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.
However, estradiol valerate is hydrolyzed into estradiol and valeric acid in the intestines, and hence, is still subject to extensive first-pass metabolism.
As such, the oral bioavailability of estradiol valerate is only around 3 to 5%, and is similar to that of oral estradiol.
All oral tablets in the cases of both estradiol and estradiol valerate seem to be micronized.
Due to its nature as a rapidly converted prodrug of estradiol, the pharmacokinetics of oral estradiol valerate are similar to those of oral estradiol.
Moreover, the pharmacodynamics and potency (after differences in molecular weight are taken into account) of oral estradiol valerate are considered to be equivalent to those of oral estradiol.
This is also notably true for effects on hepatic protein synthesis (e.g., of SHBG), again after differences in molecular weight between the two compounds are considered.

A dosage of 1 mg/day oral estradiol valerate has been found to produce approximate circulating concentrations of 50 pg/mL estradiol and 160 pg/mL estrone, while a dosage of 2 mg/day results in circulating levels of 60 pg/mL estradiol and 300 pg/mL estrone.
These concentrations of estradiol and estrone are comparable to those observed with 1 and 2 mg/day oral estradiol.
A review of selected studies reported a range of mean peak estradiol levels of 24 to 140 pg/mL occurring 1 to 12 hours after administration of 2 mg oral estradiol valerate.
A study found that, in accordance with their differences in molecular weights, oral estradiol produced higher levels of estradiol than oral estradiol valerate.
Likewise, other studies found that levels of estradiol and estrone are very similar after oral administration of roughly equimolar doses of estradiol (1.5 mg) and estradiol valerate (2 mg).
A study of high-dose oral estradiol valerate found levels of estradiol of about 250 pg/mL after a single 10-mg dose in three women.
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. However, estradiol valerate is hydrolyzed into estradiol and valeric acid in the intestines, and hence, is still subject to extensive first-pass metabolism. As such, the oral bioavailability of estradiol valerate is only around 3 to 5%, and is similar to that of oral estradiol. All oral tablets in the cases of both estradiol and estradiol valerate seem to be micronized. Due to its nature as a rapidly converted prodrug of estradiol, the pharmacokinetics of oral estradiol valerate are similar to those of oral estradiol. Moreover, the pharmacodynamics and potency (after differences in molecular weight are taken into account) of oral estradiol valerate are considered to be equivalent to those of oral estradiol. This is also notably true for effects on hepatic protein synthesis (e.g., of SHBG), again after differences in molecular weight between the two compounds are considered.
A dosage of 1 mg/day oral estradiol valerate has been found to produce approximate circulating concentrations of 50 pg/mL estradiol and 160 pg/mL estrone, while a dosage of 2 mg/day results in circulating levels of 60 pg/mL estradiol and 300 pg/mL estrone. These concentrations of estradiol and estrone are comparable to those observed with 1 and 2 mg/day oral estradiol. A review of selected studies reported a range of mean peak estradiol levels of 24 to 140 pg/mL occurring 1 to 12 hours after administration of 2 mg oral estradiol valerate. A study found that, in accordance with their differences in molecular weights, oral estradiol produced higher levels of estradiol than oral estradiol valerate. Likewise, other studies found that levels of estradiol and estrone are very similar after oral administration of roughly equimolar doses of estradiol (1.5 mg) and estradiol valerate (2 mg). A study of high-dose oral estradiol valerate found levels of estradiol of about 250 pg/mL after a single 10-mg dose in three women.
Estradiol valerate