In this context, the evaluation of urine samples cannot be underestimated as a valuable tool for detection of the real bioavailability of isoflavones whose metabolisation requires the intervention of intestinal microbiota. Those women eating or taking soy isoflavones were more likely to get pregnant. 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. Huntriss, Rosemary As expected, women with the highest soy consumption were more likely to be of Asian descent. 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). Days Soy Isoflavones were taken: 2-6 Dosage on those days: 120mg Side effects: bad: hot flushes, headaches, disturbed sleep. The two observational studies also show different limitations, in particular, one of these studies uses a follow-up of only 2 months. This could favour the bioavailability of sex hormones(Reference Kurzer60). Main characteristics of selected studies. The authors found no significant differences in reproductive outcomes (missed menstrual periods, pregnancy, live births, abortions, miscarriages, full-term deliveries, preterm deliveries, etc.) The significant inverse association between dietary isoflavone intake and live births (3% reduction, 95% CI 0, 7, P=005) was highlighted. Conclusions: These data suggest that higher intake of soy foods and soy isoflavones is associated with lower sperm concentration. Although some works investigate the relationship between consumption of soy formulations in infancy and age at menarche, as well as the onset of puberty or pre-puberty reproductive organ size, these outcomes are not strictly related to fertility in reproductive age(Reference Andres, Moore and Linam69Reference Sinai, Ben-Avraham and Guelmann-Mizrahi71). Regarding observational studies, in 2015 Andrews and colleagues conducted a prospective cohort study on 246 American women with normal menstrual cycle, aged 1844 and with 13% of participants of Asian ethnicity, for a follow-up of 12 whole menstrual cycles(Reference Andrews, Schliep and Wactawski-Wende41). After 6 months, estradiol levels of patients in the intervention group were higher compared with basal (P<005), whereas luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were unchanged. The study's strength include a large consumption of soy and by consistent inter-individual variability among participants (total intake of 379261g/d), which allows better detection of cross-sectional correlations. Participants were classified by ethnicity; however, the population sample size did not allow to perform stratification of outcomes based on this aspect. 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). Furthermore, women with PCOS display a higher prevalence of hyperinsulinemia, dyslipidemia, insulin resistance and obesity compared to healthy population. However, levels of progesterone, estradiol, free estradiol, estrone and SHBG did not show significant differences. Soy as an endocrine disruptor: cause for caution? This phenomenon highlights how in literature there is greater attention to phytoestrogens and their effect, frequently underestimating the role of other components that have a marginal interest. The concentration of isoflavones in the amniotic fluid was related to soy intake, but there was no significant association between soy intake or phytoestrogens in the amniotic fluid and complications of pregnancy or previous infertility. Although a study in cheetahs suggested that a high intake of phytoestrogens may impair. Adapted from Moher, Main cellular mechanism for isoflavones. Isoflavones also show effects that do not imply ER and ER involvement. Last but not least, soy isoflavones can act through an antioxidant mechanism through the stimulation of enzymes responsible for xenobiotics metabolism and oxidative stress reduction in vitro at a range of 5100M(Reference Wei, Wei and Frenkel87). However, the mechanisms underlying isoflavones effects on human health are manifold. Furthermore, no characterisation was made on the possible presence of equol-producers among the participants. The consumption of soy over time, the possible use of certain foods considered healthy in seeking pregnancy or the willingness to avoid pregnancy could generate spurious associations. 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. This could be done by empirically monitoring ovulation to get a real information of menstrual phase, such as quantifying the urinary LH peak as a marker of ovulation, as done by Wu et al. Luteal phase deficiency can represent a relevant aspect for pregnancy outcomes and fertility disorders. A weak, not clinically relevant effect has been highlighted on cycle length and hormonal status. The only study found about the effect of exposure to soy in childhood and reproductive functions is the retrospective study by Strom and colleagues(Reference Strom, Schinnar and Ziegler30). The urinary or serum levels of isoflavones did not affected progesterone levels in the multiple regression analysis. 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 clinical trial was limited to a small sample size, lacking of control/placebo group and there was no characterisation of equol-competence. On the other hand, many perplexities have been raised about possible negative mechanisms leading to endocrine disruptor effects(Reference Bar-El and Reifen20). 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