Effects of soy isoflavones on estrogen and phytoestrogen metabolism in premenopausal women

Isoflavones and lignans are soy phytoestrogens that have been suggested to be anticarcinogenic, The mechanisms by which they exert cancer-preventive e ffects may involve modulation of estrogen synthesis and metabolism, To eval uate this hypothesis, a randomized, cross-over soy isoflavone feeding study was performed in 12 healthy premenopausal women, The study consisted of th ree diet periods, each separated by a washout of similar to 3 weeks. Each d iet period lasted for three menstrual cycles plus 9 days (averaging similar to 100 days), during which subjects consumed their habitual diets suppleme nted with soy protein powder providing 0.16 (control diet), 1.01, or 2.01 m g of total isoflavones per kg of body weight per day (10 +/- 1.1, 65 +/- 9. 4, or 129 +/- 16 mg/day, respectively), A 72-h urine sample was collected d uring the midfollicular phase (days 7-9) of the fourth menstrual cycle in e ach diet period. Urine samples were analyzed for 10 phytoestrogens and 15 e ndogenous estrogens and their metabolites by a capillary gas chromatography -mass spectrometry method. Urinary excretion of isoflavonoids and lignans s ignificantly increased with increased isoflavone consumption. Compared,vith the control diet, increased isoflavone consumption decreased urinary excre tion of estradiol, estrone, estriol, and total estrogens, as well as excret ion of the hypothesized genotoxic estrogen metabolites, 16 alpha-hydroxyest rone, 4-hydroxyestrone, and 4-hydroxyestradiol. Of importance are the obser vations of a significant increase in the 2-hydroxyestrone/16 alpha-hydroxye strone ratio and a decrease in the genotoxic/total estrogens ratio. These d ata suggest that soy isoflavone consumption may exert cancer-preventive eff ects by decreasing estrogen synthesis and altering metabolism away from gen otoxic metabolites toward inactive metabolites.