Effects of soy protein and isoflavones on circulating hormone concentrations in pre- and post-menopausal women: A systematic review and meta-analysis

Human Reproduction Update

Volumn 15, Issue 4, 2009, Pages 423-440

  Hooper, L ^a   Ryder, J J ^a   Kurzer, M S ^b,c   Lampe, J W ^d   Messina, M J ^e   Phipps, W R ^f   Cassidy, A ^a  

^a UNIVERSITY OF EAST ANGLIA   (United Kingdom)

^b UNIVERSITY OF MINNESOTA   (United States)

^c UNIVERSITY OF MINNESOTA MEDICAL SCHOOL   (United States)

^d UNIVERSITY OF WASHINGTON   (United States)

^e LOMA LINDA UNIVERSITY   (United States)

^f UNIVERSITY OF ROCHESTER   (United States)

Author keywords

Estradiol; Gonadotrophins; Isoflavones; Sex hormone binding globulin; Soy foods

Indexed keywords

ESTRADIOL; ESTROGEN; ESTRONE; ESTRONE SULFATE; FOLLITROPIN; ISOFLAVONE DERIVATIVE; LIOTHYRONINE; LUTEINIZING HORMONE; PROGESTERONE; SEX HORMONE BINDING GLOBULIN; SOMATOMEDIN BINDING PROTEIN 1; SOYBEAN PROTEIN; THYROID HORMONE; THYROXINE;

CLIMACTERIUM; CLINICAL TRIAL; DRUG EFFICACY; DRUG MECHANISM; FOLLICULAR PHASE; GASTROINTESTINAL DISEASE; HORMONAL REGULATION; HORMONE DETERMINATION; HORMONE SUBSTITUTION; HUMAN; LUTEAL PHASE; MENSTRUAL CYCLE; META ANALYSIS; OUTCOME ASSESSMENT; PATIENT COMPLIANCE; POSTMENOPAUSE; PREMENOPAUSE; PRIORITY JOURNAL; REVIEW; SENSITIVITY ANALYSIS; SYSTEMATIC REVIEW;

ADULT; AGED; FEMALE; GONADAL STEROID HORMONES; HUMANS; ISOFLAVONES; MENSTRUAL CYCLE; MIDDLE AGED; POSTMENOPAUSE; PREMENOPAUSE; SOY FOODS;

EID: 66749171779     PISSN: 13554786     EISSN: 14602369     Source Type: Journal    
DOI: 10.1093/humupd/dmp010     Document Type: Review

References (129)

