CONTEXT: Genistein, a soy isoflavone, has received wide attention over the last few years because of its potential preventive role for cardiovascular disease. OBJECTIVE: To assess the effects of genistein administration (54 mg/day) on some predictors of cardiovascular risk in osteopenic, postmenopausal women. DESIGN: Randomized, double-blind, placebo-controlled trial.

SETTING: Three Italian university medical centers. INTERVENTION: After a 4-week 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 D₃. OUTCOME MEASURES: Blood lipid profiles, fasting glucose and insulin, HOMA-IR, fibrinogen, sICAM-1, sVCAM-1, F2-isoprostanes and osteoprotegerin (OPG) at baseline and after 12 and 24 months of treatment were measured. RESULTS: Compared to placebo, genistein significantly reduced fasting glucose and insulin as well as HOMA-IR after both 12 and 24 months of treatment. By contrast, genistein administration did not affect blood lipid levels though fibrinogen, F2-isoprostanes, sICAM-1 and sVCAM-1 decreased significantly compared to placebo after 24 months. Serum OPG was higher in the genistein group compared to placebo. At 24 months, the genistein group showed no change in endometrial thickness compared to 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 of genistein plus calcium, vitamin D₃ and a healthy diet was associated with favourable effects on both glycemic control and some cardiovascular risk markers in a cohort of osteopenic, postmenopausal women.