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 is metabolized slowly and minimally, and is not transformed into other estrogens such as estradiol, estrone, or estriol. This is related to the fact that estetrol is already an end-stage product of phase I estrogen metabolism in humans. The medication is conjugated via glucuronidation and to a lesser extent via sulfation. The biological half-life of estetrol is about 28 hours, with a range of 18 to 60 hours. The blood half-lives of estradiol and estriol, at about 1 to 2 hours and 20 minutes, respectively, are far shorter than that of estetrol, whereas the biological half-life of ethinylestradiol, at approximately 20 hours, is more similar to that of estetrol. Enterohepatic recirculation may occur with estetrol, similarly to other steroidal estrogens, although it has also been reported that estetrol does not seem to enter the enterohepatic circulation. Estetrol is excreted mostly or completely in urine, virtually entirely in the form of conjugates (unconjugated accounting for 0.2–0.7%). In one study, a median of 79.7% (range 61.1–99.0%) was recovered from urine; this was primarily as estetrol glucuronide (median 60.7%, range 47.6–77.2%), and, to a lesser extent, as estetrol sulfate (median 17.6%, range 13.2–22.1%).