Estrogen (medication)
Estradiol, estrone, and estriol have all been approved as pharmaceutical drugs and are used medically. Estetrol is currently under development for medical indications, but has not yet been approved in any country. A variety of synthetic estrogen esters, such as estradiol valerate, estradiol cypionate, estradiol acetate, estradiol benzoate, estradiol undecylate, and polyestradiol phosphate, are used clinically. The aforementioned compounds behave as prodrugs to estradiol, and are much longer-lasting in comparison when administered by intramuscular or subcutaneous injection. Esters of estrone and estriol also exist and are or have been used in clinical medicine, for example estrone sulfate (e.g., as estropipate), estriol succinate, and estriol glucuronide (as Emmenin and Progynon).
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.