Extracted or synthesized soybean isoflavones reduce menopausal hot flash frequency and severity: Systematic review and meta-analysis of randomized controlled trials

Menopause

Volumn 19, Issue 7, 2012, Pages 776-790

  Taku, Kyoko ^a   Melby, Melissa K ^b   Kronenberg, Fredi ^c   Kurzer, Mindy S ^d   Messina, Mark ^e  

^a NATIONAL INSTITUTE OF HEALTH AND NUTRITION   (Japan)

^b UNIVERSITY OF DELAWARE   (United States)

^c STANFORD UNIVERSITY   (United States)

^d UNIVERSITY OF MINNESOTA   (United States)

^e LOMA LINDA UNIVERSITY   (United States)

Author keywords

Genistein; Hot flashes; Isoflavones; Meta analysis; Soy; Systematic review

Indexed keywords

GENISTEIN; ISOFLAVONE; PLACEBO; SOYBEAN ISOFLAVONE; UNCLASSIFIED DRUG;

CLIMACTERIUM; DISEASE SEVERITY; DRUG EFFECT; DRUG EFFICACY; DRUG ISOLATION; DRUG SYNTHESIS; HOT FLUSH; HUMAN; MENOPAUSE; META ANALYSIS; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SCORING SYSTEM; SOYBEAN; SYSTEMATIC REVIEW;

DIETARY SUPPLEMENTS; FEMALE; HOT FLASHES; HUMANS; ISOFLAVONES; MENOPAUSE; RANDOMIZED CONTROLLED TRIALS AS TOPIC; SOYBEANS; TREATMENT OUTCOME;

EID: 84862988809     PISSN: 10723714     EISSN: 15300374     Source Type: Journal    
DOI: 10.1097/gme.0b013e3182410159     Document Type: Review

References (97)

