Finally, they show antioxidant activity: a shared property among polyphenols(Reference Patel, Boersma and Crawford19). In 2015, a longitudinal study found no differences in sexual organ development at 5 years of age between cow milk formula, breast milk and soy formula feeding(Reference Andres, Moore and Linam69). Find Best Western Hotels & Resorts nearby Sponsored. For this reason, they are classified as phytoestrogensplant-derived compounds with estrogenic activity (1). Regarding the two mentioned studies, the use of very high amounts of isoflavones is noteworthy because it is not possible to obtain such a dose through diet, therefore the effects found can be interpreted as a pharmacological and not nutritional intervention. Recently, in a prospective study by Levine et al., 326 American women eumenorrheic aged 1840 were followed for 12 months or until pregnancy(Reference Levine, Kim and Purdue-Smithe45). Notably, during manuscript preparation, Messina and colleagues published a technical review on endocrine effect of soy and isoflavones(Reference Messina, Mejia and Cassidy90). for this article. The significant inverse association between dietary isoflavone intake and live births (3% reduction, 95% CI 0, 7, P=005) was highlighted. Published by Cambridge University Press on behalf of The Nutrition Society. Recently, Haudum and colleagues conducted a longitudinal case-control clinical trial on forty-four Australian patients (twenty-four PCOS and twenty healthy controls) using 400ml/d of soy milk (containing approximately 50mg of isoflavones, 132g protein) for a 3-d pilot study(Reference Haudum, Lindheim and Ascani46). [1] Patients showed plasma androgens levels above or at the upper limit the normal range, at baseline. Concerns that the phytoestrogens (isoflavones) in soy may feminize men continue to be raised. 16 Although much of the concern is based on animal research, 16 a sufficient amount of fertility-relevant human research, including both epidemiologic and clinical studies, has been conducted; therefore, conclusions about the impact of soy on fertility can be Hostname: page-component-7fc98996b9-pxj8b This latter aspect suggests a differential capacity for metabolising isoflavones even if these differences were no longer significant when corrected for the intake of isoflavones and estradiol levels were not significantly associated with urinary excretion of isoflavones. 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 Baroni1). Furthermore, the intervention group showed lower rates of miscarriage (n: 2, 31% v. n: 6, 87%; P<005) and higher rates of pregnancy (n: 13, 200% v. n: 3, 44%; P<005) compared with placebo. Soy is a key food in human nutrition. DPO you got your BFP: 14dpo. 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 individual conversion capacity, equol-competence, offers a useful tool for estimating the biological effect of these compounds(Reference Zubik and Meydani15). This may have influenced the presence of large confidence intervals. They evaluated the hormonal variations during menstrual cycle through the composite construct that considered the cumulative information of the day of menstrual cycle for specimens. 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. Furthermore, the individuals recruited were seeking for a pregnancy and this could have changed their behaviour. A systematic consultation of literature was launched on four search engines (PubMed, ScienceDirect, Cochrane Trials Library and ClinicalTrials.gov) using the following keywords: (Soy OR Soy Foods OR Soybeans OR Genistein OR Daidzein OR Isoflavones OR Phytoestrogens) AND (Fertility OR Infertility OR Fecundability). Conclusions: These data suggest that higher intake of soy foods and soy isoflavones is associated with lower sperm concentration. 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). The influence on SHBG levels can have a beneficial effect from an endocrine point of view, without negative effects on ovulation. Why did you take Soy Isoflavones: I had tried most other things so decided to be a guinea pig. The diagnosis of PCOS occurs in the presence of at least two of the three Rotterdam Criteria: oligo or anovulation, polycystic ovary morphology and biochemical or clinical hyperandrogenism(Reference Pfieffer67). Furthermore, there was no evaluation of metabolic utilisation capacity of isoflavones and their absorption by measuring serum and urinary levels. The ethnicity assessment of participants was useful in identifying, as might be expected, a greater consumption of soy foods by Asian individuals. 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. No restrictions were applied using filters and results were collected from search engines by the inception through 4 April 2021. For these reasons, studies that evaluated the ovarian hormones secretion were aimed at exploring the potential beneficial effect of soy on breast cancer prevention, but they were not designed for the evaluation of endocrine consequences, including fertility. Pettitt, Claire 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 ). There was no relationship between isoflavone intake and reported problems becoming pregnant. Metabolic, endocrine, inflammation, and oxidative stress . For this reason, the clinical data were meta-ana Furthermore, the absence of gynecological issues was only based on self-reported information. However, in multiple regression analysis, this reduction seemed to be significantly associated with the intake of genistein and daidzein or their concentration in urine. Moreover, difficulties related to data collection about nutritional intakes