Hostname: page-component-cd9895bd7-dk4vv Total loading time: 0 Render date: 2024-12-28T04:30:11.841Z Has data issue: false hasContentIssue false
  • English
  • Français

Health potential of soy isoflavones for menopausal women

Published online by Cambridge University Press:  02 January 2007

John JB Anderson ,
Mary S Anthony ,
J Mark Cline ,
Scott A Washburn  and
Sanford C Garner
John JB Anderson*
Affiliation:
Department of Nutrition, UNC Schools of Public Health and Medicine, Chapel Hill, NC 27599-7400, USA
Mary S Anthony
Affiliation:
Department of Pathology, Wake Forest University School of Medicine, Winston Salem, NC, USA
J Mark Cline
Affiliation:
Department of Pathology, Wake Forest University School of Medicine, Winston Salem, NC, USA
Scott A Washburn
Affiliation:
Department of Obstetrics and Gynecology, Wake Forest University School of Medicine and Lyndhurst Clinic, Winston Salem, NC, USA
Sanford C Garner
Affiliation:
Department of Surgery, Duke University School of Medicine, Durham, NC, USA
*
*Corresponding author: Email: jjb_anderson@unc.edu
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.
Objective:

To review the current literature on the effects of soy isoflavones, one class of phyto-oestrogens, on cardiovascular diseases, osteoporosis, cancer and climacteric symptoms.

Design:

Many study designs were employed in the reports reviewed here, including prospective human trials, observational human studies, animal experiments and in vitro cell studies that explored the protective or preventive effects of soy isoflavones (genistein, daidzein and glycitein alone or mixed).

Setting:

Diverse settings were employed, depending on study design.

Subjects:

Human subjects, mostly menopausal or postmenopausal, were included, as were animal models and specific cell types.

Results:

The findings were: (i) isoflavones plus soy protein together were needed to obtain the highly significant beneficial results on blood lipids and arterial dimensions; (ii) isoflavone treatments alone at high doses (relative to above) consistently improved bone parameters in rodent ovariectomized models, but not in humans or primates; (iii) isoflavones were not consistent in exerting positive effects regarding the prevention or treatment of cancers of the mammary glands, uterus and colon; and (iv) the effects of isoflavones on climacteric symptoms were not clear-cut.

Conclusions:

The promise of soy isoflavones reducing chronic disease risk seems to be non-uniform, with the most conclusive benefits occurring in the prevention of cardiovascular diseases, but other organ systems, such as skeletal and reproductive tissues, may also benefit from the consumption of soy and soy-derived products.

Keywords

Phyto-oestrogensIsoflavonesGenisteinCardiovascular diseasesBlood lipidsOsteoporosisCancerClimacteric symptomsMenopauseSERMs
Type
Review Article
Information
Public Health Nutrition , Volume 2 , Issue 4 , April 1999 , pp. 489 - 504
Copyright
Copyright © CABI Publishing 1999

