Estradiol, the active form of<unk> . Pharmacodynamics<unk>  is an estradiol ester, or a prodrug of estradiol. As such, it is an estrogen, or an agonist of the estrogen receptors.<unk>  has very low affinity for the ERs, on the order of 100-fold less than that of estradiol. As such,<unk>  is regarded as essentially inactive in terms of estrogenic effect itself, acting solely as a prodrug to estradiol.<unk>  is of about 38% higher molecular weight than estradiol due to the presence of its C3<unk>  ester. Because<unk>  is a prodrug of estradiol, it is considered to be a natural and bioidentical form of estrogen. Estrogenic potency In the case of intramuscular injections of either<unk>  or estradiol valerate in oil solution, the maturation dosage for the vaginal epithelium is 5 to 7 mg once per week and the endometrial proliferation dosage is 7 to 10 mg once per week. The total endometrial proliferation dosage of<unk>  in oil solution by intramuscular injection over 14 days is 25 to 35 mg. The full endometrial transformation dosage of<unk> /progesterone in oil solution is 1 to 2 mg<unk>  and 20 to 25 mg progesterone by intramuscular injection daily for 10 to 14 days, whereas the full endometrial transformation dosage of<unk> /progesterone in microcrystalline aqueous suspension is a single intramuscular injection of 10 mg<unk>  and 200 mg progesterone. For comparison, the full endometrial transformation dosage of estradiol valerate and hydroxyprogesterone caproate in oil solution (brand name Gravibinon) is a single intramuscular injection of 10 mg estradiol valerate and 250 to 375 mg hydroxyprogesterone caproate. Endometrial transformation normally occurs during the luteal phase of the menstrual cycle; it is induced by endogenous progesterone following adequate priming by endogenous estradiol. The decidua (pregnancy-type endometrium) induction dosage of<unk> /progesterone in oil solution is 2 to 5 mg<unk>  and 20 to 100 mg progesterone by intramuscular injection daily for 5 to 7 weeks, whereas the decidua induction dosage of<unk> /progesterone in microcrystalline aqueous suspension is 10 to 20 mg<unk>  and 200 to 250 mg progesterone in microcrystalline aqueous suspension by intramuscular injection once per week for about 6 weeks. For comparison, the decidua induction dosage of estradiol valerate and hydroxyprogesterone caproate in oil solution is about the same as that of microcrystalline<unk> /progesterone in aqueous suspension. The decidua induction dosages of estrogen and progestogen combinations are pseudopregnancy dosages. Pharmacokinetics Following administration,<unk>  acts as a prodrug of estradiol via cleavage by esterases into estradiol and the natural fatty acid benzoic acid. This cleavage occurs not only in the liver, but also in the blood and in tissues. Esters of estradiol like<unk>  are readily hydrolyzed to estradiol, but have an extended duration when administered in via intramuscular or subcutaneous injection due to a depot effect afforded by their fatty acid ester moiety and consequent high lipophilicity. A long-lasting local tissue depot is formed by the injection that slowly releases<unk>  into the circulation. Intramuscular injection Oil solution The duration of action of<unk>  in oil solution by intramuscular injection at typical clinical doses (e.g., 0.33–1.66 mg) is said to be 2 to 3 days. A single dose of 2.5 mg<unk>  in oil solution by intramuscular injection was found to produce plasma estradiol levels of greater than 400 pg/mL, measured 24 hours post-injection, in a group of patients with minimal baseline levels of estradiol (due to GnRH analogue therapy with triptorelin). The elimination half-life of<unk>  in oil solution by intramuscular injection has been reported to be 48 to 120 hours (2 to 5 days). A single intramuscular injection of 5 mg<unk>  in oil solution has been found to result in peak circulating concentrations of 940 pg/mL estradiol and 343 pg/mL estrone, which occurred at about 2 days post-injection. Compared to two other commonly used estradiol esters,<unk>  had the shortest duration, at approximately 4 to 5 days, whereas estradiol valerate and estradiol cypionate were found to last for 7 to 8 days and 11 days, respectively. This is because<unk>  has a shorter and less bulky fatty acid chain, and in relation to this, is comparatively less lipophilic. For a given estradiol ester, the shorter or less bulky the fatty acid chain is, the less lipophilic, shorter-lasting, and less uniform/plateau-like the resultant levels of estradiol are as well as the higher (and hence more spike-like) the peak/maximal levels are. Daily intramuscular injections of 1 mg<unk>  in oil solution have been found to produce estradiol excretion rates almost double those of the normal luteal phase. This is in accordance with known production rates of estradiol in women (e.g., 300 µg/day in the luteal phase). Aqueous suspension Microcrystalline<unk>  in aqueous suspension (brand names Agofollin Depot and Ovocyclin M alone and Follivirin in combination with testosterone isobutyrate) has been found to have a longer duration of action than amorphous<unk>  in oil solution when administered via intramuscular injection. Whereas the duration of a single intramuscular injection of<unk>  in oil solution is 6 days, the duration of a single intramuscular injection of microcrystalline<unk>  in aqueous suspension is 16 to 21 days. Its duration also surpasses that of estradiol valerate and estradiol cypionate. The duration of microcrystalline aqueous suspensions administered by intramuscular injection is dependent both on concentration and on crystal size. Other routes The duration of<unk>  is not prolonged if it is administered directly into the circulation via intravenous injection, in contrast to intramuscular injection.<unk>  is active with oral and sublingual administration, similarly to estradiol valerate and estradiol acetate. However, it is not marketed in any formulation for use by these routes. Oral<unk>  has been reported to possess about one-third to half the potency of intramuscular injection of<unk> . This level of oral potency has been described as remarkably high. The sublingual potency of<unk>  is similar to that of estradiol. A study found that the total dose of<unk>  needed for endometrial proliferation in women was 60 to 140 mg, relative to 60 to 180 mg for estradiol. Both estradiol and<unk>  has a persistence of estrogenic effect with single administration of one day. Subcutaneous implantation of crystalline<unk>  pellets has been studied, but no<unk>  pellet implants have been marketed.
Estradiol benzoate
Estradiol undecylate
Estradiol dienantate
Estradiol furoate
Estradiol enantate
Estradiol valerate
Estradiol dipropionate
Estradiol cypionate