1. Nelson HD, Haney E, Humphrey L, et al. Management of menopuaserelated symptoms. Summary, Evidence Report/Technology Assessment No. 120 (Prepared by the Oregon Evidence-based Practice Center, under contract No. 290-02-0024). AHRQ Pub. No. 05-E016-1. Rockville, MD: Agency for Health Research Quality; 2005 March.
2. Maclennan AH, Broadbent JL, Lester S, et al. Oral oestrogen and combined oestrogen/progestogen therapy versus placebo for hot flushes. Cochrane Database Syst Rev 2004;4:CD002978.
3. Kronenberg F. Hot flashes: epidemiology and physiology. Ann N Y Acad Sci 1990;592:52-86; discussion 123-133. (Pubitemid 20273207)
4. Grady D, Herrington D, Bittner V, et al. Cardiovascular disease outcomes during 6.8 years of hormone therapy: Heart and Estrogen/progestin Replacement Study follow-up (HERS II). JAMA 2002;288:49-57. (Pubitemid 34705518)
5. Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial. JAMA 2002;288:321-333. (Pubitemid 34761611)
6. Beral V. Breast cancer and hormone-replacement therapy in the Million Women Study. Lancet 2003;362:419-427. (Pubitemid 36999703)
7. Hill DA, Hill SR. Counseling patients about hormone therapy and alternatives for menopausal symptoms. Am Fam Physician 2010;82:801-807.
8. Tsai SA, Stefanick ML, Stafford RS. Trends in menopausal hormone therapy use of US office-based physicians, 2000-2009. Menopause 2011; 18:385-392.
9. Kronenberg F, Cushman LF, Wade CM, et al. Race/ethnicity and women's use of complementary and alternative medicine in the United States: results of a national survey. Am J Public Health 2006;96:1236-1242. (Pubitemid 43967849)
10. Lock M. Contested meanings of the menopause. Lancet 1992;337: 1270-1272.
11. Lock M. Encounters With Aging: Mythologies of Menopause in Japan and North America. Berkeley, CA: University of California Press, 1993.
12. Adlercreutz H, Hamalainen E, Gorbach S, et al. Dietary phyto-oestrogens and the menopause in Japan. Lancet 1992;339:1233.
13. Nagata C, Shimizu H, Takami R, et al. Hot flashes and other menopausal symptoms in relation to soy product intake. Climacteric 1999;2:6-12. (Pubitemid 29253920)
14. Nagata C, Takatsuka N, Kawakami N, et al. Soy product intake and hot flashes in Japanese women: results from a community-based prospective study. Am J Epidemiol 2001;153:790-793. (Pubitemid 32319707)
15. Melby MK. Chilliness: a vasomotor symptom in Japan. Menopause 2007;14:752-759. (Pubitemid 47051970)
16. Melby MK, Watanabe S, Whitten PL, et al. Sensitive high-performance liquid chromatographic method using coulometric electrode array detection for measurement of phytoestrogens in dried blood spots. J Chromatogr B Analyt Technol Biomed Life Sci 2005;826:81-90. (Pubitemid 41446438)
17. Murkies AL, Lombard C, Strauss BJ, et al. Dietary flour supplementation decreases post-menopausal hot flushes: effect of soy and wheat. Maturitas 1995;21:189-195.
18. Howes LG, Howes JB, Knight DC. Isoflavone therapy for menopausal flushes: a systematic review and meta-analysis. Maturitas 2006;55: 203-211. (Pubitemid 44397351)
19. Williamson-Hughes PS, Flickinger BD, Messina MJ, et al. Isoflavone supplements containing predominantly genistein reduce hot flash symptoms: a critical review of published studies. Menopause 2006;13:831-839. (Pubitemid 44435039)
20. Nelson HD, Vesco KK, Haney E, et al. Nonhormonal therapies for menopausal hot flashes: systematic review and meta-analysis. JAMA 2006;295:2057-2071. (Pubitemid 44794007)
21. Kronenberg F, Fugh-Berman A. Complementary and alternative medicine for menopausal symptoms: a review of randomized, controlled trials. Ann Intern Med 2002;137:805-813. (Pubitemid 35334452)
22. Krebs EE, Ensrud KE, MacDonald R, et al. Phytoestrogens for treatment of menopausal symptoms: a systematic review. Obstet Gynecol 2004;104: 824-836. (Pubitemid 40458814)
23. Nedrow A, Miller J, Walker M, et al. Complementary and alternative therapies for the management of menopause-related symptoms: a systematic evidence review. Arch Intern Med 2006;166:1453-1465. (Pubitemid 44125864)
24. Lethaby A, Brown J, Marjoribanks J, et al. Phytoestrogens for vasomotor menopausal symptoms. Cochrane Database Syst Rev 2007;4:CD001395.
25. Tempfer CB, Bentz EK, Leodolter S, et al. Phytoestrogens in clinical practice: a review of the literature. Fertil Steril 2007;87:1243-1249. (Pubitemid 46829161)
26. Bolanos R, Del Castillo A, Francia J. Soy isoflavones versus placebo in the treatment of climacteric vasomotor symptoms: systematic review and meta-analysis. Menopause 2010;17:660-666.
27. Jacobs A, Wegewitz U, Sommerfeld C, et al. Efficacy of isoflavones in relieving vasomotor menopausal symptomsVa systematic review. Mol Nutr Food Res 2009;53:1084-1097.
