Catechol-O-methyltransferase (COMT) plays a crucial role in the regulation of central dopaminergic systems by catalyzing the inactivation of catechol-amines. It is widely distributed in most tissues in soluble and membrane-bound forms. COMT-mediated methylation metabolism of catecholamine neurotransmitters is a first-line detoxification pathway. A Val158Met polymorphism of the COMT gene affects activity of the enzyme and influences performance and efficiency of the prefrontal cortex of the brain. Sequential conversion of estradiol to methoxyestradiol by COMT, contributes to the antimitogenic effects of estradiol on vascular smooth muscle cell growth via estrogen receptor-independent mechanisms.