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Associations between Phytoestrogens, Glucose Homeostasis, and Risk of Diabetes in Women: A Systematic Review and Meta-Analysis.
Glisic, M, Kastrati, N, Gonzalez-Jaramillo, V, Bramer, WM, Ahmadizar, F, Chowdhury, R, Danser, AJ, Roks, AJ, Voortman, T, Franco, OH, et al
Advances in nutrition (Bethesda, Md.). 2018;(6):726-740
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Abstract
Phytoestrogens might have advantageous effects on diabetes in women. We performed a systematic review and meta-analysis to determine the effect of phytoestrogens on glucose homeostasis and the risk of type 2 diabetes (T2D) among women. Randomized controlled trials (RCTs) and prospective observational studies that assessed associations of phytoestrogens (supplementation, dietary intake, or biomarkers) with fasting glucose or insulin, homeostatic model assessment of insulin resistance (HOMA-IR), or with the risk of T2D were included. We identified 18 RCTs (n = 1687 individuals) investigating the effect of phytoestrogen supplementation on glucose homeostasis and 9 prospective population-based studies (n = 212,796 individuals) examining the association between phytoestrogen intake and the risk of T2D. Compared with placebo, phytoestrogen supplementation resulted in improvements in fasting glucose and HOMA-IR: the pooled mean differences of changes were -0.12 mmol/L (95% CI: -0.20, -0.03 mmol/L) and -0.24 mmol/L (95% CI: -0.45, -0.03 mmol/L), respectively. Although there was no significant decrease in insulin concentrations with overall phytoestrogen supplementation, the pooled mean difference in changes was -0.99 pmol/L (95% CI: -4.65, 2.68 pmol/L). However, the results of RCTs varied by type of phytoestrogens: soy-derived isoflavones and genistein improved glucose homeostasis, whereas isoflavone mix and daidzein had no effect or were associated with an adverse glycemic profile. Higher dietary phytoestrogen intake was associated with a 10% lower risk of developing T2D in observational studies (pooled RR: 0.90; 95% CI: 0.85, 0.96; for the highest compared with the lowest quantiles). Results were similar when the analyses were restricted to only medium- and high-quality studies. Overall, phytoestrogens may have a positive influence on glycemia and could be used for diabetes prevention in women. However, for some individual types of phytoestrogens, such as mixed isoflavones, caution is needed in recommending their use in women, because their use could lead to an adverse glycemic profile in women.
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Effect of phytoestrogens on sexual function in menopausal women: a systematic review and meta-analysis.
Najaf Najafi, M, Ghazanfarpour, M
Climacteric : the journal of the International Menopause Society. 2018;(5):437-445
Abstract
OBJECTIVE This systematic review and meta-analysis aimed to critically evaluate the effectiveness of phytoestrogens on sexual disorders and severity of dyspareunia. MATERIALS AND METHODS Relevant studies were identified through a systematic search of major databases such as PubMed, Cochrane Library, ISI Web of Science, and Scopus up to 29 September 2017, without any time limit. Two independent reviewers screened all abstracts and full-text articles. The final version of Jadad scale was used for evaluating the quality of trials. RESULTS Soy did not have an effect on sexual function (standardized mean difference [SMD] = 1.099 [95% CI: -3.033 to 0.835, p = 0.265]; heterogeneity I2 = 80%; p = 0.006; random-effect model; three trials) but improved dyspareunia (p > 0.05). Red clover showed no significant effect on sexual function (SMD = -0.087 [95% CI: -0.936 to 0.763, p = 0.842]; heterogeneity I2 = 0%, p = 0.397; fixed-effect model; two trials) and sexual satisfaction (p > 0.05). Phytoestrogens isolated from Lepidium meyenii, Foeniculum vulgare, and maritime pine bark as well as Trigonella foenum-graecum L. significantly improved sexual function. In contrast, phytoestrogens isolated from Korean red ginseng and flaxseed did not lead to significant effect on sexual function. The positive effects of Trigonella foenum-graecum L. were observed on libido. CONCLUSION Phytoestrogens have various effects on sexual function. Published reports show that maritime pine bark, T. foenum-graecum L., and F. vulgare could be considered as agents to overcome sexual dysfunctions while soy, red clover, genistein, and flaxseed had no promising effects on these conditions.
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Phytoestrogens and risk of prostate cancer: an updated meta-analysis of epidemiologic studies.
