Estradiol esters
Marketed
Many esters of estradiol have been marketed, including the following major esters:[1][2]
- Estradiol acetate (Femring, Femtrace, Menoring)
- Estradiol benzoate (Agofollin Depot, Progynon-B; Duogynon, Primosiston, Sistocyclin)
- Estradiol cypionate (Depo-Estradiol, Depofemin, Estradep; Cyclofem, Lunelle)
- Estradiol dipropionate (Agofollin, Di-Ovocyclin, Progynon-DP; EP Hormone Depot)
- Estradiol enantate (Perlutal, Topasel, Unalmes, Yectames)
- Estradiol undecylate (Delestrec, Progynon Depot)
- Estradiol valerate (Delestrogen, Progynon Depot, Progynova; Gravibinon, Mesigyna, Mesygest)
- Polyestradiol phosphate (Estradurin) (an estradiol ester in polymeric form)
And the following less commonly used esters:[1][2]
- Cloxestradiol acetate (Genovul; diacetate ester of cloxestradiol, or estradiol 17β-chloral hemiacetal ether)
- Estradiol benzoate butyrate (Redimen, Soluna, Unijab, Unimens)
- Estradiol butyrylacetate (Follikoside)
- Estradiol dibutyrate (Triormon Depositum)
- Estradiol dienantate (Climacteron, Lactimex, Lactostat)
- Estradiol diundecylate (Estrolent; Trioestrine Retard)
- Estradiol diundecylenate (Etrosteron)
- Estradiol furoate (Di-Folliculine)
- Estradiol hemisuccinate (Eutocol; Hosterona)
- Estradiol hemihydrate (Estrofem)
- Estradiol hexahydrobenzoate (Benzo-Ginoestril A.P., BenzoGynoestryl Retard, Ginestryl-15-Depot, Menodin, Tardoginestryl)
- Estradiol palmitate (Esmopal)
- Estradiol phenylpropionate (Dimenformon Prolongatum; Estandron Prolongatum, Lynandron Prolongatum, Mixogen)
- Estradiol pivalate (Estrotate; Estrotate with Progesterone)
- Estradiol propionate (estradiol 17β-propionate) (Acrofollin, Akrofollin, Follhormon)
- Estradiol propoxyphenylpropionate (Durovex)
- Estradiol stearate (Depofollan)
- Estradiol sulfate (a minor constituent of conjugated estrogens (Premarin))
The following nitrogen mustard ester of estradiol is a cytostatic antineoplastic agent and has been marketed:[1][2]
Never marketed
A number of other estradiol esters which have not been marketed include:[2]
The following cytostatic antineoplastic nitrogen mustard esters of estradiol have not been marketed:[2]
Estrone esters
Marketed
Esters of estrone that have been marketed include:[1][2]
Never marketed
Other estrone esters which are notable but have not been marketed include:
Estriol esters
Marketed
Esters of estriol that have been marketed include:[1][2]
Never marketed
The following ester of estriol was never marketed:
Esters of other steroidal estrogens
Marketed
The following esters of other estrogens exist and have been marketed:[1]
Marketed
A number of estrogen ethers also exist and have been marketed, including:[22][1]
- Clomestrone (Arterolo, Atheran, Colesterel, Iposclerone, Liprotene, Persclerol) – the 3-methyl ether of 16α-chloroestrone
- Cloxestradiol acetate (Genovul) – the O,O-diacetate ester of cloxestradiol (estradiol 17β-chloral hemiacetal ether)
- Mestranol (Devocin, Ovastol, Tranel) (component of Enovid, Enavid, Ortho-Novin, Femigen, Norbiogest) – the 3-methyl ether of ethinylestradiol
- Moxestrol (Surestryl) – the 11β-methoxy derivative of ethinylestradiol (and hence the 11β-methyl ether of the 11β-hydroxyl derivative of ethinylestradiol)
- Nilestriol (Wei Ni An) – the 3-cyclopentyl ether of ethinylestriol
- 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 ethinylestradiol
Never marketed
A few other estrogen ethers which are notable but have not been marketed include:[22]
Diethylstilbestrol esters
Marketed
Major esters of diethylstilbestrol include:
- Diethylstilbestrol dipropionate (Agostilben, Biokeral, Clinestrol, Cyclen, Estilbin, Estril, Neobenzoestrol, Orestol, Oroestrol, Ostregenin, Prostilbene, Stilbestriol DP, Stilboestrolum Dipropionicum, Stilboestrol, Synestrin, Willestrol)
- Fosfestrol (diethylstilbestrol diphosphate) (Honvan, Difostilben, Fosfostilben, Fostrolin, Stilbol, Stilphostrol, Vagestrol)
Less commonly used esters of diethylstilbestrol include:
Never marketed
