title: Increased urinary excretion of 2-hydroxyestrone but not 16alpha-hydroxyestrone in premenopausal women during a soya diet containing isoflavones.
abstract: 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 17beta-estradiol, 4- and 16alpha-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 17beta-estradiol to 2- and 16alpha-hydroxylated products. Eight pre-menopausal 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 16alpha-hydroxyestrone. Subjects excreted measurable amounts of daidzein (11.6-39.2 mg/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 (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 16alpha-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 16alpha-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 17beta-estradiol levels and the long-term risk for breast cancer.
authors.affiliation: Department of Preventive Medicine and Community Health, The University of Texas Medical Branch, Galveston 77555-1110, USA. LLu@UTMB.EDU
authors.forename: L J
authors.initials: LJ
authors.lastname: Lu
authors.forename: M
authors.initials: M
authors.lastname: Cree
authors.forename: S
authors.initials: S
authors.lastname: Josyula
authors.forename: M
authors.initials: M
authors.lastname: Nagamani
authors.forename: J J
authors.initials: JJ
authors.lastname: Grady
authors.forename: K E
authors.initials: KE
authors.lastname: Anderson
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D004032:Diet; D005260:Female; D006801:Humans; D006894:Hydroxyestrones / Q000652:urine*; D007529:Isoflavones / Q000008:administration & dosage*; D009376:Neoplasms, Hormone-Dependent / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D017697:Premenopause; D013025:Glycine max
chemical_list: D006894:Hydroxyestrones; D007529:Isoflavones; C026702:16-hydroxyestrone; C024980:2-hydroxyestrone