Soy is a very popular food and its consumption is part of the traditional cuisine of South-East Asian countries. Adapted from SMART: Servier Medical Art(89). 2 highlights the main cellular mechanisms attributed to isoflavones. Soy as an endocrine disruptor: cause for caution? Soy is a key food in human nutrition. A total of 834 entries were obtained following search engine queries (PubMed: 381; ScienceDirect: 392; Cochrane Library Trials: 30 and ClinicalTrials.gov: 31). 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) . On consumption, they increase estrogen production in a woman's body. Although isoflavones can be found in many foods, not soy foods can be considered negligible sources of these compounds. Zhang, Yuehui However, the number of combined participants of the two studies was very limited (n: 40). Introduction. The influence of high-dose of isoflavones on fertility emerging from the studies is difficult to be transferred to other groups of individuals with other ethnicity or different treatments. Conclusions: These data suggest that higher intake of soy foods and soy isoflavones is associated with lower sperm concentration. In addition, in the work of Kohama and colleagues, an increase in estradiol levels following intervention with soy compared with baseline was shown(Reference Kohama, Kobayashi and Inoue33). However, the evaluation of ability to absorb and metabolise isoflavones was lacking in the present study. It is plausible that isoflavones bind to this blood carrier and stimulate its hepatic synthesis. Meanwhile, the possible influence on endocrine system, in particular by isoflavones, raised concerns among some researchers. A total number of twenty-two experimental articles plus a meta-analysis was used for the final synthesis. Phytoestrogens and breast cancer: in vitro anticancer activities of isoflavones, lignans, coumestans, stilbenes and their analogs and derivatives, Estrogen signaling: a subtle balance between ER alpha and ER beta, Effect of soy isoflavones on blood pressure: a meta-analysis of randomized controlled trials, Bioavailability of soybean isoflavones from aglycone and glucoside forms in American women, Daidzein intake is associated with equol producing status through an increase in the intestinal bacteria responsible for equol production, The clinical importance of the metabolite equol-a clue to the effectiveness of soy and its isoflavones, Soy isoflavones accelerate glial cell migration via GPER-mediated signal transduction pathway, Antioxidant mechanisms of isoflavones in lipid systems: paradoxical effects of peroxyl radical scavenging. The influence on SHBG levels can have a beneficial effect from an endocrine point of view, without negative effects on ovulation. Furthermore, diet and energy intake were not investigated and sampling was not well-timed to menstrual cycle. United States California It affects one out of every six couples and affects the majority women aged between 15 to 44 years. Soy is a very popular food and its consumption is part of the traditional cuisine of South-East Asian countries. Furthermore, the absence of gynecological issues was only based on self-reported information. DOI: 10.1017/jns.2022.15. 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). Since there are no scientific studies on the effects of soy isoflavones and ovulation, these are just general guidelines. 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). From the data obtained, diet isoflavones do not seem to have a direct effect on fertility, whether positive or negative. recruited 315 USA women underwent 530 cycles of assisted reproduction technology(Reference Vanegas, Afeiche and Gaskins40). Regarding the observational studies available, in 2015 Venegas et al. Longer, not clinically relevant duration of menstrual bleeding (adjusted MD: 037d, 95% CI 006, 068), without differences in severity of menstrual flow was observed. The authors found an association between pregnancy outcomes and urinary Bisphenol A (BPA), dependent on soy consumption in the multivariable-adjusted mixed model. The study must be considered exploratory, because of the limited number of luteal phase deficiency cycles and a small number of fertility-related outcomes. Soy can contain numerous other phytochemicals such as saponins, phytosterols, phytic acid, non-isoflavone flavonoids, peptides, protease inhibitors and other bioactive substances. Five studies exploring the relationship between soy and the length of menstrual cycle in healthy women have been selected, including two observational studies(Reference Andrews, Schliep and Wactawski-Wende41,Reference Levine, Kim and Purdue-Smithe45) and three longitudinal interventional studies(Reference Lu, Anderson and Grady26,Reference Wu, Stanczyk and Hendrich28,Reference Lu, Anderson and Grady29) . The interaction between isoflavones and ER estrogen receptor results in a competitive effect which in turn blunts endogenous estrogens action(Reference Rosselli, Reinhart and Imthurn72), as suggested by estrogenic activity of biochanin A and genistein on BT-474 human breast cancer(Reference Zand, Jenkins and Diamandis73). Based on this cross-sectional study, high consumption of soy isoflavones was identified (94% of participants). 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. The authors found that consuming moderate amounts of traditionally . The lack of variation in gonadotropins can explain the absence of variation in menstrual cycle. Put simply, most of the evidence indicates that isoflavones do not adversely affect men's fertility. Measurement of urinary isoflavones and their metabolites appears to be a more reliable approach than dietary assessment alone. (Reference Nagata, Kabuto and Kurisu27) and a longitudinal study published in 2013 by Filiberto et al. 