Archives of Gynecology and Obstetrics

, Volume 276, Issue 5, pp 463–469

Non-hormonal therapy of post-menopausal vasomotor symptoms: a structured evidence-based review

Review Article



Interest in non-hormonal therapies for the treatment of menopausal symptoms has increased since the publication of adverse effects of estrogen replacement therapy.


To provide information on the efficacy of non-hormonal therapies for menopausal vasomotor symptoms based on evidence from published randomised controlled studies.


The Cochrane Database of Systematic Reviews (CDSR), MEDLINE, Alternative Therapies in Health and Medicine database (ATHMD) and Allied and Complementary Medicine database (AMED) were searched for randomised controlled trials in the English language reporting data on treatment of menopausal vasomotor symptoms. Trials including cancer breast patients were included.


Our search identified 58 randomised controlled trials of which 11 involved the use of clonidine, six for SSRIs, four for gabapentin, seven for black cohosh, seven for red clover, 18 for phytoestrogens, two for ginseng, one for evening primrose, one for dong quai and one for vitamin E. Most trials had methodological deficiencies.


There is evidence that clonidine, paroxetine, venlafaxine, gabapentin and black cohosh may be beneficial in the treatment of menopausal vasomotor symptoms in some women. Current evidence does not support the use of fluoxetine, red clover, phytoestrogens, Ginseng, evening primrose, dong quai and vitamin E. The side effects profile of these therapies should be considered.


Menopause Vasomotor symptoms Hormone replacement therapy Non-hormonal Complimentary Herbal and alternative therapy 


