The duration of menstrual cycle, especially in luteal phase, can also have a direct influence on the mammary gland proliferation, through a reduction in exposure of the epithelium to proliferative hormones. M. A. S. contributed to drafting and revising the manuscript. 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. This, in turn, stimulates ovulation and can make you ready for pregnancy. 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). The obtained results were evaluated for duplicates and then screened for titles and abstracts information. Jia, Liyan No changes in progesterone and SHBG concentrations from baseline were observed. Other weak aspects of the population sample characterisation are given by a lack of stratification by ethnicity and equol-producers. On the other hand, many perplexities have been raised about possible negative mechanisms leading to endocrine disruptor effects(Reference Bar-El and Reifen20). 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). Those women eating or taking soy isoflavones were more likely to get pregnant. The clinical studies selection included one retrospective study, two cross-sectional studies, eight longitudinal cohort studies, five parallel-designed interventional studies and six longitudinal interventional studies. 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). Progesterone and sex hormone-binding globulin (SHGB) levels were not significantly changed by soy intake. Qin, Zhen Soy is a very popular food and its consumption is part of the traditional cuisine of South-East Asian countries. 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, in multiple regression analysis, this reduction seemed to be significantly associated with the intake of genistein and daidzein or their concentration in urine. PMCID: PMC8922143. In addition, full-text bibliographic lists from selected papers were screened to retrieve further relevant articles. Regarding the observational studies available, in 2015 Venegas et al. Furthermore, even at high concentrations, they did not show a clear influence on fertility. 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). Pending further confirmation, soy and its components do not appear to have a clinically relevant influence on menstrual cycle in healthy women. 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. Such shorter menstrual cycle length seemed not clinically relevant because shorter than 1d. Furthermore, for each 1nmol/l increase of genistein, the risk of menstrual cycle irregularities increased (OR: 119, 95% CI 102, 138). 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). Individuals who are not equol-producers have likely limited response to isoflavone intake(Reference Iino, Shimoyama and Iino16). The study involved a large number of couples seeking pregnancy. These aspects considerably reduce the reliability of results, favouring data misinterpretation. 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 type of dietary survey carried out in the proposed environmental questionnaire was not clear. The sooner you take it the more eggs start to mature and the later it focuses on the quality of the most maturing egg, or at least this is what I read. However, ethnicity was not used for outcomes stratification. United States California However, the subjects enrolled were women with secondary amenorrhea and therefore this variation could have a different meaning compared with results discussed in this section, obtained in the healthy population. (Reference Moher, Liberati and Tetzlaff24). Regarding isoflavones, the equol metabolite derives from the precursor daidzein by the action of intestinal bacteria. 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. (Reference Wu, Stanczyk and Hendrich28). This allowed to exclude the already summarised articles in meta-analysis from a detailed discussion. Although the clinical trial was quasi-randomised, with a placebo group, double-blinded, authors did not characterise the dietary regimen of individuals as well as their ability to effectively absorb and metabolise soy isoflavones. was a pilot study without a characterisation of diet among participants and without data on soy composition (isoflavone or antioxidant contents). These also included non-soy derived phytoestrogens, such as lignans. Introduction. Soya Isoflavones and Vitamins The Group for those Using, Abusing and thinking about taking over the counter items to boost fertility. FSH levels were not significantly changed after genistein intervention. 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) . However, levels of progesterone, estradiol, free estradiol, estrone and SHBG did not show significant differences. 4 Center for Complementary Medicine, Department of Internal Medicine II, Faculty of Medicine, University of Freiburg, Freiburg, Germany. 3 Department of Human Sciences and Promotion of the Quality of Life, San Raffaele Roma Open University, 00166 Rome, Italy. Isoflavones are produced via a branch of the general phenylpropanoid pathway that produces flavonoid compounds in higher plants. It is widely used in eastern traditional cuisine and it has recently diffused among self-conscious and vegetarian diets. Soya Isoflavones are derived from soya beans. They can bind G-protein-coupled estrogen receptor 1 (GPR30), with effects driven by both genomic and non-genomic regulation involving different cellular signalling pathways, such as intracellular increase of calcium or NO levels(Reference Ropero, Alonso-Magdalena and Ripoll75), as observed in human endothelial cells after stimulation with equol 100nM(Reference Rowlands, Chapple and Siow76). 