References

1Adlercreutz, HL, ed. Balliere's Clinical Endocrinology and Metabolism, Vol. 12. London: Ballière Tyndall, 1998.Google Scholar
2Adlercreutz, HL, Mazur, W. Phyto-oestrogens and western diseases. Ann. Med. 1997; 29: 95–120.CrossRefGoogle ScholarPubMed
3Adlercruetz, H, Markkanen, H, Watanabe, S. Plasma concentrations of phytoestrogens in Japanese men. Lancet 1993; 342: 1209–10.CrossRefGoogle Scholar
4Wang, H-J, Murphy, PA. Isoflavone content in commercial soybean foods. J. Agric. Food Chem. 1994; 42: 1666–73.CrossRefGoogle Scholar
5Franke, AA, Custer, LJ, Cerna, CM, Narala, KK. Quantitation of phytoestrogens in legumes by HPLC. J. Agric. Food Chem. 1994; 42: 1905–13.CrossRefGoogle Scholar
6Kurzer, MS, Xu, X. Dietary phytoestrogens. Annu. Rev. Nutr. 1997; 17: 353–81.CrossRefGoogle ScholarPubMed
7Fukutake, M, Takahashi, M, Ishida, K, Kawamura, H, Sugimura, T, Wakabayashi, K. Quantification of genistein and genistin in soybeans and soybean products. Food Chem. Toxicol. 1996; 34: 457–61.CrossRefGoogle ScholarPubMed
8Kaufman, PB, Duke, JA, Brielmann, H, Boik, J, Hoyt, JE. A comparative study of leguminous plants as sources of isoflavones, genistein and daidzein: implications for human nutrition and health. J. Alternat. Complementary Med. 1997; 3: 7–12.CrossRefGoogle ScholarPubMed
9Miksicek, RJ. Commonly occurring plant flavonoids have estrogenic activity. Mol. Pharmacol. 1993; 44: 37–43.Google ScholarPubMed
10Kuiper, GGJM, Lemmen, JG, Carlsson, B, et al. Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor β. Endocrinology 1998; 139: 4252–63.CrossRefGoogle ScholarPubMed
11Miksicek, RJ. Interaction of naturally occurring nonsteroidal estrogens with expressed recombinant human estrogen receptor. J. Steroid Biochem. Mol. Biol. 1994; 49: 153–60.CrossRefGoogle ScholarPubMed
12Adlercreutz, H, Fotsis, T, Bannwart, C, et al. Determination of urinary lignans and phytoestrogen metabolites, potential antiestrogens and anticarcinogens, in urine of women on various habitual diets. J. Steroid Biochem. 1986; 25: 791–7.CrossRefGoogle ScholarPubMed
13King, RA, Bursill, DB. Plasma and urinary kinetics of the isoflavones daidzein and genistein after a single soy meal in humans. Am. J. Clin. Nutr. 1998; 67: 867–72.CrossRefGoogle ScholarPubMed
14Sfakianos, J, Coward, L, Kirk, M, Barnes, S. Intestinal uptake and biliary excretion of the isoflavone genistein in rats. J. Nutr. 1997; 127: 1260–8.CrossRefGoogle ScholarPubMed
15Bennetts, HW, Underwood, EJ, Shier, FL. A specific breeding problem of sheep on subterranean clover pastures in Western Australia. Aust. Vet. J. 1946; 22: 2–12.CrossRefGoogle ScholarPubMed
16Nemere, I. Nongenomic effects of 1,25-dihydroxyvitamin D3: potential relation to a plasmalemmal receptor to the acute enhancement of intestinal calcium transport in chicks. J. Nutr. 1995; 125: S1695–8.Google Scholar
17Machelon, V, Nome, F, Grosse, B, Lieberherr, M. Progesterone triggers rapid transmembrane calcium influx and/or calcium mobilization from endoplasmic reticulum, via a pertussis-insensitive G-protein in granulosa cells in relation to luteinization process. J. Cell. Biochem. 1996; 61: 619–28.3.0.CO;2-A>CrossRefGoogle ScholarPubMed
18Barrett-Connor, E, Grady, D. Hormone replacement therapy, heart disease, and other considerations. Annu. Rev. Public Health 1998; 19: 55–72.CrossRefGoogle ScholarPubMed
19Brett, KM, Madans, JH. Use of postmenopausal hormone replacement therapy estimates from a nationally representative cohort study. Am. J. Epidemiol. 1997; 145: 536–45.CrossRefGoogle ScholarPubMed
