However, after removing data from studies with elevated bias risk, three studies were included in the sensitivity analysis with consequent loss of statistical significance. (2001), Isolation and determination of anthocyanins in seed coats of black soybean (, Oyawoye O, Abdel Gadir A, Garner A, et al. Although not strictly related to the aspect of fertility, the study is still ongoing (Clinicaltrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT00616395","term_id":"NCT00616395"}}NCT00616395) intending to follow the participants to evaluate effects on reproductive functions, later in life. Previously, Petrakis and colleagues proposed an interventional study with a soy isolate (374g of soy protein containing 374mg of genistein) on twenty-four women (pre- and post-menopause) followed for 6 months plus 3 months pre-intervention and 3 months post-washout(25). The adjustment for male partner intake of soy in the subgroup analysis did not change the association. Researchers did not observe any clinical improvement, alteration of menstrual cycle or hormonal alteration (estradiol, SHBG, DHEAS, androstenedione, testosterone, FSH, LH) compared with baseline levels. Miso intake was inversely associated with SHBG levels. A total of 834 entries were obtained following search engine queries (PubMed: 381; ScienceDirect: 392; Cochrane Library Trials: 30 and ClinicalTrials.gov: 31). However, among fertile individuals, it may have a neutral effect, as discussed in the previous paragraphs. Similarly, the stratification by ethnicity and equol-producers may suggest the nature of interactions between soy and fertility. Following the removal of eighty-four duplicates, the selection was made through titles, abstracts and full-text reading. In addition, other studies investigated the urinary concentrations of isoflavones and metabolites, including equol(39,45). Regarding the observational studies available, in 2015 Venegas et al. Furthermore, there was no evaluation of metabolic utilisation capacity of isoflavones and their absorption by measuring serum and urinary levels. 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. No changes were highlighted for DHEA, DHEAS, dihydrotestosterone (DHT) concentration or LH:FSH ratio. The limitations of these studies have already been discussed in the previous paragraph. Furthermore, from the multiple regression analysis of ten women in the second trial(29), the reduction of estradiol in both luteal and follicular phases was positively associated with serum and urinary isoflavone levels but not with individual changes in the intake. (2019), Dietary patterns and outcomes of assisted reproduction, Andres A, Moore MB, Linam LE, 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. Consistent with the previously cited data, no significant alteration in the cycle length was found among participants following the intervention. It would have been useful to have retrospective information on soy consumption to assess the potential effect on previous fertility problems. Marginal reduction of luteal phase for an increase of 10mg/d IF intake in the adjusted model (aOR: 138, 95% CI 099, 192, Increased fertility (assessed with live birth rates, implantation and clinical pregnancy rates) with higher soy intake through interaction with urinary BPA, compared with no-soy consumption, Soy IF intake reduced the free androgen index (0020005, USA Canada Denmark/Caucasian, African-American, Asian, Hispanic, others, No association between IF intake and fertility (assessed by per-cycle probability of conception) with some marginal evidence of amelioration over 30 years associated with IF, USA/Caucasian, African-American, Hispanic, other, Urinary Ph levels were inversely associated in adjusted regression models with cycle length; urinary Gen levels were associated with cycle irregularity (assessed by fertility monitors and daily journals), Fertility amelioration (based on androgens and AMH levels) among equol-producers in the whole cohort compared with non equol-producers. 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. Accessibility 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. In the first clinical trial by Unifer and colleagues, 1500mg/d of isoflavones from soy or placebo were administered for 10d to 134 women who had been infertile for at least 2 years, undergoing intrauterine insemination after 100mg/d for 5d of clomiphene citrate treatments (an ovulation inducer)(31). 16 Although much of the concern is based on animal research, 16 a sufficient amount of fertility-relevant human research, including both epidemiologic and clinical studies, has been conducted; therefore, conclusions about the impact of soy on fertility can be . (2019), 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, Schmidt M, Arjomand-Wlkart K, Birkhuser MH, et al. Adapted from Moher et al.(24). Soy Isoflavones experiment November 22, 2022 | by happyone18 I'm going to document my experience taking soy isoflavones (SI) this cycle. Pending further confirmation, soy and its components do not appear to have a clinically relevant influence on menstrual cycle in healthy women. Polycystic ovary syndrome (PCOS) is a major endocrine and metabolic disorder in women(62,63). 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). 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(46). On consumption, they increase estrogen production in a woman's body. However, the mechanisms underlying isoflavones effects on human health are manifold. No changes in progesterone, LH or SHBG after soy intervention, USA/Caucasian, Hispanic, African-American, E2 levels were inversely associated with soy intake, assessed with multiple adjusted spearman rank correlation coefficients. No investigation into the individual's ability to absorb and use isoflavones from soy milk was performed. 