The Differential Effect of the Phytoestrogen Genistein on Cardiovascular Risk Factors in Postmenopausal Women: Relationship With the Metabolic Status

Abstract

Soy supplements with genistein and other phytoestrogens have become an alternative to hormone replacement therapy in postmenopausal women, although there are conflicting findings on their benefit. Some clinical trials have shown that soy supplementation improves cardiovascular risk factors in postmenopausal women but other studies have found little such benefit. This randomized placebo-controlled study investigated the effect of genistein on glucose and lipid metabolism and on vascular reactivity in postmenopausal women with differing metabolic status. Fifty fasting postmenopausal women were randomized to 1 of 2 treatment groups for at least 24 weeks: group A (n = 30) were given an oral dose of 54 mg/day of genistein and group B (n = 20) received a placebo. Patients in group A were classified as normoinsulinemic (n = 14) and hyperinsulinemic (n = 12). Measured parameters included the body mass index and other anthropometric criteria, serum hormones and lipids, the oral glucose tolerance test, and glycemic, insulin, and C-peptide plasma levels. Insulin sensitivity was examined both with euglycemic-hyperinsulinemic clamps and a homeostasis model assessment for insulin resistance. Endothelial function (vascular reactivity) was analyzed by ultrasound. Compared with the placebo, basal fasting insulin levels were significantly decreased at 24 weeks by genistein treatment; insulin sensitivity (assessed by homeostasis model assessment for insulin resistance) and glucose levels were significantly improved. Among normoinsulinemic patients, a significant reduction was noted in both fasting glucose and area under the curve (AUC) glucose plasma levels after genistein treatment in comparison to the placebo. Conversely, among hyperinsulinemic patients, genistein treatment reduced insulin, C-reactive peptide, and AUC-insulin levels. No significant variation in the lipid profile occurred in the normoinsulinemic group after genistein, whereas there was a significant improvement in high-density lipoprotein cholesterol levels in the hyperinsulinemic women. Among normoinsulinemic but not hyperinsulinemic patients, genistein enhanced the endothelial response to stimuli both in flow-mediated and nitrate-mediated dilatation. These findings show that 6-month treatment with genistein significantly improves glycemic metabolism and endothelial function in postmenopausal women. Among normoinsulinemic patients especially, there is improvement in glycemic and vascular reactivity indexes. In contrast, among hyperinsulinemic patients, genistein seems to improve insulin sensitivity indexes and the lipid profile.