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

Asian diets high in soy are associated with lower risk for breast cancer compared with Western diets. Moreover, higher levels of two putative carcinogenic metabolites of 17β-estradiol, 4- and 16α-hydroxyestrogen, and lower amounts of anticarcinogenic metabolites, 2-hydroxyestrogens, have been associated with greater breast cancer risk. In this study, we tested the hypothesis that consumption of a soya diet containing the weakly estrogenic isoflavones genistein and daidzein may alter the metabolism of 17β-estradiol to 2- and 16α-hydroxylated products. Eight premenopausal women were placed on a soya-containing, constant diet in a metabolic unit. The diet provided 400 kilocalories from soymilk and 113-202 mg/day (158 ± 26 mg/day, mean ± 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 samples were collected for 24 h daily for the entire cycle during each soya diet period for the analysis of daidzein, genistein, and 2- and 16α-hydroxyestrone. Subjects excreted measurable amounts of daidzein (11.6-39.2 mg/day) and genistein (2.918.2 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 (averaged 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 16α-hydroxyestrone did not change (7.0 ± 1.14 nmol/12-h during the isoflavone-free and 7.7 ± 1.25 nmol/12-h during the isoflavone-rich diet; P = 0.36). The ratio of 2- hydroxyestrone to 16α-hydroxyestrone was higher during the 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 protective 2-hydroxylated estrogens in women, and this may play an important role in lowering 17β- estradiol levels and the long-term risk for breast cancer.