28. Balk E, Chung M, Chew P, et al. Effects of soy on health outcomes. Evidence report/technology assessment No. 126 (prepared by Tufts-New England Medical Center Evidence-based Practice Center under Contract No. 290-02-0022). AHRQ Publication No. 05-E024-2. Rockville, MD Agency for Healthcare Research and Quality; July 2005.
29. Higgins JPT, Green S, eds. Cochrane Handbook for Systematic Reviews of Interventions. Chichester, UK: John Wiley & Sons. 2008.
30. Quella SK, Loprinzi CL, Barton DL, et al. Evaluation of soy phytoestrogens for the treatment of hot flashes in breast cancer survivors: a North Central Cancer Treatment Group trial. J Clin Oncol 2000;18:1068-1074. (Pubitemid 30123785)
31. Colacurci N, Zarcone R, Borrelli A, et al. Effects of soy isoflavones on menopausal neurovegetative symptoms. Minerva Ginecol 2004;56: 407-412. (Pubitemid 40039216)
32. Kupperman HS, Wetchler BB, Blatt MH. Contemporary therapy of the menopausal syndrome. JAMA 1959;171:1627-1637.
33. Greene JG. Constructing a standard climacteric scale. Maturitas 1998;29: 25-31. (Pubitemid 28247565)
34. Duffy C, Cyr M. Phytoestrogens: potential benefits and implications for breast cancer survivors. J Womens Health (Larchmt) 2003;12:617-631. (Pubitemid 37266005)
35. Macgregor CA, Canney PA, Patterson G, et al. A randomised doubleblind controlled trial of oral soy supplements versus placebo for treatment of menopausal symptoms in patients with early breast cancer. Eur J Cancer 2005;41:708-714. (Pubitemid 40342553)
36. Secreto G, Chiechi LM, Amadori A, et al. Soy isoflavones and melatonin for the relief of climacteric symptoms: a multicenter, double-blind, randomized study. Maturitas 2004;47:11-20. (Pubitemid 38050011)
37. File SE, Hartley DE, Elsabagh S, et al. Cognitive improvement after 6 weeks of soy supplements in postmenopausal women is limited to frontal lobe function. Menopause 2005;12:193-201. (Pubitemid 40464288)
38. Campagnoli C, Abba C, Ambroggio S, et al. Polyunsaturated fatty acids (PUFAs) might reduce hot flushes: an indication from two controlled trials on soy isoflavones alone and with a PUFA supplement. Maturitas 2005;51:127-134. (Pubitemid 40726110)
39. Crisafulli A, Marini H, Bitto A, et al. Effects of genistein on hot flushes in early postmenopausal women: a randomized, double-blind EPT-and placebo-controlled study. Menopause 2004;11:400-404. (Pubitemid 40372093)
40. D'Anna R, Cannata ML, Atteritano M, et al. Effects of the phytoestrogen genistein on hot flushes, endometrium, and vaginal epithelium in postmenopausal women: a 1-year randomized, double-blind, placebocontrolled study. Menopause 2007;14:648-655. (Pubitemid 47051957)
41. D'Anna R, Cannata ML, Marini H, et al. Effects of the phytoestrogen genistein on hot flushes, endometrium, and vaginal epithelium in postmenopausal women: a 2-year randomized, double-blind, placebocontrolled study. Menopause 2009;16:301-306.
42. Faure ED, Chantre P, Mares P. Effects of a standardized soy extract on hot flushes: a multicenter, double-blind, randomized, placebo-controlled study. Menopause 2002;9:329-334. (Pubitemid 36701892)
43. Ferrari A. Soy extract phytoestrogens with high dose of isoflavones for menopausal symptoms. J Obstet Gynaecol Res 2009;35:1083-1090.
44. Imhof M, Gocan A, Imhof M, Schmidt M. Improvement of menopausal symptoms by soy isoflavones: a randomized double-blind study. Planta Med 2008;94:928 (abstract SL86).
45. Hachul H, Brandao LC, D'Almeida V, et al. Isoflavones decrease insomnia in postmenopause. Menopause 2011;18:178-184.
46. Khaodhiar L, Ricciotti HA, Li L, et al. Daidzein-rich isoflavone aglycones are potentially effective in reducing hot flashes in menopausal women. Menopause 2008;15:125-132.
47. Nahas EA, Nahas-Neto J, Orsatti FL, et al. Efficacy and safety of a soy isoflavone extract in postmenopausal women: a randomized, double-blind, and placebo-controlled study. Maturitas 2007;58:249-258. (Pubitemid 350103531)
48. Penotti M, Fabio E, Modena AB, et al. Effect of soy-derived isoflavones on hot flushes, endometrial thickness, and the pulsatility index of the uterine and cerebral arteries. Fertil Steril 2003;79:1112-1117. (Pubitemid 36547847)
49. Scambia G, Mango D, Signorile PG, et al. Clinical effects of a standardized soy extract in postmenopausal women: a pilot study. Menopause 2000;7:105-111. (Pubitemid 30151397)
50. Upmalis DH, Lobo R, Bradley L, et al. Vasomotor symptom relief by soy isoflavone extract tablets in postmenopausal women: a multicenter, doubleblind, randomized, placebo-controlled study. Menopause 2000;7:236-242. (Pubitemid 30445953)
