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From the data obtained, diet isoflavones do not seem to have a direct effect on fertility, whether positive or negative. With regards to available clinical trials, Lu and colleagues conducted two interventional studies using 36 Oz of soy milk (about one litre) divided into three daily intakes for a total daily intake of about 200mg of isoflavones(Reference Lu, Anderson and Grady26,Reference Lu, Anderson and Grady29) . 1. Furthermore, phytoestrogens appear to act on SHBG synthesis by altering mRNA levels in hepatocarinoma human cells treated with genistein 20M(Reference Mousavi and Adlercreutz85), and modulating the balance between bound and free steroids or competing with endogenous sex hormones for the active site binding of the carrier(Reference Dchaud, Ravard and Claustrat86). In the first clinical trial by Unifer and colleagues, 1500mg/d of isoflavones from soy or placebo were administered for 10d to 134 women who had been infertile for at least 2 years, undergoing intrauterine insemination after 100mg/d for 5d of clomiphene citrate treatments (an ovulation inducer)(Reference Unfer, Casini and Costabile31). SHBG levels were not associated with the intake of soy foods, except in the case of miso intake on the 22nd day of cycle (r: 036, P=002). Therefore, the lack of fecundity is called sterility(Reference Wood47). Pending further confirmation, soy and its components do not appear to have a clinically relevant influence on menstrual cycle in healthy women. Since there are no scientific studies on the effects of soy isoflavones and ovulation, these are just general guidelines. On the other hand, many perplexities have been raised about possible negative mechanisms leading to endocrine disruptor effects(Reference Bar-El and Reifen20). Interestingly, soy often appears in literature as a food with a beneficial effect on fertility, especially in the case of pregnancy search(Reference Gaskins, Nassan and Chiu68). The dietary intake of isoflavones did not appear to be associated with fertility in the two cohorts but some marginal evidence of amelioration of fertility was related to a higher intake of isoflavones among 30 years old individuals after age stratification (Fecundability Ratios: 112, 95% CI 994, 134 and 119, 95% CI 092, 155 in the two cohorts comparing 90th with <24th percentile). for this article. The advantages of observational cohort studies include longer times and wider population samples. The FFQ was not specifically designed for phytoestrogen assessment and this may have underestimated intakes. However, a clear effect on reproductive system has never been highlighted, especially due to the absence of observational studies designed for this purpose. Find Best Western Hotels & Resorts nearby Sponsored. Table 1. The lack of variation in gonadotropins can explain the absence of variation in menstrual cycle. There was a significant correlation between dietary soy consumption and fertilisation rate (77% v. 71%, P=0004), age-adjusted pregnancy (52% v. 41%, P=003) or age-adjusted live birth rate (44% v. 31%, P=0007) among soy consumers compared with non-consumers. View all Google Scholar citations Similarly, the duration of interventions is limited and equol-producers have not been identified. Corrections for confounding factors, such as diet, demographics, lifestyle factors, age, body composition and ethnicity, indicated reliable analysis. Soy isoflavones can help induce ovulation in such women. Published online by Cambridge University Press: Conversely, the improvements in ovulation were seen only in two patients from the control group. Good: strong ovulation pains and increased ewcm. Fig. Day 22 should correspond to the mid-luteal phase, however, the authors pointed out that participants exhibited different lengths of menstrual cycle and this could have been a source of heterogeneity that was used as a covariate in the regression model. Those women eating or taking soy isoflavones were more likely to get pregnant. However, the association between soy and isoflavones with the reduction of luteal phase seems weak. In the only clinical trial available, even if it is considered a pilot study, it emerges that a significant role could be played not only by isoflavones, but also by phytochemicals present in soy, particularly in black soy. Recently, the anti-Mllerian hormone (AMH) concentrations have proved to be a useful tool for predicting female fertility, especially because it is independent of the cycle phase(Reference Dewailly and Laven48). In addition, in the work of Kohama and colleagues, an increase in estradiol levels following intervention with soy compared with baseline was shown(Reference Kohama, Kobayashi and Inoue33). PMCID: PMC8922143. The authors wish to thank Sandra De Dominici for language revision assistance. 