Adapted from Moher et al. Similar to the previous trial, the number of participants was limited. A weak, not clinically relevant effect has been highlighted on cycle length and hormonal status. Instead, in the cohort study by Filiberto and colleagues, 259 American women were followed for at least 2 menstrual cycles. Regarding the observational studies available, in 2015 Venegas et al. 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. Keywords were searched in titles and abstracts and combined with MeSH terms, where available, adapting the query format based on the search engine used. After the soy intervention, the length of menstrual cycle marginally increased (from 28319 to 31851d, P=006). and 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). 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. Consistent with the previously cited data, no significant alteration in the cycle length was found among participants following the intervention. Get the latest business insights from Dun & Bradstreet. 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). 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. In the first clinical trial by Unifer and colleagues, 1500mg/d of isoflavones from soy or placebo were administered for 10d to 134 women who had been infertile for at least 2 years, undergoing intrauterine insemination after 100mg/d for 5d of clomiphene citrate treatments (an ovulation inducer)(Reference Unfer, Casini and Costabile31). Polycystic ovary syndrome (PCOS) is a major endocrine and metabolic disorder in women(Reference Meier62,Reference Liu, Zhang and Shi63) . Among the limitations of this review of literature, we must include the possible avoidance of studies that considered fertility as a secondary outcome and which therefore may have escaped from the manuscript selection. The intervention period was extended only to one menstrual cycle. Multiple regression analysis including various set of possible confounders highlighted more in-depth correlations. However, this omission does not necessarily imply that the assessment has not been carried out. 1. 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). For this reason, they are classified as phytoestrogensplant-derived compounds with estrogenic activity (1). The significant inverse association between dietary isoflavone intake and live births (3% reduction, 95% CI 0, 7, P=005) was highlighted. Fertility is closely associated with menstrual cycle functions and a longer time to pregnancy is associated with shorter menstrual cycles(Reference Crawford, Pritchard and Herring56Reference Wise, Mikkelsen and Rothman58). Isoflavones show several biological properties, acting as selective tissue estrogenic activity regulators (STEARs), thanks to the differential distribution pattern of estrogen receptors in body tissues(Reference Matthews and Gustafsson13) and the differentiated affinity between the two isoforms of estrogen receptors, called alpha and beta. However, the evaluation of ability to absorb and metabolise isoflavones was lacking in the present study. Soya Isoflavones are derived from soya beans. was a pilot study without a characterisation of diet among participants and without data on soy composition (isoflavone or antioxidant contents). 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. 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. Moreover, urinary concentrations seem to reflect the isoflavone intakes in a short time window. Soy isoflavones have also been found to inhibit tyrosine kinases (14), enzymes that play critical roles in the signaling pathways that stimulate cell proliferation. 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). You should take them like Clomid hun so cd 1-5, 2-6, 3-7, 4-8 or 5-9. 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. [cited 2021 Jul 26]. 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). In addition, no significant changes in progesterone, LH or SHBG were found in the whole study sample. The lack of variation in gonadotropins can explain the absence of variation in menstrual cycle. 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. The generalisation of these results is complex due to the type of study, which does not allow to define a causal relationship. Soy isoflavones have repeatedly shown a mild estrogenic effect but at high concentrations they may have enough power to act on hypothalamus and pituitary gland, reducing the ovarian synthesis of estrogens. This, in turn, stimulates ovulation and can make you ready for pregnancy. After the intervention period, four patients became pregnant and twelve patients showed ovulation improvements based on ultrasonography (P<005). Furthermore, hormone levels were evaluated only at baseline, without taking into account the differences between the two groups. 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). The results of selected manuscripts were grouped according to the outcomes used, for a clear comparison. 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) . It would have been useful to have retrospective information on soy consumption to assess the potential effect on previous fertility problems. RANCHO CUCAMONGA. conducted another prospective cohort study on 239 American women undergoing assisted reproductive technology(Reference Chavarro, Mnguez-Alarcn and Chiu42). 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. 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). 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 possible correlation between menstrual cycle length and soy does not seem convincing either. Soy is a very popular food and its consumption is part of the traditional cuisine of South-East Asian countries. 