S-equol: A Potential Nonhormonal Agent for Menopause-Related Symptom Relief

Journal of Women's Health

Volumn 24, Issue 3, 2015, Pages 200-208

  Utian, Wulf H ^a   Jones, Michelle ^b   Setchell, Kenneth D R ^c  

^a Rapid Medical Research   (United States)

^b Wilmington Health Associates   (United States)

^c UNIVERSITY OF CINCINNATI COLLEGE OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DAIDZEIN; EQUOL; ESTRADIOL; ESTROGEN RECEPTOR BETA; GENISTEIN; ISOFLAVONE DERIVATIVE; PHYTOESTROGEN;

ARTICLE; DRUG EFFICACY; DRUG HALF LIFE; DRUG SAFETY; ENDOMETRIUM; FEMALE; HOT FLUSH; HUMAN; MENOPAUSE RELATED DISORDER; POSTMENOPAUSE; PRIORITY JOURNAL; SOYBEAN; VASOMOTOR DISORDER; CLINICAL TRIAL (TOPIC); DOSE RESPONSE; DRUG EFFECTS; HOT FLASHES; MENOPAUSE; METABOLISM; MIDDLE AGED; QUALITY OF LIFE; TREATMENT OUTCOME; UNITED STATES; WOMEN'S HEALTH;

CLINICAL TRIALS AS TOPIC; DOSE-RESPONSE RELATIONSHIP, DRUG; EQUOL; FEMALE; HOT FLASHES; HUMANS; ISOFLAVONES; MENOPAUSE; MIDDLE AGED; PHYTOESTROGENS; QUALITY OF LIFE; SOYBEANS; TREATMENT OUTCOME; UNITED STATES; WOMEN'S HEALTH;

EID: 84924746246     PISSN: 15409996     EISSN: 1931843X     Source Type: Journal    
DOI: 10.1089/jwh.2014.5006     Document Type: Article

References (55)