  1. 1. Cited 30 Mar 2007)Google Scholar
  2. 2.
    Bachmann GA (1999) Vasomotor flushes in menopausal women. Am J Obstet Gynecol 180:S312–S316PubMedCrossRefGoogle Scholar
  3. 3.
    Rossouw JE, Anderson GL, Prentice RL,LaCroix AZ, Kooperberg C, Stefanil ML et al (2002) Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative randomized clinical trial. JAMA 288:321–333PubMedCrossRefGoogle Scholar
  4. 4.
    Beral V (2003) Million Women Study Collaborators Breast cancer and hormone replacement therapy in the Million Women Study. Lancet 362: 419–427PubMedCrossRefGoogle Scholar
  5. 5.
    Hersh AL, Stefanik ML, Stafford RS (2004) National use of postmenopausal hormone therapy. JAMA 291:47–53PubMedCrossRefGoogle Scholar
  6. 6.
    Lawton B, Rose, McLeod D, Dowell A (2003) Changes in use of hormone replacement therapy after the report from Women’s Health Initiative: cross sectional survey of users. BMJ 327:845–846PubMedCrossRefGoogle Scholar
  7. 7.
    Nelson HD, Vesco KK, Haney E, Fu R, Nedrow A, Miller J, Nicolaides C, Walker M, Humphrey L (2006) Nonhormonal therapies for menopausal hot flashes: systematic review and meta-analysis. JAMA 295:2057–2071PubMedCrossRefGoogle Scholar
  8. 8.
    Goldberg RM, Loprinzi CL, O’Fallon JR et al (1994) Transdermal clonidine for ameliorating tamoxifen-induced hot flashes. Clin Oncol 12:155–158Google Scholar
  9. 9.
    Pandya KJ, Raubertas RF, Flynn PJ et al (2002) Oral clonidine in postmenopausal patients with breast cancer experiencing tamoxifen induced hot flashes: a University of Rochester Cancer Center Community Clinical Oncology Program study. Ann Intern Med 132:788–793Google Scholar
  10. 10.
    Edington RF, Chagnon (1980) Clonidine (Dixarit) for menopausal flushing. Can Med Assoc J 123:23–26PubMedGoogle Scholar
  11. 11.
    Nagamani M, Kelver ME, Smith ER (1987) Treatment of menopausal hot flashes with transdermal administration of clonidine. Am J Obstet Gynecol 156:561–565PubMedGoogle Scholar
  12. 12.
    Clayden JR, Bell JW, Pollard P (1974) Menopausal flushing: double-blind trial of a non-hormonal medication. BMJ 1(5905):409–412PubMedGoogle Scholar
  13. 13.
    Bolli P, Simpson FO (1975) Clonidine in menopausal flushing: a double blind trial. A N Z Med J 82:1196–1197Google Scholar
  14. 14.
    Lindsay R, Hart DM (1978) Failure of response of menopausal vasomotor symptoms to clonidine. Maturitas 1:21–25PubMedCrossRefGoogle Scholar
  15. 15.
    Salmi T, Punnonen R (1979) Clonidine in treatment of menopausal symptoms. Int J Gynaecol Obstet 16:422–426PubMedGoogle Scholar
  16. 16.
    Wren BG, Brown LB (1986) A double-blind trial with clonidine and a placebo to treat hot flushes. Med J Aust 144:369–370PubMedGoogle Scholar
  17. 17.
    Nappi C, Petraglia F, de Chiara BM et al (1991) The effect of various drugs with neuroendocrine activity and transdermal estradiol on plasma gonadotropin concentrations after ovariectomy in reproductive-aged women. Acta Obstet Gynecol Scand 70:435–439PubMedGoogle Scholar
  18. 18.
    Sadovsky R (2000) Clonidine reduces tamoxifen-induced hot flushes. Am Fam Physician 62(9):2115Google Scholar
  19. 19.
    Stearns V, Beebe KL, Iyengar M, Dube E (2003) Paroxetine controlled release in the treatment of menopausal hot flashes: a randomized controlled trial. JAMA 289:2827–2834PubMedCrossRefGoogle Scholar
  20. 20.
    Stearns V, Slack R, Greep N et al (2005) Paroxetine is an effective treatment for hot flashes: results from a prospective randomized clinical trial. J Clin Oncol 23:6919–6930PubMedCrossRefGoogle Scholar
  21. 21.
    Evans ML, Pritts E, Vittinghoff E, McClish K, Morgan KS, Jaffe RB (2005) Management of postmenopausal hot flashes with venlafaxine hydrochloride: a randomized, controlled trial. Obstet Gynecol 105:61–66Google Scholar
  22. 22.
    Loprinzi C, Kugler J, Sloan J, Mailliard J, LaVasseur B, Barton D, Novotny P, Dakhil S, Rodger K, Rummans T (2000) Venlafaxine in management of hot flashes in survivors of breast cancer: a randomised controlled trial. Lancet 356(9247):2059–2063PubMedCrossRefGoogle Scholar
