10.1016/j.mce.2010.02.006. ISSN 0303-7207. 
  8. ^ a b c Susan Blackburn (14 April 2014). Maternal, Fetal, & Neonatal Physiology. Elsevier Health Sciences. pp. 39, 93. ISBN 978-0-323-29296-2. 
  9. ^ a b Girgert, Rainer; Emons, Günter; Gründker, Carsten (2014). "Inhibition of GPR30 by estriol prevents growth stimulation of triple-negative breast cancer cells by 17β-estradiol". BMC Cancer. 14 (1): 935. doi:10.1186/1471-2407-14-935. ISSN 1471-2407. 
  10. ^ Ann M. Gronowski (6 May 2004). Handbook of Clinical Laboratory Testing During Pregnancy. Springer Science & Business Media. pp. 84–. ISBN 978-1-59259-787-1. 
  11. ^ Jerome Frank Strauss; Robert L. Barbieri (13 September 2013). Yen and Jaffe's Reproductive Endocrinology. Elsevier Health Sciences. pp. 256–. ISBN 978-1-4557-2758-2. 
  12. ^ Zutshi (1 January 2005). Hormones in Obstetrics and Gynaecology. Jaypee Brothers Publishers. pp. 101–. ISBN 978-81-8061-427-9. 
  13. ^ J. Elks (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 899–. ISBN 978-1-4757-2085-3. 
  14. ^ D. Platt (6 December 2012). Geriatrics 3: Gynecology · Orthopaedics · Anesthesiology · Surgery · Otorhinolaryngology · Ophthalmology · Dermatology. Springer Science & Business Media. pp. 6–. ISBN 978-3-642-68976-5. 
  15. ^ Sicotte NL, Liva SM, Klutch R, Pfeiffer P, Bouvier S, Odesa S, Wu TC, Voskuhl RR (October 2002). "Treatment of multiple sclerosis with the pregnancy hormone estriol". Ann. Neurol. 52 (4): 421–8. doi:10.1002/ana.10301. PMID 12325070. 
  16. ^ Melamed M, Castaño E, Notides AC, Sasson S (November 1997). "Molecular and kinetic basis for the mixed agonist/antagonist activity of estriol". Mol. Endocrinol. 11 (12): 1868–78. doi:10.1210/me.11.12.1868. PMID 9369454. 
  17. ^ Lappano R, Rosano C, De Marco P, De Francesco EM, Pezzi V, Maggiolini M (May 2010). "Estriol acts as a GPR30 antagonist in estrogen receptor-negative breast cancer cells". Mol. Cell. Endocrinol. 320 (1–2): 162–70. doi:10.1016/j.mce.2010.02.006. PMID 20138962. 
  18. ^ Sites CK (March 2008). "Bioidentical hormones for menopausal therapy". Women's Health (Lond Engl). 4 (2): 163–71. doi:10.2217/17455057.4.2.163. PMID 19072518.  (free subscription required)
  19. ^ Derzko, C (2009). "Bioidentical Hormone Therapy at Menopause" (pdf). Endocrinology Rounds. 9 (6): 1–6. 
  20. ^ Pagana TJ, Pagana KD (2009). Mosby's Manual of Diagnostic and Laboratory Tests. St. Louis: Mosby. p. 240. ISBN 0-323-05747-0.