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The Role of Phytoestrogens in the management of menopausal symptoms

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by Tania van Avendonk



Menopause reflects a change in the woman’s physiological hormonal status and is regarded as a pivotal point in a woman’s life. The commonest symptoms experienced by women during the menopause are hot flushes and night sweats. Although HRT remains the gold standard for thetreatment of menopausal symptoms, certain controversial studies have led to a shift against the regular use of HRT. Many physicians and women have turned to alternative ‘natural’ products, hoping that these can substitute the need for HRT. The evidence base for the efficacy and safety of phytoestrogens, in particular isoflavones, will be discussed.


Menopause reflects a change in the woman’s physiological hormonal status, and although not equivalent to an illness, it is regarded as a pivotal point in a woman’s life. Its management should not be neglected because while some women may go through it without noticing, it is generally accompanied by a variety of disorders. Top of the list in 40% to 80% of Western women are hot flushes and night sweats which can result in decreased quality of life.¹ Increased public expectations and awareness of health issues have contributed to an increased demand for products related to menopausal symptoms.

The gold standard for the treatment of menopausal symptoms is the conventional HRT that actually corrects the underlying lack of female hormones. Results of major RCTs including the Women Health InitiativeHeartEstrogen/Progestin Replacement Study II³ and the large British observational study the Million Women Study4have demonstrated an increased risk of cardiovascular disease and cancer of the breast with HRT use. Following these controversial studies over 90% of family physicians in Malta  have changed their prescribing habits of HRT.5 Due to the fear of these adverse effects and possible long-term risks of HRT, many women are reluctant to use HRT and have turned to alternative ‘natural’ products hoping that these can substitute the need for HRT.

A number of epidemiological studies suggest that the female populations in Asian nations like Japan, China and South-east Asia, are less burdened by menopausal symptoms than those of Western countries. It has been postulated that these differences may be due to the traditional Asian diet that is rich in Soy, which contains substances that are structurally similar to estrogen and bind to ER and hence have been called phytoestrogens. Since their binding affinity to ER is preferential, i.e. stronger binding affinity to ERβ than to ERα, they are better classified as SERMs.

Media coverage has led to an increased consumer awareness of soy, which has resulted in skyrocketing sales of soy products and supplements. Many advertising campaigns have specifically targeted females and depicted soy and other phytoestrogens as the alternative to conventional HRT for menopausal symptoms with the added benefits of possible protective properties against breast cancer and heart disease. These products are classified underCAM and not as medicinals. Although they are freely available in health shops and pharmacies as over-the-counter products, many women request information and advice from their GP and other health practitioners about the effectiveness, safety and tolerability of these products before purchase.



vvWhat is the evidence base to support the effectiveness of phytoestrogen therapy in menopausal vvwomen for the control of hot flushes? 

CAM products tend to lack a research tradition and infrastructure, since funding is generally limited compared with the amount spent by the pharmaceutical industry on conventional drugs. However over the past 10 years several studies both of experimental animal type and clinical trials have been carried out to test the efficacy and tolerability of phytoestrogens derived from both Soy and Red Clover.

 It is therefore important that proper recommendations are based on appropriate and good quality evidence.EBM orEBP aims to apply the best available evidence gained from the scientific method to clinical decision making.The strongest evidence quality is derived from systematic reviews of double/triple blind RCT followed by that of individual properly designed RCTs.

The evidence base from systematic reviews of studies about efficacy of phytoestrogens is sometimes conflicting. Several reviews have evaluated the clinical evidence relating isoflavone treatment to the relief of menopausal hot flash symptoms. The majority of these reviews included a variety of isoflavone sources, often without differentiatingbetween the identities of individual isoflavones contained in the study product. Hence reports concluding that isoflavone supplements do not significantly reduce hot flash symptoms may be incorrect. The lack of differentiation  between individual isoflavones contained in heterogeneous isoflavone mixtures from differing sources can be misleading when designing studies, interpreting results, and conducting reviews.

One critical review conducted by Williamson-Hughes et al.6 has demonstrated that a statistically significant reduction of hot flushes is achieved only in those studies which provided more than 15mg genistein (type of isoflavone).Another review by Bolanoset al.7analyzed 19 RCTs and demonstrated an overall significant reduction in hot flushed with soy preparations. The systematic review and meta-analysis conducted by Taku et al,8 alsoconcluded thatsoy isoflavone supplements, derived by extraction or chemical synthesis, are significantly more effective than placebo in reducing the frequency and severity of hot flushes.

As described, several double-blinded RCTs with particular standardised formulations of isoflavoneshave demonstrated positive effects incontrolling hot flushes.6,7,8,9 The strongest evidence is for formulations containing specifically genistein.6,10It was also suggested that genistein may have a favourable effect on some cardiovascular markers.11 This positive effect of genistein without any adverse effects on the endometrium and vagina after 1 year treatment were also demonstrated by another RCT.12 The safety concerns of isoflavones were also addressed in another RCT with no effects on the endometrium and the breast, demonstrated by biopsy specimens.13

Less evidence exists to address the effects of soy isoflavones on bone metabolism in postmenopausal women and their place in the prevention and treatment of postmenopausal osteoporosis. In vitro and animal studies have shown that they act in multiple ways to exert their bone-supporting effects by acting on both osteoblasts and osteoclasts. Epidemiological studies and clinical trials suggest that soy isoflavones have beneficial effects on bone mineral density, bone turnover markers, and bone mechanical strength in postmenopausal women.14