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) . The chemical structure similarity between soy isoflavones and endogenous estrogens has always stimulated the attention for this class of compounds. 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) . Main cellular mechanism for isoflavones. In particular, information about the adequate choice of updated nutritional tables as well as specific nutritional choices, such as increased soy consumption due to pre-existing socio-cultural and physiological aspects should be collected. Concerns that the phytoestrogens (isoflavones) in soy may feminize men continue to be raised. Furthermore, women with PCOS display a higher prevalence of hyperinsulinemia, dyslipidemia, insulin resistance and obesity compared to healthy population. The present study used a community-based approach with recruitment of couples seeking pregnancy. Render date: 2023-03-02T11:20:28.481Z Corrections for confounding factors, such as diet, demographics, lifestyle factors, age, body composition and ethnicity, indicated reliable analysis. Servier Medical Art. This suggests a protective effect of soy against fertility disturbance by BPA. Despite the sample size and full follow-up for endpoints evaluation, the study displays limitations. Han, Jing In the first of the two papers by Lu and colleagues(Reference Lu, Anderson and Grady26), the intake of 36 Oz/d of soy milk (~200mg/d IF) for 1 month caused a reduction in mean estradiol levels of 31% at days 57, P=009; 81% at days 1214, P=003; 49% at days 2022, P=002, compared with the baseline. They may be useful in alleviating menopause symptoms or preventing osteoporosis in postmenopausal women. Fig. 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%). 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. However, only 106 individuals provided information on soy intake. Similar to the previous observational study, Chavarro et al. DPO you got your BFP: 14dpo. The ethnicity assessment of participants was useful in identifying, as might be expected, a greater consumption of soy foods by Asian individuals. Published online by Cambridge University Press: These changes may have resulted in the mild, non-clinically relevant prolongation of menstrual cycle, as discussed in the previous section. Most women taking soy isoflavones to induce ovulation take around 150-200 mg a day on cycle day 3 -7 or 5-9. Furthermore, the search for sources has been extended to the single manuscripts reference lists. 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). 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 another prospective study, 471 healthy American women were followed for 12 months or until delivery without showing significant correlations between urinary isoflavones, quantified by HPLC-MS analysis, and fertility, defined with adjusted Cox Model using time-to-pregnancy assessment(Reference Mumford, Sundaram and Schisterman39), while lignan concentrations in urine were significantly associated with shorter time to pregnancy. Participants were divided into four categories: non-consumers and tertiles of soy intake. hasContentIssue true, Proposed mechanisms of isoflavones action, This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (, Copyright The Author(s), 2022. Good: strong ovulation pains and increased ewcm. 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). Likewise, equol-producers showed lower AMH levels in the whole cohort as well as in participants in PCOS or control groups. Notably, during manuscript preparation, Messina and colleagues published a technical review on endocrine effect of soy and isoflavones(Reference Messina, Mejia and Cassidy90). The only study found about the effect of exposure to soy in childhood and reproductive functions is the retrospective study by Strom and colleagues(Reference Strom, Schinnar and Ziegler30). 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). Furthermore, considering soy as a mere source of isoflavones is extremely reductive. WHAT IS IT? 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. 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 study did not evaluate circulating or urinary levels of isoflavones to verify the ability to metabolise isoflavones. 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, 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). Presumably, treatment with pharmacological concentrations of soy phytoestrogens allows mitigating the negative effect of clomiphene citrate on endometrial tissue, thus facilitating embryo implantation. Furthermore, diet and energy intake were not investigated and sampling was not well-timed to menstrual cycle. In response, your body starts a cascade of events to boost estrogen production. However, soy diet reduced progesterone (45%, P<00001) and estradiol levels (23%, P<001), compared with baseline. Flowchart for studies selection. Regarding isoflavones, the equol metabolite derives from the precursor daidzein by the action of intestinal bacteria. Eating Places. 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. 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). In two studies, women having fertility treatment took part in research looking at the amount of soya they ate, and whether that affected the success of their treatment. Based on this cross-sectional study, high consumption of soy isoflavones was identified (94% of participants). We use cookies to distinguish you from other users and to provide you with a better experience on our websites. 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. 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 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. 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