The pharmacodynamics of oral estradiol are complex and depend on the route of administration:
Pharmacology of estrogens and progestogens: influence of different routes of administration
CLIMACTERIC 2005; 8(Suppl 1):3–63
"After oral administration, the pharmacokinetics of estradiol differs from that of most other sex steroids. While the serum concentrations of EE [ethinyl estradiol], estriol and the progestogens are characterized by a rapid rise, up to a maximum after 1–3 h and followed by a rapid decline, the levels of estradiol remain elevated for up to 12 h and decrease slowly during the following time.
This peculiarity is due to the special metabolism of estradiol, which is rapidly and extensively transformed in the intestinal tract and liver to estrone and estrone sulfate. Both metabolites are circulating in high concentrations and serve as a hormonally inert reservoir from which estradiol is continuously delivered after reconversion."
Note, however, it appears the bioavailability AUC [AUC = area under the curve] is more important than peak plasma levels:
"The systemic exposure to estradiol during a 24-h period, as expressed by the AUC, did not differ between the
intranasal therapy with 300 mcg estradiol and the oral therapy with 2 mg micronized estradiol or the transdermal therapy with 50 mcg estradiol.
Therefore, the short-term bolus of high estradiol concentrations is as effective as the relatively sustained estradiol levels observed during transdermal or oral HRT. This is based on a rapid accumulation of estradiol in the target cells and a high [affinity] of binding to nuclear ERs [estrogen receptors]. The ligand–receptor complex remains at the estrogen-responsive elements of the DNA for more than 24 h and induces all estrogen specific effects."
Hope that helped,
Terri