51. Evans M, Elliott JG, Sharma P, et al. The effect of synthetic genistein on menopause symptom management in healthy postmenopausal women: a multi-center, randomized, placebo-controlled study. Maturitas 2011;68: 189-196.
52. Cheng G, Wilczek B, Warner M, et al. Isoflavone treatment for acute menopausal symptoms. Menopause 2007;14:468-473.
53. Han KK, Soares JM, Haidar MA, et al. Benefits of soy isoflavone therapeutic regimen on menopausal symptoms. Obstet Gynecol 2002;99: 389-394. (Pubitemid 34188398)
54. Jou HJ, Wu SC, Chang FW, et al. Effect of intestinal production of equol on menopausal symptoms in women treated with soy isoflavones. Int J Gynaecol Obstet 2008;102:44-49.
55. Petri Nahas E, Nahas Neto J, De Luca L, et al. Benefits of soy germ isoflavones in postmenopausal women with contraindication for conventional hormone replacement therapy. Maturitas 2004;48:372-380. (Pubitemid 38993251)
56. Nikander E, Kilkkinen A, Metsa-Heikkila M, et al. A randomized placebocontrolled crossover trial with phytoestrogens in treatment of menopause in breast cancer patients. Obstet Gynecol 2003;101:1213-1220. (Pubitemid 36694346)
57. Albertazzi P, Steel SA, Bottazzi M. Effect of pure genistein on bone markers and hot flushes. Climacteric 2005;8:371-379. (Pubitemid 41617486)
58. Collins A, Landgren BM. Psychosocial factors associated with the use of hormonal replacement therapy in a longitudinal follow-up of Swedish women. Maturitas 1997;28:1-9. (Pubitemid 27475579)
59. Messina M, Hughes C. Efficacy of soyfoods and soybean isoflavone supplements for alleviating menopausal symptoms is positively related to initial hot flush frequency. J Med Food 2003;6:1-11. (Pubitemid 36576609)
60. Schulz KF, Chalmers I, Hayes RJ, et al. Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials. JAMA 1995;273:408-412.
61. Hooper L, Ryder JJ, Kurzer MS, et al. Effects of soy protein and isoflavones on circulating hormone concentrations in pre-and postmenopausal women: a systematic review and meta-analysis. Hum Reprod Update 2009;15:423-440.
62. Loprinzi CL, Barton DL, Sloan JA, et al. Mayo Clinic and North Central Cancer Treatment Group hot flash studies: a 20-year experience. Menopause 2008;15:655-660.
63. Guttuso T, Evans M. Minimum trial duration to reasonably assess longterm efficacy of nonhormonal hot flash therapies. J Womens Health (Larchmt) 2010;19:699-702.
64. Muthyala RS, Ju YH, Sheng S, et al. Equol, a natural estrogenic metabolite from soy isoflavones: convenient preparation and resolution of Rand S-equols and their differing binding and biological activity through estrogen receptors > and A. Bioorg Med Chem 2004;12:1559-1567. (Pubitemid 38304880)
65. Oseni T, Patel R, Pyle J, et al. Selective estrogen receptor modulators and phytoestrogens. Planta Med 2008;74:1656-1665.
66. Lieberman S. Are the differences between estradiol and other estrogens, naturally occurring or synthetic, merely semantical? J Clin Endocrinol Metab 1996;81:850-851. (Pubitemid 26055711)
67. Hwang CS, Kwak HS, Lim HJ, et al. 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. (Pubitemid 44604448)
68. Carmignani LO, Pedro AO, Costa-Paiva LH, et al. The effect of dietary soy supplementation compared to estrogen and placebo on menopausal symptoms: a randomized controlled trial. Maturitas 2010;67: 262-269.
69. Clarkson TB, Utian WH, Barnes S, et al. The role of soy isoflavones in menopausal health: report of The North American Menopause Society/Wulf H. Utian Translational Science Symposium in Chicago, IL (October 2010). Menopause 2011;18:732-753.
70. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of health claims related to soy isoflavones and protection of DNA, proteins and lipids from oxidative damage (ID 1286, 4245), maintenance of normal blood LDL-cholesterol concentrations (ID 1135, 1704a, 3093a), reduction of vasomotor symptoms associated with menopause (ID 1654, 1704b, 2140, 3093b, 3154, 3590), maintenance of normal skin tonicity (ID 1704a), contribution to normal hair growth (ID 1704a, 4254), Bcardiovascular health[ (ID 3587), treatment of prostate cancer (ID 3588), and Bupper respiratory tract[ (ID 3589) pursuant to Article 13(1) of Regulation (EC) No 1924/2006. EFSA Journal 2011;9(7):2264. [44 pp.]. doi:10.2903/j.efsa.2011.2264. Available at: www.efsa.europa.eu/efsajournal. Accessed February 16, 2012.
71. Kotsopoulos D, Dalais FS, Liang Y-L, et al. The effects of soy protein containing phytoestrogens on menopausal symptoms in postmenopausal women. Climacteric 2000;3:161-167.
72. St. Germain A, Peterson CT, Robinson JG, et al. Isoflavone-rich or isoflavone-poor soy protein does not reduce menopausal symptoms during 24 weeks of treatment. Menopause 2001;8:17-26. (Pubitemid 32066576)
