Despite the sample size and full follow-up for endpoints evaluation, the study displays limitations. Soaking, fermentation, and heating may reduce problematic antinutrients contained in soy. However, only 106 individuals provided information on soy intake. Go. Among selected prospective cohort studies, in 2012 Jarrell and colleagues conducted an observational study of 323 Canadian women with late pregnancy (aged at least 35) followed from the second month of pregnancy until delivery(Reference Jarrell, Foster and Kinniburgh36). 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. Conclusions: These data suggest that higher intake of soy foods and soy isoflavones is associated with lower sperm concentration. 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. With regards to available clinical trials, Lu and colleagues conducted two interventional studies using 36 Oz of soy milk (about one litre) divided into three daily intakes for a total daily intake of about 200mg of isoflavones(Reference Lu, Anderson and Grady26,Reference Lu, Anderson and Grady29) . Introduction. 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. These alterations easily lead to hyperandrogenism and irregular menstrual cycles. This suggests a protective effect of soy against fertility disturbance by BPA. 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, urinary phytoestrogen levels were only detected at baseline and this increased the correlation uncertainty. (As part of this process, a group of eggs matures so that one will be ready for release during ovulation .) In the present study, the intervention group showed improvements in hormonal circulating levels compared with baseline, which consisted in the reduction of LH levels (94%, P=0000), testosterone (56%, P=0000) and DHEAS (87%, P=0000), with no significant changes in the control group. 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. 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. Genistein treatment reduced LDL cholesterol and triglycerides levels. The study must be considered exploratory, because of the limited number of luteal phase deficiency cycles and a small number of fertility-related outcomes. Eating a few servings of soy each week could improve fertility and metabolic aspects of PCOS. No significant differences were appreciated for free testosterone and DHEAS. Isoflavones also show effects that do not imply ER and ER involvement. 4 Center for Complementary Medicine, Department of Internal Medicine II, Faculty of Medicine, University of Freiburg, Freiburg, Germany. Products; Resources; My Account; Talk to a D&B Advisor 1-800-280-0780. Business Directory. 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. 2. Similarly, the stratification by ethnicity and equol-producers may suggest the nature of interactions between soy and fertility. Moreover, couples with male infertility issues were excluded. However, after removing data from studies with elevated bias risk, three studies were included in the sensitivity analysis with consequent loss of statistical significance. 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. Legumes, particularly soybeans, are the richest . Flowchart for studies selection. 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). Furthermore, hormone levels were evaluated only at baseline, without taking into account the differences between the two groups. It would have been useful to have retrospective information on soy consumption to assess the potential effect on previous fertility problems. Similar to the previous trial, the number of participants was limited. In October 1999, the US Food and Drug Administration (FDA) approved labeling for foods containing soy protein as protective against coronary heart disease. It is important to evaluate the levels of hormones that fluctuate during the cycle at several points. This could have introduced other confounding factors such as the influence of male on couple's fertility or possible changes in habits caused by the desire to conceive. Isoflavones are produced via a branch of the general phenylpropanoid pathway that produces flavonoid compounds in higher plants. This could be due to the scarcity of studies on the topic and the presence of few clinical trials, adequately designed to evaluate soy effect on fertility with consistent timing, with an adequate number of participants, blinding, and randomisation for physiological conditions and the presence of equol-producer individuals. 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. However, for articles selection, we used search engines both for scientific literature and specific for clinical trials, without filters application that could have limited the results. No changes in progesterone and SHBG concentrations from baseline were observed. Isoflavones concentrations did not show significant differences between participants at baseline. The strength of these studies was the assessment of hormone levels based on the menstrual cycle phase. Furthermore, the nutritional habits of Adventists differ from the Western population ones and they show soy consumption more similar to populations in South-East Asia(Reference Messina53). Furthermore, the type of dietary survey carried out in the proposed environmental questionnaire was not clear. Review the D&B Business Directory at DandB.com to find more. 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). 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) . . Furthermore, diet and energy intake were not investigated and sampling was not well-timed to menstrual cycle. Green, Eulalee In the only clinical trial available, even if it is considered a pilot study, it emerges that a significant role could be played not only by isoflavones, but also by phytochemicals present in soy, particularly in black soy. Although isoflavones can be found in many foods, not soy foods can be considered negligible sources of these compounds. 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. 