Dietary soy protein and isoflavones: minimal beneficial effects on bone and no effect on the reproductive tract of sexually mature ovariectomized Sprague-Dawley rats Janice M. Bahr, PhD, 1 Masaaki Nakai, PhD, 1 Alexander Rivera, 1 Jane Walsh, PhD, 1 Glenda L. Evans, PhD, 2 Sutada Lotinun, PhD, 2 Russell T. Turner, PhD, 2 Molly Black, 3 and Elizabeth H. Jeffery, PhD 3 ABSTRACT Objective: The present study was conducted to determine the effects of dietary soy protein and isoflavones on bone and the reproductive tract in the absence of the ovary. Design: Three-month-old Sprague-Dawley rats (n = 56) were either sham-operated or ovari- ectomized and then fed diets containing casein or soy protein ± isoflavone extract for 12 weeks. The amounts of casein, soy protein, and extract (per kg diet) in each group were as follows: (1) Ovariectomy, 200 g of casein; (2) Ovariectomy+low soy, 100 g of casein + 100 g of soy protein; (3) Ovariectomy+high soy, 200 g of soy protein; (4) Ovariectomy+low extract, 200 g of casein + 17.2 g of extract; (5) Ovariectomy+high extract, 200 g of casein + 34.4 g of extract; (6) Ovary intact, 200 g of casein; (7) Ovariectomy+estradiol-17b, 200 g of casein. Diet consumption, body weight, uterine weight, urine deoxypyridinoline, and bone mineral density of the femur and lumbar vertebrae were measured. The femur rigidity was evaluated by histomorphometry. The reproductive tract (uterus, vagina, and cervix) was studied histologically. Results: The Ovariectomy group showed significant increases in body weight, diet consumption, and deoxypyridinoline, decreases in uterine weight and bone mineral density, and negative changes in histomorphometry compared with the Ovary intact group. Neither soy protein nor extract diets abrogated these alterations, except for the Ovariectomy+high extract group that showed statistically significant positive changes in histomorphometric parameters. There were no histological differ- ences in the reproductive tract among Ovariectomy, Ovariectomy+soy, and Ovariectomy+extract groups. The estradiol-17b replacement abrogated ovariectomy-induced alterations. Conclusion: Dietary intake of isoflavones by sexually mature ovariectomized rats has a minimal beneficial effect on bone with no effect on the reproductive tract. Key Words: Bone – Isoflavones – Ovariectomized rat – Reproductive tract – Soy. P ostmenopausal osteoporosis is a major health problem as women today can expect to live at least one third of their active lives after meno- pause. According to the National Osteoporosis Foundation (http://www.nof.org/), 44 million Ameri- cans have low bone mineral density and thus are at risk for osteoporosis. Currently, 10 million adults have osteoporosis, with the majority being women. Cessa- tion of estrogen production at menopause results in unregulated bone turnover and bone loss, because estrogen normally plays a major role in the regulation of Received February 26, 2004; revised and accepted May 11, 2004. From the 1 Department of Animal Sciences and 3 Department of Food Science and Human Nutrition, University of Illinois, Urbana, IL; and 2 Department of Orthopedics, Mayo Graduate School of Medicine, Rochester, MN. This study was supported in part by National Institutes of Health Grant AG17521 (J.M.B./R.T.T./E.H.J.) and National Institute of Environmen- tal Health Science Grant ES07326 (A.R.). Address correspondence to: Janice M. Bahr, PhD, Professor, Department of Animal Sciences, University of Illinois at Urbana-Champaign, 1207 West Gregory Drive, Urbana, IL 61801. E-mail: jbahr@uiuc.edu JOBNAME: meno 12#2 2005 PAGE: 1 OUTPUT: Thu March 10 20:45:01 2005 lww/meno/82367/GME150916 Prod#: GME150916 Menopause: The Journal of The North American Menopause Society Vol. 12, No. 2, pp. 165-173 DOI: 10.1097/01.GME.0000135246.04349.AA Ó 2005 The North American Menopause Society ‘ s Text printed on acid-free paper. Menopause, Vol. 12, No. 2, 2005 165