  23. 23.
    Loprinzi CL, Sloan JA, Perez EA, Quella SK, Stella PJ, Mailliard JA et al (2002) Phase III evaluation of fluoxetine for treatment of hot flashes. J Clin Oncol 20:1578–1583PubMedCrossRefGoogle Scholar
  24. 24.
    Suvanto-Luukkonen E, Koivunen R, Sundstrom H (2005) Citalopram and fluoxetine in the treatment of postmenopausal symptoms: a prospective, randomized, 9-month, placebo-controlled, double-blind study. Menopuase 12(1):18–26CrossRefGoogle Scholar
  25. 25.
    Guttuso TJ, Kurlan R, McDermott MP, Kieburtz K (2003) Gabapentin’s effect on hot flashes in postmenopausal women: a randomized controlled trial. Obstet Gynecol 101:337–345PubMedCrossRefGoogle Scholar
  26. 26.
    Pandaya KJ, Morrow GR, Roscoe JA, Zhao H, Hickok JT, Pajon E, Sweeney TJ, Banerjee TK, Flynn PJ (2005) Gabapentin for hot flashes in 420 women with breast cancer: a randomized double-blind placebo-controlled trial. Lancet 366(9488):818–824CrossRefGoogle Scholar
  27. 27.
    Reddy SY, Warner H, Guttuso T, Messing S, DiGrazio W, Thornburg L, Guzick DS (2006) Gabapentin, estrogen and placebo for treating hot flushes: a randomized controlled trial. Obstet Gynecol 108:41–48PubMedGoogle Scholar
  28. 28.
    Loprinzi CL, Kugler JW, Barton DL, Dueck AC, Tschetter LK, Nelimark RA et al (2007) Phase III trial of gabapentin alone or in conjunction with an antidepressant in the management of hot flashes in women who have inadequate control with an antidepressant alone: NCCTG N03C5. Clin Oncol 25:308–312CrossRefGoogle Scholar
  29. 29.
    Uebelhack R, Blohmer JU, Graubaum HJ, Busch R, Gruenwald J, Wernecke KD (2006) Black cohosh and St. John’s wort for climacteric complaints: a randomized trial. Obstet Gynecol 107:247–255PubMedGoogle Scholar
  30. 30.
    Osmers R, Friede M, Liske E (2005) Efficacy and safety of isopropanolic black cohosh extract for climacteric symptoms. Obstet Gynecol 105:1074–1078PubMedGoogle Scholar
  31. 31.
    Wuttke W, Seidlove-Wuttke, Gorkow (2003) The Cimicifuga preparation BNO 1055 vs. conjugated estrogens in a double-blind placebo-controlled study: effects on menopause symptoms and bone markers. Maturitas 14(44 Suppl 1):67–77CrossRefGoogle Scholar
  32. 32.
    Pockaj BA, Gallagher JG, Loprinzi CL, Stella PJ, Barton DL (2006) Phase III double-blind, randomized, placebo-controlled crossover trial of black cohosh in the management of hot flashes. J Clin Oncol 24(18):2836–2841PubMedCrossRefGoogle Scholar
  33. 33.
    Newton KM, Reed SD, Grothaus L, Ehrlich K, Guiltinan J, Ludman E, Lacroix AZ (2001) Randomized trial of black cohosh for the treatment of hot flashes among women with a history of breast cancer. J Clin Oncol 19(10):2739–2745Google Scholar
  34. 34.
    Verhoeven MO, Van der Mooren MJ, Van de Weijer PH (2005) Effect of a combination of isoflavones and Actaea racemosa Linnaeus on climacteric symptoms in healthy symptomatic perimenopausal women: a 12-week randomized, placebo-controlled, double-blind study. Menopause 12(4):412–420PubMedCrossRefGoogle Scholar
  35. 35.
    Frei-Kleiner S, Schaffner W, Rahlfs VW (2005) Cimicifuga racemosa dried ethanolic extract in menopausal disorders: a double-blind placebo-controlled clinical trial. Maturitas 51(4):397–404PubMedCrossRefGoogle Scholar
  36. 36.
    Van de Weijer, Barentsen R (2002) Isoflavones from red clover (Promensil) significantly reduce menopausal hot flush symptoms compared with placebo. Maturitas 42(3):187–189PubMedCrossRefGoogle Scholar
  37. 37.
    Hidalgo L, Chedraui P, Morocho N, Ross S (2005) The effect of red clover isoflavones on menopausal symptoms, lipids and vaginal cytology in menopausal women: a randomized, double-blind, placebo-controlled study. Gynecol Endocrinol 21(5):257–264PubMedCrossRefGoogle Scholar
  38. 38.
    Jeri AR (2002) The use of an isoflavone supplement to relieve hot flashes. Female patient 27:35–37Google Scholar
  39. 39.
