HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 75/3/477    most recent biolreprod.106.052142v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Wood, C. E. Articles by Cline, J. M. Search for Related Content PubMed PubMed Citation Articles by Wood, C. E. Articles by Cline, J. M. Agricola Articles by Wood, C. E. Articles by Cline, J. M.

Effects of High-Dose Soy Isoflavones and Equol on Reproductive Tissues in Female Cynomolgus Monkeys¹

Department of Pathology/Section on Comparative Medicine,³ Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157-1040 Cancer Research Center of Hawaii,⁴ Honolulu, Hawaii 96813 Division of Biochemical Toxicology,⁵ National Center for Toxicological Research, United States Food and Drug Administration, Jefferson, Arkansas 72079

ABSTRACT

Soy isoflavonoids have well-established estrogenic properties in cell culture and rodent models, raising concerns that high isoflavonoid intake may promote development of uterine and breast cancers. To address this concern we evaluated the effects of high-dose isoflavonoid supplements on reproductive tissues in a postmenopausal primate model. Thirty adult female ovariectomized monkeys (Macaca fascicularis) were randomized to receive a control diet 1) alone, 2) with 509 mg/day of the soy isoflavones genistein and daidzein (IF), or 3) with 1020 mg/day of racemic equol (EQ), an isoflavan, for approximately 1 mo. Doses are expressed in aglycone units as calorically scaled human equivalents. Total serum isoflavonoid levels 4 h postfeeding were <20 nmol/L, 2570.7 nmol/L, and 6944.8 nmol/L for control, IF, and EQ groups, respectively. Equol was the predominant serum isoflavonoid in both IF (72.5%) and EQ (99.7%) groups. Aglycones represented 0.9% (IF) and 0.5% (EQ) of total serum isoflavonoids. Histologically, uteri and mammary glands were diffusely atrophic in all groups. Uterine weight, endometrial thickness, glandular area, and epithelial proliferation in the uterus were not significantly different among treatment groups (ANOVA P > 0.1 for all). Endometrial progesterone receptor gene expression was significantly increased in the IF group (P = 0.02), while protein expression was not altered (ANOVA P > 0.1). Within the mammary gland, proliferation and indicators of estrogen exposure did not differ among treatment groups (ANOVA P > 0.1 for all). These findings indicate that high doses of dietary soy isoflavonoids have minimal uterotrophic or mammotrophic effects in an established primate model.

estradiol, estrogen receptor, female reproductive tract, mammary glands, uterus

¹ Supported by grants from the National Institutes of Health (NCCAM R01-AT00639, NCRR T32 RR 07009, NCI P30-CA71789) and the American Cancer Society (IRG-93-035-09).

² Correspondence: Charles E. Wood, Department of Pathology/Section on Comparative Medicine, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1040. FAX: 336 716 1515; chwood{at}wfubmc.edu