2 mg/day oral estradiol valerate on HDL cholesterol and triglycerides. 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. 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 ), again after differences in molecular weight between the two compounds are considered. A dosage of 1 mg/day oral estradiol