Estradiol undecylate

Estradiol undecylate
Clinical data
Pronunciation ESS-tra-DYE-ole un-deh-sil-ate
Trade names Progynon Depot 100, Delestrec, Depogin, Primogyn Depot, Progynon Depot, Oestradiol-Retard Theramex
Routes of
administration		 Intramuscular injection[1]
ATC code G03CA03 (WHO)
Legal status
Legal status
  • ℞ (Prescription only)
Identifiers
Synonyms RS-1047, SQ-9993
CAS Number 3571-53-7
PubChem (CID) 19135
ChemSpider 18055
UNII H3N3A8MFJC
KEGG D04065
ChEMBL CHEMBL1697794
Chemical and physical data
Formula C29H44O3
Molar mass 440.658 g/mol
3D model (Jmol) Interactive image

Estradiol undecylate (INN, USAN) (brand name Progynon Depot 100, others), or estradiol undecanoate, is a synthetic, steroidal estrogen and an estrogen ester – specifically, the 17β-undecanoate ester of estradiol – which is or has been marketed in Europe, including in Germany, the Netherlands, Switzerland, and Monaco.[2][3] It acts as a prodrug of estradiol, and hence, is considered to be a natural, bioidentical form of estrogen.[4]

Medical uses

Estradiol undecylate was formerly often used in very high doses (100 mg intramuscular injection every 3 weeks or once per month)[5][6] to treat prostate cancer, but has since largely been superseded for this indication by newer agents with fewer adverse effects (e.g., gynecomastia and cardiovascular complications) like GnRH analogues and non-steroidal antiandrogens.[1][7] Along with estradiol valerate, estradiol cypionate, and estradiol benzoate, estradiol undecylate is or has been used as an intramuscular estrogen in hormone replacement therapy for transgender women.[8]

Estradiol undecylate, in combination with norethisterone acetate (at doses of 5 mg and 50 mg, respectively), was studied as a combined injectable contraceptive, but ultimately was not marketed for this purpose.[9]

Side effects

Estradiol undecylate has been used at very high dosages in the treatment of prostate cancer. At these high dosages, it has been associated with a considerable incidence of cardiovascular complications.[10] In a 6-month study of 25 patients administered 100 mg/month intramuscular estradiol undecylate for the treatment of prostate cancer, it was reported that 8 cases of severe cardiovascular complications, including 2 deaths, occurred.[10]

Pharmacology

Esters of estradiol like estradiol undecylate are readily hydrolyzed prodrugs of estradiol, but have an extended duration when administered in oil via intramuscular injection due to a depot effect afforded by their fatty acid ester moiety.[11] As prodrugs of estradiol, estradiol undecylate and other estradiol esters are estrogens.[11]

Antigonadotropic activity

A phase III clinical trial comparing high-dose intramuscular cyproterone acetate (300 mg/week) and high-dose intramuscular estradiol undecylate (100 mg/month) in the treatment of prostate cancer found that estradiol undecylate suppressed testosterone levels into the castrate range (<50 ng/dL)[12] within at least 3 months whereas testosterone levels with cyproterone acetate were significantly higher and above the castrate range even after 6 months of treatment.[5] With estradiol undecylate, testosterone levels fell from 416 ng/dL to 38 ng/mL after 3 months and to 29.6 ng/dL after 6 months, whereas with cyproterone acetate, testosterone levels fell from 434 ng/dL to 107 ng/mL at 3 months and to 102 ng/mL at 6 months.[5] In accordance, whereas estrogens are well-established as able to suppress testosterone levels into the castrate range at sufficiently high dosages,[13] progestogens like cyproterone acetate are able to decrease testosterone levels only up to an apparent maximum of around 70 to 80%.[14][15]

Pharmacokinetics

The pharmacokinetics of estradiol undecylate in humans have been studied and reported.[16][17]

Chemistry

See also: Estrogen ester

Estradiol undecylate is an estrane (C18) steroid and the C17β undecylate (or undecanoate) fatty acid ester of estradiol. It is also known as estra-1,3,5(10)-triene-3,17β-diol 17β-undecanoate. Two related estradiol esters include estradiol diundecylate and estradiol diundecylenate.

Estradiol undecylate is a relatively long-chain ester of estradiol. Its ester chain contains 11 carbon atoms. For comparison, the ester chains of estradiol acetate, estradiol valerate, and estradiol enanthate have 2, 5, and 7 carbon atoms, respectively.