Zhang, Q, Feng, H, Qluwakemi, B, Wang, J, Yao, S, Cheng, G, Xu, H, Qiu, H, Zhu, L, Yuan, M
International journal of food sciences and nutrition. 2017;(1):28-42
Abstract
This updated meta-analysis was performed to clarify the relationship between phytoestrogens and prostate cancer risk. Twenty one case-control and two cohort studies were finally selected for this meta-analysis, totaling 11,346 cases and 140,177 controls. Analytical results showed that daidzein (OR = 0.85; 95% CI: 0.75-0.96), genistein (OR = 0.87; 95% CI: 0.78-0.98), and glycitein (OR = 0.89; 95% CI: 0.81-0.98) were associated with a reduction of prostate cancer risk, but total isoflavones (OR = 0.93; 95% CI: 0.84-1.04), equol (OR = 0.86; 95% CI: 0.66-1.14), total lignans (OROgna.05; 95% CI: 0.54-2.04), secoisolariciresinol (OR = 1.02; 95% CI: 0.83-1.24), matairesinol (OR = 0.91; 95% CI: 0.75-1.11), enterolactone (OR = 0.94; 95% CI: 0.73-1.20), and coumestrol (OR = 0.89; 95% CI: 0.76-1.06) were not. Sensitivity and publication bias analyses demonstrated that the pooled estimates were stable and reliable. The results support the notion that some phytoestrogens may have a role in decreasing the risk of prostate cancer. Additional large and well-designed cohort studies are needed to confirm these relationships.
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Cardiac glycosides and breast cancer risk: A systematic review and meta-analysis of observational studies.
Karasneh, RA, Murray, LJ, Cardwell, CR
International journal of cancer. 2017;(5):1035-1041
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Abstract
Cardiac glycosides are phytoestrogens and have been linked to the risk of estrogen sensitive cancers such as uterus cancer. However, the association between use of cardiac glycosides and risk of breast cancer remains unclear. We investigated the association between cardiac glycosides use and the risk of breast cancer by systematically reviewing the published literature and performing meta-analyses. A comprehensive literature search was performed using MEDLINE, EMBASE, Web of Science and SCOPUS to identify all relevant articles published up to November 2015. Risk estimates, and accompanying standard errors, for the association between cardiac glycoside use and breast cancer were extracted from identified studies. Meta-analysis models were used to calculate a combined hazard ratio (HR), and 95% confidence interval (CI), and to investigate heterogeneity between studies. In total, nine studies were identified investigating cardiac glycosides use and risk of developing breast cancer. Overall, there was evidence to suggest an association between cardiac glycosides use and breast cancer risk (HR = 1.34; 95% CI 1.25, 1.44; p < 0.001) with little variation in the association between studies (I2 = 16%, p for heterogeneity = 0.30). Results were little altered when analysis was restricted to studies with high quality scores or cohort studies. Overall, there was a 34% increase in breast risk with use of cardiac glycosides but it is unclear whether this association reflects confounding or is causal. Further observational studies are required to examine this association particularly for estrogen receptor positive breast cancer and to explore the role of potential confounding variables.
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Use of Plant-Based Therapies and Menopausal Symptoms: A Systematic Review and Meta-analysis.
