Simplified schematic presentation of enzymes involved in estrogen biosynthesis and metabolism. CYP1A1 and CYP1B1 are also involved in metabolism of environmental chemicals. 17β-Estradiol can be metabolised into the hydroxylated catecholestrogens, 2-OHE2 and 4-OHE2 by CYP1A1 and CYP1B1, respectively. These catecholestrogens can be cleared via the methylation pathway catalysed by COMT. Alternatively the 4-OHE2 can be oxidised into the semiquinone, which can undergo non-enzymatic conversion to its quinone generating superoxide radical. E2: 17β-estradiol; 2-OHE2: 2-hydroxyestradiol; 4-OHE2: 4-hydroxyestradiol; COMT: catechol-O-methyl transferase.