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. Clinical trials can provide solid causal inferences, but they often have limitations in terms of study duration or intervention design. 3 Department of Human Sciences and Promotion of the Quality of Life, San Raffaele Roma Open University, 00166 Rome, Italy. 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. Sampling involved synchronisation on the third day of menstrual cycle follicular phase, spontaneous or pharmacologically induced. However, levels of progesterone, estradiol, free estradiol, estrone and SHBG did not show significant differences. Bora, Shabana Although a study in cheetahs suggested that a high intake of phytoestrogens may impair. Total loading time: 0 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. A weak, not clinically relevant effect has been highlighted on cycle length and hormonal status. 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. "useRatesEcommerce": false Furthermore, women with PCOS display a higher prevalence of hyperinsulinemia, dyslipidemia, insulin resistance and obesity compared to healthy population. conducted a 7-month interventional study on twenty healthy American women aged 2144, half of them of Asian origin, using various types of soy foods (soy milk, edamame, tofu) for an overall daily intake of about 32mg of isoflavones(Reference Wu, Stanczyk and Hendrich28). RANCHO CUCAMONGA. Overall, a trend toward improvement can be appreciated but further studies are necessary to confirm the beneficial effect. However, the intakes of isoflavones in the studied cohorts were limited (range: 0331mg/d). The reduction of estradiol and progesterone could postpone ovulation by lengthening the menstrual cycle. Get company information for Twins Club, Inc. in RANCHO CUCAMONGA, CA. 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). 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). Soy is a very popular food and its consumption is part of the traditional cuisine of South-East Asian countries. In addition, full-text bibliographic lists from selected papers were screened to retrieve further relevant articles. Additional considerations regarding hormonal influences will be discussed in the next paragraph. 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). If we eat soy, do we keep the beneficial effects of the Mediterranean diet? The individual conversion capacity, equol-competence, offers a useful tool for estimating the biological effect of these compounds(Reference Zubik and Meydani15). 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. These alterations easily lead to hyperandrogenism and irregular menstrual cycles. SMART [Internet]. The Adventist Church is a community with very homogeneous habits and a high prevalence of vegetarians (54% lacto-ovo vegetarian and 7% vegan from this study)(Reference Kent, Morton and Ward51,Reference McBride, Bailey and Landless52) . Adapted from SMART: Servier Medical Art(89). However, urinary phytoestrogen levels were only detected at baseline and this increased the correlation uncertainty. 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 generalisation of these results is complex due to the type of study, which does not allow to define a causal relationship. 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). Major equol production was associated with a reduction in androgens levels (total testosterone, free testosterone and androstenedione), in the whole cohort. 2023. 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) . Furthermore, the type of dietary survey carried out in the proposed environmental questionnaire was not clear. Soy consumption is supposed to have protective effects against cardiovascular disease by cholesterol-lowering and blood pressure improvement action and in the prevention of cancer or diabetes and it also supports bone health and the management of menopause symptoms(Reference Ding, Pan and Manson2Reference Mosallanezhad, Mahmoodi and Ranjbar8). Consequently, the absence of fertility, called infertility, is a disease characterised by the failure to establish a clinical pregnancy and it can depend on various factors including predisposition and behavioural/environmental aspects. Although isoflavones can be found in many foods, not soy foods can be considered negligible sources of these compounds. No significant differences were found in the spontaneous abortion rate, the number and quality of embryos transferred or oocytes fertilised. The two observational studies also show different limitations, in particular, one of these studies uses a follow-up of only 2 months. Smaoui, Slim 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). 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). Uses. 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. Therefore, the lack of fecundity is called sterility(Reference Wood47). The same authors admitted that they had no information on the type of soy used and about the last ingestion. 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. Progesterone and sex hormone-binding globulin (SHGB) levels were not significantly changed by soy intake. The disease etiology is still debated but it seems to involve inflammatory mechanisms and oxidative stress(Reference Escobar-Morreale, Luque-Ramrez and Gonzlez65,Reference Showell, Mackenzie-Proctor and Jordan66) . and 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. M. A. S. contributed to drafting and revising the manuscript. Hostname: page-component-7fc98996b9-pxj8b 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. 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). 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. Any later it delays ovulation. 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). A list of the selected clinical studies with their characteristics is summarised in Table 1. conducted another prospective cohort study on 239 American women undergoing assisted reproductive technology(Reference Chavarro, Mnguez-Alarcn and Chiu42). Soy is a very popular food and its consumption is part of the traditional cuisine of South-East Asian countries. However, results are questionable due to the lack of hormone level measurements or reproductive functions. No restrictions were applied using filters and results were collected from search engines by the inception through 4 April 2021. (As part of this process, a group of eggs matures so that one will be ready for release during ovulation .) The advantages of observational cohort studies include longer times and wider population samples. After the intervention period, four patients became pregnant and twelve patients showed ovulation improvements based on ultrasonography (P<005). Phytoestrogens and breast cancer promoters or protectors? 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. 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. Feature Flags: { The study involved a large number of couples seeking pregnancy. 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. The procedure was carried out following the most recent PRISMA guidelines(Reference Liberati, Altman and Tetzlaff23). Microbial alpha diversity and glucose homeostasis improved in PCOS group after isoflavone intervention, resembling the control group profile at baseline. Since there are no scientific studies on the effects of soy isoflavones and ovulation, these are just general guidelines. Adapted from Moher et al.(24). The obtained meta-analysis was included in the final summary because it assessed aspects relating to the topic of this review. Presumably, treatment with pharmacological concentrations of soy phytoestrogens allows mitigating the negative effect of clomiphene citrate on endometrial tissue, thus facilitating embryo implantation. Moreover, couples with male infertility issues were excluded. Recently, Wesselink and colleagues evaluated the fertility of 7778 healthy American or Canadian women in two cohort studies that followed participants for 12 months or until pregnancy(Reference Wesselink, Hatch and Mikkelsen44). These also included non-soy derived phytoestrogens, such as lignans. 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