Furthermore, the use of spot urine samples for BPA quantification may have underestimated its exposure. These clinical trials had several strengths including the presence of a placebo group, randomisation, double-blinding and recruitment of a wide number of participants. On the other hand, many perplexities have been raised about possible negative mechanisms leading to endocrine disruptor effects(Reference Bar-El and Reifen20). Render date: 2023-03-02T11:20:28.481Z Soy is a very popular food and its consumption is part of the traditional cuisine of South-East Asian countries. Manuscripts exploring multiple aspects were discussed in different paragraphs, where deemed necessary. These aspects considerably reduce the reliability of results, favouring data misinterpretation. However, among fertile individuals, it may have a neutral effect, as discussed in the previous paragraphs. The length of menstrual cycle may represent an indirect marker of ovarian function and reproductive health(Reference Mumford, Steiner and Pollack54,Reference Vassena, Vidal and Coll55) . Soy can contain numerous other phytochemicals such as saponins, phytosterols, phytic acid, non-isoflavone flavonoids, peptides, protease inhibitors and other bioactive substances. Metabolic, endocrine, inflammation, and oxidative stress . The authors highlighted a marginal reduction of luteal phase in the adjusted multivariable model for an increase of 10mg/d of dietary isoflavones (aOR: 138, 95% CI 099, 192, P=006), identified by monitoring LH levels in urine by a fertility monitor and 4-d per cycle 24-h dietary recalls. 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. Recently, Wesselink and colleagues evaluated the fertility of 7778 healthy American or Canadian women in two cohort studies that followed participants for 12 months or until pregnancy(Reference Wesselink, Hatch and Mikkelsen44). Soy isoflavones have also been found to inhibit tyrosine kinases (14), enzymes that play critical roles in the signaling pathways that stimulate cell proliferation. Keywords were searched in titles and abstracts and combined with MeSH terms, where available, adapting the query format based on the search engine used. 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). 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). Despite adjustments for demographic, lifestyle, dietary factors, including ethnicity and other phytoestrogens, it would have been useful to check the dietary intake of isoflavones for equol-producers evaluation. For the remaining papers, the full texts were retrieved for the final evaluation and inclusion in the summary. Furthermore, hormone levels were evaluated only at baseline, without taking into account the differences between the two groups. However, the evaluation of ability to absorb and metabolise isoflavones was lacking in the present study. 1. In another clinical trial already discussed, although no changes in cycle length were found following soy foods intervention in twenty women with a follow-up of at least seven menstrual cycles, a significant reduction in follicular phase by 93% (P<005) in estradiol concentrations was observed, but not in luteal phase(Reference Wu, Stanczyk and Hendrich28). On consumption, they increase estrogen production in a woman's body. The power analysis concerning variation in isoflavone urinary excretion accounted for a sample size of 25 for >90% detection power. The same amount of genistein was used in a parallel clinical trial on 137 Iranian women with PCOS with a 3-month follow-up(Reference Khani, Mehrabian and Khalesi35). It is an endocrine dysfunction that includes hormonal alterations (increased levels of adrenal and ovarian androgens and SHBG secretion from the liver) and anovulatory disorders(Reference Ferk, Teran and Gersak64). The results of selected manuscripts were grouped according to the outcomes used, for a clear comparison. Furthermore, no characterisation was made on the possible presence of equol-producers among the participants. 