Animal models of the cardiovascular effects of exogenous hormones.

As early as the 1950s, animal studies showed that exogenous estrogen could inhibit coronary atherosclerosis. Since then, additional animal studies have helped to further elucidate the cardiovascular effects of hormone replacement therapy and the importance of the timing of therapy initiation. Although estrogen's cardioprotective effects in women are believed to be related, in part, to its effects on lipoprotein levels, studies in monkeys show that estrogen acutely modulates the vasomotor response of atherosclerotic coronary arteries without significantly changing lipoprotein levels, indicating a direct vascular effect. Studies in both rats and primates indicate that some of the antiatherogenic effects of estrogens may be counteracted by specific progestins. Models using a nonselective estrogen receptor (ER) antagonist (ICI 182,780) indicate that the antiatherogenic effects of 17 beta-estradiol are mediated via ERs. Recent studies with ER knockout mice indicate that ER-alpha and ER-beta mediate the protective effects of estrogen on the vasculature. Additional studies are ongoing to define the mechanisms through which specific estrogens and progestins affect cardiovascular function and to clarify the impact of the timing of initiation of therapy on the atherosclerotic process.