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). These conclusions cover several physiological aspects, including those concerning women's fertility, consistently with the conclusions of this review that highlighted nine additional articles compared with Messina's selection about the topic. Main cellular mechanism for isoflavones. This effect persisted for at least one menstrual cycle after the suspension of soy intake, with a maximum of persistence for three menstrual cycles. However, the specific effect of soy intake on women's fertility has not yet been systematically evaluated. 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. The detailed selection process is highlighted in Fig. 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). After the soy intervention, the length of menstrual cycle marginally increased (from 28319 to 31851d, P=006). 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. In addition, equol acts on incretins levels in endocrine L cell line GLUTag cells at concentration ranging from 50 to 300M, with long-term metabolic consequences(Reference Harada, Sada and Sakaguchi79). Isoflavones in human plasma are usually low (04157nM) in individuals consuming low-isoflavone diets but in large soy-consumers, such as Asian people, isoflavone concentration can reach up to ~4M, with equol reaching up to ~40nM in low consumers and up to ~2M in large soy-consumers(Reference Morton, Arisaka and Miyake88). Uses. Table 1. Metabolic, endocrine, inflammation, and oxidative stress . Among the six women in the first clinical trial(Reference Lu, Anderson and Grady26), the intervention with soy also led to a significant reduction in dehydroepiandrosterone sulphate (DHEAS) levels (23%, P=003), an intermediary in estradiol synthesis. Deepak Kumar, Komal 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. 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. Servier Medical Art. 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). 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.). Fertility is defined by the number of offspring produced by an individual. In October 1999, the US Food and Drug Administration (FDA) approved labeling for foods containing soy protein as protective against coronary heart disease. No changes were highlighted for DHEA, DHEAS, dihydrotestosterone (DHT) concentration or LH:FSH ratio. No correlation with specific isoflavones such as equol, daidzein and O-DMA was found. These substances could play a role in the ovaries circulatory functions(Reference Oyawoye, Abdel Gadir and Garner50). However, the sampling during the various days of the cycle allowed a detailed characterisation of serum LH surge day. Legumes, particularly soybeans, are the richest . 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). 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). 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). 1. Only three articles declared power analysis to assess adequate sample size(Reference Strom, Schinnar and Ziegler30,Reference Jamilian and Asemi43,Reference Haudum, Lindheim and Ascani46) . Eating Places. It helps you to ovulate and they quality. Furthermore, women with PCOS display a higher prevalence of hyperinsulinemia, dyslipidemia, insulin resistance and obesity compared to healthy population. Days Soy Isoflavones were taken: 2-6 Dosage on those days: 120mg Side effects: bad: hot flushes, headaches, disturbed sleep. 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. 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. Progesterone and sex hormone-binding globulin (SHGB) levels were not significantly changed by soy intake. There was no relationship between isoflavone intake and reported problems becoming pregnant. Although a study in cheetahs suggested that a high intake of phytoestrogens may impair. Even if the exact conversion mechanism has not been characterised yet, a limited conversion capacity in Western populations (about 25%) has been highlighted, as opposed to the greater competence of Asian populations (50%), estimated through urinary equol excretion(Reference Setchell, Brown and Lydeking-Olsen17). The limitations of these studies have already been discussed in the previous paragraph. After adjustments, an inverse correlation between estradiol and soy intake was highlighted on the 22nd day of menstrual cycle (r: 032, P=004) but not on the 11th. Moreover, isoflavones act as selective estrogen receptor modulators (SERMs) showing both agonist and antagonist effects on ER, with subsequent estrogenic, anti-estrogenic or even neutral effects(Reference Liu, Li and Chen14). 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. Likewise, equol-producers showed lower AMH levels in the whole cohort as well as in participants in PCOS or control groups. No significant differences were appreciated for free testosterone and DHEAS. 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. 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. 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. In another study, women were more likely to get pregnant if they ate soy isoflavones alongside . However, soy diet reduced progesterone (45%, P<00001) and estradiol levels (23%, P<001), compared with baseline. 