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. (1982), Calculation of free and bound fractions of testosterone and estradiol-17 beta to human plasma proteins at body temperature, Dysbiosis of gut microbiota associated with clinical parameters in polycystic ovary syndrome, The (TAAAA)n microsatellite polymorphism in the SHBG gene influences serum SHBG levels in women with polycystic ovary syndrome, Escobar-Morreale HF, Luque-Ramrez M & Gonzlez F (2011), Circulating inflammatory markers in polycystic ovary syndrome: a systematic review and metaanalysis, Showell MG, Mackenzie-Proctor R, Jordan V, et al. However, the evaluation of ability to absorb and metabolise isoflavones was lacking in the present study. (2020), Soy isoflavones accelerate glial cell migration via GPER-mediated signal transduction pathway, Patel RP, Boersma BJ, Crawford JH, et al. Furthermore, women with PCOS display a higher prevalence of hyperinsulinemia, dyslipidemia, insulin resistance and obesity compared to healthy population. Steroid hormones (estradiol, progesterone and DHEAS) play a role in epithelial cell proliferation in mammals. 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. (2004), High dose of phytoestrogens can reverse the antiestrogenic effects of clomiphene citrate on the endometrium in patients undergoing intrauterine insemination: a randomized trial, Unfer V, Casini ML, Gerli S, et al. Corrections for confounding factors, such as diet, demographics, lifestyle factors, age, body composition and ethnicity, indicated reliable analysis. 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(28). . (2010), Estradiol or genistein prevent Alzheimer's disease-associated inflammation correlating with an increase PPAR gamma expression in cultured astrocytes, Harada K, Sada S, Sakaguchi H, et al. The clinical studies selection included one retrospective study, two cross-sectional studies, eight longitudinal cohort studies, five parallel-designed interventional studies and six longitudinal interventional studies. Soy isoflavones seem to act also through a non-genomic regulation, activating specific cellular signalling pathways(18). 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. It is important to evaluate the levels of hormones that fluctuate during the cycle at several points. 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(17). (2020). The interaction between isoflavones and ER estrogen receptor results in a competitive effect which in turn blunts endogenous estrogens action(72), as suggested by estrogenic activity of biochanin A and genistein on BT-474 human breast cancer(73). Isoflavones concentrations did not show significant differences between participants at baseline. In addition to the interventional study by Kohama and colleagues, we found three longitudinal cohort observational studies(36,39,44) and a cross-sectional study(38) that investigated the association between soy and fertility. 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. This could favour the bioavailability of sex hormones(60). Participants recruited were seeking for pregnancy and this could have been a source of confounders. Among the limitations of this review of literature, we must include the possible avoidance of studies that considered fertility as a secondary outcome and which therefore may have escaped from the manuscript selection. between 128 women fed with soy-based formula and 268 women fed with cow milk formula during infancy. 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(28). It does not appear to be randomised and blinded, but the nature of outcomes should not be affected by these limitations. As it does not contain phytoestrogens, you can safely use soy sauce. If we eat soy, do we keep the beneficial effects of the Mediterranean diet? To our knowledge, this is the first comprehensive review on soy effect on women's fertility. Phytoestrogens and breast cancer promoters or protectors? These types of products contain phytoestrogens in much higher concentrations than traditional whole-food sources. The evaluation of isoflavones circulating levels and their urinary excretion allowed to show a wide inter-individual variation of metabolic and absorption capacity. Furthermore, it should be considered that, as already discussed, many studies display several limitations including inadequate sampling of hormone concentrations during all phases of cycle, low number of participants and the lack of a placebo group. (2004), 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, Romualdi D, Costantini B, Campagna G, et al. The estrogen-like effects of isoflavones underlie concerns about soy and fertility. Among the studies already cited, however, we must consider the work of Kohoama and colleagues(33), which showed fertility improvements following intervention with black soy extract in individuals with secondary amenorrhea, including patients with PCOS. Sampling involved synchronisation on the third day of menstrual cycle follicular phase, spontaneous or pharmacologically induced. The success of soy mainly depends on versatility and supposed healthy properties of soy foods and soy components. Before recruited 315 USA women underwent 530 cycles of assisted reproduction technology(40). No significant differences were found in the spontaneous abortion rate, the number and quality of embryos transferred or oocytes fertilised. Women who try soy isoflavones to conceive should understand the following: Do not take soy isoflavones and vitex (chaste berry) at the same time. conducted another prospective cohort study on 239 American women undergoing assisted reproductive technology(42). In a logical perspective, the effect of soy cannot be attributed to the effect of its isoflavones alone. (2015), Dietary factors and luteal phase deficiency in healthy eumenorrheic women, Chavarro JE, Mnguez-Alarcn L, Chiu Y-H, 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. The site is secure. Manuscripts exploring multiple aspects were discussed in different paragraphs, where deemed necessary. However, the difference became not significant after adjustment for isoflavone intake. 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. A. F. contributed to drafting and revising the manuscript. Moreover, urinary concentrations seem to reflect the isoflavone intakes in a short time window. 