20Hulley, S, Grady, D, Bush, T, et al. for the Heart and Estrogen/progestin Replacement Study (HERS) GroupRandomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. JAMA 1998; 280: 605–13.CrossRefGoogle Scholar
21Anderson, JW, Johnstone, BM, Cook-Newell, ME. Meta-analysis of the effects of soy protein intake on serum lipids. N. Engl. J. Med. 1995; 333: 276–82.CrossRefGoogle ScholarPubMed
22Crouse, JR, Morgan, TM, Terry, JG, Ellis, J, Vitolins, M., Burke, GL. A randomized trial comparing the effect of casein with that of soy protein containing varying amounts of isoflavones on plasma concentrations of lipids and lipoproteins, Arch. Intern. Med., in press.Google Scholar
23Baum, JA, Teng, H, Erdman, JW, et al. Long-term intake of soy protein improves blood lipid profiles and increases mononuclear cell low-density-lipoprotein receptor messenger RNA in hypercholesterolemic, postmenopausal women. Am. J. Clin. Nutr. 1998; 68: 545–51.CrossRefGoogle ScholarPubMed
24Anthony, MS, Clarkson, TB, Bullock, BC, Wagner, JD. Soy protein versus soy phytoestrogens in the prevention of diet-induced coronary artery atherosclerosis of male cynomolgus monkeys. Arterioscler. Thromb. Vasc. Biol. 1997; 17: 2524–31.CrossRefGoogle ScholarPubMed
25Anthony, MS, Clarkson, TB, Williams, JK, Effect of soy isoflavones on atherosclerosis potential mechanisms. Am. J. Clin. Nutr. 1998; 68 (Suppl. 6): S1390–3.CrossRefGoogle ScholarPubMed
26Clarkson, TB, Anthony, MS, Williams, JK, Honore, EK, Cline, JM. The potential of soybean phytoestrogens for postmenopausal hormone replacement therapy. Proc. Soc. Exp. Biol. Med. 1998; 217: 365–8.CrossRefGoogle ScholarPubMed
27Anthony, MS, Clarkson, TB. Comparison of soy phytoestrogens and conjugated equine estrogens on atherosclerosis progression in postmenopausal monkeys. Circulation 1998; 97: 829 (abstract).Google Scholar
28Clarkson, TB, Anthony, MS. Effect of hormone replacement therapy on internal carotid artery atherosclerosis of postmenopausal monkeys. Circulation 1998; 97: 830 (abstract).Google Scholar
29Nestel, PJ, Yamashita, T, Sasahara, T, et al. Soy isoflavones improve systemic arterial compliance but not plasma lipids in menopausal and perimenopausal women. Arterioscler. Thromb. Vasc. Biol. 1997; 17: 3392–8.CrossRefGoogle Scholar
30Hodgson, JM, Puddey, IB, Beilin, LJ, Mori, TA, Croft, KD. Supplementation with isoflavonoid phytoestrogens does not alter serum lipid concentrations: a randomized controlled trial in humans. J. Nutr. 1998; 128: 728–32.CrossRefGoogle Scholar
31Greaves, KA, Parks, JS, Williams, JK, Wagner, JD. Intact dietary soy protein, but not an isoflavone-rich soy extract added to casein protein improves plasma lipids in ovariectomized cynomolgus monkeys. J. Nutr., in press.Google Scholar
32Honoré, EK, Williams, JK, Anthony, MS, Clarkson, TB. Soy isoflavones enhance vascular reactivity in atherosclerotic female macaques. Fertil. Steril. 1997; 67: 148–54.CrossRefGoogle ScholarPubMed
33Hodgson, JM, Croft, KD, Puddey, IB, Mori, TA, Beillin, LJ. Soybean isoflavonoids and their metabolic products inhibit in vitro lipoprotein oxidation in serum. J. Nutr. Biochem. 1996; 7: 664–9.CrossRefGoogle Scholar
34Ruiz-Larrea, MB, Mohan, AR, Paganga, G, Miller, NJ, Bolwell, GP, Rice-Evans, CA. Antioxidant activity of phytoestrogenic isoflavones. Free Radic. Res. 1997; 26: 63–70.CrossRefGoogle ScholarPubMed
35Witztum, JL, Steinberg, D. Role of oxidized low density lipoprotein in atherogenesis. J. Clin. Invest. 1991; 88: 1785–92.CrossRefGoogle ScholarPubMed
36Fujio, Y, Yamada, F, Takahashi, K, Shibata, N. Responses of smooth muscle cells to platelet-derived growth factor are inhibited by herbimycin-A tyrosine kinase inhibitor. Biochem. Biophys. Res. Commun. 1993; 195: 79–83.CrossRefGoogle ScholarPubMed