07 March 2022. The detailed selection process is highlighted in Fig. The evaluation of isoflavones circulating levels and their urinary excretion allowed to show a wide inter-individual variation of metabolic and absorption capacity. Furthermore, hormone levels were evaluated only at baseline, without taking into account the differences between the two groups. Soy consumption was not related to estradiol levels or endometrial thickness. Has data issue: true However, even in the West, it is currently widely used, especially due to its versatility in plant-based products for health purposes and vegetarian diets (Reference Rizzo and Baroni 1).Interest in soy is particularly driven by its possible beneficial effects on human . Furthermore, the use of spot urine samples for BPA quantification may have underestimated its exposure. In October 1999, the US Food and Drug Administration (FDA) approved labeling for foods containing soy protein as protective against coronary heart disease. Eating a few servings of soy each week could improve fertility and metabolic aspects of PCOS. Why did you take Soy Isoflavones: I had tried most other things so decided to be a guinea pig. Despite the sample size and full follow-up for endpoints evaluation, the study displays limitations. However, the difference became not significant after adjustment for isoflavone intake. Five studies exploring the relationship between soy and the length of menstrual cycle in healthy women have been selected, including two observational studies(Reference Andrews, Schliep and Wactawski-Wende41,Reference Levine, Kim and Purdue-Smithe45) and three longitudinal interventional studies(Reference Lu, Anderson and Grady26,Reference Wu, Stanczyk and Hendrich28,Reference Lu, Anderson and Grady29) . The authors found an association between pregnancy outcomes and urinary Bisphenol A (BPA), dependent on soy consumption in the multivariable-adjusted mixed model. In the first of the two papers by Lu and colleagues(Reference Lu, Anderson and Grady26), the intake of 36 Oz/d of soy milk (~200mg/d IF) for 1 month caused a reduction in mean estradiol levels of 31% at days 57, P=009; 81% at days 1214, P=003; 49% at days 2022, P=002, compared with the baseline. Although this was a randomised, placebo-controlled and double-blinded trial with a sample size appropriate to the power of detection, there was no evaluation of serum and urinary levels of isoflavones and/or metabolites. Only 6% of participants had not soy isoflavone intake. Both isoflavones are found in soy at several mg 100 g 1 ( Bennetau-Pelissero, 2013 ). The small number of participants significantly limited the quality of results. The success of soy mainly depends on versatility and supposed healthy properties of soy foods and soy components. Furthermore, it should be considered that, as already discussed, many studies display several limitations including inadequate sampling of hormone concentrations during all phases of cycle, low number of participants and the lack of a placebo group. The urinary or serum levels of isoflavones did not affected progesterone levels in the multiple regression analysis. Interest in soy is particularly driven by its possible beneficial effects on human health. A. F. contributed to drafting and revising the manuscript. Eating Places. Adapted from Moher, Main cellular mechanism for isoflavones. Furthermore, no characterisation was made on the possible presence of equol-producers among the participants. Furthermore, the individuals recruited were seeking for a pregnancy and this could have changed their behaviour. This is justified by the fact that the study was not designed for the specific assessment of dietary soy concerning fertility-related outcomes. There are clues about the association between soy intake and the increase in SHBG levels. While the observational data better reflect the effects of diet in free-living conditions compared with experimental settings of clinical trials, the use of food frequency questionnaires exposes to possible misclassification and measurement errors. From a sub-analysis on ethnic characteristics, it was further highlighted that only Asian women showed a significant reduction in follicular estradiol from baseline (174%). Journal of Clinical Endocrinology and Metabolism randomized 70 women with PCOS into two groups to take either 50 mg/d soy isoflavones or a placebo for 12 weeks. However, the intakes of isoflavones in the studied cohorts were limited (range: 0331mg/d). Individuals who are not equol-producers have likely limited response to isoflavone intake(Reference Iino, Shimoyama and Iino16). Ma, Haoyue Consistent with the previously cited data, no significant alteration in the cycle length was found among participants following the intervention. Soy supplementation also appears to affect thyroid function in an inconsistent manner, as studies have shown both increases and decreases in the same parameters of thyroid activity. In the present study, the intervention group showed improvements in hormonal circulating levels compared with baseline, which consisted in the reduction of LH levels (94%, P=0000), testosterone (56%, P=0000) and DHEAS (87%, P=0000), with no significant changes in the control group. Mildly increased levels of SHBG were associated with higher dietary isoflavone intakes (Q4 [16788mg/d] v. Q1 [0003mg/d]) in the adjusted linear mixed model (: 009, 95% CI 002, 016), but no correlation was found for estradiol, progesterone, LH, FSH levels or anovulatory events. The interaction between isoflavones and ER estrogen receptor results in a competitive effect which in turn blunts endogenous estrogens action(Reference Rosselli, Reinhart and Imthurn72), as suggested by estrogenic activity of biochanin A and genistein on BT-474 human breast cancer(Reference Zand, Jenkins and Diamandis73). The procedure was carried out following the most recent PRISMA guidelines(Reference Liberati, Altman and Tetzlaff23). In the first study, the authors administered soy milk to six American women aged 2229 for 1 month, comparing outcomes with baseline(Reference Lu, Anderson and Grady26). The estrogen-like effects of isoflavones underlie concerns about soy and fertility. Only three articles declared power analysis to assess adequate sample size(Reference Strom, Schinnar and Ziegler30,Reference Jamilian and Asemi43,Reference Haudum, Lindheim and Ascani46) . In order to assess the