1. Adams NR. Detection of the effects of phytoestrogens on sheep and cattle. J Anim Sci 1995;73:1509-1515.
2. Adler-creutz H, Mazur W. Phyto-oestrogens and Western diseases. Ann Med 1997;29:95-120.
3. Alekel DL, Germain AS, Peterson CT, Hanson KB, Stewart JW, Toda T. Isoflavone-rich soy protein isolate attenuates bone loss in the lumbar spine of perimenopausal women. Am J Clin Nut 2000;72:844- 852.
4. An JP, Tzagarakis-Foster C, Scharschmidt TC, Lomri N, Leitman DC. Estrogen receptor beta-selective transcriptional activity and recruitment of coregulators by phytoestrogens. J Biol Chem 2001; 276:17808-17814.
5. Anon. Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.0 [updated February 2008]. The Cochrane Collaboration, 2008. www.cochrane-handbook.org.
6. Arjmandi BH, Khalil DA, Smith BJ, Lucas EA, Juma S, Payton ME, Wild RA. Soy protein has a greater effect on bone in postmenopausal women not on hormone replacement therapy, as evidenced by reducing bone resorption and urinary calcium excretion. J Clin Endocrinol Metab 2003; 88 1048-1054.
7. Arjmandi BH, Khalil DA, Lucas EA, Smith BJ, Sinichi N, Hodges SB, Juma S, Munson ME, Payton ME, Tivis RD et al. Soy protein may alleviate osteoarthritis symptoms. Phytomedicine 2004; 11:567-575.
8. Arjmandi BH, Lucas EA, Khalil DA, Devareddy L, Smith BJ, McDonald J, Arquitt AB, Payton ME, Mason C. One year soy protein supplementation has positive effects on bone formation markers but not bone density in postmenopausal women. Nutr J 2005;4:8.
9. Atteritano M, Marini H, Minutoli L, Polito F, Bitto A, Altavilla D, Mazzaferro S, D'Anna R, Cannata ML, Gaudio A et al. Effects of the phytoestrogen genistein on some predictors of cardiovascular risk in osteopenic, postmenopausal women: A two-year randomized, double-blind, placebo-controlled study. J Clin Endocrinol Metab 2007; 3068-3075.
10. Aubertin-Leheudre M, Lord C, Khalil A, Dionne IJ. Effect of 6 months of exercise and isoflavone supplementation on clinical cardiovascular risk factors in obese postmenopausal women: A randomized, double-blind study. Menopause 2007;14:624-629.
11. Axelson M, Sjovall J, Gustafsson BE, Setchell KD. Soya - a Dietary source of the non-steroidal estrogen equol in man and animals. J Endocrinol 1984;102:49-56.
12. Baird DD, Umbach DM, Lansdell L, Hughes CL, Setchell KD, Weinberg CR, Haney AF, Wilcox AJ, McLachlan JA. Dietary intervention study to assess estrugenicity of dietary soy among postmenopausal women. J Clin Endocrinol Metab 1995;80:1685-1690.
13. Balk E, Chung M, Chew P, Ip S, Raman G, Kupelnick B, Tatsioni A, Sun Y, Devine D, Lau J. Effects of soy on health outcomes. Evid Rep Technol Assess (Summ) 2005; 126:1-8.
14. Baum JA, Teng H, Erdman JW, Weigel RM, Klein BP, Persky VW, Freels S, Surya P, Bakhit RM, Ramos E 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;68:545-551.
15. Bennetts 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.
16. Brink E, Coxam V, Robins S, Wahala K, Cassidy A, Branca F. Long-term consumption of isoflavone-enriched foods does not affect bone mineral density, bone metabolism, or hormonal status in early postmenopausal women: A randomized, double-blind, placebo-controlled study. Am J Clin Nutr 2008;87:761-770.
17. Brooks JD, Ward WE, Lewis JE, Hilditch J, Nickell L, Wong E, Thompson LU. Supplementation with flaxseed alters estrogen metabolism in postmenopausal women to a greater extent than does supplementation with an equal amount of soy. Am J Clin Nutr 2004;79:318-325.
18. Brown BD, Thomas W, Hutchins A, Martini MC, Slavin JL. Types of dietary fat and soy minimally affect hormones and biomarkers associated with breast cancer risk in premenopausal women. Nutr Cancer 2002;43 22-30.
19. Bruce B, Messina M, Spiller GA. Isoflavone supplements do not affect thyroid function in iodine-replete postmenopausal women. J Med Food 2003;6:309-316.
