Postmenopausal oestrogen replacement therapy and atherosclerosis: can current compounds provide cardiovascular protection?

The natural oestrogen. 17 beta -oestradiol, has been implicated in protecti on from atherosclerosis, a chronic systemic vascular disease with an inflam matory component accounting for the majority of morbidity and mortality in Western countries. Despite the protective effects of 17 beta -oestradiol in premenopausal women and experimental evidence demonstrating inhibitory eff ects of oestrogen on atherosclerosis progression it is currently unclear wh ether hormone replacement therapy can affect cardiovascular morbidity and m ortality in postmenopausal women. The recent advances in understanding the mechanisms of oestrogen action demonstrated roles for different oestrogen r eceptors and oestrogen metabolites in the pathogenesis of vascular injury a nd endothelial cell dysfunction. However, their respective role in the proc ess of atherogenesis remains yet to be elucidated. Moreover. the availabili ty of novel drugs with tissue- and/or receptor-specific actions will help t o understand the role of oestrogen in cardiovascular diseases. Several ongo ing large-scale clinical trials using opposed or unopposed replacement ther apy with natural or synthetic oestrogens, or selective oestrogen receptor m odulators (SERMs) will resolve the question whether the drugs currently ava ilable have therapeutic potential to interfere with the progression of athe rosclerosis and its complications.