37Shimokado, K, Yokota, T, Umezawa, K, Sasaguri, T, Ogata, J. Protein tyrosine kinase inhibitors inhibit chemotaxis of vascular smooth muscle cells. Arterioscler. Thromb. 1994; 14: 973–981.CrossRefGoogle ScholarPubMed
38Shimokado, K, Umezawa, K, Ogata, J. Tyrosine kinase inhibitors inhibit multiple steps of the cell cycle of vascular smooth muscle cells. Exp. Cell. Res. 1995; 220: 266–73.CrossRefGoogle ScholarPubMed
39Kuruvilla, A, Putcha, G, Poulos, E, Shearer, WT. Tyrosine phosphorylation of phospholipase C concomitant with its activation by platelet-activating factor in a human B cell line. J. Immunol. 1993; 151: 637–48.CrossRefGoogle Scholar
40Murphy, CT, Kellie, S, Westwick, J. Tyrosine-kinase activity in rabbit platelets stimulated with platelet-activating factor. The effect of inhibiting tyrosine kinase with genistein on platelet-signal-molecule elevation and functional responses. Eur. J. Biochem. 1993; 216: 639–51.CrossRefGoogle ScholarPubMed
41Asahi, M, Yanagi, S, Ohta, S, et al. Thrombin-induced human platelet aggregation is inhibited by protein-tyrosine kinase inhibitors, ST638 and genistein. FEBS Lett. 1992; 309: 10–14.CrossRefGoogle ScholarPubMed
42McNicol, A. The effects of genistein on platelet function are due to thromboxane receptor antagonism rather than inhibition of tyrosine kinase. Prostaglandins Leukot. Essent. Fatty Acids 1993; 48: 379–84.CrossRefGoogle ScholarPubMed
43Helmeste, DM, Tang, SW. Tyrosine kinase inhibitors regulate serotonin uptake in platelets. Eur. J. Pharmacol. 1995; 280: R5–7.CrossRefGoogle ScholarPubMed
44Anderson, JJB, Garner, SC. Phytoestrogens and bone. In: Adlercreutz, HL, ed. Balliere's Clinical Endocrinology and Metabolism, Vol. 12. London: Ballière Tyndall, 1998; 1–16.Google Scholar
45Lees, C, Ginn, TA. Soy protein isolate diet does not prevent increased cortical bone turnover in ovariectomized macaques. Calcif. Tissue Int. 1998; 62: 557–8.CrossRefGoogle Scholar
46Arjmandi, BH, Alekel, L, Hollis, BW, et al. Dietary soybean protein prevents bone loss in an ovariectomized rat model of osteoporosis. J. Nutr. 1996; 126: 161–7.CrossRefGoogle Scholar
47Anderson, JJB, Ambrose, WW, Garner, SC. Biphasic effects of genistein on bone tissue in the ovariectomized, lactating rat model. Proc. Soc. Exp. Biol. Med. 1998; 217: 345–50.CrossRefGoogle Scholar
48Blair, HC, Jordan, SE, Peterson, TG, Barnes, S. Variable effects of tyrosine kinase inhibitors on avian oseoclastic activity and reduction of bone loss in ovariectomized rats. J. Cell. Biochem. 1996; 61: 629–37.3.0.CO;2-A>CrossRefGoogle ScholarPubMed
49Potter, SM, Baum, JA, Teng, H, Stillman, RJ, Erdman, JW. JrSoy protein and isoflavones: their effects on blood lipids and bone density in postmenopausal women. Am. J. Clin. Nutr. 1998; 68 (Suppl. 6): S1375–S1379.CrossRefGoogle ScholarPubMed
50Parkin, DM, Muir, CS, Whelan, SL, Gao, YT, Ferlay, J, Powell, J. Cancer Incidence in Five Continents. IARC Scientific Publication No. 120. Lyon: International Agency for Research on Cancer, 1992.Google ScholarPubMed
51Wynder, EL, Fujita, Y, Harris, RE, Hirayama, T, Hiyama, T. Comparative epidemiology of cancer between the United States and Japan: a second look. Cancer 1991; 67: 746–63.3.0.CO;2-1>CrossRefGoogle ScholarPubMed
52Yu, H, Harris, RE, Gao, YT, Gao, R, Wynder, EL. Comparative epidemiology of cancers of the colon, rectum, prostate and breast in Shanghai, China versus the United States. Int. J. Epidemiol. 1991; 20: 76–81.CrossRefGoogle ScholarPubMed
53Ziegler, RG, Hoover, RN, Pike, MC, et al. Migration patterns and breast cancer risk in Asian–American women. J. Natl. Cancer Inst. 1993; 85: 1819–27.CrossRefGoogle ScholarPubMed
