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Carcinogenesis Advance Access published online on October 9, 2006
Carcinogenesis, 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
Received May 24, 2006
Revised July 13, 2006
Accepted August 16, 2006

CANCER PREVENTION

Soy isoflavonoid effects on endogenous estrogen metabolism in postmenopausal female monkeys

Charles E. Wood 1 *, Thomas C. Register 1, and J. Mark Cline 1

1 Department of Pathology/Section on Comparative Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA

* To whom correspondence should be addressed.
Charles E. Wood, E-mail: chwood{at}wfubmc.edu


  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: (1) isoflavonoid-depleted soy protein isolate (SPI-) (n=29); (2) soy protein isolate with 129 mg isoflavonoids/1800 kcal diet (8.6 mg isoflavonoids/kg body weight, expressed in aglycone units) (SPI+) (n=29); or (3) 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 body weight) (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 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.

Keywords: estrogen metabolism; breast cancer; soy isoflavonoid; phytoestrogen; equol.
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L. M. Scott, X. Xu, T. D. Veenstra, J. A. Tooze, C. E. Wood, T. C. Register, N. D. Kock, and J. M. Cline
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