Estrogen ester

Estrogen esters are used in hormone therapy, hormonal contraception, and high-dose estrogen therapy (e.g., for prostate cancer and breast cancer), among other indications. One of the most widely used estradiol esters is estradiol valerate, which was first introduced in 1954. Other major estradiol esters that are or have been used in medicine include estradiol acetate, estradiol cypionate, estradiol dipropionate, estradiol enantate, estradiol undecylate, and polyestradiol phosphate (an estrogen ester polymer), as well as the nitrogen mustard alkylating antineoplastic agent estramustine phosphate (estradiol normustine phosphate). The most common vehicles for injections of steroids and steroid esters are oil solutions, but aqueous solutions, aqueous suspensions, and emulsions have also been used. The durations of estrogen esters are not prolonged if they are given orally, vaginally, or by intravenous injection. ==Pharmacology==

Estrogen esters are essentially inactive themselves, with esters such as estradiol valerate and estradiol sulfate having about 2% of the affinity of estradiol for the estrogen receptor. Likewise, the estrogen ether mestranol (ethinylestradiol 3-methyl ether) has about 1% of the affinity of estradiol for the estrogen receptor. As such, estrogen esters do not bind to the estrogen receptor except at extremely high concentrations. The residual affinity of estrogen esters for the estrogen receptor in bioassays may actually be due to conversion into the parent estrogen, as attempts to prevent or limit this conversion have been found to abolish binding to the estrogen receptor and estrogenicity. In general, the longer the fatty acid ester chain of an estrogen ester, the greater its lipophilicity, and the longer the duration of the estrogen ester with intramuscular injection. Estradiol enantate (ester of 7 carbons) has a duration of around 20 days.--> Likewise, estradiol undecylate (ester of 10 carbons) has a very extended duration, which is longer than that of all of the aforementioned esters. Polyestradiol phosphate is an atypical estradiol ester. It is a phosphoric acid ester of estradiol in the form of a polymer, with an average polymer chain length of approximately 13 repeat units of estradiol phosphate. Instead, polyestradiol phosphate is taken up rapidly into the bloodstream following injection (by 90% within 24 hours), where it circulates, and is accumulated in the reticuloendothelial system. ==Chemistry==

plus the fatty acid valeric acid (valerate) equals estradiol valerate, a C17β ester of estradiol and one of the most widely used estrogen esters. , a polymer of estradiol phosphate, the C17β phosphoric acid ester of estradiol. It has on average of 13 repeat units. Estradiol esters have an ester moiety, usually a straight-chain fatty acid (e.g., valeric acid) or an aromatic fatty acid (e.g., benzoic acid), attached at the C3 and/or C17β positions of the steroid nucleus. These alkoxy moieties are substituted in place of the hydroxyl groups present in the unesterified estradiol molecule. Fatty acid esters serve to increase the lipophilicity of estradiol, increasing its solubility in fat. This causes them to form a depot with intramuscular or subcutaneous injection and gives them a long duration when administered by these routes. Some estradiol esters have other moieties instead of fatty acids as the esters. Such esters include sulfuric acid (as in estradiol sulfate), sulfamic acid (as in estradiol sulfamate), phosphoric acid (as in estradiol phosphate), glucuronic acid (as in estradiol glucuronide, and others (e.g., estramustine phosphate (estradiol 3-normustine 17β-phosphate)). These esters are all hydrophilic, and have greater water solubility than estradiol or fatty acid estradiol esters. Unlike fatty acid estradiol esters, water-soluble estradiol esters can be administered by intravenous injection. A few estrogen esters are polymers. These include polyestradiol phosphate and polyestriol phosphate, which are polymers of estradiol phosphate and estriol phosphate monomers, respectively. The monomers are connected in both cases by phosphate groups via the C3 and C17β positions. Polyestradiol phosphate has an average polymer chain length of approximately 13 repeat units of estradiol phosphate. That is, each polyestradiol phosphate molecule is a polymer consisting on average of 13 estradiol phosphate molecules bonded together. These polymeric estrogen esters are hydrophilic and water-soluble. Upon intramuscular injection, they do not form a depot and instead are rapidly absorbed into the circulation. However, they are only slowly cleaved into monomers, and as a result, have a very long duration in the body even outlasting that of many longer-chain fatty-acid estrogen esters. ==See also==