Context: Genistein, a soy isoflavone, has received wide attention over the last few years because of its potential preventive role for cardiovascular disease.

Objective: Our objective was to assess the effects of genistein administration (54 mg/d) on some predictors of cardiovascular risk in osteopenic, postmenopausal women.

Design and setting: We conducted a randomized, double-blind, placebo-controlled trial at three Italian university medical centers.

Intervention: After a 4-wk stabilization on a standard isocaloric, fat-reduced diet, participants were randomly assigned to receive genistein (n = 198) or placebo (n = 191) daily for 24 months. Both intervention and placebo contained calcium and vitamin D(3).

Outcome measures: Blood lipid profiles, fasting glucose and insulin, homeostasis model assessment for insulin resistance, fibrinogen, soluble intercellular adhesion molecule-1, soluble vascular cellular adhesion molecule-1, F2-isoprostanes, and osteoprotegerin at baseline and after 12 and 24 months of treatment were measured.

Results: Compared with placebo, genistein significantly reduced fasting glucose and insulin as well as homeostasis model assessment for insulin resistance after both 12 and 24 months of treatment. By contrast, genistein administration did not affect blood lipid levels although fibrinogen, F2-isoprostanes, soluble intercellular adhesion molecule-1, and soluble vascular cellular adhesion molecule-1 decreased significantly compared with placebo after 24 months. Serum osteoprotegerin was higher in the genistein group compared with placebo. At 24 months, the genistein group showed no change in endometrial thickness compared with placebo. Most treatment-related adverse events were moderate and composed of gastrointestinal side effects [genistein, n = 37 (19%); placebo, n = 15 (8%)].

Conclusions: These results suggest that 54 mg genistein plus calcium, vitamin D(3), and a healthy diet was associated with favorable effects on both glycemic control and some cardiovascular risk markers in a cohort of osteopenic, postmenopausal women.