However, this omission does not necessarily imply that the assessment has not been carried out. Mildly increased levels of SHBG were associated with higher dietary isoflavone intakes (Q4 [16788mg/d] v. Q1 [0003mg/d]) in the adjusted linear mixed model (: 009, 95% CI 002, 016), but no correlation was found for estradiol, progesterone, LH, FSH levels or anovulatory events. The present study used a community-based approach with recruitment of couples seeking pregnancy. Furthermore, considering soy as a mere source of isoflavones is extremely reductive. 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. 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. 1. 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). However, urinary phytoestrogen levels were only detected at baseline and this increased the correlation uncertainty. Following the removal of eighty-four duplicates, the selection was made through titles, abstracts and full-text reading. PMID: 35320928. Those women eating or taking soy isoflavones were more likely to get pregnant. Live birth odds in the multivariable-adjusted analysis was higher among women in the second tertile of soy intake, consuming 264755mg/d of soy isoflavones (OR: 187; 95% CI 112, 314) and among women in the third tertile of soy intake, consuming 7562789mg/d of isoflavones (OR: 177; 95% CI 103, 303) compared with no consumption, but without a significant linear trend. 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). } Adapted from Moher, Main cellular mechanism for isoflavones. 2. In particular, among selected studies, only the intervention study by Haudum and colleagues explored the stratification of participants for equol-competence(Reference Haudum, Lindheim and Ascani46). The authors highlighted a marginal reduction of luteal phase in the adjusted multivariable model for an increase of 10mg/d of dietary isoflavones (aOR: 138, 95% CI 099, 192, P=006), identified by monitoring LH levels in urine by a fertility monitor and 4-d per cycle 24-h dietary recalls. Interest in soy is particularly driven by its possible beneficial effects on human health. It would have been useful to have retrospective information on soy consumption to assess the potential effect on previous fertility problems. 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. 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). Steroid hormones (estradiol, progesterone and DHEAS) play a role in epithelial cell proliferation in mammals. 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). Main characteristics of selected studies. Moreover, couples with male infertility issues were excluded. 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. Major equol production was associated with a reduction in androgens levels (total testosterone, free testosterone and androstenedione), in the whole cohort. Excretion of daidzein and its metabolites dihydrodaidzein and O-desmethylangolensin (3601, 314 and 227mg, respectively) accounted for 421% of daidzein ingested. As expected, women with the highest soy consumption were more likely to be of Asian descent. The detailed selection process is highlighted in Fig. The concomitant treatment with soybean phytoestrogens significantly increased the implantation rate (254% v. 202%; P<005), the pregnancy rate (393% v. 209%; P<005) and the pregnancy-to-delivery rate (303% v. 162%; P<005) compared with placebo. 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) . 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. Phytoestrogens and breast cancer promoters or protectors? 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). However, a suggestive positive influence has been shown among women with fertility issues and during assisted reproductive technologies. 3 Department of Human Sciences and Promotion of the Quality of Life, San Raffaele Roma Open University, 00166 Rome, Italy. Participants recruited were seeking for pregnancy and this could have been a source of confounders. The urinary or serum levels of isoflavones did not affected progesterone levels in the multiple regression analysis. In a logical perspective, the effect of soy cannot be attributed to the effect of its isoflavones alone. Total loading time: 0 Any later it delays ovulation. 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. 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. 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). Overall, a trend toward improvement can be appreciated but further studies are necessary to confirm the beneficial effect. Jacobsen and colleagues included 11688 American women aged 3050 years of age who participated in Adventist Health Study-2 (AHS-2)(Reference Jacobsen, Jaceldo-Siegl and Knutsen38). Polycystic ovary syndrome (PCOS) is a major endocrine and metabolic disorder in women(Reference Meier62,Reference Liu, Zhang and Shi63) . Compliance with the intervention was suggested by urinary excretion of isoflavones. 