Estrogen ester
An estrogen ester is an ester of an endogenous, steroidal estrogen, generally estradiol but also estrone or estriol.[1] Esterification renders these drugs into metabolically-resistant prohormones of their respective parent estrogen, improving oral bioavailability.[2] In addition, with intramuscular injection, they have improved lipophilicity, which results in a longer duration when given as a depot in oil.[1]
Estrogen esters are used in hormone replacement therapy and as hormonal contraceptives, among other indications.
The first estrogen ester to be marketed was estradiol benzoate in 1936,[3][4] which was followed by many more. The most widely used estrogen ester is estradiol valerate,[citation needed] which was first introduced in 1954.[5]
Estradiol esters
Many esters of estradiol have been marketed, including the following major esters:[6][7]
- Estradiol acetate (Femring, Femtrace, Menoring)
- Estradiol benzoate (Agofollin, Diffolisterol, Progynon-B)
- Estradiol cypionate (Depo-Estradiol, Depofemin, Estradep)
- Estradiol enanthate (Anafertin, Deladroxate, Perlutan, Topasel, all in combination with dihydroxyprogesterone acetophenide)
- Estradiol undecylate (Delestrec, Depogin, Primogyn Depot, Progynon Depot, Oestradiol-Retard Theramex)
- Estradiol valerate (Altadiol, Climaval, Deladiol, Delestrogen, Estraval, Progynon Depot, Progynova, Valergen)
- Polyestradiol phosphate (Estradurin) (an estradiol ester in polymeric form)
And the following less commonly used esters:[6][7]
- Estradiol butyrylacetate (Follikoside)
- Estradiol dienanthate (Climacteron, in combination with estradiol benzoate and testosterone esters)
- Estradiol dipropionate (Agofollin, Diovocyclin, Progynon-DP)
- Estradiol diundecylate (Estrolent)
- Estradiol diundecylenate (Etrosteron)
- Estradiol furoate (Di-Folliculine)
- Estradiol hemisuccinate (Eutocol)
- Estradiol hexahydrobenzoate (Benzo-Ginoestril, Ginestryl-15-Depot, Menodin, Tardoginestryl)
- Estradiol monopropionate (estradiol 17β-propionate) (Acrofollin, Akrofollin, Follhormon)
- Estradiol palmitate (Esmopal)
- Estradiol phenylpropionate (Dimenformon Prolongatum, Mixogen, all in combination with estradiol benzoate and/or testosterone esters)
- Estradiol pivalate (Estrotate)
- Estradiol propoxyphenylpropionate (Durovex)
- Estradiol stearate (Depofollan)
- Estradiol sulfate (a minor constituent of Premarin)
A few other estradiol esters which are notable but have not been marketed include:[7]
- Estradiol 3-propionate (not to be confused with estradiol monopropionate (estradiol 17β-propionate))
- Estradiol butyrate benzoate (estradiol 3-benzoate 17β-n-butyrate)
- Estradiol cyclooctyl acetate (E2CoA)[8]
- Estradiol decanoate (estradiol 17β-decanoate)[9]
- Estrapronicate (estradiol 3-propionate 17β-nicotinate)
- Orestrate (estradiol 3-propionate 17β-(1-cyclohexenyl) ether)
Nitrogen mustard esters
The following nitrogen mustard ester of estradiol is an alkylating antineoplastic agent and has been marketed:[6][7]
- Estramustine (Emcyt, Estracit)
The following alkylating antineoplastic nitrogen mustard esters of estradiol have not been marketed:[7]
- Alestramustine (estradiol 3-(bis(2-chloroethyl)carbamate), 17-ester with L-alanine)
- Atrimustine (KM-2210; bestrabucil, busramustine)
- Estradiol mustard (NSC-112259; chlorphenacyl estradiol diester)
- Estromustine (Leo 271 f; estrone 17β-3-N-bis(2-chloroethyl)carbamate, estrone-cytostatic complex)
Estrone esters
Esters of estrone that have been marketed include:[6][7]
- Estrone acetate (Hovigal)
- Estrone sulfate (as the primary component of Premarin)
- Estropipate (Ogen, Ortho-Est) (a salt of estrone sulfate and piperazine)
- Estrone tetraacetylglucoside (Glucovex, Glycovex)
Other estrone esters which are notable but have not been marketed include:
