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Carcinogenesis Advance Access originally published online on October 9, 2006
Carcinogenesis 2007 28(4):801-808; doi:10.1093/carcin/bgl163
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© The Author 2006. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Soy isoflavonoid effects on endogenous estrogen metabolism in postmenopausal female monkeys

Charles E. Wood*, Thomas C. Register and J.Mark Cline

Department of Pathology, Section on Comparative Medicine, Wake Forest University School of Medicine Medical Center Boulevard, Winston-Salem, North Carolina 27157-1040, USA

*To whom requests for reprints and correspondence should be addressed. Tel: +1 336 716 1636; Fax: +1 336 716 1515; E-mail: chwood{at}wfubmc.edu

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 (E1) 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 16{alpha}-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 E1, 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.

Abbreviations: BW, body weight; CEE, conjugated equine estrogens; E1, estrone; E2, estradiol; E1G, estrone glucuronide; E1S, estrone sulfate; 2OH-E1, 2-hydroxyestrone; 16{alpha}OH-E1, 16{alpha}-hydroxyestrone; OC, oral contraceptives

Received May 24, 2006; revised July 13, 2006; accepted August 16, 2006.


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