Skip to main content
Log in

Effect of high-dose isoflavones on cognition, quality of life, androgens, and lipoprotein in post-menopausal women

  • Original Articles
  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

Context: Recent interventional studies indicate that post-menopausal hormone replacement therapy is associated with an increased risk of cardiovascular mortality and breast cancer. Isoflavones, a class of plant estrogens, have structural similarities to estradiol. Hence, isoflavones may exert beneficial estrogenic health effects in postmenopausal women with fewer adverse effects. Objective: To evaluate the effect of high-dose isoflavones on self-reported quality of life (QOL), cognition, lipoproteins and androgen status in post-menopausal women. Design and subjects: Double-blind, randomized, placebo-controlled, 12-week trial of 93 healthy, ambulatory, post-menopausal women (mean age 56 yr). The study was conducted at a tertiary care center in the United States. Intervention: Participants were randomly assigned to receive 20 g of soy protein containing 160 mg of total isoflavones vs taste-matched placebo (20 g whole milk protein). Both soy and the placebo were provided in the form of a powder to be mixed with beverages. Main outcome measures: QOL was judged by the Menopause-specific Quality of Life (MENQOL) questionnaire while cognitive function was assessed with standard instruments. Total, free, and bioavailable testosterone, gonadotropins, SHBG, and fasting lipids were measured. Results: Eighty-four women (90%) completed the study (active=38, placebo=46). There was a significant improvement in all 4 QOL subscales (vasomotor, psychosexual, physical, and sexual) among the women taking isoflavones, while no changes were seen in the placebo group. No significant changes in cognition, serum androgens or plasma lipids were seen within any of the groups. However, at the end of the study, a group-by-time interaction was observed such that total testosterone and HDL levels were significantly lower in the isoflavones compared to placebo groups. Conclusion: High-dose isoflavones is associated with improved QOL among women who have become menopausal recently. Hence, the timing of isoflavone supplementation with regards to the onset of menopause appears to be important. The use of isoflavones, as an alternative to estrogen therapy, may be potentially useful and seemingly safe in this group of women who are looking for relief from menopausal symptoms.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Manson JE, Martin KA. Postmenopausal hormone-replacement therapy. N Engl J Med 2001, 345: 34–40.

    Article  PubMed  CAS  Google Scholar 

  2. Nelson HD. Commonly used types of postmenopausal estrogen for treatment of hot flashes: scientific review. JAMA 2004, 291: 1610–20.

    Article  PubMed  CAS  Google Scholar 

  3. Lindsay R, Gallagher JC, Kleerekoper M, Pickar JH. Effect of lower doses of conjugated equine estrogens with and without medroxyprogesterone acetate on bone in early postmenopausal women. JAMA 2002, 287: 2668–76.

    Article  PubMed  CAS  Google Scholar 

  4. Hulley S, Grady D, Bush T, et al. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/progestin Replacement Study (HERS) Research Group. JAMA 1998, 280: 605–13.

    Article  PubMed  CAS  Google Scholar 

  5. Rossouw JE, Anderson GL, Prentice RL, et al; Writing Group for the Women’s Health Initiative Investigators. 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: 321–33.

    Article  PubMed  CAS  Google Scholar 

  6. Chlebowski RT, Hendrix SL, Langer RD, et al; WHI Investigators. Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women: the Women’s Health Initiative Randomized Trial. JAMA 2003, 289: 3243–53.

    Article  PubMed  CAS  Google Scholar 

  7. Espeland MA, Rapp SR, Shumaker SA, et al. Conjugated equine estrogens and global cognitive function in postmenopausal women: Women’s Health Initiative Memory Study. JAMA 2004, 291: 2959–68.

    Article  PubMed  CAS  Google Scholar 

  8. Murkies AL, Wilcox G, Davis SR. Clinical review 92: Phytoestrogens. J Clin Endocrinol Metab 1998, 83: 297–303.

    PubMed  CAS  Google Scholar 

  9. Kuiper GG, Lemmen JG, Carlsson B, et al. Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta. Endocrinology 1998, 139: 4252–63.

