Estrogen replacement therapy (ERT) is one of the most challenging issues women and their physicians have to face. Clinical and epidemiological studies have provided conflicting data regarding the cardiovascular benefit versus risk in women using ERT. Although ERT may improve several risk factors of coronary heart disease such as favorable changes in lipid profile, an associated increased incidence of uterine and breast tumors has jeopardized the clinical use of ERT. We reported here that the phytoestrogen alpha-zearalanol is effective against atherosclerotic development without overt growth-promoting effects in the uterus compared to estrogen. These results suggest clinical potential of this phytoestrogen as a "safe estrogen" with less risk of tumorogenesis.