Increased urinary excretion of 2-hydroxyestrone but not 16 alpha-hydroxyestrone in premenopausal women during a soya diet containing isoflavones

Asian diets high in soy are associated with lower risk for breast cancer co mpared with Western diets. Moreover, higher levels of two putative carcinog enic metabolites of 17 beta-estradiol, 4- and 16 alpha-hydroxyestrogen, and lower amounts of anticarcinogenic metabolites, 2-hydroxyestrogens, have be en associated with greater breast cancer risk. In this study, we tested the hypothesis that consumption of a soya diet containing the weakly estrogeni c isoflavones genistein and daidzein may alter the metabolism of 17 beta-es tradiol to 2- and 16 alpha-hydroxylated products. Eight premenopausal women were placed on a soya-containing, constant diet in a metabolic unit. The d iet provided 400 kilocalories from soymilk and 113-202 mg/day (158 +/- 26 m g/day, mean a SD) isoflavones daily for a complete menstrual cycle. After a washout period of 4 months, the subjects consumed the same diet, but with soymilk that contained <4.5 mg/day isoflavones ("isoflavone-free"). Urine s amples were collected for 24 h daily for the entire cycle during each soya diet period for the analysis of daidzein, genistein, and 2- and 16 alpha-hy droxyestrone, Subjects excreted measurable amounts of daidzein (11.6-39.2 m g/day) and genistein (2.9-18.2 mg/day) during the isoflavone-rich soya diet but not during the isoflavone-free soya diet. The diet rich in isoflavones increased the cycle mean daily urinary excretion of 2-hydroxyestrone (aver aged over the entire cycle) from 11.6 +/- 2.06 to 17.0 +/- 2.96 nmol/12-h ( P = 0.03), a 47% increase, However, the mean daily excretion of 16 alpha-hy droxyestrone did not change (7.0 +/- 1.14 nmol/12-h during the isoflavone-f ree and 7.7 +/- 1.25 nmol/12h during the isoflavone-rich diet; P = 0.36), T he ratio of 2-hydroxyestrone to 16 alpha-hydroxyestrone was higher during t he isoflavone-rich soya diet (2.6 +/- 0.34) than during the isoflavone-free diet (2.0 +/- 0.32; P = 0.01), a 27% increase. These results suggest that soya isoflavones increase the metabolism of endogenous estrogens to the pro tective 2-hydroxylated estrogens in women, and this may play an important r ole in lowering 17 beta-estradiol levels and the long-term risk for breast cancer.