    PubMed  CAS  Google Scholar 

  10. Chen Z, Zheng W, Custer LJ, et al. Usual dietary consumption of soy foods and its correlation with the excretion rate of isoflavonoids in overnight urine samples among Chinese women in Shanghai. Nutr Cancer 1999, 33: 82–7.

    Article  PubMed  CAS  Google Scholar 

  11. de Kleijn MJ, van der Schouw YT, Wilson PW, et al. Intake of dietary phytoestrogens is low in postmenopausal women in the United States: the Framingham study. J Nutr 2001,131: 1826–32.

    PubMed  Google Scholar 

  12. Parkin DM. Cancers of the breast, endometrium and ovary: geographic correlations. Eur J Cancer Clin Oncol 1989, 25: 1917–25.

    Article  PubMed  CAS  Google Scholar 

  13. Nagata C, Shimizu H, Takami R, et al. Hot flushes and other menopausal symptoms in relation to soy product intake inJapanese women. Climacteric 1999, 2: 6–12.

    Article  PubMed  CAS  Google Scholar 

  14. 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.

    Article  PubMed  CAS  Google Scholar 

  15. 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: 329–34.

    Article  PubMed  Google Scholar 

  16. 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: 389–94.

    Article  PubMed  CAS  Google Scholar 

  17. Burke GL, Legault C, Anthony M, et al. Soy protein and isoflavone effects on vasomotor symptoms in peri- and postmenopausal women: the Soy Estrogen Alternative Study. Menopause 2003, 10: 147–53.

    Article  PubMed  Google Scholar 

  18. Baber RJ, Templeman C, Morton T, Kelly GE, West L. Randomized placebo-controlled trial of an isoflavone supplement and menopausal symptoms in women. Climacteric 1999, 2: 85–92.

    Article  PubMed  CAS  Google Scholar 

  19. File SE, Jarrett N, Fluck E, Duffy R, Casey K, Wiseman H. Eating soya improves human memory. Psychopharmacology (Berl) 2001, 157: 430–6.

    Article  CAS  Google Scholar 

  20. Kritz-Silverstein D, Von Muhlen D, Barrett-Connor E, Bressel MA. Isoflavones and cognitive function in older women: the SOy and Postmenopausal Health In Aging (SOPHIA) Study. Menopause 2003, 10: 196–202.

    Article  PubMed  Google Scholar 

  21. Kreijkamp-Kaspers S, Kok L, Grobbee DE, et al. Effect of soy protein containing isoflavones on cognitive function, bone mineral density, and plasma lipids in postmenopausal women: a randomized controlled trial. JAMA 2004, 292: 65–74.

    Article  PubMed  CAS  Google Scholar 

  22. Anderson 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.

    Article  PubMed  CAS  Google Scholar 

  23. 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: 118–21.

    Article  PubMed  CAS  Google Scholar 

  24. Hilditch JR, Lewis J, Peter A, et al. A menopause-specific quality of life questionnaire: development and psychometric properties. Maturitas 1996, 24: 161–75.

    Article  PubMed  CAS  Google Scholar 

  25. Vermeulen A, Verdonck L, Kaufman JM. A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab 1999, 84: 3666–72.

    Article  PubMed  CAS  Google Scholar 

  26. Tang GW. The climacteric of Chinese factory workers. Maturitas 1994, 19: 177–82.

    Article  PubMed  CAS  Google Scholar 

  27. Rekers H. Mastering the menopause. In: Burger H, Boulet M, eds. A portrait of the menopause. Park Bridge, New Jersey: The Parthenon Publishing Group 1991: 23–43.

    Google Scholar 

  28. 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: 1068–74.

    PubMed  CAS  Google Scholar 

  29. Van Patten CL, Olivotto IA, Chambers GK, et al. Effect of soy phytoestrogens on hot flashes in postmenopausal women with breast cancer: a randomized, controlled clinical trial. J Clin Oncol 2002, 20: 1449–55.