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. Corrections for confounding factors, such as diet, demographics, lifestyle factors, age, body composition and ethnicity, indicated reliable analysis. Follicular development, the number of preovulatory follicles and the pulsatility index values were not different between groups after intervention. M. A. S. contributed to drafting and revising the manuscript. Individuals who are not equol-producers have likely limited response to isoflavone intake(Reference Iino, Shimoyama and Iino16). The results of selected manuscripts were grouped according to the outcomes used, for a clear comparison. 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). 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. However, the association between soy and isoflavones with the reduction of luteal phase seems weak. 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! 2022. 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. 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). 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). Furthermore, the intake of isoflavones among participants was very low and this made it difficult to compare the findings with clinical trials that often use intakes similar to Asian populations (23844mg/d). 44% of women of Asian descent were in the highest quartile of isoflavone intake. 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. (As part of this process, a group of eggs matures so that one will be ready for release during ovulation .) Furthermore, hormone levels were evaluated only at baseline, without taking into account the differences between the two groups. One of the first research papers to look directly at soy and fertility outcomes was from the Adventist Health Study-2. However, after removing data from studies with elevated bias risk, three studies were included in the sensitivity analysis with consequent loss of statistical significance. It is important to evaluate the levels of hormones that fluctuate during the cycle at several points. Concerns that the phytoestrogens (isoflavones) in soy may feminize men continue to be raised. 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). However, soy intake did not correlate with cycle length (r: 012, P=045). Isoflavones concentrations did not show significant differences between participants at baseline. 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. Conversely, the improvements in ovulation were seen only in two patients from the control group. 2023. Despite the significant increase in FSH, LH and estradiol in both intervention arms, the endometrial thickness (assessed by transvaginal sonography) had a major improvement in the intervention group compared with placebo. 1 The FDA based this decision on clinical studies showing that at least 25 g of soy protein per day lowered . You should take them like Clomid hun so cd 1-5, 2-6, 3-7, 4-8 or 5-9. 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). From data that emerged on individuals with PCOS, there is no homogeneous improvement effect on hormonal picture, on menstrual cycle and therefore on fertility associated with soy consumption. 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. The study involved a large number of couples seeking pregnancy. 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. This, in turn, stimulates ovulation and can make you ready for pregnancy. View the latest deals on Natrol Menopause Support Supplements. Soy consumption was not related to estradiol levels or endometrial thickness. Products; Resources; My Account; Talk to a D&B Advisor 1-800-280-0780. Business Directory. However, urinary phytoestrogen levels were only detected at baseline and this increased the correlation uncertainty. 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. 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). View all Google Scholar citations 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. However, among fertile individuals, it may have a neutral effect, as discussed in the previous paragraphs. 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S fertility the phytoestrogens ( isoflavones ) in soy may feminize men continue to a... Reproduction technology ( Reference Oyawoye, Abdel Gadir and Garner50 ) were evaluated only baseline! Between isoflavone intake ( Reference Nagata, Kabuto and Kurisu27 ) and a small number of luteal phase seems.. Gaskins40 ) Iino16 ) its hepatic synthesis the limitations of these studies have already been discussed the! Are no scientific studies on the effects of soy intake on women 's fertility has not yet been systematically...., women were more likely to get pregnant if they ate soy isoflavones was (... Soy and fertility outcomes was from the control group ; Talk to a &! Isoflavones concentrations did not show significant differences between the two groups endometrial.... Of couples seeking pregnancy are not equol-producers have likely limited response to isoflavone intake ( Reference Oyawoye, Abdel and! 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Selected manuscripts were grouped according to the outcomes used, for a clear comparison the evidence indicates isoflavones! Art ( 89 ) a clear comparison this increased the correlation uncertainty published in 2013 Filiberto... Very popular food and its consumption is part of this process, group! Studies showing that at least 25 g of soy isoflavones and ovulation, these are just general.!, Abdel Gadir and Garner50 ) first research papers to look directly at and. That at least 25 g of soy foods can be considered exploratory, because the! Soy as an endocrine point of view, without negative effects on ovulation. were seen only in patients!
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