54Kato, I, Tominaga, S, Kuroishi, T, Relationship between westernization of dietary habits and mortality from breast and ovarian cancers in Japan. Jpn. J. Cancer Res. 1987; 78: 349–57.Google ScholarPubMed
55Hirose, K, Tajima, K, Hamajima, N, et al. A large-scale, hospital-based case–control study of risk factors of breast cancer according to menopausal status. Jpn. J. Cancer Res. 1995; 86: 146–54.CrossRefGoogle ScholarPubMed
56Ingram, D, Sanders, K, Kolybaba, M, Lopez, D. Case–control study of phyto-oestrogens and breast cancer. Lancet 1997; 350: 990–4.CrossRefGoogle ScholarPubMed
57Lee, HP, Gourley, L, Duffy, SW, Esteve, J, Lee, J, Day, NE. Dietary effects on breast-cancer risk in Singapore. Lancet 1991; 337: 1197–200.CrossRefGoogle ScholarPubMed
58Witte, JS, Ursin, G, Siemiatycki, J, Thompson, WD, Paganini-Hill, A, Haile, RW. Diet and premenopausal bilateral breast cancer: a case–control study. Breast Cancer Res. Treat. 1997; 42: 243–51.CrossRefGoogle ScholarPubMed
59Wu, AH, Ziegler, RG, Horn-Ross, PL, et al. Tofu and risk of breast cancer in Asian–Americans. Cancer Epidemiol. Biomark. Prevent. 1996; 5: 901–6.Google ScholarPubMed
60Yuan, JM, Wang, QS, Ross, RK, Henderson, BE, Yu, MC. Diet and breast cancer in Shanghai and Tianjin, China. Br. J. Cancer 1995; 71: 1353–8.CrossRefGoogle ScholarPubMed
61Zheng, W, Dai, Q, Custer, LJ, Shu, X, Wen, W, Jin, F, Franke, AA. Urinary excretion of isoflavonoids and the risk of breast cancer. Cancer Epidemiol. Biomark. Prevent. 1999; 8: 35–40.Google ScholarPubMed
62Goodman, MT, Wilkens, LR, Hankin, JH, Lyu, LC, Wu, AH, Kolonel, LN. Association of soy and fiber consumption with the risk of endometrial cancer. Am. J. Epidemiol. 1997; 146: 294–306.CrossRefGoogle ScholarPubMed
63Le Marchand, L, Hankin, JH, Wilkens, LR, Kolonel, LN, Englyst, HN, Lyu, LC. Dietary fiber and colorectal cancer risk. Epidemiology 1997; 8: 658–65.CrossRefGoogle ScholarPubMed
64Witte, JS, Longnecker, MP, Bird, CL, Lee, ER, Frankl, HD, Haile, RW. Relation of vegetable, fruit, and grain consumption to colorectal adenomatous polyps. Am. J. Epidemiol. 1996; 144: 1015–25.CrossRefGoogle ScholarPubMed
65Lu, LJ, Anderson, KE, Grady, JJ, Nagamani, M. Effects of soya consumption for one month on steroid hormones in premenopausal women: implications for breast cancer risk reduction. Cancer Epidemiol. Biomark. Prevent. 1996; 5: 63–70.Google ScholarPubMed
66Kampman, E, Potter, JD, Slattery, ML, Caan, BJ, Edwards, S. Hormone replacement therapy, reproductive history, and colon cancer: a multicenter, case–control study in the United States. Cancer Causes Control 1997; 8: 146–58.CrossRefGoogle ScholarPubMed
67Barnes, S, The chemopreventive properties of soy isoflavonoids in animal models of breast cancer. Breast Cancer Res. Treat. 1997; 46: 169–79.CrossRefGoogle ScholarPubMed
68Lamartiniere, CA, Moore, J, Holland, M, Barnes, S. Neonatal genistein chemo prevents mammary cancer. Proc. Soc. Exp. Biol. Med. 1995; 208: 120–3.CrossRefGoogle Scholar
69Lamartiniere, CA, Murrill, WB, Manzolillo, PA, et al. Genistein alters the ontogeny of mammary gland development and protects against chemically-induced mammary cancer in rats. Proc. Soc. Exp. Biol. Med. 1998; 217: 358–64.CrossRefGoogle ScholarPubMed
70Hsieh, CY, Santell, RC, Haslam, SZ, Helferich, WG. Estrogenic effects of genistein on the growth of estrogen receptor-positive human breast cancer (MCF-7) cells in vitro and in vivo. Cancer Res. 1998; 58: 3833–8.Google ScholarPubMed
71Foth, D, Cline, JM. Effects of mammalian and plant estrogens on mammary glands and uteri of macaques. Am. J. Clin. Nutr. 1998; 68 (Suppl.): S1413–S1417.Google ScholarPubMed