20. Cassidy A, Bingham SA, Setchell KD. Biological effects of a diet of soy protein rich in isoflavones on the menstrual cycle of premenopausal women. Am J Clin Nutr 1994;60:333-340.
21. Cassidy A, Bingham S, Setchell K. Biological effects of isoflavones in young women: Importance of the chemical composition of soyabean products. Br J Nutr 1995;74:587-601.
22. Cheng G, Wilczek B, Warner M, Gustafsson JA, Landgren BM. Isoflavone treatment for acute menopausal symptoms. Menopause 2007;14 468-473.
23. Coon JT, Pittler MH, Ernst E. Trifolium pretense isoflavones in the treatment of menopausal hot flushes: A systematic review and meta-analysis. Phytomedicine 2007;14:153-159.
24. Crisafulli A, Altavilla D, Marini H, Bitto A, Cucinotta D, Frisina N, Corrado F, D'Anna R, Squadrito G, Adamo EB et al. Effects of the phytoestrogen genistein on cardiovascular risk factors in postmenopausal women. Menopause (New York, NY) 2005;12:186-192.
25. Cuevas AM, Irribarra VL, Castillo OA, Yanez MD, Germain AM. Isolated soy protein improves endothelial function in postmenopausal hypercholesterolemic women. Eur J Clin Nutr 2003;57:889-894.
26. D'Anna R, Baviera G, Corrado F, Cancellieri F, Crisafulli A, Squadrito F. The effect of the phytoestrogen genistein and hormone replacement therapy on homocysteine and C-reactive protein level in postmenopausal women. Acta Obstet Gynecol Scand 2005;84:474-477.
27. D'Anna R, Cannata ML, Atteritano M, Cancellieri F, Corrado F, Baviera G, Triolo O, Antico F, Gaudio A, Frisina N et al. Effects of the phytoestrogen genistein on hot flushes, endometrium, and vaginal epithelium in postmenopausal women: A 1-year randomized, double-blind, placebo-controlled study. Menopause 2007;14:648-655.
28. Dalais FS, Ebeling PR, Kotsopoulos D, McGrath BP, Teede HJ. The effects of soy protein containing isoflavones on lipids and indices of bone resorption in postmenopausal women. Clin Endocrinol 2003;58 704-709.
29. Deeks JJ, Higgins JP, Altman DG. Analysing data and undertaking meta-analyses. In: Higgins JPT, Green S (eds). Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.0 [updated February 2008]. The Cochrane Collaboration. 2008. 9.2.3.2. www.cochrane-handbook.org.
30. Dent SB, Peterson CT, Brace LD, Swain JH, Reddy MB, Hanson KB, Robinson JG, Alekel DL. Soy protein intake by perimenopausal women does not affect circulating lipids and lipoproteins or coagulation and fibrinolytic factors. J Nutr 2001;131:2280-2287.
31. Desroches S, Mauger JF, Ausman LM, Lichtenstein AH, Lamarche B. Soy protein favorably affects LDL size independently of isoflavones in hypercholesterolemic men and women. J Nutr 2004;134:574-579.
32. Dewell A, Hollenbeck CB, Bruce B. The effects of soy-derived phytoestrogens on serum lipids and lipoproteins in moderately hypercholesterolemic postmenopausal women. J Clin Endocrinol Metab 2002;87:118-121.
33. Duncan AM, Merz BE, Xu X, Nagel TC, Phipps WR, Kurzer MS. Soy isoflavones exert modest hormonal effects in premenopausal women. J Clin Endocrinol Metab 1999a;84:192-197.
34. Duncan AM, Underhill KE, Xu X, Lavalleur J, Phipps WR, Kurzer MS. Modest hormonal effects of soy isoflavones in postmenopausal women [erratum appears in J Clin Endocrinol Metab 2000;85:448]. J Clin Endocrinol Metab 1999b;84:3479-3484.
35. Eden JA, Mackey R, Ekangaki A. Effects of soy protein on postmenopausal women and men with elevated plasma lipids. J Nutr 2000;130 671S.
36. Elbourne DR, Altman DG, Higgins JP, Curtin F, Worthington HV, Vail A. Meta-analyses involving cross-over trials: Methodological issues. Int J Epidemiol 2002;31:140-149.
37. Endogenous Hormones and Breast Cancer Collaborative Group. Endogenous sex hormones and breast cancer postmenopausal women: Reanalysis of nine prospective studies. J Natl Cancer Inst 2002; 94:606-616.