History

Estradiol undecylate was developed, along with estradiol valerate, in 1954.[18]

See also

References

  1. 1 2 Christoph Zink (1 January 1988). Dictionary of Obstetrics and Gynecology. Walter de Gruyter. p. 85. ISBN 978-3-11-085727-6. Retrieved 20 May 2012.
  2. ↑ A. D. Roberts (1991). Dictionary of Steroids: Chemical Data, Structures, and Bibliographies. CRC Press. p. 415. ISBN 978-0-412-27060-4. Retrieved 20 May 2012.
  3. ↑ Index Nominum 2000: International Drug Directory. Taylor & Francis US. 2000. p. 405. ISBN 978-3-88763-075-1. Retrieved 20 May 2012.
  4. ↑ Michael Oettel; Ekkehard Schillinger (6 December 2012). Estrogens and Antiestrogens II: Pharmacology and Clinical Application of Estrogens and Antiestrogen. Springer Science & Business Media. pp. 261–. ISBN 978-3-642-60107-1.
  5. 1 2 3 Jacobi GH, Altwein JE, Kurth KH, Basting R, Hohenfellner R (1980). "Treatment of advanced prostatic cancer with parenteral cyproterone acetate: a phase III randomised trial". Br J Urol. 52 (3): 208–15. PMID 7000222.
  6. ↑ R. S. Satoskar; S. D. Bhandarkar &nirmala N. Rege (1973). Pharmacology and Pharmacotherapeutics. Popular Prakashan. pp. 934–. ISBN 978-81-7991-527-1.
  7. ↑ Ernst Mutschler; Hartmut Derendorf (1995). Drug Actions: Basic Principles and Therapeutic Aspects. CRC Press. p. 609. ISBN 978-0-8493-7774-7. Retrieved 30 January 2013.
  8. ↑ Gianna E. Israel; Donald E. Tarver; Joy Diane Shaffer (1 March 2001). Transgender Care: Recommended Guidelines, Practical Information, and Personal Accounts. Temple University Press. pp. 64–. ISBN 978-1-56639-852-7.
  9. ↑ Toppozada MK (1994). "Existing once-a-month combined injectable contraceptives". Contraception. 49 (4): 293–301. PMID 8013216.
  10. 1 2 Wenderoth, U. K.; Jacobi, G. H. (1983). "Gonadotropin-releasing hormone analogues for palliation of carcinoma of the prostate". World Journal of Urology. 1 (1): 40–48. doi:10.1007/BF00326861. ISSN 0724-4983.
  11. 1 2 Kuhl H (2005). "Pharmacology of estrogens and progestogens: influence of different routes of administration". Climacteric. 8 Suppl 1: 3–63. doi:10.1080/13697130500148875. PMID 16112947.
  12. ↑ Fabian M. Saleh (11 February 2009). Sex Offenders: Identification, Risk Assessment, Treatment, and Legal Issues. Oxford University Press, USA. pp. 176–. ISBN 978-0-19-517704-6.
  13. ↑ Muhammad A. Salam (2003). Principles & Practice of Urology: A Comprehensive Text. Universal-Publishers. pp. 684–. ISBN 978-1-58112-412-5.
  14. ↑ Wein AJ, Kavoussi LR, Novick AC, Partin AW, Peters CA (25 August 2011). Campbell-Walsh Urology: Expert Consult Premium Edition: Enhanced Online Features and Print, 4-Volume Set. Elsevier Health Sciences. pp. 2938–. ISBN 978-1-4160-6911-9.
  15. ↑ Kjeld JM, Puah CM, Kaufman B, Loizou S, Vlotides J, Gwee HM, Kahn F, Sood R, Joplin GF (1979). "Effects of norgestrel and ethinyloestradiol ingestion on serum levels of sex hormones and gonadotrophins in men". Clinical Endocrinology. 11 (5): 497–504. PMID 519881.
  16. ↑ Leyendecker, G., Geppert, G., Nocke, W., & Ufer, J. (1975). "Untersuchungen zur Pharmakokinetik von Östradiol-17β, Östradiol-benzoat, Östradiol-Valerianat un Östradiol-Undezylat bei der Frau: Der Verlauf der Konzentration von Östradiol-17β, Östron, LH und FSH im Serum.". Geburtshilfe Frauenheilk. Chicago (35): 370–374.
  17. ↑ Oriowo MA, Landgren BM, Stenström B, Diczfalusy E (1980). "A comparison of the pharmacokinetic properties of three estradiol esters". Contraception. 21 (4): 415–24. PMID 7389356. Clinical pharmacokinetic information (mainly in terms of plasma levels of estradiol) is available on the behaviour of a variety of intramuscularly administered estradiol esters such as the benzoate (3-6). valerate (6), unducelate (6) and enanthate (7). Only a few studies attempted to compare the pharmacokinetic profile of various esters; one investigation compared the profiles of estradiol benzoate, valerate and unducelate although at relatively high doses corresponding to the equivalent of 20 mg of estradiol (6). [...] The present data also indicate that the three estradiol esters never yielded elevated estradiol levels beyond 15 days following the administration of doses used therapeutically. These findings are in contrast with those reported by others (6) following the injection of large quantities (exceeding 20 mg) of estradiol valerate and benzoate. This seeming discrepancy underlines the importance of the dosage to be selected for pharmacokinetic investigations, which must be close to that intended for clinical (contraceptive) use.
  18. ↑ WIED GL (January 1954). "[Estradiol valerate and estradiol undecylate, two new estrogens with prolonged action; comparison with estradiol benzoate]". Geburtshilfe Und Frauenheilkunde. 14 (1): 45–52. PMID 13142295.


This article is issued from Wikipedia - version of the 11/27/2016. The text is available under the Creative Commons Attribution/Share Alike but additional terms may apply for the media files.