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. RANCHO CUCAMONGA. Moreover, difficulties related to data collection about nutritional intakes were available, and individual reporting errors must be taken into account. A list of the selected clinical studies with their characteristics is summarised in Table 1. In October 1999, the US Food and Drug Administration (FDA) approved labeling for foods containing soy protein as protective against coronary heart disease. Currently, data are insufficient to assess the effect of early-stage soy exposure on fertility-related outcomes. The chemical structure similarity between soy isoflavones and endogenous estrogens has always stimulated the attention for this class of compounds. Furthermore, there was no characterisation of dietary regimen, although it was a standard hospital diet. Close this message to accept cookies or find out how to manage your cookie settings. The generalisation of these results is complex due to the type of study, which does not allow to define a causal relationship. Genistein treatment reduced LDL cholesterol and triglycerides levels. and Introduction. The advantages of observational cohort studies include longer times and wider population samples. (Reference Filiberto, Mumford and Pollack37). However, soy diet reduced progesterone (45%, P<00001) and estradiol levels (23%, P<001), compared with baseline. Soy contains numerous phytochemicals that can be responsible for these positive effects through multiple mechanisms. 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. 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 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. The power analysis concerning variation in isoflavone urinary excretion accounted for a sample size of 25 for >90% detection power. The standard guidelines for Clomid are to take it either on cycle days 3-7 or 5-9. Such shorter menstrual cycle length seemed not clinically relevant because shorter than 1d. Furthermore, for each 1nmol/l increase of genistein, the risk of menstrual cycle irregularities increased (OR: 119, 95% CI 102, 138). 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) . Manuscripts exploring multiple aspects were discussed in different paragraphs, where deemed necessary. The dietary intake of isoflavones did not appear to be associated with fertility in the two cohorts but some marginal evidence of amelioration of fertility was related to a higher intake of isoflavones among 30 years old individuals after age stratification (Fecundability Ratios: 112, 95% CI 994, 134 and 119, 95% CI 092, 155 in the two cohorts comparing 90th with <24th percentile). Isoflavones concentrations did not show significant differences between participants at baseline. Smaoui, Slim It does not appear to be randomised and blinded, but the nature of outcomes should not be affected by these limitations. The intervention period was extended only to one menstrual cycle. The limitations of these studies have already been discussed in the previous paragraph. The clinical trial was limited to a small sample size, lacking of control/placebo group and there was no characterisation of equol-competence. 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 authors found no significant differences in reproductive outcomes (missed menstrual periods, pregnancy, live births, abortions, miscarriages, full-term deliveries, preterm deliveries, etc.) 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. Soy food and soy isoflavone intake were unrelated to sperm motility, sperm morphology or ejaculate volume. However, stratification for the control group or PCOS patients did not show a significant correlation between androgens and equol production. Legumes, particularly soybeans, are the richest . However, among fertile individuals, it may have a neutral effect, as discussed in the previous paragraphs. Soy contains phytoestrogen, a plant-derived estrogen, known as isoflavones. Only three articles declared power analysis to assess adequate sample size(Reference Strom, Schinnar and Ziegler30,Reference Jamilian and Asemi43,Reference Haudum, Lindheim and Ascani46) . Longer, not clinically relevant duration of menstrual bleeding (adjusted MD: 037d, 95% CI 006, 068), without differences in severity of menstrual flow was observed. 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). WHAT IS IT? 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). The possibility of a sexual development disorder as a neonatal programming effect is an often raised hypothesis because circulating levels of isoflavones are higher in soy-fed infants compared with cow milk formula or breastfed infants(Reference Andres, Moore and Linam69). We have twins in the family and I like the thought, so a natural remedy would be nice :) "Isoflavones are polyphenolic compounds that are capable of exerting estrogen-like effects. This could be done by empirically monitoring ovulation to get a real information of menstrual phase, such as quantifying the urinary LH peak as a marker of ovulation, as done by Wu et al. The individual conversion capacity, equol-competence, offers a useful tool for estimating the biological effect of these compounds(Reference Zubik and Meydani15). 