In a study by Jennings et al in this issue of Hypertension, the ability of endogenous estrogen to counteract the blood pressure response to angiotensin II infusion is a result of the metabolism of 17-β-estradiol to 2-hydroxyestradiol (2-OHE) by cytochrome P450 1B1 (CYP1B1) and subsequent conversion by catechol-O-methyl transferase (COMT) to 2-methoxyestradiol (2-MeE2). In contrast, production of 4-hydroxyestradiol (4-OHE) and 4-methoxyestradiol (4-MeE2) exacerbates hypertension in this model. Other 17-β-estradiol precursors or metabolites that may impact cardiovascular function include 27-hydroxycholesterol (27-OHC), 16α-hydroxyestradiol (16α-OHE), estrone (E1), and estriol (E3).