Similar to the previous observational study, Chavarro et al. In addition, other studies investigated the urinary concentrations of isoflavones and metabolites, including equol(Reference Mumford, Sundaram and Schisterman39,Reference Levine, Kim and Purdue-Smithe45) . The authors found an association between pregnancy outcomes and urinary Bisphenol A (BPA), dependent on soy consumption in the multivariable-adjusted mixed model. 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, 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. Not all isoflavones work in the same manner. Pending further confirmation, soy and its components do not appear to have a clinically relevant influence on menstrual cycle in healthy women. Interest in soy is particularly driven by its possible beneficial effects on human health. Eating a few servings of soy each week could improve fertility and metabolic aspects of PCOS. In the previously mentioned meta-analysis by Hooper and colleagues(Reference Hooper, Ryder and Kurzer59), reduction of about 22% of FSH (SMD: 045UI/l, 95% CI 079, 011, P=001) and of about 4% of LH (SMD: 034IU/l, 95% CI 068, 001, P=005) were related to the intake of soy or isoflavones. These aspects considerably reduce the reliability of results, favouring data misinterpretation. However, only 106 individuals provided information on soy intake. Guo, Tingting It does not appear to be randomised and blinded, but the nature of outcomes should not be affected by these limitations. (Reference Wu, Stanczyk and Hendrich28). Regarding isoflavones, the equol metabolite derives from the precursor daidzein by the action of intestinal bacteria. In response, your body starts a cascade of events to boost estrogen production. [cited 2021 Jul 26]. Eleven interventional studies, eleven observational studies and one meta-analysis have been selected from the results of queries. and The deleterious effects of these compounds, as metabolites of clover isoflavones, were first documented in 1946 by Bennetts and co-workers studying New Zealand ewes expressing clover disease, an infertility syndrome ( Bennetts, Underwood, & Shier, 1946 ). 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. However, the evaluation of ability to absorb and metabolise isoflavones was lacking in the present study. 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. 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). Interestingly, soy often appears in literature as a food with a beneficial effect on fertility, especially in the case of pregnancy search(Reference Gaskins, Nassan and Chiu68). Fig. Women who also have the problem of irregular periods can consume these isoflavones to get much-needed relief. 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). Soy isoflavones can help induce ovulation in such women. However, after removing data from studies with elevated bias risk, three studies were included in the sensitivity analysis with consequent loss of statistical significance. In 2000, Wu et al. Unfortunately, the work of Kohama et al. Total loading time: 0 For this reason, the clinical data were meta-ana Find Best Western Hotels & Resorts nearby Sponsored. In particular, soy contains numerous non-isoflavone constituents such as phytic acid, triterpenes and sterols, BowmanBirk protease inhibitors, unsaturated fatty acids, saponins, inositol phosphates, proteins, peptides such as lunasin;(Reference Kang, Badger and Ronis10) nevertheless, soy isoflavones have attracted much attention in the last years for its estrogenic as well as non-hormonal properties(Reference Aulisa, Binda and Padua11). These aspects were poorly characterised by self-reporting of the participants. 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). 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). Steroid hormones (estradiol, progesterone and DHEAS) play a role in epithelial cell proliferation in mammals. However, among fertile individuals, it may have a neutral effect, as discussed in the previous paragraphs. Correction for covariates included demographics, education, income, lifestyle, dietary and behavioural factors. Furthermore, hormone levels were evaluated only at baseline, without taking into account the differences between the two groups. The adjustment for male partner intake of soy in the subgroup analysis did not change the association. As expected, women with the highest soy consumption were more likely to be of Asian descent. However, ethnicity was not used for outcomes stratification. 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). 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). 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. Improvements were observed only in lipid profile (circulating total cholesterol, LDL and LDL/HDL ratio and triglycerides). This suggests a protective effect of soy against fertility disturbance by BPA. Soaking, fermentation, and heating may reduce problematic antinutrients contained in soy. Products; Resources; My Account; Talk to a D&B Advisor 1-800-280-0780. Business Directory. 