Franco, OH, Chowdhury, R, Troup, J, Voortman, T, Kunutsor, S, Kavousi, M, Oliver-Williams, C, Muka, T
JAMA. 2016;(23):2554-63
Abstract
IMPORTANCE Between 40% and 50% of women in Western countries use complementary therapies to manage menopausal symptoms. OBJECTIVE To determine the association of plant-based therapies with menopausal symptoms, including hot flashes, night sweats, and vaginal dryness. DATA SOURCES The electronic databases Ovid MEDLINE, EMBASE, and Cochrane Central were systematically searched to identify eligible studies published before March 27, 2016. Reference lists of the included studies were searched for further identification of relevant studies. STUDY SELECTION Randomized clinical trials that assessed plant-based therapies and the presence of hot flashes, night sweats, and vaginal dryness. DATA EXTRACTION Data were extracted by 2 independent reviewers using a predesigned data collection form. MAIN OUTCOMES AND MEASURES Hot flashes, night sweats, and vaginal dryness. RESULTS In total, 62 studies were identified, including 6653 individual women. Use of phytoestrogens was associated with a decrease in the number of daily hot flashes (pooled mean difference of changes, -1.31 [95% CI, -2.02 to -0.61]) and vaginal dryness score (pooled mean difference of changes, -0.31 [95% CI, -0.52 to -0.10]) between the treatment groups but not in the number of night sweats (pooled mean difference of changes, -2.14 [95% CI, -5.57 to 1.29]). Individual phytoestrogen interventions such as dietary and supplemental soy isoflavones were associated with improvement in daily hot flashes (pooled mean difference of changes, -0.79 [-1.35 to -0.23]) and vaginal dryness score (pooled mean difference of changes, -0.26 [-0.48 to -0.04]). Several herbal remedies, but not Chinese medicinal herbs, were associated with an overall decrease in the frequency of vasomotor symptoms. There was substantial heterogeneity in quality across the available studies, and 46 (74%) of the included randomized clinical trials demonstrated a high risk of bias within 3 or more areas of study quality. CONCLUSIONS AND RELEVANCE This meta-analysis of clinical trials suggests that composite and specific phytoestrogen supplementations were associated with modest reductions in the frequency of hot flashes and vaginal dryness but no significant reduction in night sweats. However, because of general suboptimal quality and the heterogeneous nature of the current evidence, further rigorous studies are needed to determine the association of plant-based and natural therapies with menopausal health.
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Gene polymorphisms in the ornithine decarboxylase-polyamine pathway modify gastric cancer risk by interaction with isoflavone concentrations.
Cho, LY, Yang, JJ, Ko, KP, Ma, SH, Shin, A, Choi, BY, Kim, HJ, Han, DS, Song, KS, Kim, YS, et al
Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association. 2015;(3):495-503
Abstract
BACKGROUND The study aimed to examine the association between genes encoding molecules in the ornithine decarboxylase (ODC)-polyamine pathway (ODC1, AMD1, NQO1, NOS2A, and OAZ2) and gastric cancer risk and whether the gene-phytoestrogen interaction modifies gastric cancer risk. METHODS Among 76 gastric cancer cases and their 1:4 matched controls within the Korean Multi-center Cancer Cohort, a total of 30 SNPs in five genes involved in the ODC pathway were primarily analyzed. The second-stage genotyping in 388 matched case-control sets was conducted to reevaluate the significant SNPs interacting with phytoestrogens during the primary analysis. The summary odds ratios (ORs) [95 % confidence intervals (CIs)] for gastric cancer were estimated. Interaction effects between the SNPs and plasma concentrations of phytoestrogens (genistein, daidzein, equol, and enterolactone) were evaluated. RESULTS In the pooled analysis, NQO1 rs1800566 showed significant genetic effects on gastric cancer without heterogeneity [OR 0.83 (95 % CI 0.70-0.995)] and a greater decreased risk at high genistein/daidzein levels [OR 0.36 (95 % CI 0.15-0.90) and OR 0.26 (95 % CI 0.10-0.64), respectively; p interaction < 0.05]. Risk alleles of AMD1 rs1279599, AMD1 rs7768897, and OAZ2 rs7403751 had a significant gene-phytoestrogen (genistein and daidzein) interaction effect to modify the development of gastric cancer. They had an increased gastric cancer risk at low isoflavone levels, but a decreased risk at high isoflavone levels (p interaction < 0.01). CONCLUSIONS Our findings suggest that common variants in the genes involved in the ODC pathway may contribute to the risk of gastric cancer possibly by modulating ODC polyamine biosynthesis or by interaction between isoflavones and NQO1, OAZ2, and AMD1.
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Phytoestrogens and risk of prostate cancer: a meta-analysis of observational studies.
He, J, Wang, S, Zhou, M, Yu, W, Zhang, Y, He, X
World journal of surgical oncology. 2015;:231
Abstract
BACKGROUND Epidemiologic studies have reported various results relating phytoestrogens to prostate cancer (PCa). The aim of this study was to provide a comprehensive meta-analysis on the extent of the possible association between phytoestrogens (including consumption and serum concentration) and the risk of PCa. METHODS Eligible studies were retrieved via both computer searches and review of references. The summary relative risk ratio (RR) or odds ratio (OR) and 95% confidence interval (CI) were calculated with random effects models. RESULTS A total of 11 studies (2 cohort and 9 case-control studies) on phytoestrogen intake and 8 studies on serum concentration were included in the meta-analysis. The pooled odds ratio (OR) showed a significant influence of the highest phytoestrogens consumption (OR 0.80, 95% CI 0.70-0.91) and serum concentration (OR 0.83, 95% CI 0.70-0.99) on the risk of PCa. In stratified analysis, high genistein and daidzein intake and increased serum concentration of enterolactone were associated with a significant reduced risk of PCa. However, no significant associations were observed for isoflavone intake, lignans intake, or serum concentrations of genistein, daidzein, or equol. CONCLUSIONS The overall current literature suggests that phytoestrogen intake is associated with a decreased risk of PCa, especially genistein and daidzein intake. Increased serum concentration of enterolactone was also associated with a significant reduced risk of PCa. Further efforts should be made to clarify the underlying biological mechanisms.
