The oral bioavailability of EE is 45% on average, with a wide range of 20% to 74% (though most commonly between 38 and 48%) that is due to high interindividual variability. Although relatively low, the oral bioavailability of EE is considerably higher than that of micronized estradiol (5%). Following a single 20 μg dose of EE in combination with 2 mg norethisterone acetate in postmenopausal women, EE concentrations have been found to reach a maximum of 50 pg/mL within an average of 1.5 hours. Following the first dose, mean levels of EE in general further increase by about 50% until steady-state concentrations are reached; steady-state is reached after one week of daily administration. For comparison, the mean peak levels of estradiol achieved with 2 mg micronized estradiol or estradiol valerate are 40 pg/mL following the first dose and 80 pg/mL after three weeks of administration. These maximal concentrations of estradiol are in the same range as the concentrations of EE that are produced by an oral dose of EE that is 100 times lower by weight, which is in accordance with the approximately 100-fold increased oral potency of EE relative to estradiol. In accordance with the high interindividual variability in the oral bioavailability of EE, there is a large degree of interindividual variation in EE levels. A dosage of EE of 50 μg/day has been found to achieve a wide range of circulating EE levels of about 100 to 2,000 pg/mL. Taking EE in combination with a high-fat meal has been found to significantly decrease its peak concentrations.