38. Erdman JW Jr, Badger TM, Lampe JW, Setchell KD, Messina M. Not All soy products are created equal: Caution needed in interpretation of research results. J Nutr 2004;134:1229S-1233S.
39. Follmann D, Elliott P, Suh I, Cutler JA. Variance imputation for overviews of clinical trials with continuous response. J Clin Epidemiol 1992; 45:769-773.
40. Fritz KL, Seppanen CM, Kurzer MS, Csallany SA. The in vivo antioxidant activity of soybean isoflavones in human subjects. Nutr Res 2003; 23:479-487.
41. Gallo D, Zannoni GF, Apollonio P, Martinelli E, Ferlini C, Passetti G, Riva A, Morazzoni P, Bombardelli E, Scambia G. Characterization of the pharmacologic profile of a standardized soy extract in the ovariectomized rat model of menopause: Effects on bone, uterus, and lipid profile. Menopause 2005;12:589-600.
42. Gann PH, Kazer R, Chatterton R, Gapstur S, Thedford K, Helenowski I, Giovanazzi S, Van Horn L. Sequential, randomized trial of a low-fat, high-fiber diet and soy supplementation: Effects on circulating IGF-I and its binding proteins in premenopausal women. Int J Cancer 2005; 116:297-303.
43. Gardner CD, Newell KA, Cherin R, Haskell WL. The effect of soy protein with or without isoflavones relative to milk protein on plasma lipids in hypercholesterolemic postmenopausal women. Am J Clin Nutr 2001; 73:728-735.
44. 2 receptor density but not plasma lipids in menopausal women. Maturitas 2006;54:270-276.
45. Goldin BR, Brauner E, Adlercreutz H, Ausman LM, Lichtenstein AH. Hormonal response to diets high in soy or animal protein without and with isoflavones in moderately hypercholesterolemic subjects. Nutr Cancer 2005;51:1-6.
46. Greany KA, Nettleton JA, Wangen KE, Thomas W, Kurzer MS. Probiotic consumption does not enhance the cholesterol-lowering effect of soy in postmenopausal women. J Nutr 2004;134:3277-3283.
47. Greany KA, Nettleton JA, Wangen KE, Thomas W, Kurzer MS. Consumption of isoflavone-rich soy protein does not alter homocysteine or markers of inflammation in postmenopausal women. Eur J Clin Nutr 2008;62 1419-1425.
48. Han KK, Soares JM Jr, Haidar MA, de Lima GR, Baracat EC. Benefits of soy isoflavone therapeutic regimen on menopausal symptoms. Obstet Gynecol 2002;99:389-394.
49. Harkness LS, Fiedler K, Sehgal AR, Oravec D, Lerner E. Decreased bone resorption with soy isoflavone supplementation in postmenopausal women. J Womens Health 2004;13:1000-1007.
50. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003;327:557-560.
51. Howes LG, Howes JB, Knight DC. Isoflavone therapy for menopausal flushes: A systematic review and meta-analysis. Maturitas 2006; 55:211.
52. Huang HY, Yang HP, Yang HT, Yang TC, Shieh MJ, Huang SY. One-year soy isoflavone supplementation prevents early postmenopausal bone loss but without a dose-dependent effect. J Nutr Biochem 2006;17 509-517.
53. Hwang CS, Kwak HS, Lim HJ, Lee SH, Kang YS, Choe TB, Hur HG, Han KO. Isoflavone metabolites and their in vitro dual functions: They can act as an estrogenic agonist or antagonist depending on the estrogen concentration. J Steroid Biochem Mol Biol 2006;101:246-253.
54. Jayagopal V, Albertazzi P, Kilpatrick ES, Howarth EM, Jennings PE, Hepburn DA, Atkin SL. Beneficial effects of soy phytoestrogen intake in postmenopausal women with type 2 diabetes. Diabetes Care 2002; 25:1709-1714.
55. Kelsey JL, Gammon MD, John EM. Reproductive factors and breast cancer. Epidemiol Rev 1993;15:36-47.
56. Knight DC, Howes JB, Eden JA, Howes LG. Effects on menopausal symptoms and acceptability of isoflavone-containing soy powder dietary supplementation. Climacteric 2001;4:13-18.
57. Kotsopoulos D, Dalais FS, Liang YL, McGrath BP, Teede HJ. The effects of soy protein containing phytoestrogens on menopausal symptoms in postmenopausal women. Climacteric 2000;3:161-167.
