title: Soy isoflavonoid effects on endogenous estrogen metabolism in postmenopausal female monkeys.
abstract: Endogenous estrogens are important determinants of breast cancer risk in postmenopausal women. In this study we evaluated the effects of dietary soy isoflavonoids on endogenous estrogen metabolism in a postmenopausal primate model. Ovariectomized female cynomolgus monkeys were randomized to receive one of three diets for 36 months: (i) isoflavonoid-depleted soy protein isolate (SPI-) (n = 29); (ii) soy protein isolate with 129 mg isoflavonoids/1800 kcal diet (8.6 mg isoflavonoids/kg body weight (BW), expressed in aglycone units) (SPI+) (n = 29) or (iii) isoflavonoid-depleted soy protein isolate with conjugated equine estrogens (CEE) at a dose of 0.625 mg/1800 kcal diet (0.042 mg CEE/kg BW) (n = 30). Mean plasma isoflavonoid concentrations in the SPI+ group were 946.9 +/- 135.9 nmol/l, and equol was the primary circulating isoflavonoid (549.7 +/- 61.6 nmol/l). The SPI+ diet resulted in lower serum estrone (E(1)) after 29 (-26%, P = 0.03) and 34 months (-21%, P = 0.04) compared to the SPI- diet, while urinary 2-hydroxyestrone (P = 0.005) and the 2 to 16alpha-hydroxyestrone ratio (P < 0.0001) were markedly higher in the SPI+ group compared to SPI-. Isoflavonoid treatment did not significantly alter gene markers of estrogen metabolism or estrogen receptor agonist activity in breast tissue. Within the SPI+ group, higher concentrations of serum equol (but not daidzein or genistein) corresponded to significantly lower serum E(1), mammary gland epithelial area and uterine weight (P < 0.01 for all). These findings suggest that long-term exposure to soy isoflavonoids, equol in particular, may facilitate endogenous estrogen clearance and catabolism to more benign 2-hydroxylated metabolites.
authors.affiliation: Department of Pathology, Section on Comparative Medicine, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina 27157-1040, USA. chwood@wfubmc.edu
authors.forename: Charles E
authors.initials: CE
authors.lastname: Wood
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Register
authors.forename: J Mark
authors.initials: JM
authors.lastname: Cline
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D004032:Diet; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D007529:Isoflavones / Q000008:administration & dosage* / Q000097:blood; D008252:Macaca fascicularis; D008321:Mammary Glands, Animal / Q000187:drug effects* / Q000378:metabolism; D010052:Ovariectomy; D017698:Postmenopause; D011960:Receptors, Estrogen / Q000378:metabolism; D011987:Receptors, Steroid / Q000378:metabolism; D030262:Soybean Proteins / Q000008:administration & dosage; D013025:Glycine max / Q000737:chemistry*; D014599:Uterus / Q000187:drug effects* / Q000378:metabolism
chemical_list: D015415:Biomarkers; D004967:Estrogens; D007529:Isoflavones; D011960:Receptors, Estrogen; D011987:Receptors, Steroid; D030262:Soybean Proteins