1. The North American Menopause Society/Wulf H. 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.
2. 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.
3. Kronenberg F, Cushman LF, Wade CM, Kalmuss D, Chao MT. 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.
4. Nelson HD, Vesco KK, Haney E, et al. Nonhormonal therapies for menopausal hot flashes: systematic review and meta-analysis. JAMA 2006;295:2057-2071.
5. Utian W. Recent developments in pharmacotherapy for vasomotor symptoms. Curr Obstet Gynecol Rep 2012;1:43-49.
6. Files JA, Ko MG, Pruthi S. Bioidentical hormone therapy. Mayo Clin Proc 2011;86:673-680, quiz 80.
7. Jackson RL, Greiwe JS, Schwen RJ. Emerging evidence of the health benefits of S-equol, an estrogen receptor beta agonist. Nutr Rev 2011;69:432-48.
8. Lampe JW. Is equol the key to the efficacy of soy foods? Am J Clin Nutr 2009;89:1664S-1667S.
9. Setchell KD, Brown NM, Lydeking-Olsen E. The clinical importance of the metabolite equol-a clue to the effectiveness of soy and its isoflavones. J Nutr 2002;132:3577-3584.
10. Messina M, Barnes S. The role of soy products in reducing risk of cancer. J Natl Cancer Inst 1991;83:541-546.
11. Sarkar FH, Li Y. Soy isoflavones and cancer prevention. Cancer Invest 2003;21:744-757.
12. Setchell KD, Clerici C. Equol: history, chemistry, and formation. J Nutr 2010;140:1355S-1362S.
13. Abiru Y, Kumemura M, Ueno T, Uchiyama S, Masaki K. Discovery of an S-equol rich food stinky tofu, a traditional fermented soy product in Taiwan. Int J Food Sci Nutr 2012;63:964-970.
14. Hoikkala A, Mustonen E, Saastamoinen I, et al. High levels of equol in organic skimmed Finnish cow milk. Mol Nutr Food Res 2007;51:782-786.
15. King RA, Mano MM, Head RJ. Assessment of isoflavonoid concentrations in Australian bovine milk samples. J Dairy Res 1998;65:479-489.
16. Kuhnle GG, Dell'Aquila C, Aspinall SM, Runswick SA, Mulligan AA, Bingham SA. Phytoestrogen content of foods of animal origin: Dairy products, eggs, meat, fish, and seafood. J Agric Food Chem 2008;56:10099-10104.
17. Mustonen EA, Tuori M, Saastamoinen I, et al. Equol in milk of dairy cows is derived from forage legumes such as red clover. Br J Nutr 2009;102:1552-1556.
18. Rui X, Xu X, Wu H, et al. A survey of equol contents in Chinese stinky tofu with emphasis on the effects of cooking methods. Int J Food Sci Nutr 2014;65:667-672.
19. Saitoh S, Sato T, Harada H, Matsuda T. Biotransformation of soy isoflavone-glycosides in laying hens: Intestinal absorption and preferential accumulation into egg yolk of equol, a more estrogenic metabolite of daidzein. Biochim Biophys Acta 2004;1674:122-130.
20. Sakakibara H, Viala D, Ollier A, Combeau A, Besle JM. Isoflavones in several clover species and in milk from goats fed clovers. Biofactors 2004;22:237-239.
21. Muthyala RS, Ju YH, Sheng S, et al. Equol, a natural estrogenic metabolite from soy isoflavones: convenient preparation and resolution of R- and S-equols and their differing binding and biological activity through estrogen receptors alpha and beta. Bioorg Med Chem 2004;12:1559-1567.
22. 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.
23. Setchell KD, Clerici C, Lephart ED, et al. S-equol, a potent ligand for estrogen receptor beta, is the exclusive enantiomeric form of the soy isoflavone metabolite produced by human intestinal bacterial flora. Am J Clin Nutr 2005;81:1072-1079.
24. Marrian GF, Haslewood GA. Equol, a new inactive phenol isolated from the ketohydroxyoestrin fraction of mares' urine. Biochem J 1932;26:1227-1232.
25. Axelson M, Kirk DN, Farrant RD, Cooley G, Lawson AM, Setchell KD. The identification of the weak oestrogen equol [7-hydroxy-3-(4'-hydroxyphenyl)chroman] in human urine. Biochem J 1982;201:353-357.
26. Atkinson C, Frankenfeld CL, Lampe JW. Gut bacterial metabolism of the soy isoflavone daidzein: exploring the relevance to human health. Exp Biol Med (Maywood) 2005;230:155-170.
27. Setchell KD, Clerici C. Equol: Pharmacokinetics and biological actions. J Nutr 2010;140:1363S-1368S.
28. Taku K, Melby MK, Kronenberg F, Kurzer MS, Messina M. Extracted or synthesized soybean isoflavones reduce menopausal hot flash frequency and severity: Systematic review and meta-analysis of randomized controlled trials. Menopause 2012;19:776-790.
29. Jackson RL, Greiwe JS, Desai PB, Schwen RJ. Single-dose and steady-state pharmacokinetic studies of S-equol, a potent nonhormonal, estrogen receptor beta-agonist being developed for the treatment of menopausal symptoms. Menopause 2011;18:185-193.
30. Kuiper GG, Enmark E, Pelto-Huikko M, Nilsson S, Gustafsson JA. Cloning of a novel receptor expressed in rat prostate and ovary. Proc Natl Acad Sci USA 1996;93:5925-5930.