58. Kuiper G, Carlsson B, Grandien K, Enmark E, Haggblad J, Nilsson S, Gustafsson JA. Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta. Endocrinology 1997;138:863-870.
59. Kuiper GG, Lemmen JG, Carlsson B, Corton JC, Safe SH, van der Saag PT, van der Burg B, Gustafsson JA. Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta. Endocrinology 1998; 139:4252-4263.
60. Kumar NB, Cantor A, Allen K, Riccardi D, Cox CE. The specific role of isoflavones on estrogen metabolism in premenopausal women. Cancer 2002;94:1166-1174.
61. Lacey M, Bohday J, Fonseka SM, Ullah AI, Whitehead SA. Dose-response effects of phytoestrogens on the activity and expression of 3beta-hydroxysteroid dehydrogenase and aromatase in human granulosa-luteal cells. J Steroid Biochem Mol Biol 2005;96 279-286.
62. Lethaby AE, Brown J, Morjoribanks J, Kronenberg F, Roberts H, Eden J. Phytoestrogens for vasomotor menopausal symptoms. Cochrane Database Syst Rev 2007: CD001395.
63. Lewis JE, Nickell LA, Thompson LU, Szalai JP, Kiss A, Hilditch JR. A randomized controlled trial of the effect of dietary soy and flaxseed muffins on quality of life and hot flashes during menopause. Menopause (New York, NY) 2006;13:631-642.
64. Lichtenstein AH, Jalbert SM, Adlercreutz H, Goldin BR, Rasmussen H, Schaefer EJ, Ausman LM. Lipoprotein response to diets high in soy or animal protein with and without isoflavones in moderately hypercholesterolemic subjects. Arterioscler Thromb Vasc Biol 2002; 22:1852-1858.
65. Ma DF, Qin LQ, Wang PY, Katoh R. Soy isoflavone intake increases bone mineral density in the spine of menopausal women: Meta-analysis of randomized controlled trials. Clin Nutr 2008;27:57-64.
66. Mackey R, Ekangaki A, Eden JA. The effects of soy protein in women and men with elevated plasma lipids. Biofactors 2000;12:251-257.
67. Marini H, Minutoli L, Polito F, Bitto A, Altavilla D, Atteritano M, Gaudio A, Mazzaferro S, Frisina A, Frisina N et al. Effects of the phytoestrogen genistein on bone metabolism in osteopenic postmenopausal women: A randomized trial. Ann Intern Med 2007;146:839-847.
68. Martini MC, Dancisak BB, Haggans CJ, Thomas W, Slavin JL. Effects of soy intake on sex hormone metabolism in premenopausal women. Nutr Cancer 1999;34:133-139.
69. Maskarinec G, Franke AA, Williams AE, Stanczyk FC. The effects of an isoflavone intervention on the urinary excretion of hormone metabolites in premenopausal women. IARC Sci Pub 2002a;156:375-377.
70. Maskarinec G, Williams AE, Inouye JS, Stanczyk FZ, Franke AA. A randomized isoflavone intervention among premenopausal women. Cancer Epidemiol Biomarkers Prev 2002b;11:195-201.
71. Maskarinec G, Williams AE, Carlin L. Mammographic densities in a one-year isoflavone intervention. Eur J Cancer Prev 2003;12 165-169.
72. Maskarinec G, Franke AA, Williams AE, Hebshi S, Oshiro C, Murphy S, Stanczyk FZ. Effects of a 2-year randomized soy intervention on sex hormone levels in premenopausal women. Cancer Epidemiol Biomarkers Prev 2004;13:1736-1744.
73. Maskarinec G, Takata Y, Murphy SP, Franke AA, Kaaks R. Insulin-like growth factor-I and binding protein-3 in a 2-year soya intervention among premenopausal women. Br J Nutr 2005;94:362-367.
74. Merz-Demlow BE, Duncan AM, Wangen KE, Xu X, Carr TP, Phipps WR, Kurzer MS. Soy isoflavones improve plasma lipids in normocholesterolemic, premenopausal women. Am J Clin Nutr 2000;71:1462-1469.
75. Messina M. The safety and benefits of soybean isoflavones. A natural alternative to conventional hormone therapy? Menopause 2007;14 958.
76. Messina M, McCaskill-Stevens W, Lampe JW. Addressing the soy and breast cancer relationship: Review, commentary, and workshop proceedings. J Natl Cancer Inst 2006a;98:1275-1284.
77. Messina M, Nagata C, Wu AH. Estimated Asian adult soy protein and isoflavone intakes. Nutr Cancer 2006b;55:1-12.
