Estradiol enantate
Estradiol enantate, sold under the brand names Perlutal and Topasel among others, is an estrogen medication which is used in hormonal birth control. It is formulated in combination with dihydroxyprogesterone acetophenide (DHPA; algestone acetophenide), a progestin, and is used as a combined injectable contraceptive. Estradiol enantate is not available alone. The medication is given by injection into muscle once a month.
Side effects of estradiol enantate include breast tenderness, breast enlargement, nausea, headache, and fluid retention. The drug is a synthetic estrogen and hence is an agonist of the estrogen receptor (ER), the biological target of estrogens like estradiol. Estradiol enantate is an estrogen ester and a long-lasting prodrug of estradiol in the body. Because of this, it is considered to be a natural and bioidentical form of estrogen.
Estradiol enantate was first described by 1954, and was first studied in combination with DHPA as a combined injectable contraceptive in 1964. The combination was introduced for clinical use by the mid-1970s. Estradiol enantate is not available as a standalone medication (i.e., by itself without DHPA). The combination is available in Latin America and Hong Kong, and was also previously marketed in Spain and Portugal.
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.