The influence of 20 or 50 μg/day oral ethinylestradiol on coagulation factors and HDL cholesterol is markedly greater than that of 2 mg/day oral estradiol valerate.Estradiol-containing birth control pills, which contain 1 to 3 mg/day estradiol or estradiol valerate, have been found to increase sex hormone-binding globulin (SHBG) levels by 1.5-fold. Oral estradiol valerate at 6 mg/day has been found to increase SHBG levels by 2.5- to 3-fold in transgender women. For comparison, combined birth control pills containing ethinylestradiol and a progestin with minimal androgenic or antiandrogenic activity have been found to increase SHBG levels by about 3- to 4-fold. Pharmacokinetics
Regardless of the route of administration, estradiol valerate behaves as a prodrug of estradiol via cleavage by esterases into estradiol and the natural fatty acid valeric acid. This cleavage occurs not only in the liver, but also in the blood and in tissues, and the hydrolysis of estradiol valerate into estradiol and valeric acid is complete regardless of whether the medication is administered orally or parenterally. High levels of circulating estradiol are found after an intravenous injection of estradiol valerate, and this indicates very rapid cleavage of the medication upon entering circulation. Oral administration
Esterification of the C17β position of estradiol as in estradiol valerate reduces the metabolism of estradiol valerate by 17β-hydroxysteroid dehydrogenase (17β-HSD). As approximately 80% of estradiol is metabolized into estrone (and estrone sulfate) by 17β-HSD during first-pass metabolism, this improves the metabolic stability and hence bioavailability of estradiol valerate.
A third study, in contrast to the preceding study, found that a single 10 mg intramuscular injection of estradiol valerate resulted in maximal estradiol levels of 506 to 544 pg/mL and maximal estrone levels of 205 to 219 pg/mL in postmenopausal women.With intramuscular injections of estradiol valerate, it has been reported that a dose of 5 mg has a duration of 7 to 8 days, 10 mg a duration of 10 to 14 days, 40 mg a duration of 2 to 3 weeks (14 to 21 days), and 100 mg a duration of 3 to 4 weeks (21 to 28 days).A study of pseudopregnancy with intramuscular injections of 40 mg/week estradiol valerate and 250 mg/week hydroxyprogesterone caproate in women with estrogen deficiency observed estradiol levels of about 3,100 pg/mL at 3 months of therapy and 2,500 pg/mL at 6 months of therapy. Subcutaneous injection
Estradiol esters like estradiol valerate and estradiol cypionate can be given by subcutaneous injection instead of intramuscular injection. Intravenous injection
The administration of estradiol valerate by intravenous injection has been studied. It has been found to be very rapidly cleaved into estradiol. The bioavailability and metabolism of estradiol valerate does not differ with intravenous versus intramuscular injection. Conversely, intravenous injection of estradiol valerate has a very short duration, whereas intramuscular injection has a long duration and elimination half-life. Chemistry
Estradiol valerate is a synthetic estrane steroid and the C17β valerate (pentanoate) fatty acid ester of estradiol. It is also known as estradiol 17β-valerate or as estra-1,3,5(10)-triene-3,17β-diol 17β-pentanoate.