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. The affinity of estradiol valerate for the estrogen receptor has been reported to be 50 times less than that of estradiol, and estradiol valerate and<unk>  have been found to possess similar affinity for the estrogen receptor. Both<unk>  and estradiol valerate are rapidly cleaved into estradiol in the body, and estradiol valerate has been found to be unable to reach target tissues in any concentration of significance. As such, estradiol valerate is regarded as essentially inactive in terms of estrogenic effect itself, acting solely as a prodrug to estradiol, and<unk>  is described as a prodrug of estradiol similarly.<unk>  is of about 46% higher molecular weight than estradiol due to the presence of its C17β<unk>  ester, and contains about 69% of the amount of estradiol by weight. Because<unk>  is a prodrug of estradiol, it is considered to be a natural and bioidentical form of estrogen. Effects on liver protein synthesis A study compared the combination of 5 mg<unk>  and 25 mg medroxyprogesterone acetate as a combined injectable contraceptive (which has been associated with peak estradiol levels of around 300 pg/mL) with an ethinylestradiol-containing combined birth control pill and found that whereas the birth control pill produced significant changes in coagulation parameters, there were no significant prothrombotic effects of the combined injectable contraceptive on levels of fibrinogen, factors VII and X, plasminogen, or the activated prothrombin time. As such, it appears that similarly to depot medroxyprogesterone acetate, combined injectable contraceptives with 5 mg<unk>  and 25 mg medroxyprogesterone acetate have less or no procoagulant effect relative to combined birth control pills. Pharmacokinetics Intramuscular injection In contrast to oral administration, which is associated with very low bioavailability (<10%), the bioavailability of both estradiol and estradiol esters like estradiol valerate is complete (i.e., 100%) via intramuscular injection. In addition, estradiol esters like<unk>  and estradiol valerate when given as an injection of oil solution or microcrystalline aqueous suspension have a relatively long duration due to the formation of an intramuscular depot from which they are slowly released and absorbed. Upon intramuscular injection of<unk>  in an oil solution, the solvent (i.e., oil) is absorbed, and a primary microcrystalline depot is formed within the muscle at the site of injection. In addition, a secondary depot may be formed in adipose tissue. The slow release of<unk>  from the tissue depot is caused by the high lipophilicity of the estradiol ester, which in turn is due to its long fatty acid cypionic acid ester moiety.<unk>  is formulated for use alone and in combination with testosterone<unk>  as an oil solution, and for use in combination with medroxyprogesterone acetate as a microcrystalline aqueous suspension. Aqueous suspensions of steroid esters generally have longer durations by intramuscular injection than oil solutions. A single intramuscular injection of 5 mg<unk>  has been found to result in peak circulating concentrations of 338 pg/mL estradiol and 145 pg/mL estrone, which occurred at about 4 and 5 days post-injection, respectively (see right table). Compared to two other commonly used estradiol esters (which were also assessed in the study),<unk>  had the longest duration, at approximately 11 days, whereas estradiol benzoate and estradiol valerate were found to last for 4 to 5 days and 7 to 8 days, respectively. This is because<unk>  has a more extensive fatty acid chain and in relation to this is comparatively more lipophilic. For a given estradiol ester, the longer or more extensive the fatty acid chain is, the more lipophilic, longer-lasting, and more uniform/plateau-like the resultant levels of estradiol are as well as the lower the peak/maximal levels are (and hence less spike-like).<unk> /medroxyprogesterone acetate (brand names Lunelle, Cyclofem) is a combined injectable contraceptive containing 5 mg<unk>  and 25 mg medroxyprogesterone acetate in microcrystalline aqueous suspension for once-monthly intramuscular administration. With this formulations, estradiol levels peak 2 to 3 days post-injection with average maximal circulating levels of about 250 pg/mL. The elimination half-life of estradiol with these formulations is 8.4 to 10.1 days, and circulating estradiol levels return to a baseline of about 50 pg/mL approximately 14 to 24 days post-injection. Subcutaneous injection<unk>  in a microcrystalline aqueous suspension has been found to have equivalent effectiveness and virtually identical pharmacokinetics when administered by subcutaneous injection versus intramuscular injection. However, subcutaneous injection is considered to be easier and less painful relative to intramuscular injection, and for these reasons, may result in comparatively greater satisfaction and compliance.
Estradiol cypionate
Estradiol dienantate
Estradiol undecylate
Estradiol enantate
Estradiol furoate
Estradiol dipropionate
Estradiol benzoate
Estradiol valerate