    Atkinson C, Warren R, Sala E , Dowsett M, Dunning A (2004) Red clover-derived isoflavones and mammographic breast density: a double-blind, randomized, placebo-controlled trial [ISRCTN42940165]. Breast Cancer Res 6:170–179CrossRefGoogle Scholar
  40. 40.
    Tice JA, Ettinger B, Ensrud K, Wallace R, Blackwell T, Cummings SR (2003) Phytoestrogen supplements for the treatment of hot flashes: the Isoflavone Clover Extract (ICE) study: a randomized controlled trial. JAMA 290:207–214PubMedCrossRefGoogle Scholar
  41. 41.
    Knight DC, Howes JB, Eden JA (1999) The effect of Promensil, an isoflavone extract, on menopausal symptoms. Climacteric 2:79–84PubMedGoogle Scholar
  42. 42.
    Baber RJ, Templeman C, Morton T, Kelly GE, West L (1999) Randomized placebo-controlled trial of an isoflavone supplement and menopausal symptoms in women. Climacteric 2:85–92PubMedGoogle Scholar
  43. 43.
    Krebs EE, Ensrud KE, MacDonald R, Wilt TJ (2004) Phytoestrogens for treatment of menopausal symptoms: a systematic review. Obstet Gynecol 104(4):824–836PubMedGoogle Scholar
  44. 44.
    MacGregor CA, Canney PA, Patterson G, McDonald R, Paul J (2005) A randomised double-blind controlled trial of oral soy supplements versus placebo for treatment of menopausal symptoms in patients with early breast cancer. Eur J Cancer 41(5):708–714PubMedCrossRefGoogle Scholar
  45. 45.
    Van Patten CL, Olivotto IA, Chambers GK, Gelmon KA, Hislop TG, Templeton E et al (2002) Effect of soy phytoestrogens on hot flashes in postmenopausal women with breast cancer: a randomized, controlled clinical trial. J Clin Oncol 20:1449–1455PubMedCrossRefGoogle Scholar
  46. 46.
    Quella SK, Loprinzi CL, Barton DL, Knost JA, Sloan JA, LaVasseur BI et al (2000) Evaluation of soy phytoestrogens for the treatment of hot flashes in breast cancer survivors: a North Central Cancer Center Treatment Group Trial. J Clin Oncol 18:1068–1074PubMedGoogle Scholar
  47. 47.
    Secreto G, Chiechi LM, Amadori A, Miceli R, Venturelli E, Valerio T et al (2004) Soy isoflavones and melatonin for the relief of climacteric symptoms: a multicenter, double-blind, randomized study. Maturitas 47:11–20PubMedCrossRefGoogle Scholar
  48. 48.
    Lewis JE, Nickell LA, Thompson LU, Szalai JP, Kiss A, Hilditch JR (2006) A randomized controlled trial of the effect of dietary soy and flaxseed muffins on quality of life and hot flashes during menopause. Menopause 13(4):631–642PubMedCrossRefGoogle Scholar
  49. 49.
    Nikander E, Kilkkinen A, Metsä-Heikkilä M, Adlercreutz H, Pietinen P, Tiitinen A, Ylikorkala O (2003) A randomized placebo-controlled crossover trial with phytoestrogens in treatment of menopause in breast cancer patients. Obstet Gynecol 101(6):1213–1220PubMedCrossRefGoogle Scholar
  50. 50.
    Penotti M, Fabio E, Modena AB, Rinaldi M, Omodei U, Vigano P (2003) Effect of soy-derived isoflavones on hot flushes, endometrial thickness, and the pulsatility index of the uterine and cerebral arteries. Fertil Steril 79:1112–1117PubMedCrossRefGoogle Scholar
  51. 51.
    Duffy R, Wiseman H, File SE (2003) Improved cognitive function in postmenopausal women after 12 weeks of consumption of a soy extract containing isoflavones. Pharmacol Biochem Behav 75:721–729PubMedCrossRefGoogle Scholar
  52. 52.
    St Germain A, Peterson CT, Robinson JG, Alekel DL (2001) Isoflavone-rich or isoflavone-poor soy protein does not reduce menopausal symptoms during 24 weeks of treatment. Menopause 8:17–26PubMedCrossRefGoogle Scholar
  53. 53.
    Kotsopoulos D, Dalais FS, Liang YL, McGrath BP, Teede H (2000) The effects of soy protein containing phytoestrogens on menopausal symptoms in postmenopausal women. Climacteric 3:161–167PubMedCrossRefGoogle Scholar
  54. 54.
    Baber RJ, Templeman C, Morton T, Kelly GE, West L (1999) Randomized placebo-controlled trial of an isoflavone supplement and menopausal symptoms in women. Climacteric 2:85–92PubMedGoogle Scholar
  55. 55.
