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Upon ingestion, regardless of the route of administration, estradiol valerate behaves as a prodrug, being cleaved by esterases in blood plasma and the liver into 17β-estradiol and valeric acid.However, compared to estradiol itself, estradiol valerate is absorbed more slowly and possesses a longer duration, especially when given in an oil solution via intramuscular injection (in which it acts as a depot). As a result, it can be administered less frequently.
A single intramuscular injection of 4 mg estradiol valerate results in maximal plasma levels of estradiol of about 390 pg/ml within three days of administration, with levels declining to 100 pg/mL by 12-13 days.A study of high-dose combined administration of 40 mg estradiol valerate and 250 mg hydroxyprogesterone caproate in women once weekly for six months (described as a "pseudopregnancy" regimen) found that serum levels of estradiol increased from 27.8-34.8 pg/mL to 3028-3226 pg/mL after three months and to 2491-2552 pg/mL after six months of treatment.
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