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Breast and Uterine Effects of Soy Isoflavones and Conjugated Equine Estrogens in Postmenopausal Female Monkeys

Comparative Medicine Clinical Research Center, Wake Forest University Health Sciences, Winston-Salem, North Carolina 27157-1040

Address all correspondence and requests for reprints to: Charles E. Wood, D.V.M., Comparative Medicine Clinical Research Center, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina 27157-1040. E-mail: chwood{at}wfubmc.edu.

In this study we evaluated the long-term effects of soy isoflavones on intermediate markers of cancer risk in the normal postmenopausal monkey breast and uterus. Ovariectomized female cynomolgus monkeys were randomized to receive one of three diets for 36 months: 1) isoflavone-depleted soy protein isolate (SPI–) (n = 57); 2) soy protein isolate with the equivalent of 129 mg/d isoflavones (SPI+) (n = 60); or 3) isoflavone-depleted soy protein isolate with conjugated equine estrogens at a dose scaled to approximate 0.625 mg/d in women (n = 62). End points included breast and uterine proliferation markers, sex steroid receptor expression, and serum estrogens. Epithelial proliferation and progesterone receptor expression in the breast and uterus were significantly higher in the conjugated equine estrogen group, compared with SPI+ and SPI– groups, whereas no significant differences were detected between the SPI+ and SPI– groups. SPI+ treatment resulted in significantly lower serum concentrations of estrone (P < 0.01) and estradiol (P < 0.05) vs. SPI–. Within the SPI+ group, serum isoflavone concentrations were inversely correlated with serum estrone and mammary glandular area. These findings suggest that high dietary levels of soy isoflavones do not stimulate breast or uterine proliferation in postmenopausal monkeys and may contribute to an estrogen profile associated with reduced breast cancer risk.

This work was supported by Program Project Grant HL-45666 from the National Institutes of Health/National Heart, Lung, and Blood Institute, Bethesda, Maryland, NIH/National Center for Complementary and Alternative Medicine R01-AT00639, and NIH/National Center for Research Resources T32 RR 07009.

Abbreviations: BMI, Body mass index; BW, body weight; CEE, conjugated equine estrogen; E1, estrone; E2, estradiol; ER, estrogen receptor-; E1-S, estrone sulfate; H&E, hematoxylin and eosin; OC, oral contraceptive; PR, progesterone receptor; SPI+, diet of soy protein isolate with isoflavones; SPI–, diet of soy protein isolate depleted of isoflavones.

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