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. 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). There was no evaluation of dietary habits and the determination of hormone levels was performed using non-validated ELISA kits, due to limited budget. This suggests a protective effect of soy against fertility disturbance by BPA. Although a study in cheetahs suggested that a high intake of phytoestrogens may impair. The authors showed an inverse correlation between cycle length (detected via fertility monitors and daily journals) and total urinary phytoestrogen levels (0042d for 10% increase, 95% CI 0080, 0003). However, the number of combined participants of the two studies was very limited (n: 40). Eating a few servings of soy each week could improve fertility and metabolic aspects of PCOS. However, a clear effect on reproductive system has never been highlighted, especially due to the absence of observational studies designed for this purpose. The interaction between isoflavones and ER estrogen receptor results in a competitive effect which in turn blunts endogenous estrogens action(Reference Rosselli, Reinhart and Imthurn72), as suggested by estrogenic activity of biochanin A and genistein on BT-474 human breast cancer(Reference Zand, Jenkins and Diamandis73). Metabolic, endocrine, inflammation, and oxidative stress . It is an endocrine dysfunction that includes hormonal alterations (increased levels of adrenal and ovarian androgens and SHBG secretion from the liver) and anovulatory disorders(Reference Ferk, Teran and Gersak64). CA. 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) . A total of 834 entries were obtained following search engine queries (PubMed: 381; ScienceDirect: 392; Cochrane Library Trials: 30 and ClinicalTrials.gov: 31). From the sub-analysis by ethnic stratification, follicular SHBG levels were higher in non-Asians. These alterations easily lead to hyperandrogenism and irregular menstrual cycles. Manuscripts exploring multiple aspects were discussed in different paragraphs, where deemed necessary. However, the intakes of isoflavones in the studied cohorts were limited (range: 0331mg/d). 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). Corrections for confounding factors, such as diet, demographics, lifestyle factors, age, body composition and ethnicity, indicated reliable analysis. Soy contains phytoestrogen, a plant-derived estrogen, known as isoflavones. 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). 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 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). 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). It would have been useful to have retrospective information on soy consumption to assess the potential effect on previous fertility problems. PMID: 35320928. It helps you to ovulate and they quality. 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. 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. To put this into perspective, a 3.5-ounce (100-gram) serving of firm, calcium-set tofu offers about 60 mg of soy isoflavones, while 1 cup (240 mL) of soy milk contains only about 28 mg. Fig. The mice were then switched to an isoflavone-free diet - and their tumours regressed over the following nine weeks.. Main characteristics of selected studies. In a logical perspective, the effect of soy cannot be attributed to the effect of its isoflavones alone. 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). 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. Additional considerations regarding hormonal influences will be discussed in the next paragraph. 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). They have been dubbed "the natural Clomid," As they work in pretty much an identical manner. The study's strength include a large consumption of soy and by consistent inter-individual variability among participants (total intake of 379261g/d), which allows better detection of cross-sectional correlations. DOI: 10.1017/jns.2022.15. and The detailed selection process is highlighted in Fig. 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). Therefore, the lack of fecundity is called sterility(Reference Wood47). The use of surveys only through self-administered questionnaires, although validated, is easily exposed to self-reporting errors or incompleteness and misclassifications derived from the database used for food intake quantification. 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. Moreover, two recent observational cohort studies by Chavarro and colleagues evaluated the association between soy consumption and in vitro fertilisation outcomes(Reference Vanegas, Afeiche and Gaskins40,Reference Chavarro, Mnguez-Alarcn and Chiu42) . Why did you take Soy Isoflavones: I had tried most other things so decided to be a guinea pig. It affects one out of every six couples and affects the majority women aged between 15 to 44 years. The estrogen-like effects of isoflavones underlie concerns about soy and fertility. The significant inverse association between dietary isoflavone intake and live births (3% reduction, 95% CI 0, 7, P=005) was highlighted. 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. 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. The authors defined the unusual estradiol increase as erratic. The possible correlation between menstrual cycle length and soy does not seem convincing either. No changes were highlighted for DHEA, DHEAS, dihydrotestosterone (DHT) concentration or LH:FSH ratio. Furthermore, there was no evaluation of metabolic utilisation capacity of isoflavones and their absorption by measuring serum and urinary levels. While soy appears to have a negligible effect on hormonal network, menstrual cycle length and fertility outcomes of healthy women, some clues emerged from literature on its possible beneficial effect in the case of endocrine diseases such as PCOS. Furthermore, the individuals recruited were seeking for a pregnancy and this could have changed their behaviour. Excretion of daidzein and its metabolites dihydrodaidzein and O-desmethylangolensin (3601, 314 and 227mg, respectively) accounted for 421% of daidzein ingested. Furthermore, the use of spot urine samples could generate an underestimation of urinary isoflavones quantification. Soy as an endocrine disruptor: cause for caution? This latter aspect suggests a differential capacity for metabolising isoflavones even if these differences were no longer significant when corrected for the intake of isoflavones and estradiol levels were not significantly associated with urinary excretion of isoflavones. [1] 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. The soy isoflavones block the estrogen receptors in your brain and fool your body into thinking its natural estrogen levels are low. However, after removing data from studies with elevated bias risk, three studies were included in the sensitivity analysis with consequent loss of statistical significance. Furthermore, the search for sources has been extended to the single manuscripts reference lists. Compliance with the intervention was suggested by urinary excretion of isoflavones. 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). Table 2 summarises main limitations about the studies discussed. 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) . Similarly, the duration of interventions is limited and equol-producers have not been identified. SMART [Internet]. Soy is a very popular food and its consumption is part of the traditional cuisine of South-East Asian countries. Keywords were searched in titles and abstracts and combined with MeSH terms, where available, adapting the query format based on the search engine used. Flowchart for studies selection. The reduction of estradiol and progesterone could postpone ovulation by lengthening the menstrual cycle. In another study, women were more likely to get pregnant if they ate soy isoflavones alongside . It is important to evaluate the levels of hormones that fluctuate during the cycle at several points. 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 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. 1. 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). In October 1999, the US Food and Drug Administration (FDA) approved labeling for foods containing soy protein as protective against coronary heart disease. There is a limited trend in estradiol reduction related to soy consumption; however, in their interventional study, Petrakis and colleagues observed an unusual increase of estradiol levels(Reference Petrakis, Barnes and King25). Although this was a randomised, placebo-controlled and double-blinded trial with a sample size appropriate to the power of detection, there was no evaluation of serum and urinary levels of isoflavones and/or metabolites. 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) . M. L. contributed to drafting and revising the manuscript. Adapted from SMART: Servier Medical Art(89). 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. Meanwhile, the possible influence on endocrine system, in particular by isoflavones, raised concerns among some researchers. 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 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). In this context, the evaluation of urine samples cannot be underestimated as a valuable tool for detection of the real bioavailability of isoflavones whose metabolisation requires the intervention of intestinal microbiota. The authors responsibilities were as follows: G. R. study conception and drafting the manuscript. 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. Luteal phase deficiency can represent a relevant aspect for pregnancy outcomes and fertility disorders. (Reference Moher, Liberati and Tetzlaff24). Total loading time: 0 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. On consumption, they increase estrogen production in a woman's body. The clinical trial was limited to a small sample size, lacking of control/placebo group and there was no characterisation of equol-competence. 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). 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) . Get company information for Twins Club, Inc. in RANCHO CUCAMONGA, CA. 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. The article processing charge was funded by the Baden-Wuerttemberg Ministry of Science, Research and Art and the University of Freiburg in the funding programme Open Access Publishing. 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? 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