were available, and individual reporting errors must be taken into account. Li, Hang The present paper aims to conduct a review of available data on the effect of soy, soy foods and soy components on women's fertility and related outcomes. Servier Medical Art. Adapted from SMART: Servier Medical Art(89). This, in turn, stimulates ovulation and can make you ready for pregnancy. Similar to the previous observational study, Chavarro et al. The adjustment for male partner intake of soy in the subgroup analysis did not change the association. Presumably, treatment with pharmacological concentrations of soy phytoestrogens allows mitigating the negative effect of clomiphene citrate on endometrial tissue, thus facilitating embryo implantation. The purpose of this review is to collect currently available data in literature, summarising the possible interaction between soy, soy foods and components of soy (in particular isoflavones) on aspects concerning women's fertility and related outcomes. Independent Researcher, Via Venezuela 66, 98121Messina, Italy, Laboratory of Cardiovascular Endocrinology, IRCCS San Raffaele Roma, 00166Rome, Italy, Department of Human Sciences and Promotion of the Quality of Life, San Raffaele Roma Open University, 00166Rome, Italy, Center for Complementary Medicine, Department of Internal Medicine II, Faculty of Medicine, University of Freiburg, Freiburg, Germany, Reference Mosallanezhad, Mahmoodi and Ranjbar, Reference Setchell, Brown and Lydeking-Olsen, Reference Hamilton-Reeves, Vazquez and Duval, Reference Reed, Camargo and Hamilton-Reeves, Reference Oyawoye, Abdel Gadir and Garner, Reference Mumford, Sundaram and Schisterman, Reference Jacobsen, Jaceldo-Siegl and Knutsen, Reference Crawford, Pritchard and Herring, Reference Andrews, Schliep and Wactawski-Wende, Reference Sdergrd, Bckstrm and Shanbhag, Reference Escobar-Morreale, Luque-Ramrez and Gonzlez, Reference Showell, Mackenzie-Proctor and Jordan, Reference Romualdi, Costantini and Campagna, Reference Chavarro, Mnguez-Alarcn and Chiu, Reference Sinai, Ben-Avraham and Guelmann-Mizrahi, Reference Ropero, Alonso-Magdalena and Ripoll, Reference Valles, Dolz-Gaiton and Gambini, Reference Gunnarsson, Ahnstrm and Kirschner, Soy, soy foods and their role in vegetarian diets, Consumption of soy foods and isoflavones and risk of type 2 diabetes: a pooled analysis of three US cohorts, Cumulative meta-analysis of the soy effect over time, Soy, soy isoflavones, and protein intake in relation to mortality from all causes, cancers, and cardiovascular diseases: a systematic review and dose-response meta-analysis of prospective cohort studies, Consensus: soy isoflavones as a first-line approach to the treatment of menopausal vasomotor complaints, Soy isoflavones for osteoporosis: an evidence-based approach, Soy and isoflavone consumption and multiple health outcomes: umbrella review of systematic reviews and meta-analyses of observational studies and randomized trials in humans, Soy intake is associated with lowering blood pressure in adults: a systematic review and meta-analysis of randomized double-blind placebo-controlled trials, The antioxidant role of soy and soy foods in human health, Non-isoflavone phytochemicals in soy and their health effects. and DOI: 10.1017/jns.2022.15. 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. This could favour the bioavailability of sex hormones(Reference Kurzer60). This was a short pilot study with a small sample size in subgroups. The clinical trial was limited to a small sample size, lacking of control/placebo group and there was no characterisation of equol-competence. 2022. Fertility is defined by the number of offspring produced by an individual. Eating Places. These aspects were poorly characterised by self-reporting of the participants. Based on this cross-sectional study, high consumption of soy isoflavones was identified (94% of participants). 1. Isoflavones are produced via a branch of the general phenylpropanoid pathway that produces flavonoid compounds in higher plants. On consumption, they increase estrogen production in a woman's body. Higher soy products intake did not correlate with the rate of infertility. Only 6% of participants had not soy isoflavone intake. However, only 106 individuals provided information on soy intake. 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). A total number of twenty-two experimental articles plus a meta-analysis was used for the final synthesis. The intervention period was extended only to one menstrual cycle. Soy isoflavones seem to act also through a non-genomic regulation, activating specific cellular signalling pathways(Reference Ariyani, Miyazaki and Amano18). 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). Despite the sample size and full follow-up for endpoints evaluation, the study displays limitations. 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. The authors showed an inverse correlation between cycle length (detected via fertility monitors and daily journals) and total urinary phytoestrogen levels (0042d for 10% increase, 95% CI 0080, 0003). This effect persisted for at least one menstrual cycle after the suspension of soy intake, with a maximum of persistence for three menstrual cycles. In the study by Nagata and colleagues, fifty Japanese women were enrolled to evaluate the association between soy intake (using an FFQ) and hormone levels. Furthermore, the possible ameliorative influence of soy or its components in the case of assisted reproduction techniques outcomes and pregnancy seeking appears promising and worthy of interest. However, the mechanisms underlying isoflavones effects on human health are manifold. The success of soy mainly depends on versatility and supposed healthy properties of soy foods and soy components. 