78. Moeller LE, Peterson CT, Hanson KB, Dent SB, Lewis DS, King DS, Alekel DL. Isoflavone-rich soy protein prevents loss of hip lean mass but does not prevent the shift in regional fat distribution in perimenopausal women. Menopause 2003;10:322-331.
79. Murkies AL, Lombard C, Strauss BJ, Wilcox G, Burger HG, Morton MS. Dietary flour supplementation decreases post-menopausal hot flushes: effect of soy and wheat. Maturitas 1995;21:189-195.
80. Nagata C, Takatsuka N, Inaba S, Kawakami N, Shimizu H. Effect of soymilk consumption on serum estrogen concentrations in premenopausal women. J Natl Cancer Inst 1998;90:1830-1835.
81. Nahas EP, Nahas Neto J, DeLuca L, Traiman P, Pontes A, Dalben I. Benefits of soy germ isoflavone in postmenopausal women with contraindication of conventional hormone replacement therapy. Maturitas 2004;48:372-380.
82. Nelson HD, Vesco KK, Haney E, Fu R, Nedrow A, Miller J, Nicolaidis C, Walker M, Humphrey L. Nonhormonall therapies for menopausal hot flashes: systematic review and meta-analysis. JAMA 2006;295:2057-2071.
83. Nettleton JA, Greany KA, Thomas W, Wangen KE, Adlercreutz H, Kurzer MS. Plasma phytoestrogens are not altered by probiotic consumption in postmenopausal women with and without a history of breast cancer. J Nutr 2004;134:1998-2003.
84. Netdeton JA, Greany KA, Thomas W, Wangen KE, Adlercreutz H, Kurzer MS. The effect of soy consumption on the urinary 2:16-hydroxyestrone ratio in postmenopausal women depends on equol production status but is not influenced by probiotic consumption. J Nutr 2005a;135 603-608.
85. Nettleton JA, Greany KA, Thomas W, Wangen KE, Adlercreutz H, Kurzer MS. Short-term soy and probiotic supplementation does not markedly affect concentrations of reproductive hormones in postmenopausal women with and without histories of breast cancer. J Altem Complement Med (New York, N Y) 2005b;11:1067-1074.
86. Nikander E, Kilkkinen A, Metsa-Heikkila M, Adlercreutz H, Pietinen P, Tiitinen A, Ylikorkala O. A randomized placebo-controlled crossover trial with phytoestrogens in treatment of menopause in breast cancer patients. Obstet Gynecol 2003a;101:1213-1220.
87. Nikander E, Metsa-Heikkila M, Tiitinen A, Ylikorkala O. Evidence of a lack of effect of a phytoestrogen regimen on the levels of C-reactive protein, E-selectin, and nitrate in postmenopausal women. J Clin Endocrinol Metab 2003b;88:5180-5185.
88. Nikander E, Metsa-Heikkila M, Ylikorkala O, Tiitinen A. Effects of phytoestrogens on bone tumover in postmenopausal women with a history of breast cancer. J Clin Endocrinol Metab 2004a;89:1207-1212.
89. Nikander E, Tiitinen A, Laitinen K, Tikkanen M, Ylikorkala O. Effects of isolated isoflavonoids on lipids, lipoproteins, insulin sensitivity, and ghrelin in postmenopausal women. J Clin Endocrinol Metab 2004b; 89:3567-3572.
90. Nikander E, Rutanen EM, Nieminen P, Wahlstrom T, Ylikorkala O, Tiitinen A. Lack of effect of isoflavonoids on the vagina and endometrium in postmenopausal women. Fertil Steril 2005;83:137-142.
91. Persky VW, Turyk ME, Wang L, Freels S, Chatterton R Jr, Barnes SErdman J Jr, Sepkovic DW, Bradlow HL, Potter S. Effect of soy protein on endogenous hormones in postmenopausal women [erratum appears in Am J Clin Nutr 2002;76:695]. Am J Clin Nutr 2002;75 145-153.
92. Phipps WR, Wangen KE, Duncan AM, Merz-Demlow BE, Xu X, Kurzer MS. Lack of effect of isoflavonic phytoestrogen intake on leptin concentrations in premenopausal and postmenopausal women. Fertil Steril 2001; 75:1059-1064.
93. Pike ACW, Brzozowski AM, Hubbard RE, Bonn T, Thorsell AG, Engstrom O, Ljunggren J, Gustafsson JK, Carlquist M. Structure of the ligand-binding domain of oestrogen receptor beta in the presence of a partial agonist and a full antagonist. EMBO J 1999;18:4608-4616.
