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. Follicular development, the number of preovulatory follicles and the pulsatility index values were not different between groups after intervention. 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. This suggests a protective effect of soy against fertility disturbance by BPA. 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. The length of menstrual cycle may represent an indirect marker of ovarian function and reproductive health(Reference Mumford, Steiner and Pollack54,Reference Vassena, Vidal and Coll55) . Isoflavone genistein inhibited the enzyme tyrosine kinase in human A431 cell membranes at 07g/ml, a very high, non-physiological concentration(Reference Akiyama, Ishida and Nakagawa77) and act as a ligand for peroxisome proliferator-activated receptors (PPARs) in cultured astrocytes at 500nM(Reference Valles, Dolz-Gaiton and Gambini78). 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). Therefore, the lack of fecundity is called sterility(Reference Wood47). Eating Places. 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). 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). Higher soy products intake did not correlate with the rate of infertility. For the remaining papers, the full texts were retrieved for the final evaluation and inclusion in the summary. This effect persisted for at least one menstrual cycle after the suspension of soy intake, with a maximum of persistence for three menstrual cycles. The generalisation of these results is complex due to the type of study, which does not allow to define a causal relationship. [1] 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) . 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. F. contributed to drafting and revising the manuscript. Find Best Western Hotels & Resorts nearby Sponsored. 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). They may be useful in alleviating menopause symptoms or preventing osteoporosis in postmenopausal women. Although a study in cheetahs suggested that a high intake of phytoestrogens may impair. 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. Fig. 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. 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) . Soy is a very popular food and its consumption is part of the traditional cuisine of South-East Asian countries. These alterations easily lead to hyperandrogenism and irregular menstrual cycles. However, the association between soy and isoflavones with the reduction of luteal phase seems weak. Flowchart for studies selection. 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. DOI: 10.1017/jns.2022.15. The FFQ was not specifically designed for phytoestrogen assessment and this may have underestimated intakes. In another study, women were more likely to get pregnant if they ate soy isoflavones alongside . Consistent with the previously cited data, no significant alteration in the cycle length was found among participants following the intervention. Unfortunately, the work of Kohama et al. The present paper aims to conduct a review of available data on the effect of soy, soy foods and soy components on women's fertility and related outcomes. Pending further confirmation, soy and its components do not appear to have a clinically relevant influence on menstrual cycle in healthy women. 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). 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. 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). Likewise, equol-producers showed lower AMH levels in the whole cohort as well as in participants in PCOS or control groups. 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. The individual conversion capacity, equol-competence, offers a useful tool for estimating the biological effect of these compounds(Reference Zubik and Meydani15). Adapted from Moher et al.(24). In the ten women who participated in the second study(Reference Lu, Anderson and Grady29), there were no significant changes in the levels of luteinizing and follicle-stimulating hormones. These clinical trials had several strengths including the presence of a placebo group, randomisation, double-blinding and recruitment of a wide number of participants. Soy isoflavones have also been found to inhibit tyrosine kinases (14), enzymes that play critical roles in the signaling pathways that stimulate cell proliferation. 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. 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) . The same type of soy phytoestrogen intervention was subsequently used by Unifer and colleagues in a second clinical trial on 213 infertile women undergoing in vitro fertilisation with embryo transfer cycles after intramuscular progesterone treatments (50mg/d) with or without (placebo) 1500mg/d of soy isoflavones intake(Reference Unfer, Casini and Gerli32). Soy contains phytoestrogen, a plant-derived estrogen, known as isoflavones. } Soya Isoflavones are derived from soya beans. 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. 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). (Reference Moher, Liberati and Tetzlaff24). and One of the first research papers to look directly at soy and fertility outcomes was from the Adventist Health Study-2. In order to assess the association between urinary isoflavones and fertility, adjustment for various confounding factors including ethnicity, supplement use, nutrients and lifestyle aspects was applied. To our knowledge, this is the first comprehensive review on soy effect on women's fertility. The lack of variation in gonadotropins can explain the absence of variation in menstrual cycle. Furthermore, diet and energy intake were not investigated and sampling was not well-timed to menstrual cycle. Soy is a very popular food and its consumption is part of the traditional cuisine of South-East Asian countries. Soy consumption was not related to estradiol levels or endometrial thickness. Good: strong ovulation pains and increased ewcm. However, a suggestive positive influence has been shown among women with fertility issues and during assisted reproductive technologies. 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. was a pilot study without a characterisation of diet among participants and without data on soy composition (isoflavone or antioxidant contents). Furthermore, the use of spot urine samples for BPA quantification may have underestimated its exposure. 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). Luteal phase deficiency can represent a relevant aspect for pregnancy outcomes and fertility disorders. 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) . Jamilian and colleagues in 2016 conducted another parallel clinical trial on seventy Iranian women with PCOS, using 50mg/d of soy isoflavones for a 1-month follow-up(Reference Jamilian and Asemi43). This, in turn, stimulates ovulation and can make you ready for pregnancy. The adjustment for male partner intake of soy in the subgroup analysis did not change the association. 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. 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