Chemistry:Estrone sulfate (medication)

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Short description: Chemical compound
Estrone sulfate (medication)
Estrone sulfate.svg
Estrone sulfate 3D ball.png
Clinical data
Other namesE1S; 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 classEstrogen; Estrogen ester
Pharmacokinetic data
MetabolismDesulfation (via STS)[5]
Metabolites• Estrone[1]
• Estradiol[1]
Elimination half-life12 hours[4]
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
ChEBI
ChEMBL
Chemical and physical data
FormulaC18H22O5S
Molar mass350.43 g·mol−1
3D model (JSmol)
  (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.[6] 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.[5] Simultaneously, estrogen sulfotransferases transform estrone back into E1S, which results in an equilibrium between the two steroids in various tissues.[5] 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][7][8]

When estradiol is administered orally, it is subject to extensive first-pass metabolism (95%) in the intestines and liver.[9][10] A single administered dose of estradiol is absorbed 15% as estrone, 25% as E1S, 25% as estradiol glucuronide, and 25% as estrone glucuronide.[9] 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.[9] 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.[9][10] To demonstrate the importance of first-pass metabolism and the estrogen conjugate reservoir in the pharmacokinetics of estradiol,[9] the terminal half-life of oral estradiol is 13 to 20 hours[11] whereas with intravenous injection its terminal half-life is only about 1 to 2 hours.[12]

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.[13] This in part led to the introduction of conjugated estrogens (Premarin), which are primarily estrone sulfate, in 1941.[13]


The image above contains clickable links
This diagram illustrates the metabolic pathways involved in the metabolism of estrogens (i.e., estradiol, estrone, and estriol) in humans.

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.[17] It is an estrogen conjugate or ester, and is specifically the C3 sulfate ester of estrone.[17] Salts of E1S include sodium estrone sulfate and estropipate (piperazine estrone sulfate).[17][1][3]

The logP of E1S is 1.4.[18]

References

  1. ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 "Pharmacology of estrogens and progestogens: influence of different routes of administration". Climacteric 8 (Suppl 1): 3–63. August 2005. doi:10.1080/13697130500148875. PMID 16112947. 
  2. ↑ 2.0 2.1 2.2 2.3 "Drugs@FDA: FDA Approved Drug Products". United States Food and Drug Administration. http://www.accessdata.fda.gov/scripts/cder/daf/. 
  3. ↑ 3.0 3.1 3.2 3.3 Pharmacology for Women's Health. Jones & Bartlett Publishers. 8 September 2015. pp. 361–. ISBN 978-1-284-05748-5. https://books.google.com/books?id=AniUCgAAQBAJ&pg=PA361. 
  4. ↑ Brody's Human Pharmacology. Elsevier Health Sciences. 1 April 2009. pp. 456–. ISBN 978-0-323-07575-6. https://books.google.com/books?id=kfsrz_-OrMQC&pg=PA456. 
  5. ↑ 5.0 5.1 5.2 Clinical Reproductive Medicine and Surgery: A Practical Guide. Springer Science & Business Media. 22 May 2013. pp. 5–6. ISBN 978-1-4614-6837-0. https://books.google.com/books?id=TAYnR1b8jRkC&pg=PA5. 
  6. ↑ "Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta". Endocrinology 138 (3): 863–870. March 1997. doi:10.1210/endo.138.3.4979. PMID 9048584. 
  7. ↑ Williams Textbook of Endocrinology (13th ed.). Elsevier Health Sciences. 11 November 2015. pp. 607–. ISBN 978-0-323-34157-8. https://books.google.com/books?id=iPIACwAAQBAJ&pg=PA607. 
  8. ↑ Integrative Therapies for Depression: Redefining Models for Assessment, Treatment and Prevention. CRC Press. 27 April 2016. pp. 198–. ISBN 978-1-4987-0230-0. https://books.google.com/books?id=GpHwCgAAQBAJ&pg=PA198. 
  9. ↑ 9.0 9.1 9.2 9.3 9.4 Estrogens and Antiestrogens II: Pharmacology and Clinical Application of Estrogens and Antiestrogen. Springer Science & Business Media. 6 December 2012. pp. 268–. ISBN 978-3-642-60107-1. https://books.google.com/books?id=wBvyCAAAQBAJ&pg=PA268. 
  10. ↑ 10.0 10.1 Current Management of the Menopause. CRC Press. 22 June 2005. pp. 364–. ISBN 978-0-203-48612-2. https://books.google.com/books?id=WD7S7677xUUC&pg=PA364. 
  11. ↑ "Ethinyl estradiol and 17β-estradiol in combined oral contraceptives: pharmacokinetics, pharmacodynamics and risk assessment". Contraception 87 (6): 706–727. June 2013. doi:10.1016/j.contraception.2012.12.011. PMID 23375353. 
  12. ↑ "Pharmacokinetic and pharmacological features of oestradiol valerate". Maturitas 4 (4): 315–324. December 1982. doi:10.1016/0378-5122(82)90064-0. PMID 7169965. 
  13. ↑ 13.0 13.1 "Biological Properties of Estrogen Sulfates". Chemical and Biological Aspects of Steroid Conjugation. Springer. 1970. pp. 368–408. doi:10.1007/978-3-642-95177-0_8. ISBN 978-3-642-95179-4. 
  14. ↑ The Menopause (Clinical Perspectives in Obstetrics and Gynecology). New York, NY: Springer Science & Business Media. 2012. p. 64. ISBN 9781461255253. https://books.google.com/books?id=z0LuBwAAQBAJ&pg=PA64%7Cdate=6#v=onepage&q&f=false. 
  15. ↑ "Pharmacology of estrogens and progestogens: influence of different routes of administration". Climacteric : the Journal of the International Menopause Society 8 Suppl 1: 3–63. August 2005. doi:10.1080/13697130500148875. PMID 16112947. 
  16. ↑ "EC 2.4.1.17 – glucuronosyltransferase and Organism(s) Homo sapiens". EC 2.4.1.17 – glucuronosyltransferase and Organism(s) Homo sapiens. Technische Universität Braunschweig. January 2018. https://www.brenda-enzymes.org/enzyme.php?ecno=2.4.1.17&Suchword=estrone&reference=&UniProtAcc=&organism%5B%5D=Homo+sapiens. Retrieved 10 August 2018. 
  17. ↑ 17.0 17.1 17.2 The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. 14 November 2014. pp. 900–. ISBN 978-1-4757-2085-3. https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA900. 
  18. ↑ "Estrone-3-sulphate, a potential novel ligand for targeting breast cancers". PLOS ONE 8 (5): e64069. 2013. doi:10.1371/journal.pone.0064069. PMID 23717534. Bibcode: 2013PLoSO...864069B. 

Further reading



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