Estriol succinate

Estriol succinate
Clinical data
Trade names Synapause, others
Synonyms Oestriol succinate; Estriol disuccinate; Estriol hemisuccinate; Estriol 16α,17β-di(hydrogen succinate)
Routes of
administration		 By mouth, vaginal[1]
Drug class Estrogen; Estrogen ester
Identifiers
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEBI
Chemical and physical data
Formula C26H32O9
Molar mass 488.533 g/mol
3D model (JSmol)

Estriol succinate, sold under the brand name Synapause among others, is an estrogen medication which is used in the treatment of menopausal symptoms.[1] It is taken by mouth, in through the vagina, and by injection.[1][2][3]

Medical uses

Estriol succinate is used in menopausal hormone therapy in the treatment and prevention of menopausal symptoms such as hot flashes, vaginal atrophy, and osteoporosis.[1] Unlike other estrogens, depending on how it is used (i.e., how often it is taken and at what dosage), estriol succinate may not require concomitant therapy with a progestogen to prevent endometrial hyperplasia and endometrial cancer in women with intact uteruses.[1]

Available forms

Estriol succinate is and has been available in the form of 2 and 4 mg oral tablets, as a 0.1% vaginal cream, and as a 20 mg vial for use by injection.[2][3]

Side effects

Pharmacology

Estriol succinate is an estrogen ester, specifically, an ester of estriol, and acts as a prodrug of estriol in the body.[4][1] It is described as a weak estrogen in comparison to estradiol valerate.[1][5] Estriol succinate is used medically via oral and vaginal routes similarly to estriol.[1] In estriol succinate, two of the hydroxyl groups of estriol, those at the C16α and C17β positions, are esterified with succinic acid.[1] As such, a dose of 2 mg estriol succinate is equivalent to 1.18 mg unconjugated estriol.[1] Unlike other estrogen esters, such as estradiol valerate, estriol succinate is nearly not hydrolyzed in the intestinal mucosa, and in relation to this, is absorbed more slowly than is estriol.[1] Instead of in the gastrointestinal tract, estriol succinate is cleaved into estriol mainly in the liver.[1] After a single 8 mg oral dose of estriol succinate, maximum levels of circulating estriol of 40 pg/mL are attained within 12 hours, and this increases up to 80 pg/mL with continued daily administration.[1]

Oral potencies of estrogens
EstrogenTypeEPD
(mg/14 days)		EPD
(mg/day)		MSD
(mg/14 days)		MSD
(mg/day)
Estradiol (micronized)Bioidentical604.314–281.0–2.0
Estradiol valerateBioidentical604.314–281.0–2.0
EstriolBioidentical140–150a10.0–10.7a28–842.0–6.0
Estriol succinateBioidentical140–150a10.0–10.7a28–842.0–6.0
Conjugated estrogensNatural604.38.4–17.50.6–1.25
EthinylestradiolSynthetic1.0–1.50.071–0.110.280.02
MestranolSynthetic1.5–1.80.11–0.130.350.025
QuinestrolSynthetic2.0–4.00.14–0.29NDND
DiethylstilbestrolSynthetic20–301.4–2.1NDND
Diethylstilbestrol dipropionateSynthetic15–201.1–1.4NDND
Dienestrol diacetateSynthetic40–602.9–4.3NDND
Addendum: The ovulation-inhibiting dose (OID) of ethinylestradiol is 0.1 mg/day.[6] Footnotes: a = Taken in divided doses three times per day. Abbreviations: EPD = Endometrial proliferation dose. MSD = Menopausal substitution dose. Miscellaneous: Direct link to table. Sources: [7][8][9][10]

Chemistry

Estriol succinate, also known as estriol disuccinate or as estriol 16α,17β-di(hydrogen succinate), is a synthetic estrane steroid and a derivative of estriol.[4][11][12] It is specifically the C16α and C17β disuccinate ester of estriol.[4][11][12][1] The medication is provided both as estriol succinate and as estriol sodium succinate, the sodium salt.[4][11] Other marketed estriol esters besides estriol succinate include estriol acetate benzoate and estriol tripropionate, whereas estriol dihexanoate, estriol dipropionate, and estriol triacetate are estriol esters that were never marketed.[4][11] Quinestradol is an estriol ether and has also been marketed.[4][11]