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). These aspects considerably reduce the reliability of results, favouring data misinterpretation. 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) . However, stratification for the control group or PCOS patients did not show a significant correlation between androgens and equol production. Ma, Haoyue The chemical structure similarity between soy isoflavones and endogenous estrogens has always stimulated the attention for this class of compounds. 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. However, ethnicity was not used for outcomes stratification. Feature Flags: { Choose any of these varieties. "useRatesEcommerce": false Furthermore, considering soy as a mere source of isoflavones is extremely reductive. The urinary or serum levels of isoflavones did not affected progesterone levels in the multiple regression analysis. 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. Progesterone and sex hormone-binding globulin (SHGB) levels were not significantly changed by soy intake. Corrections for confounding factors, such as diet, demographics, lifestyle factors, age, body composition and ethnicity, indicated reliable analysis. 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). The authors declare that they have no conflicts of interest. However, a clear effect on reproductive system has never been highlighted, especially due to the absence of observational studies designed for this purpose. After the soy intervention, the length of menstrual cycle marginally increased (from 28319 to 31851d, P=006). PMCID: PMC8922143. For the remaining papers, the full texts were retrieved for the final evaluation and inclusion in the summary. (Reference Moher, Liberati and Tetzlaff24). These enzymes convert estrone and androstenedione into estrogen and testosterone(Reference Gunnarsson, Ahnstrm and Kirschner83,Reference Thompson and Siiteri84) . 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. 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). Eating Places. We use cookies to distinguish you from other users and to provide you with a better experience on our websites. 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. 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 Individuals who are not equol-producers have likely limited response to isoflavone intake(Reference Iino, Shimoyama and Iino16). Romualdi and colleagues in 2008 enrolled twelve Italian women with metabolic syndrome and PCOS and with a follow-up of 6 months using 36mg/d of oral genistein as an intervention(Reference Romualdi, Costantini and Campagna34). It affects one out of every six couples and affects the majority women aged between 15 to 44 years. 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. 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. Day 22 should correspond to the mid-luteal phase, however, the authors pointed out that participants exhibited different lengths of menstrual cycle and this could have been a source of heterogeneity that was used as a covariate in the regression model. In the previously mentioned meta-analysis by Hooper and colleagues(Reference Hooper, Ryder and Kurzer59), reduction of about 22% of FSH (SMD: 045UI/l, 95% CI 079, 011, P=001) and of about 4% of LH (SMD: 034IU/l, 95% CI 068, 001, P=005) were related to the intake of soy or isoflavones. Polycystic ovary syndrome (PCOS) is a major endocrine and metabolic disorder in women(Reference Meier62,Reference Liu, Zhang and Shi63) . Smaoui, Slim 1. Moreover, urinary concentrations seem to reflect the isoflavone intakes in a short time window. and PMID: 35320928. 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. 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). Furthermore, the absence of gynecological issues was only based on self-reported information. The authors of this recent literature review of available evidence from observational and interventional studies concluded that soy and its components cannot be classified as an endocrine disruptor. A total of 834 entries were obtained following search engine queries (PubMed: 381; ScienceDirect: 392; Cochrane Library Trials: 30 and ClinicalTrials.gov: 31). 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). These mechanisms involve genomic regulation with activation of both receptor's subtypes at 1M as seen in 293 human embryonal kidney cells in transient gene expression assay(Reference Kuiper, Lemmen and Carlsson74). 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. 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. was a pilot study without a characterisation of diet among participants and without data on soy composition (isoflavone or antioxidant contents). It does not appear to be randomised and blinded, but the nature of outcomes should not be affected by these limitations. Major equol production was associated with a reduction in androgens levels (total testosterone, free testosterone and androstenedione), in the whole cohort. 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.). Jia, Liyan These clinical trials had several strengths including the presence of a placebo group, randomisation, double-blinding and recruitment of a wide number of participants. Unfortunately, the work of Kohama et al. M. L. contributed to drafting and revising the manuscript. However, the evaluation of ability to absorb and metabolise isoflavones was lacking in the present study. Huntriss, Rosemary Multiple regression analysis including various set of possible confounders highlighted more in-depth correlations. 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). Deepak Kumar, Komal 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. 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%). Body composition and ethnicity, indicated reliable analysis soy and fertility isoflavone or antioxidant contents ) each... Two groups one will be ready for release during ovulation. couples with male infertility issues were.... 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