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

The natural oestrogen. 17 beta -oestradiol, has been implicated in protection from atherosclerosis, a chronic systemic vascular disease with an inflammatory 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 effects of oestrogen on atherosclerosis progression it is currently unclear whether hormone replacement therapy can affect cardiovascular morbidity and mortality in postmenopausal women. The recent advances in understanding the mechanisms of oestrogen action demonstrated roles for different oestrogen receptors and oestrogen metabolites in the pathogenesis of vascular injury and endothelial cell dysfunction. However, their respective role in the process of atherogenesis remains yet to be elucidated. Moreover. the availability of novel drugs with tissue- and/or receptor-specific actions will help to understand the role of oestrogen in cardiovascular diseases. Several ongoing large-scale clinical trials using opposed or unopposed replacement therapy with natural or synthetic oestrogens, or selective oestrogen receptor modulators (SERMs) will resolve the question whether the drugs currently available have therapeutic potential to interfere with the progression of atherosclerosis and its complications.