44% of women of Asian descent were in the highest quartile of isoflavone intake. Follicular development, the number of preovulatory follicles and the pulsatility index values were not different between groups after intervention. Ma, Haoyue 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). Both isoflavones are found in soy at several mg 100 g 1 ( Bennetau-Pelissero, 2013 ). Review the D&B Business Directory at DandB.com to find more. Isoflavones in human plasma are usually low (04157nM) in individuals consuming low-isoflavone diets but in large soy-consumers, such as Asian people, isoflavone concentration can reach up to ~4M, with equol reaching up to ~40nM in low consumers and up to ~2M in large soy-consumers(Reference Morton, Arisaka and Miyake88). Concerns that the phytoestrogens (isoflavones) in soy may feminize men continue to be raised. Overall, a trend toward improvement can be appreciated but further studies are necessary to confirm the beneficial effect. Conversely, the improvements in ovulation were seen only in two patients from the control group. 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) . While isoflavones and their metabolites were undetectable in the pre-soy phase, during intervention the 24h output of urinary excretion was 312mg for genistein (74% of the ingestion). Other weak aspects of the population sample characterisation are given by a lack of stratification by ethnicity and equol-producers. Sampling involved synchronisation on the third day of menstrual cycle follicular phase, spontaneous or pharmacologically induced. These clinical trials had several strengths including the presence of a placebo group, randomisation, double-blinding and recruitment of a wide number of participants. Go. Based on this cross-sectional study, high consumption of soy isoflavones was identified (94% of participants). WHAT IS IT? 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. 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) . 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. Since there are no scientific studies on the effects of soy isoflavones and ovulation, these are just general guidelines. } The strength of these studies was the assessment of hormone levels based on the menstrual cycle phase. Adapted from SMART: Servier Medical Art(89). No changes were highlighted for DHEA, DHEAS, dihydrotestosterone (DHT) concentration or LH:FSH ratio. Adapted from Moher et al.(24). 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). The mice were then switched to an isoflavone-free diet - and their tumours regressed over the following nine weeks.. 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). The researchers found that the isoflavones resulted in increased cell growth. 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). The authors defined the unusual estradiol increase as erratic. United States California 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. The influence on SHBG levels can have a beneficial effect from an endocrine point of view, without negative effects on ovulation. However, the number of combined participants of the two studies was very limited (n: 40). Jia, Liyan No changes in progesterone and SHBG concentrations from baseline were observed. Get the latest business insights from Dun & Bradstreet. One of the first research papers to look directly at soy and fertility outcomes was from the Adventist Health Study-2. No significant differences were found in the spontaneous abortion rate, the number and quality of embryos transferred or oocytes fertilised. A list of the selected clinical studies with their characteristics is summarised in Table 1. However, in multiple regression analysis, this reduction seemed to be significantly associated with the intake of genistein and daidzein or their concentration in urine. 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. Adapted from Moher, Main cellular mechanism for isoflavones. 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). 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). 4 Center for Complementary Medicine, Department of Internal Medicine II, Faculty of Medicine, University of Freiburg, Freiburg, Germany. Keywords were searched in titles and abstracts and combined with MeSH terms, where available, adapting the query format based on the search engine used. Major equol production was associated with a reduction in androgens levels (total testosterone, free testosterone and androstenedione), in the whole cohort. The authors found that consuming moderate amounts of traditionally . View all Google Scholar citations Consistent with the previously cited data, no significant alteration in the cycle length was found among participants following the intervention. 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. Clinical studies show no effects of soy protein or isoflavones on reproductive hormones in men: results of a meta-analysis, Neither soy nor isoflavone intake affects male reproductive hormones: an expanded and updated meta-analysis of clinical studies, The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration, Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement, Stimulatory influence of soy protein isolate on breast secretion in pre- and postmenopausal women, Effects of soya consumption for one month on steroid hormones in premenopausal women: implications for breast cancer risk reduction, Decreased serum estradiol concentration associated with high dietary intake of soy products in premenopausal Japanese women, Effects of soy foods on ovarian function in premenopausal women, Decreased ovarian hormones during a soya diet: Implications for breast cancer prevention, Exposure to soy-based formula in infancy and endocrinological