Estriol esters
Esters of estriol that have been marketed include:[6][7]
- Estriol diacetate benzoate (Holin-Depot)
- Estriol succinate (Sinapause, Styptanon, Synapause)
- Estriol sodium succinate (Pausan, Styptanon)
- Estriol tripropionate (Estriel)
The following ester of estriol was never marketed:
Esters of other estrogens
The following esters of other estrogens exist and have been marketed:[6]
- Cloxestradiol acetate (Genovul) – the O,O-diacetate ester of cloxestradiol
- Ethinyl estradiol sulfonate (Turisteron) – the 3-isopropylsulfonate ester of ethinyl estradiol
- Hydroxyestrone diacetate (Colpoginon, Colpormon, Hormobion, Hormocervix) – the 3,16α-diacetate ester of 16α-hydroxyestrone
Estrogen ethers
A number of estrogen ethers also exist and have been marketed, including:[10][6]
- Clomestrone (Arterolo, Atheran, Colesterel, Iposclerone, Liprotene, Persclerol) – the 3-methyl ether of the 16α-chlorinated derivative of estrone
- Mestranol (Devocin, Ovastol, Tranel) (component of Enovid, Enavid, Ortho-Novin, Femigen, Norbiogest) – the 3-methyl ether of ethinyl estradiol
- Moxestrol (Surestryl) – the 11-methyl ether of the 11β-methyl derivative of ethinyl estradiol
- Nilestriol (Wei Ni An) – the 3-cyclopentyl ether of ethinyl estriol
- Promestriene (Colpotrofin, Colpotrophine, Delipoderm) – the 3-propyl and 17β-methyl diether of estradiol
- Quinestradol (Colpovis, Colpovister, Pentovis) – the 3-cyclopentyl ether of estriol
- Quinestrol (Agalacto-Quilea, Basaquines, Eston, Estrovis, Estrovister, Plestrovis, Qui-lea) – the 3-cyclopentyl ether of ethinyl estradiol
A few other estrogen ethers which are notable but have not been marketed include:[10]
- Mytatrienediol – the 3-methyl ether of the 16α-methylated derivative of 16β-epiestriol
- Orestrate – the 17β-(1-cyclohexenyl) ether of estradiol 3-propionate
See also
- Steroid ester
- Progestogen ester
- Androgen ester
- List of steroidal estrogens
- Conjugated estrogen
- Esterified estrogen
References
- ^ a b R. S. Satoskar; S. D. Bhandarkar &nirmala N. Rege (1969). Pharmacology And Pharmacotherapeutics (New Revised 21 St Ed.). Popular Prakashan. p. 24. ISBN 978-81-7991-527-1. Retrieved 29 May 2012.
- ^ Gordon L. Amidon; Ping I. Lee; Elizabeth M. Topp (2000). Transport Processes in Pharmaceutical Systems. CRC Press. pp. 188–189. ISBN 978-0-8247-6610-8. Retrieved 29 May 2012.
- ^ Enrique Raviña; Hugo Kubinyi (16 May 2011). The Evolution of Drug Discovery: From Traditional Medicines to Modern Drugs. John Wiley & Sons. p. 175. ISBN 978-3-527-32669-3. Retrieved 20 May 2012.
- ^ Folley SJ (December 1936). "The effect of oestrogenic hormones on lactation and on the phosphatase of the blood and milk of the lactating cow" (PDF). The Biochemical Journal. 30 (12): 2262–72. PMC 1263335. PMID 16746289.
- ^ William Andrew Publishing (22 October 2013). Pharmaceutical Manufacturing Encyclopedia, 3rd Edition. Elsevier. pp. 1477–. ISBN 978-0-8155-1856-3.
- ^ a b c d e f g Index Nominum 2000: International Drug Directory. Taylor & Francis US. 2000. p. 404. ISBN 978-3-88763-075-1. Retrieved 29 May 2012.
- ^ a b c d e f g 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.
- ^ Dahlgren E, Crona N, Janson PO, Samsioe G (1985). "Oral replacement with estradiol-cyclooctyl acetate: a new estradiol analogue. Effects on serum lipids, proteins, gonadotrophins, estrogens and uterine endometrial morphology". Gynecol. Obstet. Invest. 20 (2): 84–90. PMID 3932144.
- ^ Luisi M, Kicovic PM, Alicicco E, Franchi F (1978). "Effects of estradiol decanoate in ovariectomized women". J. Endocrinol. Invest. 1 (2): 101–6. doi:10.1007/BF03350355. PMID 755846.
- ^ a b J. Elks (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. ISBN 978-1-4757-2085-3.