EE shows strong and disproportionate effects on liver protein synthesis relative to estradiol. The liver as well as the uterus express 17β-hydroxysteroid dehydrogenase (17β-HSD), and this enzyme serves to inactivate estradiol and effectively suppress its potency in these tissues by reversibly converting it into the far less potent estrogen estrone (which has approximately 4% of the estrogenic activity of estradiol). In contrast to estradiol, the 17α-ethynyl group of EE prevents oxidation of the C17β position of EE by 17β-HSD, and for this reason, EE is not inactivated in these tissues and has much stronger relative estrogenic activity in them. This is the mechanism of the disproportionately strong effects of EE on hepatic protein production, which results in a greatly increased magnitude of effect on VTE and cardiovascular risks relative to estradiol.