Endogenous Sex Steroids and Coronary Artery Atherosclerosis in Cynomolgus Macaques
Whether endogenous sex steroids influence the atherosclerotic process in human beings remains unclear. It is widely believed that ovarian estrogen is responsible for the relatively low risk of coronary heart disease observed in premenopausal white women; however, this relationship has not been proven by population studies of human beings. Studies of coronary risk in menopause, an estrogen deficiency state, and pregnancy, a hyperestrogenic state, and studies of the influence of estrogen treatment on coronary risk have produced contradictory results. We have previously shown that, like premenopausal white women, female cynomolgus macaques are relatively protected against coronary artery atherosclerosis (CAA). Ovariectomy results in a more atherogenic plasma lipid pattern (15–20% increase in total plasma cholesterol and 20–25% decrease in plasma HDL cholesterol concentrations) and an approximate doubling in extent of coronary artery atherosclerosis. Also, reproductively intact females with chronic ovarian endocrine deficiency cannot be distinguished from ovariectomized females in regard to plasma lipid patterns and extent of coronary artery atherosclerosis; and there is an inverse relationship between degree of ovarian deficiency and extent of coronary artery atherosclerosis. In contrast, frequent pregnancy, a hyperestrogenic state, results in 15–20% reductions in both total plasma cholesterol and HDL cholesterol concentrations and an approximate 50% reduction in extent of coronary artery atherosclerosis. Also, among pregnant females, extent of coronary artery atherosclerosis was inversely associated (p = -0.66, P ≤ 0.01) with an index of the magnitude and duration of pregnancy-induced elevations in plasma estradiol concentrations. This index was the single variable that correlated most strongly with the extent of coronary artery atherosclerosis. Females ranking in the top half of the distribution of both magnitude and duration of the pregnancy-induced estradiol elevation were virtually unaffected by coronary artery atherosclerosis (median = 0.001 mm2). These results indicate that factors that influence endogenous reproductive steroid levels also seem to influence the atherosclerotic process, and evidence exists for a relationship between circulating levels of estradiol and extent of coronary artery atherosclerosis.
KeywordsPregnant Female Total Plasma Cholesterol Cynomolgus Macaque Intact Female Plasma Estradiol
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