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.
Estetrol (medication)
Estetrol was discovered in 1965 by Egon Diczfalusy and coworkers at the Karolinska Institute in Stockholm, Sweden, via isolation from the urine of pregnant women. Basic research on estetrol was conducted from 1965 to 1984. It was established that estetrol is exclusively synthesized in the fetal liver and hence that it is a fetal estrogen. By 1984, estetrol was regarded as a weak estrogen; interest fell, and research was virtually abandoned. Subsequently a project at Pantarhei Bioscience was started to investigate estetrol with state-of-the-art technologies in 2001, with the sole reasoning that estetrol must have some biological role or function of importance as it would not be produced in such high quantities in the fetus otherwise. By 2008, estetrol was of major interest for potential clinical use, and development was in-progress. As of 2018, it is in mid- to late-stage clinical development for a variety of indications.https://adisinsight.springer.com/drugs/800034634 It was initially developed by Pantarhei Bioscience and Estetra SA (subsequently renamed Estetra SPRL), and is now being developed by Mithra Pharmaceuticals.