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. Furthermore, the use of spot urine samples could generate an underestimation of urinary isoflavones quantification. Flowchart for studies selection. Many of its components show an antioxidant activity that can at least partially explain its effectiveness(Reference Rizzo9). These enzymes convert estrone and androstenedione into estrogen and testosterone(Reference Gunnarsson, Ahnstrm and Kirschner83,Reference Thompson and Siiteri84) . However, there were also limitations: the duration of the study which was limited to two menstrual cycles and an evaluation of equol-producers among individuals was lacking. 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. However, soy intake did not correlate with cycle length (r: 012, P=045). The soy isoflavones block the estrogen receptors in your brain and fool your body into thinking its natural estrogen levels are low. However, ethnicity was not used for outcomes stratification. 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%). Soya Isoflavones and Vitamins The Group for those Using, Abusing and thinking about taking over the counter items to boost fertility. SMART [Internet]. 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). From obtained data, it seems likely that soy consumption, not only in the form of isoflavones in pharmacological quantities, could have a beneficial effect on fertility, especially in those individuals with fertility problems. Phytoestrogens and breast cancer: in vitro anticancer activities of isoflavones, lignans, coumestans, stilbenes and their analogs and derivatives, Estrogen signaling: a subtle balance between ER alpha and ER beta, Effect of soy isoflavones on blood pressure: a meta-analysis of randomized controlled trials, Bioavailability of soybean isoflavones from aglycone and glucoside forms in American women, Daidzein intake is associated with equol producing status through an increase in the intestinal bacteria responsible for equol production, The clinical importance of the metabolite equol-a clue to the effectiveness of soy and its isoflavones, Soy isoflavones accelerate glial cell migration via GPER-mediated signal transduction pathway, Antioxidant mechanisms of isoflavones in lipid systems: paradoxical effects of peroxyl radical scavenging. 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. Adapted from Moher et al.(24). Women who also have the problem of irregular periods can consume these isoflavones to get much-needed relief. Eating Places. Higher soy products intake did not correlate with the rate of infertility. 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, only 106 individuals provided information on soy intake. No correlation with specific isoflavones such as equol, daidzein and O-DMA was found. Fig. 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). For this reason, they are classified as phytoestrogensplant-derived compounds with estrogenic activity (1). However, the intakes of isoflavones in the studied cohorts were limited (range: 0331mg/d). Soy protein has gained considerable attention for its potential role in improving risk factors for cardiovascular disease (CVD). Soy is a key food in human nutrition. (Reference Moher, Liberati and Tetzlaff24). Although the clinical trial was quasi-randomised, with a placebo group, double-blinded, authors did not characterise the dietary regimen of individuals as well as their ability to effectively absorb and metabolise soy isoflavones. Feature Flags: { Hostname: page-component-7fc98996b9-pxj8b There was no evaluation of dietary habits and the determination of hormone levels was performed using non-validated ELISA kits, due to limited budget. The concentration of isoflavones in the amniotic fluid was related to soy intake, but there was no significant association between soy intake or phytoestrogens in the amniotic fluid and complications of pregnancy or previous infertility. These alterations easily lead to hyperandrogenism and irregular menstrual cycles. A total number of twenty-two experimental articles plus a meta-analysis was used for the final synthesis. 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). Additional considerations regarding hormonal influences will be discussed in the next paragraph. Isoflavones are non-steroidal compounds with a chemical structure similar to endogenous estrogens and for this reason, they are defined as phytoestrogens: a functional classification that also includes lignans, coumestans and stilbenes(Reference Basu and Maier12). Overall, a trend toward improvement can be appreciated but further studies are necessary confirm. This message to accept cookies or find out how to manage your cookie settings this have. And DHEAS ) play a role in improving risk factors for cardiovascular disease ( CVD.. 3 Department of human Sciences and Promotion of the selected clinical studies with their is... At least partially explain its effectiveness ( Reference Rizzo9 ) and testosterone Reference. Previous paragraphs cardiovascular disease ( CVD ) daidzein and O-DMA was found aspects were discussed in studied. Into estrogen and testosterone ( Reference Gunnarsson, Ahnstrm and Kirschner83, Reference Thompson and Siiteri84 ) are to it! 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