Estrogen has been traditionally regarded as a cardioprotective hormone. ost women who enter
menopause are asymptomatic for
cardiovascular disease (CVD), and 95% of the women who develop CVD do so after
menopause. Early loss of endogenous estradiol is associated with increased risk of CVD. The idea of cardioprotection is supported by numerous reports of beneficial effects of estrogen on lipoprotein profile and on vascular endothelium demonstrated at the cellular, molecular, and animal model level. Yet there is a puzzling discrepancy between many observational studies that suggest a protective role of postmenopausal estrogen treatment, and the results of pivotal clinical trials including the randomized, placebo-controlled hormone trial of theWomens Health Initiative6 and the Heart an Estrogen/progestin Replacement Study, which found a negative role for oral estrogen in primary and secondary prevention of
cardiovascular events. These divergent findings have resulted in confusion regarding the association between estrogen deficiency and CVD in postmenopausal women. Because the role of inflammation in atherothrombotic disorders is becoming increasingly recognized, it has been suggested that the beneficial effects of hormone therapy (HT) on plasma lipid levels may be counteracted by an increased thrombogenicity and inflammation leading to coronary narrowing and occlusion. Based on thorough analysis of the characteristics of the participants in the large clinical trials, it has been hypothesized that HTinitiated at the time of menopause may produce a decrease in CVD over time. In contrast, HT prescribed years after menopause may produce an increase in CVD events shortly after therapy is begun that is later followed by benefit. In the absence of evidence from controlled human trials that specifically involve initiation of HT in perimenopausal women, it is necessary to examine the pathophysiology associated with age-dependent changes within the vessel wall and to compare the effects of different types of estrogens and ogestins on vascular cells. he endothelium plays a critical role in the initiation of therosclerosis, platelet aggregation, and vascular inflammation.
A thoroughanalysis of the distribution, localization, expression, quantification, and characterization of hormonal receptor subtypes, as well as polymorphism/single-nucleotide polymorphisms and changes in structural morphology in diseased endothelial tissue, will substantially aid in our understanding of the effects of HT on cardiovascular health.