The North America Menopause Society in 2010 published a report stating that Soy-based isoflavones are modestly effective in relieving menopausal symptoms and supplements providing higher proportions of genistein(type of isoflavone) or increased S-equolcontent (isoflavan, metabolite of the soy isoflavonedaidzein) may provide more benefits. However larger studiesin younger postmenopausal women, and more research is needed to understand the modes of use of soy isoflavone supplements in women.15


There is enough evidence to support the use of isoflavones especially genistein, in the treatment of acute menopausal symptoms. Different sources and supplements of phytoestrogens are available on the market however many of them lack standardization of the content of the active ingredient which can seriously affect the bioavailability. Counseling of women regarding which preparations are most suitable and to avoid unrealistic expectations from these preparationsis very important.


CAM: Complementary and alternative medicine

EBM: Evidence-based medicine

EBP: Evidence-based Practice

ER:  Estrogen receptor

HRT: Hormone replacement Therapy

RCT: Randomized controlled trials

SERM: Selective Estrogen receptor modulator







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  1. Women’s Health Initiative Steering Committee (2004). Effects of the conjugated equine estrogen in postmenopausal women with Hysterectomy: the Women’s Health Initiative randomized controlled trial. Journal of the American Medical Association. Vol.291:1701-1712.


  1. Grady D., Herrington D., Bittner V., Blumenthal R., Davidson M., Hlatky M., Hsia J., Hulley S., Herd A., Khan S., Kristen Newby L Waters D., Vittinghoff E. & Wenger N. (2002). Cardiovascular disease outcomes during 6.8 years of hormonal therapy. Heart and Oestrogen/progestin Replacement Study: follow up. (HERS II) Journal of American Medical Association. 288: 49-57.


  1. Million Women Study Collaborators (2003). Breast cancer and hormone replacement therapy in the Million Women Study. The Lancet. Vol. 362:419-27.


  1. Van Avendonk T.(2007). Menopausal management by Maltese family physicians and the role of Hormone replacement therapy in 2007. Dissertation submitted for MSc in Primary Care and General Practice from the University of Ulster.


  1. Williamson-Hughes P., Flickinger B., Messina M., Empie M., (2006)Isoflavone supplements containing predominantly genistein reduce hot flash symptoms: a critical review of published studies. Vol.13(5):831-839.



  1. Bolaños R., Del Castillo A.,Francia, J.(2010). Soy isoflavones versus placebo in the treatment of climacteric vasomotor symptoms: systematic review and meta-analysis. Menopause: Vol. 17 (3):660-66.


  1. , Melby M., Kronenberg F., Kurzer M.,; Messina M. (2012).Extracted or synthesized soybean isoflavones reduce menopausal hot flash frequency and severity: systematic review and meta-analysis of randomized controlled trials .Menopause. 19(7):776-790.


  1. Faure E.D., Chantre P. & Mares P. (2002). Effects of a standardized soy extract on hot flushes: a multicenter, double-blind, randomized, placebo-controlled study. Menopause: 9 (5): 329-334.



  1. ,Marini H., Bitto A., Altavilla D.,Squadrito G., Romeo A., AdamoE., Marini R.,D'Anna R., Corrado F., BartoloneS., Frisina N., Squadrito F. (2004).Effects of genistein on hot flushes in early postmenopausal women: a randomized, double-blind EPT- and placebo-controlled study. Menopause: Volume 11 (4) :400-404.


  1. ,Marini H., Bitto A., Altavilla D.,Squadrito G., Romeo A., AdamoE., Marini R.,D'Anna R., Corrado F., BartoloneS., Frisina N., Squadrito F. (2005).Effects of the phytoestrogen genistein on cardiovascular risk factors in postmenopausal women Menopause: Vol. 12 (2):186-192.



  1. D'Anna R., Cannata M.L., Marini H., Atteritano M.,Cancellieri F., Corrado F., Triolo O., Rizzo P., Russo S., Gaudio A., Frisina N., Bitto A.,Polito F., Minutoli L., Altavilla D.,Adamo E.B., SquadritoF.(2009). Effects of the phytoestrogen genistein on hot flushes, endometrium, and vaginal epithelium in postmenopausal women: a 2-year randomized, double-blind, placebo-controlled study. Menopause: Vol.16 (2): 301-306.


  1. Cheng G.,Wilczek B., Warner M., Gustafsson J-A., Landgren B-M.(2007).Isoflavone treatment for acute menopausal symptoms. 14(3):468-473.



  1. Atmaca A., Kleerekoper M., Bayraktar M., Kucuk O.(2008). Soy isoflavones in the management of postmenopausal osteoporosis Menopause: 15 (4): 748-757.


  1. Clarkson T., Utian W.H., Barnes S., Gold E.B., Basaria S.,Aso T., Kronenberg F., Frankenfeld C.L., Cline J.M., Landgren B-M.,  Gallagher J.C., Weaver C., Hodis H.,  Brinton R.D., Maki P. (2011) The role of soy isoflavones in menopausal health: report of The North American Menopause Society/Wulf H. Utian Translational Science Symposium in Chicago, IL(Oct.2010. Menopause: Vol.18 (7):732-753.

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  • TheSynapse Magazines: 2012
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