    Article  PubMed  Google Scholar 

  30. Burguete MC, Torregrosa G, Perez-Asensio FJ, et al. Dietary phytoestrogens improve stroke outcome after transient focal cerebral ischemia in rats. Eur J Neurosci 2006, 23: 703–10.

    Article  PubMed  Google Scholar 

  31. Duffy R, Wiseman H, File SE. Improved cognitive function in postmenopausal women after 12 weeks of consumption of a soya extract containing isoflavones. Pharmacol Biochem Behav 2003, 75: 721–9.

    Article  PubMed  CAS  Google Scholar 

  32. File SE, Hartley DE, Elsabagh S, Duffy R, Wiseman H. Cognitive improvement after 6 weeks of soy supplements in postmenopausal women is limited to frontal lobe function. Menopause 2005, 12: 193–201.

    Article  PubMed  Google Scholar 

  33. 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: 728–35.

    PubMed  CAS  Google Scholar 

  34. Nestel PJ, Pomeroy S, Kay S, et al. Isoflavones from red clover improve systemic arterial compliance but not plasma lipids in menopausal women. J Clin Endocrinol Metab 1999, 84: 895–8.

    PubMed  CAS  Google Scholar 

  35. Simons LA, von Konigsmark M, Simons J, Celermajer DS. Phytoestrogens do not influence lipoprotein levels or endothelial function in healthy, postmenopausal women. Am J Cardiol 2000, 85: 1297–301.

    Article  PubMed  CAS  Google Scholar 

  36. Crouse JR 3rd, Morgan T, 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 1999, 159: 2070–6.

    Article  PubMed  CAS  Google Scholar 

  37. Bairey Merz CN, Johnson BD, Braunstein GD, et al. Phytoestrogens and lipoproteins in women. J Clin Endocrinol Metab 2006, 91: 2209–13.

    Article  PubMed  CAS  Google Scholar 

  38. Allen JK, Fitzgerald ST, Swank RT, Becker DM. Functional status after coronary artery bypass grafting and percutaneous transluminal coronary angioplasty. Am J Cardiol 1990, 66: 921–5.

    Article  PubMed  CAS  Google Scholar 

  39. Basaria S, Dobs AS. Controversies regarding transdermal androgen therapy in postmenopausal women. J Clin Endocrinol Metab 2006, 91: 4743–52.

    Article  PubMed  CAS  Google Scholar 

  40. Loukovaara M, Carson M, Palotie A, Adlercreutz H. Regulation of sex hormone-binding globulin production by isoflavonoids and patterns of isoflavonoid conjugation in HepG2 cell cultures. Steroids 1995, 60: 656–61.

    Article  PubMed  CAS  Google Scholar 

  41. Pino AM, Valladares LE, Palma MA, Mancilla AM, Yáñez M, Albala C. Dietary isoflavones affect sex hormone-binding globulin levels in postmenopausal women. J Clin Endocrinol Metab 2000, 85: 2797–800.

    PubMed  CAS  Google Scholar 

  42. Duncan AM, Underhill KE, Xu X, Lavalleur J, Phipps WR, Kurzer MS. Modest hormonal effects of soy isoflavones in postmenopausal women. J Clin Endocrinol Metab 1999, 84: 3479–84.

    PubMed  CAS  Google Scholar 

  43. 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 Altern Complement Med 2005, 11: 1067–74.

    Article  PubMed  Google Scholar 

  44. Rosner W, Auchus RJ, Azziz R, Sluss PM, Raff H. Position statement: Utility, limitations, and pitfalls in measuring testosterone: an Endocrine Society position statement. J Clin Endocrinol Metab 2007, 92: 405–13.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to S. Basaria MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Basaria, S., Wisniewski, A., Dupree, K. et al. Effect of high-dose isoflavones on cognition, quality of life, androgens, and lipoprotein in post-menopausal women. J Endocrinol Invest 32, 150–155 (2009). https://doi.org/10.1007/BF03345705

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03345705

Key-words

Navigation