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).
Estradiol 3-saccharinylmethyl ether
Estradiol 3-saccharinylmethyl ether, or 3-"O"-(saccharinylmethyl)-17β-estradiol, is a synthetic estrogen and estrogen ether – specifically, the C3 saccharinylmethyl ether of estradiol – which was described in the mid-1990s and was never marketed. It is a prodrug of estradiol, and has been found to be 9-fold as potent as estradiol via the oral route in rats. Similarly, its bioavailability (16%) was 5-fold greater than that of estradiol via the oral route in rats, and the elimination half-life of estradiol released from the drug was 5- to 7-fold longer than that of regular estradiol. Conversely, when estradiol 3-saccharinylmethyl ether and estradiol were given intravenously in rats, there was no difference between them in terms of potency. "In vitro" studies revealed that saccarinylmethylestradiol is not hydrolyzed to estradiol enzymatically but rather is hydrolyzed chemically in biological media such as plasma, apparently dependent on the concentration of protein. Taken together, saccarinylmethylestradiol appears to be partially protected from first-pass metabolism in the liver and intestines with oral administration and shows greatly improved oral potency compared to estradiol.