Estrogen stimulation of COX-2-derived PGI2 confers atheroprotection

Although selective cyclooxygenase-2 (COX-2) inhibitors provide relief from pain and inflammation, they also reduce the formation of the atheroprotective prostaglandin I2 (PGI2). They do not reduce the formation of the COX-1-derived thromboxane A2 (TXA2), however, which is both atherogenic and a potent vasoconstrictor. For this reason, the effects of TXA2 might be exacerbated during extended therapy with COX-2 inhibitors, potentially predisposing patients to heart attack and stroke. Recent studies have demonstrated that the atheroprotective effects of estrogen are induced through PGI2 production, through COX-2 activation. This explains how estrogen production in pre-menopausal females is beneficial for the heart and also raises the possibility that COX-2 inhibitors might be particularly hazardous to females.