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 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). Main characteristics of selected studies. 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) . . For example, it should be identified whether the interest is related to pharmacological effect, thus implying the use of high concentrations of soy components, or if the aim is to investigate soy functional effects that can be obtained mimicking eating habits, thus providing soy foods with realistic intake levels. The generalisation of these results is complex due to the type of study, which does not allow to define a causal relationship. Finally, the authors made a detailed assessment of confounders (diet, ethnicity, age and BMI). Fig. However, the specific effect of soy intake on women's fertility has not yet been systematically evaluated. Using food frequency questionnaires, researchers found that women with high isoflavone intake ( 40 mg/day) had a 3% lower lifetime probability of giving birth to a live child compared to women with a low intake (< 10mg/day). Days Soy Isoflavones were taken: 2-6 Dosage on those days: 120mg Side effects: bad: hot flushes, headaches, disturbed sleep. Go. It is important to evaluate the levels of hormones that fluctuate during the cycle at several points. They may be useful in alleviating menopause symptoms or preventing osteoporosis in postmenopausal women. Interest in soy is particularly driven by its possible beneficial effects on human health. The soy isoflavones block the estrogen receptors in your brain and fool your body into thinking its natural estrogen levels are low. 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). This allowed to exclude the already summarised articles in meta-analysis from a detailed discussion. The FFQ was not specifically designed for phytoestrogen assessment and this may have underestimated intakes. Feature Flags: { To our knowledge, this is the first comprehensive review on soy effect on women's fertility. 4 Center for Complementary Medicine, Department of Internal Medicine II, Faculty of Medicine, University of Freiburg, Freiburg, Germany. 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. 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. 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). However, among fertile individuals, it may have a neutral effect, as discussed in the previous paragraphs. It would have been useful to have retrospective information on soy consumption to assess the potential effect on previous fertility problems. In the second study by Lu and colleagues(Reference Lu, Anderson and Grady29), ten American women aged 2342 who did not consume soy regularly were followed for the duration of a menstrual cycle, during which nutritional intervention with soy was performed (36 Oz/d soy drink; 113207mg/d IF), without observing significant changes in cycle length compared to baseline and with a marginal shortening of luteal phase (6%, P=007). Live birth odds in the multivariable-adjusted analysis was higher among women in the second tertile of soy intake, consuming 264755mg/d of soy isoflavones (OR: 187; 95% CI 112, 314) and among women in the third tertile of soy intake, consuming 7562789mg/d of isoflavones (OR: 177; 95% CI 103, 303) compared with no consumption, but without a significant linear trend. However, the difference became not significant after adjustment for isoflavone intake. There is a limited trend in estradiol reduction related to soy consumption; however, in their interventional study, Petrakis and colleagues observed an unusual increase of estradiol levels(Reference Petrakis, Barnes and King25). In addition, full-text bibliographic lists from selected papers were screened to retrieve further relevant articles. In both studies, the lowering of progesterone levels in luteal phase was also significant in the case of soy intake, mean 35% (P=0002) compared with baseline. 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. These substances could play a role in the ovaries circulatory functions(Reference Oyawoye, Abdel Gadir and Garner50). Similarly, a significant correlation between isoflavone intake and nulligravidity emerged (P=003) with a 13% higher risk but with a wide range of confidence interval (95% CI 2, 26) in women with intake 40mg/d compared with lower intakes (<10mg/d). Measurement of urinary isoflavones and their metabolites appears to be a more reliable approach than dietary assessment alone. Luteal phase deficiency can represent a relevant aspect for pregnancy outcomes and fertility disorders. Based on our literature search, we also identified two observational studies: a cross-sectional study published in 1997 by Nagata et al. Moreover, couples with male infertility issues were excluded. Notably, these latter compounds are present in several foods such as legumes, cereals and seeds, whereas soy is almost the only source of isoflavones in human diet. 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. Eleven interventional studies, eleven observational studies and one meta-analysis have been selected from the results of queries. The reduction of estradiol and progesterone could postpone ovulation by lengthening the menstrual cycle. Qin, Zhen 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) . In response, your body starts a cascade of events to boost estrogen production. Flowchart for studies selection. 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