Orally, EE is on the order of 100 times as potent by weight as natural estrogens like micronized estradiol and conjugated estrogens, which is largely due to substantially greater resistance to first-pass metabolism. It is specifically in the range of 80 to 200 times as potent as estropipate (piperazine estrone sulfate), which has similar potency to micronized estradiol, in terms of systemic estrogenic potency. In contrast, the potencies of EE and natural estrogens are similar when they are administered intravenously, due to the bypassing of first-pass metabolism. Relative to its prodrug mestranol, EE is about 1.7 times as potent by weight orally.