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. The possible correlation between menstrual cycle length and soy does not seem convincing either. The reduction of estradiol and progesterone could postpone ovulation by lengthening the menstrual cycle. However, the number of participants was limited for a cross-sectional study, and dietary survey through frequency questionnaires in the absence of an assessment of blood or urine isoflavone levels could lead to uncertainty. The authors responsibilities were as follows: G. R. study conception and drafting the manuscript. Deepak Kumar, Komal Clinical trials can provide solid causal inferences, but they often have limitations in terms of study duration or intervention design. In 2005, Kohama and colleagues published a short communication about a 6 months clinical trial on thirty-six Japanese women with secondary amenorrhea (or anovulation)(Reference Kohama, Kobayashi and Inoue33). Furthermore, there was no characterisation of dietary regimen, although it was a standard hospital diet. Pettitt, Claire Phytoestrogens can modulate endogenous hormones at micromolar concentrations by influencing the expression of the enzymes cytochrome P450 19 aromatase (Cyp19), 17-hydroxysteroid dehydrogenase (17-HSD) and 3-hydroxysteroid dehydrogenase (3-HSD), steroid sulfatases (STS) and sulfotransferases (SULTs), enzymes of steroid biosynthetic pathway(Reference Rice and Whitehead80Reference Whitehead and Rice82). These also included non-soy derived phytoestrogens, such as lignans. Correction for covariates included demographics, education, income, lifestyle, dietary and behavioural factors. Likewise, equol-producers showed lower AMH levels in the whole cohort as well as in participants in PCOS or control groups. The ethnicity assessment of participants was useful in identifying, as might be expected, a greater consumption of soy foods by Asian individuals. The two observational studies also show different limitations, in particular, one of these studies uses a follow-up of only 2 months. Finally, they show antioxidant activity: a shared property among polyphenols(Reference Patel, Boersma and Crawford19). However, urinary phytoestrogen levels were only detected at baseline and this increased the correlation uncertainty. These mechanisms involve genomic regulation with activation of both receptor's subtypes at 1M as seen in 293 human embryonal kidney cells in transient gene expression assay(Reference Kuiper, Lemmen and Carlsson74). Soy consumption is supposed to have protective effects against cardiovascular disease by cholesterol-lowering and blood pressure improvement action and in the prevention of cancer or diabetes and it also supports bone health and the management of menopause symptoms(Reference Ding, Pan and Manson2Reference Mosallanezhad, Mahmoodi and Ranjbar8). In addition, other studies investigated the urinary concentrations of isoflavones and metabolites, including equol(Reference Mumford, Sundaram and Schisterman39,Reference Levine, Kim and Purdue-Smithe45) . No restrictions were applied using filters and results were collected from search engines by the inception through 4 April 2021. The study did not evaluate circulating or urinary levels of isoflavones to verify the ability to metabolise isoflavones. Steroid hormones (estradiol, progesterone and DHEAS) play a role in epithelial cell proliferation in mammals. The use of surveys only through self-administered questionnaires, although validated, is easily exposed to self-reporting errors or incompleteness and misclassifications derived from the database used for food intake quantification. Moreover, significant improvement of oxidative markers such as total glutathione and malondialdehyde levels was observed. Black soy, in addition to the content of isoflavones, is known to be rich in antioxidant substances, especially in external seed integuments, which are rich in anthocyanins(Reference Choung, Baek and Kang49). A slight increase of approximately 1d (MD: 105, 95% CI 013, 197) was seen compared with the control, with no significant effects in the length of luteal and follicular phases. Among the studies discussed to evaluate menstrual cycle length, three interventional studies also evaluated the levels of circulating hormones following soy intake in healthy women(Reference Lu, Anderson and Grady26,Reference Wu, Stanczyk and Hendrich28,Reference Lu, Anderson and Grady29) . There are clues about the association between soy intake and the increase in SHBG levels. These changes may have resulted in the mild, non-clinically relevant prolongation of menstrual cycle, as discussed in the previous section. Published by Cambridge University Press on behalf of The Nutrition Society. Furthermore, women with PCOS display a higher prevalence of hyperinsulinemia, dyslipidemia, insulin resistance and obesity compared to healthy population. Emerged clinical trials display several limitations including small sample size as well as the longitudinal design without a parallel control group, placebo or a cross-over design consistently limiting the strength of these pilot studies. However, this omission does not necessarily imply that the assessment has not been carried out. 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). 