72Thiagarajan, DG, Bennink, MR, Bourquin, LD, Kavas, FA. Prevention of precancerous colonic lesions in rats by soy flakes, soy flour, genistein, and calcium. Am. J. Clin. Nutr. 1998; 68 (Suppl.): S1394–S1399.CrossRefGoogle ScholarPubMed
73Koratkar, R, Rao, AV. Effect of soya bean saponins on azoxymethane-induced preneoplastic lesions in the colon of mice. Nutr. Cancer 1997; 27: 206–9.CrossRefGoogle ScholarPubMed
74Rao, CV, Wang, CX, Simi, B, et al. Enhancement of experimental colon cancer by genistein. Cancer Res. 1997; 57: 3717–22.Google ScholarPubMed
75Sorensen, IK, Kristiansen, E, Mortensen, A, et al. The effect of soy isoflavones on the development of intestinal neoplasia in ApcMin mouse. Cancer Lett 1998; 130: 217–25.CrossRefGoogle ScholarPubMed
76Weed, HG, McGandy, RB, Kennedy, AR. Protection against dimethylhydrazine-induced adenomatous tumors of the mouse colon by the dietary addition of an extract of soybeans containing the Bowman–Birk protease inhibitor. Carcinogenesis 1985; 6: 1239–41.CrossRefGoogle ScholarPubMed
77Folman, Y, Pope, GS. The interaction in the immature mouse of potent oestrogens with coumestrol, genistein and other utero-vaginotrophic compounds of low potency. J. Endocrinol. 1966; 34: 215–25.CrossRefGoogle ScholarPubMed
78Messina, MJ, Persky, V, Setchell, KD, Barnes, S. Soy intake and cancer risk: a review of the in vitro and in vivo data. Nutr. Cancer 1994; 21: 113–31.CrossRefGoogle Scholar
79Barnes, S, Peterson, TG. Biochemical targets of the isoflavone genistein in tumor cell lines. Proc. Soc. Exp. Biol. Med. 1995; 208: 103–8.CrossRefGoogle ScholarPubMed
80Peterson, G, Barnes, S. Genistein inhibition of the growth of human breast cancer cells: independence from estrogen receptors and the multi-drug resistance gene. Biochem. Biophys. Res. Commun. 1991; 179: 661–7.CrossRefGoogle ScholarPubMed
81Akiyama, T, Ishida, JSN, Nakagawa, S, et al. Genistein, a specific inhibitor of tyrosine-specific protein kinases. J. Biol. Chem. 1987; 262: 5592–5.CrossRefGoogle ScholarPubMed
82Constantinou, A, Huberman, E. Genistein as an inducer of tumor cell differentiation: possible mechanisms of action. Proc. Soc. Exp. Biol. Med. 1995; 208: 109–15.CrossRefGoogle ScholarPubMed
83Wei, H, Bowen, R, Cai, Q, Barnes, S, Wang, Y. Antioxidant and antipromotional effects of the soybean isoflavone genistein. Proc. Soc. Exp. Biol. Med. 1995; 208: 124–30.CrossRefGoogle ScholarPubMed
84Kiguchi, K, Glesne, D, Chubb, CH, Fujiki, H, Huberman, E. Differential induction of apoptosis in human breast tumor cells by okadaic acid and related inhibitors of protein phosphatases 1 and 2A. Cell Growth Differ. 1994; 5: 995–1004.Google ScholarPubMed
85Fotsis, T, Pepper, M, Adlercreutz, H, et al. Genistein, a dietary-derived inhibitor of in vitro angiogenesis. Proc. Natl. Acad. Sci. USA 1993; 90: 2690–4.CrossRefGoogle ScholarPubMed
86Sathyamoorthy, N, Gilsdorf, JS, Wang, TT. Differential effect of genistein on transforming growth factor beta 1 expression in normal and malignant mammary epithelial cells. Anticancer Res. 1998; 18: 2449–53.Google ScholarPubMed
87Rao, AV, Sung, MK. Saponins as anticarcinogens. J. Nutr. 1995; 125 (Suppl. 3): S717–24.Google ScholarPubMed
88Shamsuddin, AM, Inositol phosphates have novel anticancer function. J. Nutr. 1995; 125 (Suppl. 3): S725–S732.Google ScholarPubMed
89Kennedy, AR. The evidence for soybean products as cancer preventive agents. J. Nutr. 1995; 125 (Suppl. 3): S733–S743.Google ScholarPubMed
90Miksicek, RJ, Lei, Y, Wang, Y. Exon skipping gives rise to alternatively spliced forms of the estrogen receptor in breast tumor cells. Breast Cancer Res. Treat. 1993; 26: 163–74.CrossRefGoogle ScholarPubMed