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. Although not strictly related to the aspect of fertility, the study is still ongoing (Clinicaltrials.gov: NCT00616395) intending to follow the participants to evaluate effects on reproductive functions, later in life. Find Best Western Hotels & Resorts nearby Sponsored. 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 evaluation at two different times of menstrual cycle allowed to discriminate the effect between luteal and follicular phases but not day by day hormonal fluctuations. SMART [Internet]. Choose any of these varieties. It does not appear to be randomised and blinded, but the nature of outcomes should not be affected by these limitations. There was no relationship between isoflavone intake and reported problems becoming pregnant. Overall, a trend toward improvement can be appreciated but further studies are necessary to confirm the beneficial effect. In another study, women were more likely to get pregnant if they ate soy isoflavones alongside . The phytoestrogen actions of soy isoflavones may increase estrogen levels in the body and induce ovulation in women, thus, may speed up the process of pregnancy. Get the latest business insights from Dun & Bradstreet. Moreover, difficulties related to data collection about nutritional intakes were available, and individual reporting errors must be taken into account. Soy isoflavones are generally considered safe .Numerous randomized controlled trials in menopausal women reported that side effects were not significantly different between soy isoflavone and placebo groups .Adverse events were generally mild and included gastrointestinal and musculoskeletal complaints .One systematic review of over 100 studies in patients with or at risk of breast cancer . No restrictions were applied using filters and results were collected from search engines by the inception through 4 April 2021. The present study has numerous strengths: a large sample of participants with good adherence to the study, a detailed assessment of dietary habits, and comprehensive sampling during all phases of menstrual cycle. The authors found no significant differences in reproductive outcomes (missed menstrual periods, pregnancy, live births, abortions, miscarriages, full-term deliveries, preterm deliveries, etc.) Measurement of urinary isoflavones and their metabolites appears to be a more reliable approach than dietary assessment alone. However, this omission does not necessarily imply that the assessment has not been carried out. Patients showed plasma androgens levels above or at the upper limit the normal range, at baseline. Han, Jing Among the studies already cited, however, we must consider the work of Kohoama and colleagues(Reference Kohama, Kobayashi and Inoue33), which showed fertility improvements following intervention with black soy extract in individuals with secondary amenorrhea, including patients with PCOS. 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. Additionally, the enrolment criteria included only women who had stopped oral contraception less than 2 months earlier, so highly fertile individuals could have been excluded. 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. They have been dubbed "the natural Clomid," As they work in pretty much an identical manner. However, the specific effect of soy intake on women's fertility has not yet been systematically evaluated. Get Twins Club Restaurant, Rancho Cucamonga, CA, USA setlists - view them, share them, discuss them with other Twins Club Restaurant, Rancho Cucamonga, CA, USA fans for free on setlist.fm! 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). In addition, non-English papers could have provided relevant data on the topic, especially those from countries with a more consistent history of soy consumption. Isoflavones also bind to ER receptor, albeit with lower affinity. From the data obtained, diet isoflavones do not seem to have a direct effect on fertility, whether positive or negative. 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). The estrogen-like effects of isoflavones underlie concerns about soy and fertility. The article processing charge was funded by the Baden-Wuerttemberg Ministry of Science, Research and Art and the University of Freiburg in the funding programme Open Access Publishing. 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. Higher soy products intake did not correlate with the rate of infertility. However, the work had several strengths: the real evaluation of luteal and follicular phase through the dosage of urinary LH:creatinine ratio, the characterisation of sampling according to the cycle; the evaluation of isoflavone content in foods used for the intervention and quantification of urinary isoflavones to check compliance; the use of soy foods and not supplements or extracts to approach a real-life pattern; the characterisation of diet at various steps of clinical trial to avoid confounding mechanisms; the stratification by ethnicity which indirectly showed the effect on equol-producer individuals. The authors responsibilities were as follows: G. R. study conception and drafting the manuscript. Corrections for confounding factors, such as diet, demographics, lifestyle factors, age, body composition and ethnicity, indicated reliable analysis. (Reference Filiberto, Mumford and Pollack37). between 128 women fed with soy-based formula and 268 women fed with cow milk formula during infancy. Furthermore, the search for sources has been extended to the single manuscripts reference lists. However, stratification for the control group or PCOS patients did not show a significant correlation between androgens and equol production. 