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Phytoestrogen intake and risk of ovarian cancer: a meta- analysis of 10 observational studies.
Qu, XL, Fang, Y, Zhang, M, Zhang, YZ
Asian Pacific journal of cancer prevention : APJCP. 2014;(21):9085-91
Abstract
BACKGROUND Epidemiology studies have shown an inconclusive relationship between phytoestrogen intake and ovarian cancer risk and there have been no relevant meta-analyses directly regarding this topic. The purpose of the present meta-analysis was therefore to investigate any association between phytoestrogen intake and ovarian cancer in detail. MATERIALS AND METHODS We conducted a search of PubMed, EMBASE, EBSCO, the Cochrane Library, CNKI and Chinese Biomedical Database (up to April 2014) using common keywords for studies that focused on phytoestrogen and ovarian cancer risk. Study-specific risk estimates (RRs) were pooled using fixed effect or random-effect models. RESULTS Ten epidemiologic studies were finally included in the meta-analysis. The total results indicated higher phytoestrogen intake was associated with a reduced ovarian cancer risk (RR, 0.70; 95%CI: 0.56-0.87). The association was similar in sensitivity analysis. Meta regression analysis demonstrated sources and possibly types and regions as heterogeneous factors. Subgroup analysis of types, sources and regions showed that isoflavones (RR: 0.63; 95%CI: 0.46, 0.86), soy foods (RR: 0.51; 95%CI: 0.39, 0.68) and an Asian diet (RR: 0.48; 95%CI: 0.37, 0.63) intake could reduce the incidence of ovarian cancer. CONCLUSIONS Our findings show possible protection by phytoestrogens against ovarian cancer. We emphasize specific phytoestrogens from soy foods, but not all could reduce the risk. The habit of plentiful phytoestrogen intake by Asians is worthy to recommendation. However, we still need additional larger well designed observational studies to fully characterize underlying associations.
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Phytoestrogens for menopausal vasomotor symptoms.
Lethaby, A, Marjoribanks, J, Kronenberg, F, Roberts, H, Eden, J, Brown, J
The Cochrane database of systematic reviews. 2013;(12):CD001395
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Abstract
BACKGROUND Vasomotor symptoms, such as hot flushes and night sweats, are very common during the menopausal transition. Hormone therapy has traditionally been used as a highly effective treatment, but concerns about increased risk of some chronic diseases have markedly increased the interest of women in alternative treatments. Some of the most popular of these treatments are foods or supplements enriched with phytoestrogens-plant-derived chemicals that have estrogenic action. OBJECTIVES To assess the efficacy, safety and acceptability of food products, extracts and dietary supplements containing high levels of phytoestrogens when compared with no treatment, placebo or hormone therapy for the amelioration of vasomotor menopausal symptoms (such as hot flushes and night sweats) in perimenopausal and postmenopausal women. SEARCH METHODS Searches targeted the following electronic databases: the Cochrane Menstrual Disorders and Subfertility Group Specialised Register of randomised trials (29 July 2013), the Cochrane Register of Controlled Trials (CENTRAL; 29 July 2013), MEDLINE (inception to 29 July 2013), EMBASE (inception to 29 July 2013), AMED (1985 to 29 July 2013), PsycINFO (inception to 29 July 2013) and CINAHL (inception to 29 July 2013). Attempts were made to access grey literature by sending letters to pharmaceutical companies and performing searches of ongoing trial registers. Reference lists of included trials were also searched. SELECTION CRITERIA Studies were included if they were randomised, included perimenopausal or postmenopausal participants with vasomotor symptoms (hot flushes or night sweats), lasted at least 12 weeks and provided interventions such as foods or supplements with high levels of phytoestrogens (not combined with other herbal treatments). Trials that included women who had breast cancer or a history of breast cancer were excluded. DATA COLLECTION AND ANALYSIS Selection of trials, extraction of data and assessment of quality were undertaken by at least two review authors. Most trials were too dissimilar for their results to be combined in a meta-analysis, so these findings are provided in narrative 'Summary of results' tables. Studies were grouped into broad categories: dietary soy, soy extracts, red