Furthermore, even at high concentrations, they did not show a clear influence on fertility. Finally, they show antioxidant activity: a shared property among polyphenols(Reference Patel, Boersma and Crawford19). However, because of the paucity of studies exploring the impact of soy intake on women's fertility, as well as the limited population sample size, the frequently incomplete specimens collection to investigate all cycle phases and the insufficient characterisation of participants, the evidence is suggestive and it needs further in-depth research taking into account all these aspects. No correlation with specific isoflavones such as equol, daidzein and O-DMA was found. (Reference Filiberto, Mumford and Pollack37). Furthermore, the individuals recruited were seeking for a pregnancy and this could have changed their behaviour. These alterations easily lead to hyperandrogenism and irregular menstrual cycles. Soybeans are the most common source of isoflavones in human food; the major isoflavones in soybean are genistein and daidzein. Soy has been used to treat certain symptoms of menopause (such as hot flashes) and to help prevent bone loss ( osteoporosis ).Some supplement products have been found to contain possibly . No restrictions were applied using filters and results were collected from search engines by the inception through 4 April 2021. Articles concerning reviews, case series, case studies, non-human studies, in vitro studies, studies on males, editorials, letters to editor, conference abstracts, book's chapters, non-English papers, studies with no-soy isoflavones and studies with outcomes not pertinent to fertility were excluded. A. F. contributed to drafting and revising the manuscript. However, results are questionable due to the lack of hormone level measurements or reproductive functions. Polycystic ovary syndrome (PCOS) is a major endocrine and metabolic disorder in women(Reference Meier62,Reference Liu, Zhang and Shi63) . Patients showed plasma androgens levels above or at the upper limit the normal range, at baseline. Despite the 6-month duration of the clinical trial, the lack of a placebo group, the absence of characterisation of equol-competence among individuals and the limited number of participants reduced the strength of the results obtained. Furthermore, the search for sources has been extended to the single manuscripts reference lists. The significant inverse association between dietary isoflavone intake and live births (3% reduction, 95% CI 0, 7, P=005) was highlighted. Soy is a key food in human nutrition. Compliance with the intervention was suggested by urinary excretion of isoflavones. Eating Places. Four clinical trials were found among search engines results: two longitudinal pilot studies(Reference Romualdi, Costantini and Campagna34,Reference Haudum, Lindheim and Ascani46) and two interventional studies with a parallel design, both conducted in Iranian populations(Reference Khani, Mehrabian and Khalesi35,Reference Jamilian and Asemi43) . The generalisation of these results is complex due to the type of study, which does not allow to define a causal relationship. From the general linear model of the analysis of covariance, the intervention with soy reduced free androgen index (0020005 v. +0010005, P<0001), total testosterone (01005 v. +01005ng/ml, P=0008) and increased SHBG levels (+4008 v. 1408nmol/l, P<0001) compared with placebo (adjusted for baseline values). Li, Hang The strength of these studies was the assessment of hormone levels based on the menstrual cycle phase. Get the latest business insights from Dun & Bradstreet. Regarding isoflavones, the equol metabolite derives from the precursor daidzein by the action of intestinal bacteria. To put this into perspective, a 3.5-ounce (100-gram) serving of firm, calcium-set tofu offers about 60 mg of soy isoflavones, while 1 cup (240 mL) of soy milk contains only about 28 mg. Participants recruited were seeking for pregnancy and this could have been a source of confounders. The same authors admitted that they had no information on the type of soy used and about the last ingestion. Despite the sample size and full follow-up for endpoints evaluation, the study displays limitations. Presumably, treatment with pharmacological concentrations of soy phytoestrogens allows mitigating the negative effect of clomiphene citrate on endometrial tissue, thus facilitating embryo implantation. 1. 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). While soy appears to have a negligible effect on hormonal network, menstrual cycle length and fertility outcomes of healthy women, some clues emerged from literature on its possible beneficial effect in the case of endocrine diseases such as PCOS. This aspect was different from the results of the clinical trials with high intakes listed above, perhaps due to very different intakes (mean isoflavone consumption of 34mg/d in this cohort). However, after removing data from studies with elevated bias risk, two studies were included in the sensitivity analysis with a consequent loss of statistical significance for LH levels. Publication types Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't MeSH terms For these reasons, results should be interpreted with caution. WHAT IS IT? In the meta-analysis by Hooper and colleagues(Reference Hooper, Ryder and Kurzer59) from the evaluation of eleven studies on premenopausal women, ten studies were included to clarify the effect of soy on menstrual cycle length. From the data obtained, diet isoflavones do not seem to have a direct effect on fertility, whether positive or negative. It is plausible that isoflavones bind to this blood carrier and stimulate its hepatic synthesis. The