73. Knight DC, Howes JB, Eden JA, et al. Effects on menopausal symptoms and acceptability of isoflavone-containing soy powder dietary supplementation. Climacteric 2001;4:13-18. (Pubitemid 32448483)
74. Crandall C. Low-dose estrogen therapy for menopausal women: a review of efficacy and safety. J Womens Health (Larchmt) 2003;12:723-747. (Pubitemid 37361916)
75. Grady D. Clinical practice. Management of menopausal symptoms. N Engl J Med 2006;355:2338-2347. (Pubitemid 44837782)
76. Utian WH, Shoupe D, Bachmann G, et al. Relief of vasomotor symptoms and vaginal atrophy with lower doses of conjugated equine estrogens and medroxyprogesterone acetate. Fertil Steril 2001;75:1065-1079. (Pubitemid 32522600)
77. Notelovitz M, Lenihan JP, McDermott M, et al. Initial 17A-estradiol dose for treating vasomotor symptoms. Obstet Gynecol 2000;95:726-731. (Pubitemid 30210060)
78. Utian WH, Burry KA, Archer DF, et al. Efficacy and safety of low, standard, and high dosages of an estradiol transdermal system (Esclim) compared with placebo on vasomotor symptoms in highly symptomatic menopausal patients. The Esclim Study Group. Am J Obstet Gynecol 1999;181:71-79. (Pubitemid 29343333)
79. Balk E, Chung M, Chew P, et al. Effects of soy on health outcomes. Evid Rep Technol Assess (Summ) 2005;126:1-8.
80. Tempfer CB, Froese G, Heinze G, et al. Side effects of phytoestrogens: a meta-analysis of randomized trials. Am J Med 2009;122:939-946.e9.
81. Marini H, Bitto A, Altavilla D, et al. Breast safety and efficacy of genistein aglycone for postmenopausal bone loss: a follow-up study. J Clin Endocrinol Metab 2008;93:4787-4796.
82. Alekel DL, Van Loan MD, Koehler KJ, et al. The soy isoflavones for reducing bone loss (SIRBL) study: a 3-y randomized controlled trial in postmenopausal women. Am J Clin Nutr 2010;91:218-230.
83. Unfer V, Casini ML, Costabile L, et al. Endometrial effects of long-term treatment with phytoestrogens: a randomized, double-blind, placebocontrolled study. Fertil Steril 2004;82:145-148. (Pubitemid 38968790)
84. Helferich WG, Andrade JE, Hoagland MS. Phytoestrogens and breast cancer: a complex story. Inflammopharmacology 2008;16:219-226.
85. Messina MJ, Wood CE. Soy isoflavones, estrogen therapy, and breast cancer risk: analysis and commentary. Nutr J 2008;7:17.
86. Shu XO, Zheng Y, Cai H, et al. Soy food intake and breast cancer survival. JAMA 2009;302:2437-2443.
87. Kang X, Zhang Q, Wang S, et al. Effect of soy isoflavones on breast cancer recurrence and death for patients receiving adjuvant endocrine therapy. CMAJ 2010;182:1857-1862.
88. Guha N, Kwan ML, Quesenberry CP Jr, et al. Soy isoflavones and risk of cancer recurrence in a cohort of breast cancer survivors: the Life After Cancer Epidemiology study. Breast Cancer Res Treat 2009;118:395-405.
89. Caan BJ, Natarajan L, Parker BA, et al. Soy food consumption and breast cancer prognosis. Cancer Epidemiol Biomarkers Prev 2011;20:854-858.
90. Allred CD, Allred KF, Ju YH, et al. Soy processing influences growth of estrogen-dependent breast cancer tumors. Carcinogenesis 2004;25:1649-1657. (Pubitemid 39214307)
91. Allred CD, Twaddle NC, Allred KF, et al. Soy processing affects metabolism and disposition of dietary isoflavones in ovariectomized BALB/c mice. J Agric Food Chem 2005;53:8542-8550. (Pubitemid 41608911)
92. Setchell KD, Brown NM, Zao X, et al. Soy isoflavone phase II metabolism differs between rodents and humans: implications for the effect on breast cancer risk. Am J Clin Nutr 2011;94:1284-1294.
93. Foth D, Nawroth F. Effect of phytoestrogens on the endometrium? Fertil Steril 2005;83:256-257; author reply 7.
94. National Toxicology Program, US Department of Health and Human Services, Center for the Evaluation of Risks to Human Reproduction. NTPCERHR Expert Panel Report on the Reproductive and Developmental Toxicity of Soy Formula. Available at: http://ntp.niehs.nih.gov/?objectid= 54A5BC5A-F4FC-20FE-0B34E789967F9AD9. Accessed April 12, 2009.
95. Effects of hormone replacement therapy on endometrial histology in postmenopausal women. The Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial. The Writing Group for the PEPI Trial. JAMA 1996;275:370-375.
96. Sathyapalan T, Manuchehri AM, Thatcher NJ, et al. The effect of soy phytoestrogen supplementation on thyroid status and cardiovascular risk markers in patients with subclinical hypothyroidism: a randomized, double-blind, crossover study. J Clin Endocrinol Metab 2011;96: 1442-1449.
97. Butt DA, Deng LY, Lewis JE, et al. Minimal decrease in hot flashes desired by postmenopausal women in family practice. Menopause 2007;14:203-207. (Pubitemid 46673470)