As well as the following nitrogen mustard ester:
- ICI-85966 (Stilbostat; diethylstilbestrol bis(di(2-chloroethyl)carbamate))
Hexestrol esters
Never marketed
The following nitrogen mustard ester of hexestrol was never marketed:
- Phenestrol (fenestrol; hexestrol bis[4-[bis(2-chloroethyl)amino]phenylacetate)
Esters of other nonsteroidal estrogens
Diethylstilbestrol
Marketed
- Diethylstilbestrol monobenzyl ether (benzelstilbestrol) (Monozol, Hypantin, Pituitrope)
- Dimestrol (dianisylhexene, diethylstilbestrol dimethyl ether, dimethoxydiethylstilbestrol) (Depot-Ostromon, Synthila)
- Mestilbol (diethylstilbestrol monomethyl ether) (Monomestro or Monomestrol)
Ferin, J. (1952). "Relative duration of action of natural and synthetic estrogens administered parenterally in women with estrogen deficiency". The Journal of Clinical Endocrinology & Metabolism. 12 (1): 28–35. doi:10.1210/jcem-12-1-28. ISSN 0021-972X. PMID 14907837. Elger W, Wyrwa R, Ahmed G, Meece F, Nair HB, Santhamma B, Killeen Z, Schneider B, Meister R, Schubert H, Nickisch K (January 2017). "Estradiol prodrugs (EP) for efficient oral estrogen treatment and abolished effects on estrogen modulated liver functions". J. Steroid Biochem. Mol. Biol. 165 (Pt B): 305–311. doi:10.1016/j.jsbmb.2016.07.008. PMID 27449818. S2CID 26650319. Ahmed G, Elger W, Meece F, Nair HB, Schneider B, Wyrwa R, Nickisch K (October 2017). "A prodrug design for improved oral absorption and reduced hepatic interaction". Bioorg. Med. Chem. 25 (20): 5569–5575. doi:10.1016/j.bmc.2017.08.027. PMID 28886996. Nickisch, K., Santhamma, B., Ahmed, G., Meece, F., Elger, W., Wyrwa, R., & Nair, H. (2017). U.S. Patent No. 9,745,338. Washington, DC: U.S. Patent and Trademark Office. https://patents.google.com/patent/US9745338B2/en Vizzone, A.; Murari, G. (November 1966). "[Estradiol esters (3-monobenzoate and 3-benzoate-17-beta-acetate) in the therapy of the surgical menopause syndrome. Experimental and clinical results]". Quaderni di Clinica Ostetrica e Ginecologica. 21 (11): 779–790. PMID 5999221. Lokind, Kenneth B.; Lorenzen, Finn Hjort; Bundgaard, Hans (1991). "Oral bioavailability of 17β-estradiol and various ester prodrugs in the rat". International Journal of Pharmaceutics. 76 (1–2): 177–182. doi:10.1016/0378-5173(91)90356-S. ISSN 0378-5173. Falconi G, Galletti F, Celasco G, Gardi R (November 1972). "Oral long-lasting estrogenic activity of estradiol 3-benzoate 17-cyclooctenyl ether". Steroids. 20 (5): 627–38. doi:10.1016/0039-128X(72)90020-7. PMID 4654978. 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. doi:10.1159/000298978. PMID 3932144. Gleason CH, Parker JM (1959). "The duration of activity of the benziloyl hydrazones of testosterone-17-heptanoate, estrone-3-heptanoate and 17α-hydroxy-progesterone-17-heptanoate". Endocrinology. 65 (3): 508–511. doi:10.1210/endo-65-3-508. ISSN 0013-7227. PMID 13828402. Elger W, Palme HJ, Schwarz S (April 1998). "Novel oestrogen sulfamates: a new approach to oral hormone therapy". Expert Opin Investig Drugs. 7 (4): 575–89. doi:10.1517/13543784.7.4.575. PMID 15991994. Elger W, Schwarz S, Hedden A, Reddersen G, Schneider B (December 1995). "Sulfamates of various estrogens are prodrugs with increased systemic and reduced hepatic estrogenicity at oral application". J. Steroid Biochem. Mol. Biol. 55 (3–4): 395–403. doi:10.1016/0960-0760(95)00214-6. PMID 8541236. S2CID 31312. Patel JU, Prankerd RJ, Sloan KB (October 1994). "A prodrug approach to increasing the oral potency of a phenolic drug. 1. Synthesis, characterization, and stability of an O-(imidomethyl) derivative of 17 beta-estradiol". J Pharm Sci. 83 (10): 1477–81. doi:10.1002/jps.2600831022. PMID 7884673. Patel J, Katovich MJ, Sloan KB, Curry SH, Prankerd RJ (February 1995). "A prodrug approach to increasing the oral potency of a phenolic drug. Part 2. Pharmacodynamics and preliminary bioavailability of an orally administered O-(imidomethyl) derivative of 17 beta-estradiol". J Pharm Sci. 84 (2): 174–8. doi:10.1002/jps.2600840210. PMID 7738796.