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. (2021), 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, Kang J, Badger TM, Ronis MJJ, et al. Received 2022 Jan 30; Accepted 2022 Feb 7. Latest: 4 months ago | happyone18 10 Finally, they show antioxidant activity: a shared property among polyphenols(19). 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(26,28,29). (2021), Neither soyfoods nor isoflavones warrant classification as endocrine disruptors: a technical review of the observational and clinical data, https://creativecommons.org/licenses/by/4.0/, 374 g/d soy protein isolate (374mg Gen), Higher serum E2 levels during soy intervention phase were shown compared with no-soy phases. The authors declare that they have no conflicts of interest. The effects obtained from selected studies do not seem to show a clear significance regarding fertility and menstrual cycle length, as discussed in the previous paragraph. This allowed to exclude the already summarised articles in meta-analysis from a detailed discussion. (2008), Is there a role for soy isoflavones in the therapeutic approach to polycystic ovary syndrome? M. A. S. contributed to drafting and revising the manuscript. Eating a few servings of soy each week could improve fertility and metabolic aspects of PCOS. anita baker first husband; soy isoflavones fertility twins tastylia. Federal government websites often end in .gov or .mil. (2012), The utility of menstrual cycle length as an indicator of cumulative hormonal exposure, Vassena R, Vidal R, Coll O, et al. In another prospective study, 471 healthy American women were followed for 12 months or until delivery without showing significant correlations between urinary isoflavones, quantified by HPLC-MS analysis, and fertility, defined with adjusted Cox Model using time-to-pregnancy assessment(39), while lignan concentrations in urine were significantly associated with shorter time to pregnancy. I continued Intralipid after a positive and 2 more the next 2 months. Rome, Italy, 4Center for Complementary Medicine, Department of Internal Medicine II, Faculty of Medicine, University of Freiburg, Freiburg, Germany. Soy consumption was not related to estradiol levels or endometrial thickness. Yes, soy can cause ovulation problems. 2023-03-29. (2012), Early-life soy exposure and age at menarche, Sinai T, Ben-Avraham S, Guelmann-Mizrahi I, et al. However, results are questionable due to the lack of hormone level measurements or reproductive functions. No correlation with specific isoflavones such as equol, daidzein and O-DMA was found. In particular, among selected studies, only the intervention study by Haudum and colleagues explored the stratification of participants for equol-competence(46). Furthermore, the absence of gynecological issues was only based on self-reported information. 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. Soy isoflavones can help induce ovulation in such women. These alterations easily lead to hyperandrogenism and irregular menstrual cycles. 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). Similar significant association was observed for peak luteal progesterone 10ng/ml (aOR: 140, 95% CI 100, 196, P=005). Furthermore, the use of spot urine samples could generate an underestimation of urinary isoflavones quantification. The possible correlation between menstrual cycle length and soy does not seem convincing either. Furthermore, hormone levels were evaluated only at baseline, without taking into account the differences between the two groups. (2019), Daidzein intake is associated with equol producing status through an increase in the intestinal bacteria responsible for equol production, Setchell KDR, Brown NM & Lydeking-Olsen E (2002), The clinical importance of the metabolite equol-a clue to the effectiveness of soy and its isoflavones, Ariyani W, Miyazaki W, Amano I, et al. (2011), Effect of soy phytoestrogen on metabolic and hormonal disturbance of women with polycystic ovary syndrome, Jarrell J, Foster WG & Kinniburgh DW (2012), Filiberto AC, Mumford SL, Pollack AZ, et al. 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). (2000), Cellular and biochemical mechanisms by which environmental oestrogens influence reproductive function, Zand RS, Jenkins DJ & Diamandis EP (2000), Steroid hormone activity of flavonoids and related compounds, Kuiper GG, Lemmen JG, Carlsson B, et al. Furthermore, diet and energy intake were not investigated and sampling was not well-timed to menstrual cycle. The FFQ was not specifically designed for phytoestrogen assessment and this may have underestimated intakes. Participants were divided into four categories: non-consumers and tertiles of soy intake. If you look around that sight you will see several posts about just using Soy Isoflavones if Clomid isn't in your work up. Fig. However, soy intake did not correlate with cycle length (r: 012, P=045). In particular, information about the adequate choice of updated nutritional tables as well as specific nutritional choices, such as increased soy consumption due to pre-existing socio-cultural and physiological aspects should be collected. 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(26,29). Table 2 summarises main limitations about the studies discussed. was a pilot study without a characterisation of diet among participants and without data on soy composition (isoflavone or antioxidant contents). Fertility is defined by the number of offspring produced by an individual. Furthermore, no characterisation was made on the possible presence of equol-producers among the participants. 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. government site. Thus, consumption of soy containing 32-200 mg/d of isoflavones seems to increase menstrual cycle length and the ratios of 2- to 16- (OH) and 2- to 4- (OH) estrogens and to decrease plasma concentrations of estradiol, progesterone, midcycle gonadotropins and SHBG as well as urinary estrogens. 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