Estradiol (medication)
Estradiol is also widely available in combination with progestogens. It is available in combination with norethisterone acetate under the major brand names Activelle, Cliane, Estalis, Eviana, Evorel Conti, Evorel Sequi, Kliogest, Novofem, Sequidot, and Trisequens; with drospirenone as Angeliq; with dydrogesterone as Femoston, Femoston Conti; and with nomegestrol acetate as Zoely. Estradiol valerate is available with cyproterone acetate as Climen; with dienogest as Climodien and Qlaira; with norgestrel as Cyclo-Progynova and Progyluton; with levonorgestrel as Klimonorm; with medroxyprogesterone acetate as Divina and Indivina; and with norethisterone enantate as Mesigyna and Mesygest. Estradiol cypionate is available with medroxyprogesterone acetate as Cyclo-Provera, Cyclofem, Feminena, Lunelle, and Novafem; estradiol enantate with algestone acetophenide as Deladroxate and Topasel; and estradiol benzoate is marketed with progesterone as Mestrolar and Nomestrol.
Estradiol (medication)
Estradiol was first isolated in 1935. It was also originally known as "dihydroxyestrin" or "alpha-estradiol". It was first marketed, as estradiol benzoate, in 1936. Estradiol was also marketed in the 1930s under brand names such as Progynon-DH, Ovocylin, and Dimenformon. Micronized estradiol, via the oral route, was first evaluated in 1972, and this was followed by the evaluation of vaginal and intranasal micronized estradiol in 1977. Oral micronized estradiol was first approved in the United States under the brand name Estrace in 1975.
In 1931, Butenandt found that the benzoic acid ester of estrone had a prolonged duration of action. Subsequently, Schwenk and Hildebrant synthesized estradiol benzoate from estradiol in 1933, and estradiol benzoate was introduced by Schering-Kahlbaum for medical use via intramuscular injection under the brand name Progynon-B in 1936. It was the first estrogen ester to be marketed, and has since been followed by many additional esters, for instance estradiol valerate and estradiol cypionate in the 1950s. Ethinylestradiol was synthesized from estradiol by Inhoffen and Hohlweg in 1938 and was introduced for oral use by Schering in the United States under the brand name Estinyl in 1943. It remains widely used in combined oral contraceptives.