Inhibition of Postmenopausal Atherosclerosis Progression: A Comparison of the Effects of Conjugated Equine Estrogens and Soy Phytoestrogens

Abstract

Experimental evidence was sought concerning whether soy phytoestrogens (SPEs) inhibit postmenopausal atherosclerosis progression/extent and, if so, their effectiveness relative to traditional estrogen replacement therapy. Premenopausal cynomolgus monkeys were fed a moderately atherogenic diet (26 months) to induce atherosclerosis. After ovariectomy, the moderately atherogenic diet was continued, and they were treated (36 months) with a control diet (soy protein depleted of SPEs), a diet containing SPEs in soy protein isolate, or a diet containing SPE-depleted soy protein with conjugated equine estrogens (CEE; Premarin) added. SPE effects on plasma lipids were better than those of CEE (higher high density lipoprotein cholesterol and no increase in triglyceride). Relative to the control group, CEE treatment inhibited (P = 0.0001), and SPE treatment partially inhibited (P = 0.10) the progression of atherosclerosis (common iliac artery atherosclerosis before and after treatment). CEE-treated monkeys had much less coronary artery atherosclerosis than the controls (P = 0.0002), whereas SPE-treated monkeys were intermediate in lesion extent between the controls and the CEE-treated animals (P = 0.02). Both CEE and SPE significantly reduced the extent of common carotid and internal carotid artery atherosclerosis, and the two treatment groups were not significantly different.

Effects of dietary soy protein on iliac and carotid artery atherosclerosis and gene expression in male monkeys

“…The current study confirmed the results of previous studies in showing that iliac artery plaque area was highly correlated with CAA (3,8), and iliac artery gene expression was more highly correlated with CAA than was carotid artery gene expression. These findings parallel studies in human populations reporting that coronary artery calcification was more highly correlated with calcification in the iliac arteries than in the carotid arteries (17).…”

“…While carotid arteries generally develop smaller plaques than do iliac arteries (this report, 3,17), it is unknown if this is due to delayed initiation of lesion development, to slowed progression, or both, relative to iliac artery plaques. Carotid arteries had significantly lower expression of both MCP-1 and ICAM-1 than did iliac arteries, which may have resulted in less monocyte adhesion and recruitment and smaller plaque size relative to the iliac arteries.…”

“…Dietary soy has long been thought to have positive health benefits with respect to atherosclerosis-related disease (1)(2)(3)(4). However, the roles of the individual soy components, as well as the mechanisms underlying the beneficial effects of soy are poorly understood.…”

“…Studies with nonhuman primate models have demonstrated inhibitory effects of dietary SPI on atherosclerosis in both male (juvenile and adult) and female (adult) subjects (2,3,7). Sex as well as the timing of intervention may be important issues, as age and or amount of atherosclerosis at initiation may impact outcomes.…”

Effects of long-term estrogen replacement therapy on bone turnover in periarticular tibial osteophytes in surgically postmenopausal cynomolgus monkeys

“…The animals used in this study were from a study that was designed to evaluate the effects of estrogen deficiency, exogenous estrogen replacement therapy (ERT), and soy phytoestrogen treatment (SPE) on coronary artery atherosclerosis [10]. The original study included 180 feral adult female cynomolgus macaques and has previously been described in detail 7,10].…”