and reproductive outcomes in young adulthood, High dose of phytoestrogens can reverse the antiestrogenic effects of clomiphene citrate on the endometrium in patients undergoing intrauterine insemination: a randomized trial, Phytoestrogens may improve the pregnancy rate in in vitro fertilizationembryo transfer cycles: a prospective, controlled, randomized trial, The effect of soybeans on the anovulatory cycle, Is there a role for soy isoflavones in the therapeutic approach to polycystic ovary syndrome? The standard guidelines for Clomid are to take it either on cycle days 3-7 or 5-9. Finally, they show antioxidant activity: a shared property among polyphenols(Reference Patel, Boersma and Crawford19). Only 6% of participants had not soy isoflavone intake. and The results of selected manuscripts were grouped according to the outcomes used, for a clear comparison. 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. The individual conversion capacity, equol-competence, offers a useful tool for estimating the biological effect of these compounds(Reference Zubik and Meydani15). On consumption, they increase estrogen production in a woman's body. 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. From data that emerged on individuals with PCOS, there is no homogeneous improvement effect on hormonal picture, on menstrual cycle and therefore on fertility associated with soy consumption. We use cookies to distinguish you from other users and to provide you with a better experience on our websites. A total number of twenty-two experimental articles plus a meta-analysis was used for the final synthesis. The fertility concept differs from the fecundity one, which refers to reproductive potential and depends on reproductive physiology, from the production of gametes phase to the ability to carry a pregnancy to term. Furthermore, considering soy as a mere source of isoflavones is extremely reductive. However, the association between soy and isoflavones with the reduction of luteal phase seems weak. Fig. 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. 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). Nevertheless, these studies often suffer difficulties in evaluating individual effectiveness as well as in identifying possible confounding factors and population characteristics (ethnicity, health conditions, equol-competence, etc.). In October 1999, the US Food and Drug Administration (FDA) approved labeling for foods containing soy protein as protective against coronary heart disease. 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). There are clues about the association between soy intake and the increase in SHBG levels. 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 same amount of genistein was used in a parallel clinical trial on 137 Iranian women with PCOS with a 3-month follow-up(Reference Khani, Mehrabian and Khalesi35). Genistein treatment reduced LDL cholesterol and triglycerides levels. Find company research, competitor information, contact details & financial data for Lucky Twins Distribution of Rancho Cucamonga, CA. 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). They have been dubbed "the natural Clomid," As they work in pretty much an identical manner. Most women taking soy isoflavones to induce ovulation take around 150-200 mg a day on cycle day 3 -7 or 5-9. However, urinary phytoestrogen levels were only detected at baseline and this increased the correlation uncertainty. 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. The study did not evaluate circulating or urinary levels of isoflavones to verify the ability to metabolise isoflavones. Soy can contain numerous other phytochemicals such as saponins, phytosterols, phytic acid, non-isoflavone flavonoids, peptides, protease inhibitors and other bioactive substances. 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. This could have introduced other confounding factors such as the influence of male on couple's fertility or possible changes in habits caused by the desire to conceive. From the sub-analysis by ethnic stratification, follicular SHBG levels were higher in non-Asians. DOI: 10.1017/jns.2022.15. However, the terms are often interchangeably, being closely associated with the possibility of giving birth to children. In both studies, the lowering of progesterone levels in luteal phase was also significant in the case of soy intake, mean 35% (P=0002) compared with baseline. The lack of variation in gonadotropins can explain the absence of variation in menstrual cycle. The authors wish to thank Sandra De Dominici for language revision assistance. Progesterone and sex hormone-binding globulin (SHGB) levels were not significantly changed by soy intake. Isoflavones also bind to ER receptor, albeit with lower affinity. After the soy intervention, the length of menstrual cycle marginally increased (from 28319 to 31851d, P=006). Clinical trials can provide solid causal inferences, but they often have limitations in terms of study duration or intervention design. 1. A systematic consultation of literature was launched on four search engines (PubMed, ScienceDirect, Cochrane Trials Library and ClinicalTrials.gov) using the following keywords: (Soy OR Soy Foods OR Soybeans OR Genistein OR Daidzein OR Isoflavones OR Phytoestrogens) AND (Fertility OR Infertility OR Fecundability). 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