History

Estriol succinate was introduced for medical use in 1966.[13]

Society and culture

Generic names

Estriol succinate is the generic name of the drug and its INN and BAN.[4][11][14][12][13] Other synonyms include oestriol succinate, estriol disuccinate, and estriol hemisuccinate.[4][11][14][12] When provided as the sodium salt, estriol succinate is known as estriol sodium succinate (BAN) or as oestriol sodium succinate.[4][11]

Brand names

Estriol succinate has been marketed under brand names including Blissel, Evalon, Gelistrol, Hemostyptanon, Orgastyptin, Ovestin, Sinapause, Styptanon, Synapsa, Synapasa, Synapausa, and Synapause, among others.[4][11][14][12] Estriol sodium succinate has been marketed specifically under the brand names Pausan and Styptanon.[4][11]

Availability

Estriol succinate is or has been marketed in Europe, Hong Kong, and Mexico.[11][12]

Research

Estriol succinate was under development for the treatment of multiple sclerosis in the United States and worldwide, and reached phase II clinical trials for this indication, but development was discontinued due to insufficient effectiveness.[15] It had the tentative brand name Trimesta.[15]

References

  1. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Kuhl H (2005). "Pharmacology of estrogens and progestogens: influence of different routes of administration" (PDF). Climacteric. 8 Suppl 1: 3–63. doi:10.1080/13697130500148875. PMID 16112947.
  2. 1 2 R. S. Satoskar; S. D. Bhandarkar &nirmala N. Rege (1973). Pharmacology and Pharmacotherapeutics. Popular Prakashan. pp. 934–. ISBN 978-81-7991-527-1.
  3. 1 2 Axel Kleemann; Jürgen Engel (2001). Pharmaceutical substances: syntheses, patents, applications. Thieme. p. 786. ISBN 978-3-13-558404-1.
  4. 1 2 3 4 5 6 7 8 9 10 11 J. Elks (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. p. 899. ISBN 978-1-4757-2085-3.
  5. ↑ Winnifred Berg Cutler; Celso-Ramón García (1984). The medical management of menopause and premenopause: their endocrinologic basis. Lippincott Williams & Wilkins. p. 31. ISBN 978-0-397-50631-6.
  6. ↑ N. Rietbrock; A.H. Staib; D. Loew (11 March 2013). Klinische Pharmakologie: Arzneitherapie. Springer-Verlag. pp. 426–. ISBN 978-3-642-57636-2.
  7. ↑ Lauritzen C (September 1990). "Clinical use of oestrogens and progestogens". Maturitas. 12 (3): 199–214. doi:10.1016/0378-5122(90)90004-P. PMID 2215269.
  8. ↑ Alfred S. Wolf; H.P.G. Schneider (12 March 2013). Östrogene in Diagnostik und Therapie. Springer-Verlag. pp. 78–. ISBN 978-3-642-75101-1.
  9. ↑ Gunther Göretzlehner; Christian Lauritzen; Thomas Römer; Winfried Rossmanith (1 January 2012). Praktische Hormontherapie in der Gynäkologie. Walter de Gruyter. pp. 44–. ISBN 978-3-11-024568-4.
  10. ↑ Karl Knörr; Fritz K. Beller; Christian Lauritzen (17 April 2013). Lehrbuch der Gynäkologie. Springer-Verlag. pp. 212–213. ISBN 978-3-662-00942-0.
  11. 1 2 3 4 5 6 7 8 9 10 11 Index Nominum 2000: International Drug Directory. Taylor & Francis. January 2000. pp. 407–. ISBN 978-3-88763-075-1.
  12. 1 2 3 4 5 6 https://www.drugs.com/international/estriol.html
  13. 1 2 William Andrew Publishing (22 October 2013). Pharmaceutical Manufacturing Encyclopedia, 3rd Edition. Elsevier. pp. 1481–. ISBN 978-0-8155-1856-3.
  14. 1 2 3 I.K. Morton; Judith M. Hall (6 December 2012). Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Science & Business Media. pp. 114–. ISBN 978-94-011-4439-1.
  15. 1 2 https://adisinsight.springer.com/drugs/800026520


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