Estrone sulfate (medication)

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This article is about estrone sulfate as a medication. For its role as a hormone, see Estrone sulfate.
Estrone sulfate (medication)
ファイル:Estrone sulfate.svg
ファイル:Estrone sulfate 3D ball.png
Systematic (IUPAC) name
[(8R,9S,13S,14S)-13-methyl-17-oxo-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-3-yl] hydrogen sulfate
Clinical data
Pregnancy cat. ?
Legal status ?
Routes By mouth, others[1][2][3]
Pharmacokinetic data
Protein binding 90%, to albumin, and not to SHBGTooltip sex hormone-binding globulin[4]
Metabolism Desulfation (via STSTooltip steroid sulfatase)[5]
Half-life 12 hours[6]
Identifiers
CAS number 481-97-0 YesY
438-67-5 (sodium)
7280-37-7 (piperazine)
ATC code ?
PubChem CID 3001028
IUPHAR ligand 4749
DrugBank DB04574
ChemSpider 2272513 YesY
UNII QTL48N278K YesY
ChEBI CHEBI:17474 YesY
ChEMBL CHEMBL494753 YesY
Synonyms E1S; Oestrone sulfate; Estrone 3-sulfate; Estra-1,3,5(10)-trien-17-one 3-sulfate
Chemical data
Formula C18H22O5S 
 YesY (what is this?)  (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.[7] 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][8][9]

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

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.[14] This in part led to the introduction of conjugated estrogens (Premarin), which are primarily estrone sulfate, in 1941.[14]

テンプレート:Relative oral potencies of estrogens

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.


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.[15] It is an estrogen conjugate or ester, and is specifically the C3 sulfate ester of estrone.[15] Salts of E1S include sodium estrone sulfate and estropipate (piperazine estrone sulfate).[15][1][3]

The logP of E1S is 1.4.[16]

References

  1. ↑ 以下の位置に戻る: 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 Kuhl H (8月 2005). "Pharmacology of estrogens and progestogens: influence of different routes of administration". Climacteric. 8 (Suppl 1): 3–63. doi:10.1080/13697130500148875. PMID 16112947. S2CID 24616324.
  2. ↑ 以下の位置に戻る: 2.0 2.1 2.2 2.3 "Drugs@FDA: FDA Approved Drug Products". United States Food and Drug Administration. Retrieved 19 2月 2018.
  3. ↑ 以下の位置に戻る: 3.0 3.1 3.2 3.3 Brucker MC, King TL (8 9月 2015). Pharmacology for Women's Health. Jones & Bartlett Publishers. pp. 361–. ISBN 978-1-284-05748-5.
  4. ↑ Buchsbaum HJ (6 12月 2012). The Menopause. Springer Science & Business Media. pp. 63–64. ISBN 978-1-4612-5525-3.
  5. ↑ 以下の位置に戻る: 5.0 5.1 5.2 Falcone T, Hurd WW (22 5月 2013). Clinical Reproductive Medicine and Surgery: A Practical Guide. Springer Science & Business Media. pp. 5–6. ISBN 978-1-4614-6837-0.
  6. ↑ Wecker L, Watts S, Faingold C, Dunaway G, Crespo L (1 4月 2009). Brody's Human Pharmacology. Elsevier Health Sciences. pp. 456–. ISBN 978-0-323-07575-6.
  7. ↑ Kuiper GG, Carlsson B, Grandien K, Enmark E, Häggblad J, Nilsson S, Gustafsson JA (3月 1997). "Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta". Endocrinology. 138 (3): 863–870. doi:10.1210/endo.138.3.4979. PMID 9048584.
  8. ↑ Melmed S, Polonsky KS, Larsen PR, Kronenberg HM (11 11月 2015). Williams Textbook of Endocrinology (13th ed.). Elsevier Health Sciences. pp. 607–. ISBN 978-0-323-34157-8.
  9. ↑ Greenblatt JM, Brogan K (27 4月 2016). Integrative Therapies for Depression: Redefining Models for Assessment, Treatment and Prevention. CRC Press. pp. 198–. ISBN 978-1-4987-0230-0.
  10. ↑ 以下の位置に戻る: 10.0 10.1 10.2 10.3 10.4 Oettel M, Schillinger E (6 12月 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.
  11. ↑ 以下の位置に戻る: 11.0 11.1 Lauritzen C, Studd JW (22 6月 2005). Current Management of the Menopause. CRC Press. pp. 364–. ISBN 978-0-203-48612-2.
  12. ↑ Stanczyk FZ, Archer DF, Bhavnani BR (6月 2013). "Ethinyl estradiol and 17β-estradiol in combined oral contraceptives: pharmacokinetics, pharmacodynamics and risk assessment". Contraception. 87 (6): 706–727. doi:10.1016/j.contraception.2012.12.011. PMID 23375353.
  13. ↑ Düsterberg B, Nishino Y (12月 1982). "Pharmacokinetic and pharmacological features of oestradiol valerate". Maturitas. 4 (4): 315–324. doi:10.1016/0378-5122(82)90064-0. PMID 7169965.
  14. ↑ 以下の位置に戻る: 14.0 14.1 Herr F, Revesz C, Manson AJ, Jewell JB (1970). "Biological Properties of Estrogen Sulfates". Chemical and Biological Aspects of Steroid Conjugation. Springer. pp. 368–408. doi:10.1007/978-3-642-95177-0_8. ISBN 978-3-642-95179-4.
  15. ↑ 以下の位置に戻る: 15.0 15.1 15.2 Elks J (14 11月 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 900–. ISBN 978-1-4757-2085-3.
  16. ↑ Banerjee N, Fonge H, Mikhail A, Reilly RM, Bendayan R, Allen C (2013). "Estrone-3-sulphate, a potential novel ligand for targeting breast cancers". PLOS ONE. 8 (5): e64069. Bibcode:2013PLoSO...864069B. doi:10.1371/journal.pone.0064069. PMC 3661587. PMID 23717534.

Further reading

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