Pharmacokinetics of estradiol
Estradiol can be administered in the form of a very long-lasting subcutaneous pellet implant. These implants are replaced once every 6 to 12 months, and can achieve high and very constant circulating levels of estradiol. They are surgically inserted by a trained physician in a medical office or clinic and can be placed into locations including the lower abdomen, lower back, buttocks, or hips. Subcutaneous implants containing 25, 50, and 100 mg estradiol for replacement usually once every 6 months are available as approved pharmaceutical medications. Up to 800 mg estradiol per implantation has been used. Pharmaceutical estradiol implants have been said to be used almost exclusively in the United Kingdom. An estradiol implant has not been approved by the FDA as a pharmaceutical medication in the United States, but hormone implants, including estradiol implants, are available as custom compounded products in this country.
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.