In the study by Nagata and colleagues, fifty Japanese women were enrolled to evaluate the association between soy intake (using an FFQ) and hormone levels. Among the studies already cited, however, we must consider the work of Kohoama and colleagues(Reference Kohama, Kobayashi and Inoue33), which showed fertility improvements following intervention with black soy extract in individuals with secondary amenorrhea, including patients with PCOS. However, after removing data from studies with elevated bias risk, three studies were included in the sensitivity analysis with consequent loss of statistical significance. Six grams per day of black soybean powder were administered to the intervention group, whereas thirty-four individuals received no treatment as a control group. 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) . Moreover, urinary concentrations seem to reflect the isoflavone intakes in a short time window. The estrogen-like effects of isoflavones underlie concerns about soy and fertility. Fig. 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. 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). (Reference Filiberto, Mumford and Pollack37). 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). 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). Luteal phase deficiency can represent a relevant aspect for pregnancy outcomes and fertility disorders. Soy supplementation also appears to affect thyroid function in an inconsistent manner, as studies have shown both increases and decreases in the same parameters of thyroid activity. 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) . 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. However, the intakes of isoflavones in the studied cohorts were limited (range: 0331mg/d). The evaluation of isoflavones circulating levels and their urinary excretion allowed to show a wide inter-individual variation of metabolic and absorption capacity. Main characteristics of selected studies. Even if the clinical trial did not include a placebo group or randomisation, the presence of a control group and the evaluation of equol-producer individuals mitigated these issues. 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). 2023. For this reason, they are classified as phytoestrogensplant-derived compounds with estrogenic activity (1). 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. Furthermore, the evaluation of dietary pattern before infertility treatments does not exclude the possibility that soy consumption may have been influenced by the search for a healthy pattern to achieve pregnancy. M. L. contributed to drafting and revising the manuscript. 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). Although this clinical trial showed the long-term effect of soy ingestion on serum hormone levels, it was a pilot study with a limited number of participants (fourteen premenopausal women). However, this omission does not necessarily imply that the assessment has not been carried out. Adapted from Moher, Main cellular mechanism for isoflavones. Adapted from SMART: Servier Medical Art(89). Has data issue: true Those women eating or taking soy isoflavones were more likely to get pregnant. Despite the sample size and full follow-up for endpoints evaluation, the study displays limitations. 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. Estradiol levels showed increased plasma concentrations during the intervention period among premenopausal women (n: 14) in both luteal and follicular phases (composite menstrual cycle assessment). 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. Many of its components show an antioxidant activity that can at least partially explain its effectiveness(Reference Rizzo9). Studies have also shown that soybeans contribute towards lower levels of cholesterol, less risk of heart disease, breast cancer, and osteoporosis and fewer menopausal symptoms. However, urinary phytoestrogen levels were only detected at baseline and this increased the correlation uncertainty. Find Best Western Hotels & Resorts nearby Sponsored. Improvements were observed only in lipid profile (circulating total cholesterol, LDL and LDL/HDL ratio and triglycerides). Even if serum AMH concentrations appear as a useful tool for predicting female fertility, only one study from our selection used them(Reference Haudum, Lindheim and Ascani46). 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. A list of the selected clinical studies with their characteristics is summarised in Table 1. 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 authors responsibilities were as follows: G. R. study conception and drafting the manuscript. This may have influenced the presence of large confidence intervals. United States California Correction for covariates included demographics, education, income, lifestyle, dietary and behavioural factors. 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. Soy contains phytoestrogen, a plant-derived estrogen, known as isoflavones. 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). No investigation into the individual's ability to absorb and use isoflavones from soy milk was performed. The detailed selection process is highlighted in Fig. Jia, Liyan However, the specific effect of soy intake on women's fertility has not yet been systematically evaluated. Find company research, competitor information, contact details & financial data for Lucky Twins Distribution of Rancho Cucamonga, CA. Isoflavones also show effects that do not imply ER and ER involvement. The advantages of observational cohort studies include longer times and wider population samples. Flowchart for studies selection. Unfortunately, the work of Kohama et al. The authors found an association between pregnancy outcomes and urinary Bisphenol A (BPA), dependent on soy consumption in the multivariable-adjusted mixed model. The results of selected manuscripts were grouped according to the outcomes used, for a clear comparison. Bora, Shabana 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. 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 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). The authors declare that they have no conflicts of interest. 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). Despite adjustments for demographic, lifestyle, dietary factors, including ethnicity and other phytoestrogens, it would have been useful to check the dietary intake of isoflavones for equol-producers evaluation. 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. The ethnicity assessment of participants was useful in identifying, as might be expected, a greater consumption of soy foods by Asian individuals. Furthermore, the use of spot urine samples for BPA quantification may have underestimated its exposure. Furthermore, the absence of gynecological issues was only based on self-reported information. Phytoestrogens and breast cancer promoters or protectors? 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. This, in turn, stimulates ovulation and can make you ready for pregnancy. PMID: 35320928. Available from: Lin, Jing Following the removal of eighty-four duplicates, the selection was made through titles, abstracts and full-text reading. Black soy, in addition to the content of isoflavones, is known to be rich in antioxidant substances, especially in external seed integuments, which are rich in anthocyanins(Reference Choung, Baek and Kang49). Keywords were searched in titles and abstracts and combined with MeSH terms, where available, adapting the query format based on the search engine used. This suggests a protective effect of soy against fertility disturbance by BPA. Why did you take Soy Isoflavones: I had tried most other things so decided to be a guinea pig. 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. However, the intake of isoflavones in diet has not been investigated, and therefore, it was not possible to define the presence of equol-producers among participants. 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