94. Potter SM, Baum JA, Teng H, Stillman RJ, Shay NF, Erdman JW Jr. Soy protein and isoflavones: Their effects on blood lipids and bone density in postmenopausal women. Am J Clin Nutr 1998;68:1375S-1379S.
95. Rice S, Mason HD, Whitehead SA. Phytoestrogens and their low dose combinations inhibit mRNA expression and activity of aromatase in human granulosa-luteal cells. J Steroid Biochem Mol Biol 2006; 101 216-225.
96. Rosselli M, Rienhart K, Imthurn B, Keller PJ, Dubey RK. Cellular and biochemical mechanisms by which environmental oestrogens influence reproductive function. Hum Reprod Update 2000;6:332-350.
97. Rutman JY, Dancisak BB, Nagel TC, Martini MC, Slavin JL. Soy intake and oral contraceptives: Effects on sex hormones and the menstrual cycle [abstract]. Am J Clin Nutr 1997;66:214.
98. Sacks FM, Lichtenstein AH, Van Horn L, Harris W, Kris-Etherton PM, Winston MC. Soy protein, isoflavones, and cardiovascular health: A summary of a statement for professionals from the American heart association nutrition committee. Arterioscler Thromb Vasc Biol 2006; 26:1689-1692.
99. Scambia G, Mango D, Signorile PG, Angeli RA, Palena C, Gallo D, Bombardelli E, Morazzoni P, Riva A, Mancuso S. Clinical effects of a standardized soy extract in postmenopausal women: A pilot study. Menopause 2000;7:105-111.
100. Setchell KD, Cassidy A. Dietary isoflavones: Biological effects and relevance to human health. J Nutr 1999;129:758S-767S.
101. Setchell KD, Borriello SP, Hulme P, Kirk DN, Axelson M. Nonsteroidal estrogens of dietary origin - possible roles in hormone-dependent disease. Am J Clin Nutr 1984;40:569-578.
102. Setchell KD, Gosselin SJ, Welsh MB, Johnston JO, Balistreri WF, Kramer LW, Dresser BL, Tarr MJ. Dietary estrogens - a probable cause of infertility and liver disease in captive cheetahs. Gastroenterology 1987;93:225-233.
103. Spence LA, Lipscomb ER, Cadogan J, Martin B, Wastney ME, Peacock M, Weaver CM. The effect of soy protein and soy isoflavones on calcium metabolism in postmenopausal women: A randomized crossover study. Am J Clin Nutr 2005;81:916-922.
104. Squadrito F, Altavilla D, Morabito N, Crisafulli A, D'Anna R, Corrado F, Ruggeri P, Campo GM, Calapai G, Caputi AP et al. The effect of the phytoestrogen genistein on plasma nitric oxide concentrations, endothelin-1 levels and endothelium dependent vasodilation in postmenopausal women. Atherosclerosis 2002;163:339-347.
105. Squadrito F, Altavilla D, Crisafulli A, Saitta A, Cucinotta D, Morabito N, D'Anna R, Corrado F, Ruggeri P, Frisina N et al. Effect of genistein on endothelial function in postmenopausal women: A randomized, double-blind, controlled study. Am J Med 2003;114:470-476.
106. St Germain A, Peterson CT, Robinson JG, Alekel DL. Isoflavone-rich or isoflavone-poor soy protein does not reduce menopausal symptoms during 24 weeks of treatment. Menopause 2001;8:17-26.
107. Swain JH, Alekel DL, Dent SB, Peterson CT, Reddy MB. Iron indexes and total antioxidant status in response to soy protein intake in perimenopausal women. Am J Clin Nutr 2002;76:165-171.
108. Takatsuka N, Nagata C, Kurisu Y, Inaba S, Kawakami N, Shimizu H. Hypocholesterolemic effect of soymilk supplementation with usual diet in premenopausal normolipidemic Japanese women. Prev Med 2000;31 308-314.
109. Teede HJ, Dalais FS, Kotsopoulos D, Liang YL, Davis S, McGrath BP. Dietary soy has both beneficial and potentially adverse cardiovascular effects: A placebo-controlled study in men and postmenopausal women. J Clin Endocrinol Metab 2001;86:3053-3060.
110. Teede HJ, Dalais FS, McGrath BP. Dietary soy containing phytoestrogens does not have detectable estrogenic effects on hepatic protein synthesis in postmenopausal women. Am J Clin Nutr 2004;79:396-401.
111. Teede HJ, Dalais FS, Kotsopoulos D, McGrath BP, Malan E, Gan TE, Peverill RE. Dietary soy containing phytoestrogens does not activate the hemostatic system in postmenopausal women. J Clin Endocrinol Metab 2005.