association between urinary isoflavones and fertility, adjustment for various confounding factors including ethnicity, supplement use, nutrients and lifestyle aspects was applied. Even if serum AMH concentrations appear as a useful tool for predicting female fertility, only one study from our selection used them(Reference Haudum, Lindheim and Ascani46). Soy is a key food in human nutrition. Manuscripts exploring multiple aspects were discussed in different paragraphs, where deemed necessary. Progesterone and sex hormone-binding globulin (SHGB) levels were not significantly changed by soy intake. However, the terms are often interchangeably, being closely associated with the possibility of giving birth to children. The obtained results were evaluated for duplicates and then screened for titles and abstracts information. However, the intake of isoflavones in diet has not been investigated, and therefore, it was not possible to define the presence of equol-producers among participants. In addition to the interventional study by Kohama and colleagues, we found three longitudinal cohort observational studies(Reference Jarrell, Foster and Kinniburgh36,Reference Mumford, Sundaram and Schisterman39,Reference Wesselink, Hatch and Mikkelsen44) and a cross-sectional study(Reference Jacobsen, Jaceldo-Siegl and Knutsen38) that investigated the association between soy and fertility. After the intervention period, four patients became pregnant and twelve patients showed ovulation improvements based on ultrasonography (P<005). Results from a pilot study, Effect of soy phytoestrogen on metabolic and hormonal disturbance of women with polycystic ovary syndrome, Usual dietary isoflavone intake and reproductive function across the menstrual cycle, Soy isoflavone intake and the likelihood of ever becoming a mother: the adventist health study-2, Higher urinary lignan concentrations in women but not men are positively associated with shorter time to pregnancy, Soy food intake and treatment outcomes of women undergoing assisted reproductive technology, Dietary factors and luteal phase deficiency in healthy eumenorrheic women, Soy intake modifies the relation between urinary bisphenol A concentrations and pregnancy outcomes among women undergoing assisted reproduction, The effects of soy isoflavones on metabolic status of patients with polycystic ovary syndrome, Dietary phytoestrogen intakes of adult women are not strongly related to fecundability in 2 preconception cohort studies, Urinary phytoestrogens and relationship to menstrual cycle length and variability among healthy, eumenorrheic women, Impact of short-term isoflavone intervention in polycystic ovary syndrome (PCOS) patients on microbiota composition and metagenomics, Fecundity and natural fertility in humans, Isolation and determination of anthocyanins in seed coats of black soybean (, Antioxidants and reactive oxygen species in follicular fluid of women undergoing IVF: relationship to outcome, The influence of religious affiliation on participant responsiveness to the complete health improvement program (CHIP) lifestyle intervention, Health beliefs, behavior, spiritual growth, and salvation in a global population of seventh-day adventists, A brief historical overview of the past two decades of soy and isoflavone research, The utility of menstrual cycle length as an indicator of cumulative hormonal exposure, Menstrual cycle length in reproductive age women is an indicator of oocyte quality and a candidate marker of ovarian reserve, Prospective evaluation of luteal phase length and natural fertility, Menstrual cycle characteristics and fecundability in a North American preconception cohort, A prospective cohort study of menstrual characteristics and time to pregnancy, Effects of soy protein and isoflavones on circulating hormone concentrations in pre- and post-menopausal women: a systematic review and meta-analysis, Hormonal effects of soy in premenopausal women and men, Calculation of free and bound fractions of testosterone and estradiol-17 beta to human plasma proteins at body temperature, Dysbiosis of gut microbiota associated with clinical parameters in polycystic ovary syndrome, The (TAAAA)n microsatellite polymorphism in the SHBG gene influences serum SHBG levels in women with polycystic ovary syndrome, Circulating inflammatory markers in polycystic ovary syndrome: a systematic review and metaanalysis, Dietary patterns and outcomes of assisted reproduction, Compared with feeding infants breast milk or cow-milk formula, soy formula feeding does not affect subsequent reproductive organ size at 5 years of age, Early-life soy exposure and age at menarche, Consumption of soy-based infant formula is not associated with early onset of puberty, Cellular and biochemical mechanisms by which environmental oestrogens influence reproductive function, Steroid hormone activity of flavonoids and related compounds, Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta, Rapid endocrine disruption: Environmental estrogen actions triggered outside the nucleus, Equol-stimulated mitochondrial reactive oxygen species activate endothelial nitric oxide synthase and redox signaling in endothelial cells: roles for F-actin and GPR30, Genistein, a specific inhibitor of tyrosine-specific protein kinases, Estradiol or genistein prevent Alzheimer's disease-associated inflammation correlating with an increase PPAR gamma expression in cultured astrocytes, Bacterial metabolite S-equol modulates glucagon-like peptide-1 secretion from enteroendocrine L cell line GLUTag cells via actin polymerization. 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