soy isoflavones block the estrogen receptors in your brain and fool your body into thinking its natural estrogen levels are low. The study must be considered exploratory, because of the limited number of luteal phase deficiency cycles and a small number of fertility-related outcomes. Fertility is defined by the number of offspring produced by an individual. Even if the clinical trial did not include a placebo group or randomisation, the presence of a control group and the evaluation of equol-producer individuals mitigated these issues. Clinical trials can provide solid causal inferences, but they often have limitations in terms of study duration or intervention design. Researchers did not observe any clinical improvement, alteration of menstrual cycle or hormonal alteration (estradiol, SHBG, DHEAS, androstenedione, testosterone, FSH, LH) compared with baseline levels. The possibility of a sexual development disorder as a neonatal programming effect is an often raised hypothesis because circulating levels of isoflavones are higher in soy-fed infants compared with cow milk formula or breastfed infants(Reference Andres, Moore and Linam69). 07 March 2022. Overall, soy and soy components consumption do not seem to perturb healthy women's fertility and can have a favourable effect among subjects seeking pregnancy. Luteal phase deficiency can represent a relevant aspect for pregnancy outcomes and fertility disorders. Ma, Haoyue In a logical perspective, the effect of soy cannot be attributed to the effect of its isoflavones alone. 1. This allowed to exclude the already summarised articles in meta-analysis from a detailed discussion. Furthermore, the type of dietary survey carried out in the proposed environmental questionnaire was not clear. Zhang, Yuehui Products; Resources; My Account; Talk to a D&B Advisor 1-800-280-0780. Business Directory. 1 The FDA based this decision on clinical studies showing that at least 25 g of soy protein per day lowered . CA. It is widely used in eastern traditional cuisine and it has recently diffused among self-conscious and vegetarian diets. Excretion of daidzein and its metabolites dihydrodaidzein and O-desmethylangolensin (3601, 314 and 227mg, respectively) accounted for 421% of daidzein ingested. There was no evaluation of dietary habits and the determination of hormone levels was performed using non-validated ELISA kits, due to limited budget. Furthermore, there was no evaluation of metabolic utilisation capacity of isoflavones and their absorption by measuring serum and urinary levels. 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. Choose any of these varieties. Soy isoflavones have also been found to inhibit tyrosine kinases (14), enzymes that play critical roles in the signaling pathways that stimulate cell proliferation. Moreover, urinary concentrations seem to reflect the isoflavone intakes in a short time window. 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%). After the soy intervention, the length of menstrual cycle marginally increased (from 28319 to 31851d, P=006). However, among fertile individuals, it may have a neutral effect, as discussed in the previous paragraphs. Good: strong ovulation pains and increased ewcm. Nevertheless, these studies often suffer difficulties in evaluating individual effectiveness as well as in identifying possible confounding factors and population characteristics (ethnicity, health conditions, equol-competence, etc.). Guo, Tingting The fertility concept differs from the fecundity one, which refers to reproductive potential and depends on reproductive physiology, from the production of gametes phase to the ability to carry a pregnancy to term. Four papers were found about assisted reproduction technology, two of which were interventional studies by Unifer and colleagues, using high intakes of soy phytoestrogens as adjuvant(Reference Unfer, Casini and Costabile31,Reference Unfer, Casini and Gerli32) . The lack of variation in gonadotropins can explain the absence of variation in menstrual cycle. Pending further confirmation, soy and its components do not appear to have a clinically relevant influence on menstrual cycle in healthy women. One of the first research papers to look directly at soy and fertility outcomes was from the Adventist Health Study-2. Soy isoflavones have repeatedly shown a mild estrogenic effect but at high concentrations they may have enough power to act on hypothalamus and pituitary gland, reducing the ovarian synthesis of estrogens. 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. Furthermore, from the multiple regression analysis of ten women in the second trial(Reference Lu, Anderson and Grady29), the reduction of estradiol in both luteal and follicular phases was positively associated with serum and urinary isoflavone levels but not with individual changes in the intake. Adapted from Moher et al. However, the specific effect of soy intake on women's fertility has not yet been systematically evaluated. From the sub-analysis by ethnic stratification, follicular SHBG levels were higher in non-Asians. The ethnicity assessment of participants was useful in identifying, as might be expected, a greater consumption of soy foods by Asian individuals. The deleterious effects of these compounds, as metabolites of clover isoflavones, were first documented in 1946 by Bennetts and co-workers studying New Zealand ewes expressing clover disease, an infertility syndrome ( Bennetts, Underwood, & Shier, 1946 ). 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. Improvements were observed only in lipid profile (circulating total cholesterol, LDL and LDL/HDL ratio and triglycerides). 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