112. Tormala RM, Nikander E, Tiitinen A, Vaisanen-Tommiska M, Ylikorkala O, Mikkola TS. Serum cholesterol efflux potential in postmenopausal women treated with isolated isoflavones. Menopause 2006;13:96-101.
113. Uesugi T, Toda T, Okuhira T, Chen JT. Evidence of estrogenic effect by the three-month-intervention of isoflavone on vaginal maturation and bone metabolism in early postmenopausal women. Endocr J 2003;50 613-619.
114. Uesugi S, Watanabe S, Ishiwata N, Uehara M, Ouchi K. Effects of isoflavone supplements on bone metabolic markers and climacteric symptoms in Japanese women. Biofactors 2004;22:221-228.
115. Upmalis DH, Wiita B, Cone FL, Lamia CA, Warren M, Bradley L. Improvement of menopausal symptoms and quality of life by oral soy extract tablets. J Nutr 1999;130:707S.
116. Upmalis DH, Lobo R, Bradley L, Warren M, Cone FL, Lamia CA. Vasomotor symptom relief by soy isoflavone extract tablets in postmenopausal women: A multicenter, double-blind, randomized, placebo-controlled study. Menopause (New York, NY) 2000;7:236-242.
117. Vega-Lopez S, Yeum K-J, Lecker JL, Ausman LM, Johnson EJ, Devaraj S, Jialal I, Lichtenstein AH. Plasma antioxidant capacity in response to diets high in soy or animal protein with or without isoflavones. Am J Clin Nutr 2005;81:43-49.
118. Wang Y, Jones PJ, Ausman LM, Lichtenstein AH. Soy protein reduces triglyceride levels and triglyceride fatty acid fractional synthesis rate in hypercholesterolemic subjects. Atherosclerosis 2004;173 269-275.
119. Wangen KE, Duncan AM, Merz-Demlow BE, Xu X, Marcus R, Phipps WR, Kurzer MS. Effects of soy isoflavones on markers of bone turnover in premenopausal and postmenopausal women. J Clin Endocrinol Metab 2000;85:3043-3048.
120. Wangen KE, Duncan AM, Xu X, Kurzer MS. Soy isoflavones improve plasma lipids in normocholesterolemic and mildly hypercholesterolemic postmenopausal women. Am J Clin Nutr 2001;73:225-231.
121. Williamson-Hughes PS, Flickinger BD, Messina M, Empie MW. Isoflavone supplements containing predominantly genistein reduce hot flash symptoms: A critical review of published studies. Menopause 2006; 13:831-839.
122. Woods M, Speigelman D, Hertzmark E, LaBrode A, Longcope C. Dietary soy supplement and menopausal hormones and hot flashes. J Nutr 2000; 130:671S.
123. Wu AH, Stanczyk FZ, Martinez C, Tseng CC, Hendrich S, Murphy P, Chaikittisilpa S, Stram D, Pike MC. A controlled 2-mo dietary fat reduction and soy food supplementation study in postmenopausal women. Am J Clin Nutr 2005;81:1133-1141.
124. Wu J, Oka J, Higuchi M, Tabata I, Toda T, Fujioka M, Fuku N, Teramoto T, Okuhira T, Ueno T et al. Cooperative effects of isoflavones and exercise on bone and lipid metabolism in postmenopausal Japanese women: a randomized placebo-controlled trial. Metabolism 2006a;55 423-433.
125. Wu J, Oka J, Tabata I, Higuchi M, Toda T, Fuku N, Ezaki J, Sugiyama F, Uchiyama S, Yamada K et al. Effects of isoflavone and exercise on BMD and fat mass in postmenopausal Japanese women: A 1-year randomized placebo-controlled trial. J Bone Miner Res 2006b;21:780-789.
126. Wu AH, Yu MC, Tseng C-C, Pike MC. Epidemiology of soy exposure and breast cancer risk. Br J Cancer 2008;98:9-14.
127. Xu X, Duncan AM, Merz BE, Kurzer MS. Effects of soy isoflavones on estrogen and phytoestrogen metabolism in premenopausal women. Cancer Epidemiol Biomarkers Prev 1998;7:1101-1108.
128. Xu X, Duncan AM, Wangen KE, Kurzer MS. Soy consumption alters endogenous estrogen metabolism in postmenopausal women. Cancer Epidemiol Biomarkers Prev 2000;9:781-786.
129. Zittermann A, Geppert J, Baier S, Zehn N, Gouni-Berthold I, Berthold HK, Reinsberg J, Stehle P. Short-term effects of high soy supplementation on sex hormones, bone markers, and lipid parameters in young female adults. Eur J Nutr 2004;43:100-108.