91Zhang, QX, Hilsenbeck, SG, Fuqua, SA, Borg, A. Multiple splicing variants of the estrogen receptor are present in individual human breast tumors. J. Steroid Biochem. Mol. Biol. 1996; 59: 251–60.CrossRefGoogle ScholarPubMed
92Makela, S, Davis, VL, Tally, WC, et al. Dietary estrogens act through estrogen receptor mediated processes and show no antiestrogenicity in cultured breast cancer cells. Environ. Health Perspect. 1994; 102: 572–8.CrossRefGoogle ScholarPubMed
93McMichael-Phillips, DF, Harding, C, Morton, M, et al. Effects of soy-protein supplementation on epithelial proliferation in the histologically normal human breast. Am. J. Clin. Nutr. 1998; 68 (Suppl.): S1431–S1435.CrossRefGoogle ScholarPubMed
94Clarke, RB, Howell, A, Potten, CS, Anderson, E. Dissociation between steroid receptor expression and cell proliferation in the human breast. Cancer Res. 1997; 57: 4987–91.Google ScholarPubMed
95Kelly, GE, Joannou, GE, Reeder, AY, Nelson, C, Waring, MA. The variable metabolic response to dietary isoflavones in humans. Proc. Soc. Exp. Biol. Med. 1995; 208: 40–3.CrossRefGoogle ScholarPubMed
96Boulet, MJ, Odden, BJ, Lehert, P, Vemer, HM, Visser, A. Climacteric and menopause in seven southeast Asian countries. Maturitas 1994; 19: 157–76.CrossRefGoogle Scholar
97Notelovitz, M. Estrogen replacement therapy indications, contraindications, and agent selection. Am. J. Obstet. Gynecol. 1989; 161: 8–17.CrossRefGoogle ScholarPubMed
98Adlercreutz, H. Western diets and western diseases: some hormonal and biochemical mechanisms and associations. Scand. J. Clin. Lab. Invest. 1990; 50 (Suppl.): 3–23.CrossRefGoogle Scholar
99Hughes, CL. Effects of phytoestrogens on GnRH-induced luteinizing hormone secretion in ovariectomized rats. Reprod. Toxicol. 1988; 1: 179–81.CrossRefGoogle Scholar
100Hughes, CL, Kaldas, RS, Weisinger, AS, McCants, CE, Basham, KB. Acute and subacute effects of naturally occurring estrogens on luteinizing hormone secretion in the ovariectomized rat: 1. Reprod. Toxicol. 1991; 5: 127–32.CrossRefGoogle Scholar
101: Hughes, CL, Chakinali, MM, Reece, SG, Miller, RN, Schomberg, DW, Basham, KB. Acute and subacute effects of naturally occurring estrogens on luteinizing hormone secretion in the ovariectomized rat: 2. Reprod. Toxicol. 1991; 5: 133–7.CrossRefGoogle Scholar
102: Cassidy, A, Bingham, S, Setchell, KDR. Biological effects of a diet of soy protein rich in isoflavones on the menstrual cycle of premenopausal women. Am. J. Clin. Nutr. 1994; 60: 333–40.CrossRefGoogle Scholar
103: Murkies, AL, Lombard, C, Strauss, BJG, Wikcox, G, Burger, HG, Morton, MS. Dietary flour supplementation decreases post-menopausal hot flushes: effect of soy and wheat. Maturitas 1995; 21: 189–95.CrossRefGoogle ScholarPubMed
104: Brzezinski, A, Adlercreutz, H, Shaoul, R, Shmueli, A, Reosler, A, Schenker, JG. Phytoestrogen-rich diet for postmenopausal women. Fifth World Congress on Gynecology, Endocrinology,Barcelona, Spain,1996. Abstract FC.H-02.Google Scholar
105: Albertazzi, P, Pansini, F, Bonaccorsi, G, Zanotti, L, Forini, E, De Aloysio, D. The effect of dietary soy supplementation on hot flushes. Obstet. Gynecol. 1998; 91: 6–11.CrossRefGoogle ScholarPubMed
106: Washburn, SA, Burke, GL, Morgan, TG, Anthony, MS. Effect of soy protein supplementation on serum lipoproteins, blood pressure, and menopausal symptoms in perimenopausal women. Menopause 1999; 6: 7–13.Google ScholarPubMed
107: Anthony, MS, Clarkson, TB, Hughes, CL. Plant and mammalian estrogen effects on plasma lipids of female monkeys. Circulation 1994; 90: 1–235 (abstract).Google Scholar