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. 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. It would have been useful to have retrospective information on soy consumption to assess the potential effect on previous fertility problems. Furthermore, there was no characterisation of dietary regimen, although it was a standard hospital diet. 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). Additionally, isoflavones can act as antioxidants in vitro (15), but the extent to which they contribute to the antioxidant status of humans is not yet clear. The beneficial efficacy of soy is often attributed to the presence of isoflavones, capable of mitigating the excesses of endogenous estrogens, through the competition with estrogen receptors or by the activation of receptors, in the presence of low levels of endogenous estrogens. 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. The chemical structure similarity between soy isoflavones and endogenous estrogens has always stimulated the attention for this class of compounds. 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. 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) . From the analysis of urinary excretion of isoflavones normalised for creatinine during the intervention with soy, Asian women had significantly greater excretion of isoflavones than non-Asian women. 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. Not all isoflavones work in the same manner. Both isoflavones are found in soy at several mg 100 g 1 ( Bennetau-Pelissero, 2013 ). Furthermore, there was no evaluation of metabolic utilisation capacity of isoflavones and their absorption by measuring serum and urinary levels. In particular, soy contains numerous non-isoflavone constituents such as phytic acid, triterpenes and sterols, BowmanBirk protease inhibitors, unsaturated fatty acids, saponins, inositol phosphates, proteins, peptides such as lunasin;(Reference Kang, Badger and Ronis10) nevertheless, soy isoflavones have attracted much attention in the last years for its estrogenic as well as non-hormonal properties(Reference Aulisa, Binda and Padua11). 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. Soy contains phytoestrogen, a plant-derived estrogen, known as isoflavones. 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). 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. Manuscripts exploring multiple aspects were discussed in different paragraphs, where deemed necessary. [cited 2021 Jul 26]. 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) . Previously, Petrakis and colleagues proposed an interventional study with a soy isolate (374g of soy protein containing 374mg of genistein) on twenty-four women (pre- and post-menopause) followed for 6 months plus 3 months pre-intervention and 3 months post-washout(Reference Petrakis, Barnes and King25). Adapted from Moher, Main cellular mechanism for isoflavones. The evaluation of isoflavones circulating levels and their urinary excretion allowed to show a wide inter-individual variation of metabolic and absorption capacity. The effects of phytoestrogen genistein on steroidogenesis and estrogen receptor expression in porcine granulosa cells of large follicles, Endocrine-disrupting chemicals as modulators of sex steroid synthesis, Amplification of HSD17B1 and ERBB2 in primary breast cancer, Utilization of oxygen and reduced nicotinamide adenine dinucleotide phosphate by human placental microsomes during aromatization of androstenedione, Genistein is an effective stimulator of sex hormone-binding globulin production in hepatocarcinoma human liver cancer cells and suppresses proliferation of these cells in culture, Xenoestrogen interaction with human sex hormone-binding globulin (hSHBG), Inhibition of tumor promoter-induced hydrogen peroxide formation in vitro and in vivo by genistein, Phytoestrogen concentrations in serum from Japanese men and women over forty years of age, Neither soyfoods nor isoflavones warrant classification as endocrine disruptors: a technical review of the observational and clinical data, Flowchart for studies selection. 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. Based on our literature search, we also identified two observational studies: a cross-sectional study published in 1997 by Nagata et al. The clinical trial was limited to a small sample size, lacking of control/placebo group and there was no characterisation of equol-competence. 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). Flowchart for studies selection. Similar to the previous trial, the number of participants was limited. In response, your body starts a cascade of events to boost estrogen production. Fig. It helps you to ovulate and they quality. 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).
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