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      Isoflavone Supplements for Menopausal Women: A Systematic Review

      review-article
      1 , 2 , 1 , 3 , 4 , *
      Nutrients
      MDPI
      isoflavone, daidzein, genistein, equol, menopause

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          Abstract

          Isoflavones have gained popularity as an alternative treatment for menopausal symptoms for people who cannot or are unwilling to take hormone replacement therapy. However, there is still no consensus on the effects of isoflavones despite over two decades of vigorous research. This systematic review aims to summarize the current literature on isoflavone supplements, focusing on the active ingredients daidzein, genistein, and S-equol, and provide a framework to guide future research. We performed a literature search in Ovid Medline using the search terms “isoflavone” and “menopause”, which yielded 95 abstracts and 68 full-text articles. We found that isoflavones reduce hot flashes even accounting for placebo effect, attenuate lumbar spine bone mineral density (BMD) loss, show beneficial effects on systolic blood pressure during early menopause, and improve glycemic control in vitro. There are currently no conclusive benefits of isoflavones on urogenital symptoms and cognition. Due to the lack of standardized research protocols including isoflavone component and dosage, outcomes, and trial duration, it is difficult to reach a conclusion at this point in time. Despite these limitations, the evidence thus far favors the use of isoflavones due to their safety profile and benefit to overall health.

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          Most cited references65

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

          This analysis was conducted to determine the efficacy of extracted or synthesized soybean isoflavones in the alleviation of hot flashes in perimenopausal and postmenopausal women. PubMed and The Cochrane Controlled Clinical Trials Register Database were searched for relevant articles reporting double-blinded randomized controlled trials through December 14, 2010. References within identified articles, as well as peer-reviewed articles that had come to the attention of the authors through other means, were also examined for suitability. This systematic review and meta-analysis, which evaluated the effects of isoflavones on the frequency, severity, or composite score (frequency × severity) of hot flashes compared with placebo was conducted according to Cochrane Handbook guidelines. From 277 potentially relevant publications, 19 trials (reported in 20 articles) were included in the systematic review (13 included hot flash frequency; 10, severity; and 3, composite scores), and 17 trials were selected for meta-analyses to clarify the effect of soybean isoflavones on hot flash frequency (13 trials) and severity (9 trials). Meta-analysis revealed that ingestion of soy isoflavones (median, 54 mg; aglycone equivalents) for 6 weeks to 12 months significantly reduced the frequency (combined fixed-effect and random effects model) of hot flashes by 20.6% (95% CI, -28.38 to -12.86; P < 0.00001) compared with placebo (heterogeneity P = 0.0003, I = 67%; random effects model). Meta-analysis also revealed that isoflavones significantly reduced hot flash severity by 26.2% (95% CI: -42.23 to -10.15, P = 0.001) compared with placebo (heterogeneity, P < 0.00001, I = 86%; random effects model). Isoflavone supplements providing more than 18.8 mg of genistein (the median for all studies) were more than twice as potent at reducing hot flash frequency than lower genistein supplements. Soy isoflavone supplements, derived by extraction or chemical synthesis, are significantly more effective than placebo in reducing the frequency and severity of hot flashes. Additional studies are needed to further address the complex array of factors that may affect efficacy, such as dose, isoflavone form, baseline hot flash frequency, and treatment duration.
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            Soy isoflavones improve systemic arterial compliance but not plasma lipids in menopausal and perimenopausal women.

            The possibility that the heightened cardiovascular risk associated with the menopause, which is said to be ameliorated by soybeans, can be reduced with soy isoflavones was tested in 21 women. Although several were perimenopausal, all have been included. A placebo-controlled crossover trial tested the effects of 80-mg daily isoflavones (45 mg genistein) over 5- to 10-week periods. Systemic arterial compliance (arterial elasticity), which declined with age in this group, improved 26% (P < .001) compared with placebo. Arterial pressure and plasma lipids were unaffected. The vasodilatory capacity of the microcirculation was measured in nine women; high acetylcholine-mediated dilation in the forearm vasculature was similar with active and placebo treatments. LDL oxidizability measured in vitro was unchanged. Thus, one important measure of arterial health, systemic arterial compliance, was significantly improved in perimenopausal and menopausal women taking soy isoflavones to about the same extent as is achieved with conventional hormone replacement therapy.
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              Soy isoflavone intake increases bone mineral density in the spine of menopausal women: meta-analysis of randomized controlled trials.

              The effects of isoflavones on bone loss appear inconsistent in randomized controlled trials. Therefore, we used a statistical method of combining these diverse data to clarify the effects of soy isoflavone intake on spine bone loss. We identified randomized controlled trials related to the effects of soy isoflavone intake on spine bone mineral density or spine bone mineral content and performed meta-analysis with Review Manager 4.2 software. Ten studies with a total of 608 subjects were selected for meta-analysis. The spine bone mineral density in subjects who consumed isoflavones increased significantly by 20.6 mg/cm(2) (95% confidence interval: 4.5-36.6 mg/cm(2)) in comparison to that in subjects who did not consume isoflavones. Isoflavone intake vs placebo intake increased spine bone mineral content by 0.93 g (95% confidence interval: -0.37 to 2.24 g) with borderline significance. Increases in the spine bone mineral density with isoflavone intake of more than 90 mg/day and with treatment lasting 6 months were 28.5mg/cm(2) (95% confidence interval: 8.4-48.6 mg/cm(2)) and 27 mg/cm(2) (95% confidence interval: 8.3-45.8 mg/cm(2)), respectively. Isoflavone intervention significantly attenuates bone loss of the spine in menopausal women. These favorable effects become more significant when more than 90 mg/day of isoflavones are consumed. And soy isoflavone consumption for 6 months can be enough to exert beneficial effects on bone in menopausal women.
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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                04 November 2019
                November 2019
                : 11
                : 11
                : 2649
                Affiliations
                [1 ]Department of Physical Medicine and Rehabilitation, Mackay Memorial Hospital, Taipei 10449, Taiwan; gracealex168@ 123456gmail.com (L.-R.C.); Naiyuko@ 123456gmail.com (N.-Y.K.)
                [2 ]Department of Mechanical Engineering, National Chiao-Tung University, Hsinchu 300, Taiwan
                [3 ]Department of Obstetrics and Gynecology, Taipei Tzu-Chi Hospital, The Buddhist Tzu-Chi Medical Foundation, Taipei 23142, Taiwan
                [4 ]School of Medicine, Tzu-Chi University, Hualien 970, Taiwan
                Author notes
                [* ]Correspondence: alexgfctw@ 123456yahoo.com.tw ; Tel.: +886-2-6628-9779
                [†]

                These authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0002-4758-0351
                Article
                nutrients-11-02649
                10.3390/nu11112649
                6893524
                31689947
                1bc5d8ac-ede4-4e4a-ba0b-6e6a95691f83
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 17 September 2019
                : 29 October 2019
                Categories
                Review

                Nutrition & Dietetics
                isoflavone,daidzein,genistein,equol,menopause
                Nutrition & Dietetics
                isoflavone, daidzein, genistein, equol, menopause

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