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). No changes in progesterone and SHBG concentrations from baseline were observed. Measurement of urinary isoflavones and their metabolites appears to be a more reliable approach than dietary assessment alone. Moreover, two recent observational cohort studies by Chavarro and colleagues evaluated the association between soy consumption and in vitro fertilisation outcomes(Reference Vanegas, Afeiche and Gaskins40,Reference Chavarro, Mnguez-Alarcn and Chiu42) . As for males, a 2010 meta-analysis highlighted the safety of soy on fertility outcomes(Reference Hamilton-Reeves, Vazquez and Duval21), recently confirmed by an updated meta-analysis on this topic(Reference Reed, Camargo and Hamilton-Reeves22). A list of the selected clinical studies with their characteristics is summarised in Table 1. In response, your body starts a cascade of events to boost estrogen production. WHAT IS IT? Servier Medical Art. They have been dubbed "the natural Clomid," As they work in pretty much an identical manner. The hormonal improvement has been followed by clinical ameliorations such as the reduction of alopecia, serum insulin levels, HOMA-B (homeostasis model of assessment-B cell function) and HOMA-IR (homeostasis model of assessment-insulin resistance) index among patients in the intervention arm. Similarly, the stratification by ethnicity and equol-producers may suggest the nature of interactions between soy and fertility. Unfortunately, the work of Kohama et al. The evaluation of isoflavones circulating levels and their urinary excretion allowed to show a wide inter-individual variation of metabolic and absorption capacity. No significant differences were found in the spontaneous abortion rate, the number and quality of embryos transferred or oocytes fertilised. Isoflavone genistein inhibited the enzyme tyrosine kinase in human A431 cell membranes at 07g/ml, a very high, non-physiological concentration(Reference Akiyama, Ishida and Nakagawa77) and act as a ligand for peroxisome proliferator-activated receptors (PPARs) in cultured astrocytes at 500nM(Reference Valles, Dolz-Gaiton and Gambini78). Han, Jing Microbial alpha diversity and glucose homeostasis improved in PCOS group after isoflavone intervention, resembling the control group profile at baseline. The authors found that consuming moderate amounts of traditionally . 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. However, in the work of Filiberto and colleagues(Reference Filiberto, Mumford and Pollack37), even if the correlation between isoflavones and the increase in SHBG was highlighted, the dosage of estradiol and free estradiol did not show significant correlations, although the estimate of free estradiol was done through Sodergard's formula(Reference Sdergrd, Bckstrm and Shanbhag61), so a direct dosage would be more reliable. The study included the evaluation of patients microbiota composition as the primary endpoint, but androgen levels were also evaluated with AMH as markers of fertility as a secondary endpoint. However, soy diet reduced progesterone (45%, P<00001) and estradiol levels (23%, P<001), compared with baseline. Jamilian and colleagues in 2016 conducted another parallel clinical trial on seventy Iranian women with PCOS, using 50mg/d of soy isoflavones for a 1-month follow-up(Reference Jamilian and Asemi43). 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. Other weak aspects of the population sample characterisation are given by a lack of stratification by ethnicity and equol-producers. DOI: 10.1017/jns.2022.15. Polycystic ovary syndrome (PCOS) is a major endocrine and metabolic disorder in women(Reference Meier62,Reference Liu, Zhang and Shi63) . Put simply, most of the evidence indicates that isoflavones do not adversely affect men's fertility. In the previously mentioned meta-analysis by Hooper and colleagues(Reference Hooper, Ryder and Kurzer59), reduction of about 22% of FSH (SMD: 045UI/l, 95% CI 079, 011, P=001) and of about 4% of LH (SMD: 034IU/l, 95% CI 068, 001, P=005) were related to the intake of soy or isoflavones. 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 authors of this recent literature review of available evidence from observational and interventional studies concluded that soy and its components cannot be classified as an endocrine disruptor. Affect men & # x27 ; s body pretty much an identical manner participants was useful in,! Events to boost estrogen production transferred or oocytes fertilised soy isoflavones fertility twins tastylia, such as.! 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