31. Speirs V, Carder PJ, Lane S, Dodwell D, Lansdown MR, Hanby AM. Oestrogen receptor beta: what it means for patients with breast cancer. Lancet Oncol 2004;5:174-181.
32. Setchell KD, Zhao X, Jha P, Heubi JE, Brown NM. The pharmacokinetic behavior of the soy isoflavone metabolite S-(-)equol and its diastereoisomer R- (+) equol in healthy adults determined by using stable-isotope-labeled tracers. Am J Clin Nutr 2009;90:1029-1037.
33. Setchell KD, Zhao X, Shoaf SE, Ragland K. The pharmacokinetics of S-(-)equol administered as SE5-OH tablets to healthy postmenopausalwomen. J Nutr 2009;139:2037-2043.
34. Uchiyama S UT, Masaki K, Shimizu S, Aso T, Shirota T. The cross-sectional study of the relationship between soy isoflavones, equol and the menopausal symptoms in Japanese women. J Jpn Menopause Soc 2007 2006;15:28-37.
35. Newton KM, Reed SD, Uchiyama S, et al. A cross-sectional study of equol producer status and self-reported vasomotor symptoms. Menopause 2014 [Epub ahead of print]; DOI:10.1097/gme.0000000000000363.
36. Ishiwata N, Melby MK, Mizuno S, Watanabe S. New equol supplement for relieving menopausal symptoms: Randomized, placebo-controlled trial of Japanese women. Menopause 2009;16:141-148.
37. Aso T. Equol improves menopausal symptoms in Japanese women. J Nutr 2010;140:1386S-1389S.
38. Aso T, Uchiyama S, Matsumura Y, et al. A natural s-equol supplement alleviates hot flushes and other menopausal symptoms in equol nonproducing postmenopausal Japanese women. J Womens Health (Larchmt) 2012;21:92-100.
39. Jenks BH, Iwashita S, Nakagawa Y, et al. A pilot study on the effects of S-equol compared to soy isoflavones on menopausal hot flash frequency. J Womens Health (Larchmt) 2012;21:674-682.
40. Jou HJ, Wu SC, Chang FW, Ling PY, Chu KS, Wu WH. Effect of intestinal production of equol on menopausal symptoms in women treated with soy isoflavones. Int J Gynaecol Obstet 2008;102:44-49.
41. Crawford SL, Jackson EA, Churchill L, Lampe JW, Leung K, Ockene JK. Impact of dose, frequency of administration, and equol production on efficacy of isoflavones for menopausal hot flashes: A pilot randomized trial. Menopause 2013;20:936-945.
42. Liu ZM, Ho SC, Woo J, Chen YM, Wong C. Randomized controlled trial of whole soy and isoflavone daidzein on menopausal symptoms in equol-producing Chinese postmenopausal women. Menopause 2014;21:653-660.
43. Usui T, Tochiya M, Sasaki Y, et al. Effects of natural Sequol supplements on overweight or obesity and metabolic syndrome in the Japanese, based on sex and equol status. Clin Endocrinol (Oxf) 2013;78:365-372.
44. Tousen Y, Abe F, Ishida T, Uehara M, Ishimi Y. Resistant starch promotes equol production and inhibits tibial bone loss in ovariectomized mice treated with daidzein. Metabolism 2011;60:1425-1432.
45. Jackson RL, Greiwe JS, Schwen RJ. Ageing skin: oestrogen receptor beta agonists offer an approach to change the outcome. Exp Dermatol 2011;20:879-882.
46. Stevenson S, Thornton J. Effect of estrogens on skin aging and the potential role of SERMs. Clin Interv Aging 2007;2:283-297.
47. Oyama A, Ueno T, Uchiyama S, et al. The effects of natural S-equol supplementation on skin aging in postmenopausal women: a pilot randomized placebo-controlled trial. Menopause 2012;19:202-210.
48. Hsieh 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;58:3833-3838.
49. Messina M, Caan BJ, Abrams DI, Hardy M, Maskarinec G. It's time for clinicians to reconsider: Their proscription against the use of soyfoods by breast cancer patients. Oncology 2013:430-437.
50. Chi F, Wu R, Zeng YC, Xing R, Liu Y, Xu ZG. Postdiagnosis soy food intake and breast cancer survival: a meta-analysis of cohort studies. Asian Pac J Cancer Prev 2013;14:2407-2412.
51. Ju YH, Fultz J, Allred KF, Doerge DR, Helferich WG. Effects of dietary daidzein and its metabolite, equol, at physiological concentrations on the growth of estrogendependent human breast cancer (MCF-7) tumors implanted in ovariectomized athymic mice. Carcinogenesis 2006;27:856-863.
52. Onoda A, Ueno T, Uchiyama S, Hayashi SI, Kato K, Wake N. Effects of S-equol and natural S-equol supplement (SE5-OH) on the growth of MCF-7 in vitro and as tumors implanted into ovariectomized athymic mice. Food Chem Toxicol 2011;49:2279-2284.
53. Setchell KD, Brown NM, Zhao 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.
54. Fuhrman BJ, Teter BE, Barba M, et al. Equol status modifies the association of soy intake and mammographic density in a sample of postmenopausal women. Cancer Epidemiol Biomarkers Prev 2008;17:33-42.
55. Tseng M, Byrne C, Kurzer MS, Fang CY. Equol-producing status, isoflavone intake, and breast density in a sample of U.S. Chinese women. Cancer Epidemiol Biomarkers Prev 2013;22:1975-1983.