Hormone replacement therapy andatherosclerosis-postmenopausal women and HRT:the fallen myth of the cardiovascular protectiveeffects of hormone replacement therapy

摘要

The marked sex difference in risk of coronary heart disease (CHD) has been noted for many decades and was the impetus for early animal experiments of estrogen effects on atherosclerosis [1].These studies demonstrated that estrogen could prevent atherogenesis in animal models for atherosclerosis.Moreover, in the last 2 decades of the last century, many observational studies have found lower prevalence of CHD both in women taking estrogen or estrogen/progestin than in women not receiving postmenopausal hormone replacement therapy (HRT) [2].These results, besides the estrogen beneficial changes in intermediate markers such as lipid parameters [3,4], led to a belief that HRT could be an important weapon for preventing CHD.Regardless of those strong experimental, observational and mechanistic evidences, no large clinical trials had been done to evaluate HRT protection against CHD until 5 years ago Women taking hormone therapy in observational studies differ from non-users in many aspects like general health status, health awareness (they are "compliant" per definition), profile of coronary risk factors or socioeconomic status Observational data are not convincing as results from randomized placebo-controlled trials, in which randomization hands out known and unknown biases in an even manner Guiding therapy by mechanistic evidence is also not safe. The legacy of the CAST study has shown us that treating a patophysiologic processes (suppressing ventricular arrhythmia that is associated with sudden death) is not sufficient to warrant better outcome-patients can die with the surrogate outcome apparently corrected [5].