    Crisafulli A, Marini H, Bitto A et al (2004) Effects of genistein on hot flushes in early postmenopausal women: a randomized, double-blind EPT- and placebo-controlled study. Menopause 11:400–404PubMedCrossRefGoogle Scholar
  56. 56.
    Han KK, Soares JM Jr, Haidar MA, de Lima GR, Baracat EC (2002) Benefits of soy isoflavone therapeutic regimen on menopausal symptoms. Obstet Gynecol 99:389–394PubMedCrossRefGoogle Scholar
  57. 57.
    Faure E, Chantre P, Mares P (2002) Effects of a standardized soy extract on hot flushes: a multicenter, double-blind, randomized, placebo-controlled study. Menopause 9:329–334PubMedCrossRefGoogle Scholar
  58. 58.
    Upmalis DH, Lobo R, Bradley L, Warren M, Cone FL, Lamia CA (2000) Vasomotor symptom relief by soy isoflavone extract tablets in postmenopausal women: a multicenter, double-blind, randomized, placebo-controlled study. Menopause 7:236–242PubMedCrossRefGoogle Scholar
  59. 59.
    Washburn S, Burke GL, Morgan T, Anthony M (1999) Effect of soy protein supplementation on serum lipoproteins, blood pressure, and menopausal symptoms in perimenopausal women. Menopause 6:7–13PubMedCrossRefGoogle Scholar
  60. 60.
    Murkies AL, Lombard C, Stauss BJ, Wilcox G, Burger HG, Morton MS (1995) Dietary flour supplementation decreases postmenopausal hot flushes: effect of soy and wheat. Maturitas 21:189–195PubMedCrossRefGoogle Scholar
  61. 61.
    Wiklund IK, Mattsson LA, Lindgren R, Limoni C (1999) Effects of standardized ginseng extract on quality of life and physiological parameters in symptomatic postmenopausal women: a double-blind, placebo-controlled trial. Int J Clin Pharmacol Res 19:89–99PubMedGoogle Scholar
  62. 62.
    Hartley DE, Elsabagh S, File SE (2004) Gincosan (a combination of Ginkgo biloba and Panax ginseng): the effects on mood and cognition of 6 and 12 weeks’ treatment in post-menopausal women. Nutr Neurosci 7(5–6):325–333PubMedCrossRefGoogle Scholar
  63. 63.
    Chenoy R, Hussain S, Tayob Y, O’Brien PM, Moss MY, Morse PF (1994) Effect of oral gamolenic acid from evening primrose oil on menopausal flushing. BMJ 308:501–503PubMedGoogle Scholar
  64. 64.
    Hirata JD, Swiersz LM, Zell B, Small R, Ettinger B (1997) Does dong quai have estrogenic effects in postmenopausal women? A double-blind, placebo-controlled trial. Fertil Steril 68:981–986PubMedCrossRefGoogle Scholar
  65. 65.
    Barton DL, Loprinzi CL, Quella SK, Sloan JA, Veeder MH, Egner JR et al (1998) Prospective evaluation of vitamin E for hot flashes in breast cancer survivors. J Clin Oncol 16:495–500PubMedGoogle Scholar
  66. 66.
    Guttuso TJ (2000) Gabapentin’s effect on hot flashes and hypothermia. Neurology 54:2161–2163PubMedGoogle Scholar
  67. 67.
    FugateS, Church C (2004) Nonestrogen treatment modalities for vasomotor symptoms associated with menopause. Ann Pharmacother 38:1482–1499CrossRefGoogle Scholar
  68. 68.
    Mahady GB, Gyllenhall C, Fong HH, Farnsworth NR (2000) Ginsengs: a review of safety and efficacy. Nutr Clin Care 3:90–101CrossRefGoogle Scholar
  69. 69.
    World Health Organization. WHO monographs on selected medicinal plants. Geneva: World Health Organization, 1999Google Scholar
  70. 70.
    Nelson HD (2004) Commonly used types of postmenopausal estrogen for treatment of hot flashes: scientific review. JAMA 291:1610–1620PubMedCrossRefGoogle Scholar
  71. 71.
    Lobo RA, Belisle S, Creasman WT, Frankel NR, Goodman NF, Hall JE et al (2006) Should symptomatic menopausal women be offered hormone therapy? MedGenMed 8(3):40PubMedGoogle Scholar
  72. 72.
    Newton KM, Reed SD, LaCroix AZ, Grothaus LC, Ehrlich K, Guiltinan J (2006) Treatment of vasomotor symptoms of menopause with black cohosh, multibotanicals, soy, hormone therapy, or placebo: a randomized trial. Ann Intern Med 145(12):869–879PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Deepti Cheema
    • 1
  • Arri Coomarasamy
    • 2
  • Tarek El-Toukhy
    • 2
  1. 1.Royal Worcestershire HospitalWorcesterUK
  2. 2.The Assisted Conception UnitGuy’s and St. Thomas HospitalLondonUK

Personalised recommendations