clover extracts, genistein extracts and other types of phytoestrogens. Five trials used Promensil, a red clover extract; results of these trials were combined in a meta-analysis, and summary effect measures were calculated. MAIN RESULTS A total of 43 randomised controlled trials (4,364 participants) were included in this review. Very few trials provided data suitable for inclusion in a meta-analysis. Among the five trials that yielded data assessing the daily frequency of hot flushes suitable for pooling, no significant difference overall was noted in the incidence of hot flushes between participants taking Promensil (a red clover extract) and those given placebo (mean difference (MD) -0.93, 95% confidence interval (CI) -1.95 to 0.10, I(2) = 31%). No evidence indicated a difference in percentage reduction in hot flushes in two trials between Promensil and placebo (MD 20.15, 95% CI -12.08 to 52.38, I(2) = 82%). Four trials that were not combined in meta-analyses suggested that extracts with high (> 30 mg/d) levels of genistein consistently reduced the frequency of hot flushes. Individual results from the remaining trials were compared in broad subgroups such as dietary soy, soy extracts and other types of phytoestrogens that could not be combined. Some of these trials found that phytoestrogen treatments alleviated the frequency and severity of hot flushes and night sweats when compared with placebo, but many trials were small and were determined to be at high risk of bias. A strong placebo effect was noted in most trials, with a reduction in frequency ranging from 1% to 59% with placebo. No indication suggested that discrepant results were due to the amount of isoflavone in the active treatment arm, the severity of vasomotor symptoms or trial quality factors. Also, no evidence indicated that these treatments caused oestrogenic stimulation of the endometrium or the vagina or other adverse effects when used for up to two years. AUTHORS' CONCLUSIONS No conclusive evidence shows that phytoestrogen supplements effectively reduce the frequency or severity of hot flushes and night sweats in perimenopausal or postmenopausal women, although benefits derived from concentrates of genistein should be further investigated.
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Effects of soy isoflavones and genistein on glucose metabolism in perimenopausal and postmenopausal non-Asian women: a meta-analysis of randomized controlled trials.
Ricci, E, Cipriani, S, Chiaffarino, F, Malvezzi, M, Parazzini, F
Menopause (New York, N.Y.). 2010;(5):1080-6
Abstract
OBJECTIVE Several randomized controlled trials (RCTs) have examined the role of soy isoflavones on cardiovascular risk factors in perimenopausal and postmenopausal women and have yielded inconsistent results. This meta-analysis aimed to assess the overall effect of soy isoflavones on glucose metabolism: fasting blood glucose, insulin, and insulin resistance. METHODS We searched for all articles published in English and indexed in Medline from January 1990 to December 2009. We included RCTs for soy isoflavone supplementation in perimenopausal and postmenopausal women not taking hormone therapy, selecting non-Asian women only. The main outcomes were fasting blood glucose changes from baseline. RESULTS We identified 10 eligible RCTs containing blood glucose data of 794 women. The main result was that soy isoflavones did not affect fasting blood glucose significantly. Under a random-effects model, the average difference in fasting blood glucose values between women assigned to isoflavones and women assigned to placebo was -2.16 mg/dL (95% CI, -5.21 to 0.89 mg/dL; P = 0.17). In genistein studies, the mean difference was -7.15 mg/dL (95% CI, -11.47 to -2.82). However, the effects on insulin and homeostasis model assessment insulin resistance were significant: -1.37 microIU/mL (95% CI, -1.92 to -0.81 microIU/mL) and -0.39 (95% CI, -0.65 to -0.14), respectively. Subgroup analyses did not show a significant effect of isoflavone dose, whereas isoflavone mixtures and genistein had a different effect on fasting blood glucose. CONCLUSIONS This meta-analysis of RCTs showed that isoflavone use was not associated with a significant glycemia reduction in perimenopausal and postmenopausal non-Asian women. However, the few studies that reported insulin and homeostasis model assessment insulin resistance changes suggested that soy isoflavones and genistein alone had a beneficial effect on glucose metabolism.