Cloxestradiol acetate and promestriene are ether prodrugs of estradiol that have been introduced for medical use as estrogens as well, although they are little known and rarely used.Synthetic derivatives of estradiol used as estrogens include ethinylestradiol, ethinylestradiol sulfonate, mestranol, methylestradiol, moxestrol, and quinestrol, all of which are 17α-substituted estradiol derivatives. Synthetic derivatives of estradiol used in scientific research include 8β-VE2 and 16α-LE2. History
Estradiol was first discovered and synthesized in 1933 via reduction of estrone. Subsequently, estradiol was isolated for the first time in 1935. It was also originally known as dihydroxyestrin, dihydrofolliculin, or alpha-estradiol.Estradiol was first introduced for medical use, in the form of estradiol benzoate, a short-acting ester prodrug of estradiol administered by intramuscular injection in oil solution, under the brand name Progynon B in 1933. Estradiol itself was also marketed in the 1930s and 1940s in the form of oral tablets and solutions, vaginal suppositories, and topical ointments under a variety of brand names including Dimenformon, Gynoestryl, Ovocyclin, Progynon, and Progynon DH. Marketed vaginal estradiol suppositories were also used rectally. Estradiol dipropionate, another short-acting ester of estradiol in oil solution for use by intramuscular injection, was marketed under the brand name Di-Ovocylin by 1939. In contrast to estrone, estradiol was never marketed in oil solution for intramuscular injection.
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