Progesterone and sex hormone-binding globulin (SHGB) levels were not significantly changed by soy intake. However, soy intake did not correlate with cycle length (r: 012, P=045). 44% of women of Asian descent were in the highest quartile of isoflavone intake. In addition, no significant changes in progesterone, LH or SHBG were found in the whole study sample. This effect persisted for at least one menstrual cycle after the suspension of soy intake, with a maximum of persistence for three menstrual cycles. 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). 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(6971). Fertility is defined by the number of offspring produced by an individual. (2014), Menstrual cycle length in reproductive age women is an indicator of oocyte quality and a candidate marker of ovarian reserve, Crawford NM, Pritchard DA, Herring AH, et al. There are clues about the association between soy intake and the increase in SHBG levels. The reduction of estradiol and progesterone could postpone ovulation by lengthening the menstrual cycle. Furthermore, the possible ameliorative influence of soy or its components in the case of assisted reproduction techniques outcomes and pregnancy seeking appears promising and worthy of interest. (2010), Clinical studies show no effects of soy protein or isoflavones on reproductive hormones in men: results of a meta-analysis, Reed KE, Camargo J, Hamilton-Reeves J, et al. Updated at 2:23 p.m. Soy isoflavones have also been found to inhibit tyrosine kinases (14), enzymes that play critical roles in the signaling pathways that stimulate cell proliferation. Other weak aspects of the population sample characterisation are given by a lack of stratification by ethnicity and equol-producers. The phytoestrogen actions of soy isoflavones may increase estrogen levels in the body and induce ovulation in women, thus, may speed up the process of pregnancy. 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). (2017), Prospective evaluation of luteal phase length and natural fertility, Wesselink AK, Wise LA, Hatch EE, et al. There is a discussion board about taking Soy Isoflavones with Clomid that provided a research study by an REI that says take 200 mg CD1-5 and Clomid CD5-9. 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. The possible correlation between menstrual cycle length and soy does not seem convincing either. (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. Improvements were observed only in lipid profile (circulating total cholesterol, LDL and LDL/HDL ratio and triglycerides). 1Independent Researcher, Via Venezuela 66, 98121 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. (2013), Usual dietary isoflavone intake and reproductive function across the menstrual cycle, Jacobsen BK, Jaceldo-Siegl K, Knutsen SF, et al. This could favour the bioavailability of sex hormones(60). 2 highlights the main cellular mechanisms attributed to isoflavones. soy isoflavones fertility twins tastylia. 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. It would have been useful to have retrospective information on soy consumption to assess the potential effect on previous fertility problems. This is justified by the fact that the study was not designed for the specific assessment of dietary soy concerning fertility-related outcomes. In the only clinical trial available, even if it is considered a pilot study, it emerges that a significant role could be played not only by isoflavones, but also by phytochemicals present in soy, particularly in black soy. Similar significant association was observed for peak luteal progesterone 10ng/ml (aOR: 140, 95% CI 100, 196, P=005). The beneficial efficacy of soy is often attributed to the presence of isoflavones, capable of mitigating the excesses of endogenous estrogens, through the competition with estrogen receptors or by the activation of receptors, in the presence of low levels of endogenous estrogens. Conversely, the improvements in ovulation were seen only in two patients from the control group. Individuals who are not equol-producers have likely limited response to isoflavone intake(16). These changes may have resulted in the mild, non-clinically relevant prolongation of menstrual cycle, as discussed in the previous section. How soy isoflavones help to induce ovulation Soy isoflavones have been found effective in inducing ovulation in women with irregular ovulation or anovulation. The consumption of soy over time, the possible use of certain foods considered healthy in seeking pregnancy or the willingness to avoid pregnancy could generate spurious associations. The advantages of observational cohort studies include longer times and wider population samples. 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. 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%). Polycystic ovary syndrome (PCOS) is a major endocrine and metabolic disorder in women(62,63). Following the removal of eighty-four duplicates, the selection was made through titles, abstracts and full-text reading. Furthermore, even at high concentrations, they did not show a clear influence on fertility. These aspects considerably reduce the reliability of results, favouring data misinterpretation. Instead, in the cohort study by Filiberto and colleagues, 259 American women were followed for at least 2 menstrual cycles. (2014), Higher urinary lignan concentrations in women but not men are positively associated with shorter time to pregnancy, Vanegas JC, Afeiche MC, Gaskins AJ, et al. In the previously mentioned meta-analysis by Hooper and colleagues(59), 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. The role of soy and soy isoflavones on women's fertility and related outcomes: an update eCollection 2022. 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. Available from: Messina M, Mejia SB, Cassidy A, et al. Furthermore, the search for sources has been extended to the single manuscripts reference lists. However, a clear effect on reproductive system has never been highlighted, especially due to the absence of observational studies designed for this purpose. 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)(33). 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. 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). However, the specific effect of soy intake on women's fertility has not yet been systematically evaluated. These alterations easily lead to hyperandrogenism and irregular menstrual cycles. (2000), Effects of soy foods on ovarian function in premenopausal women, Lu LJ, Anderson KE, Grady JJ, et al. Received 2022 Jan 30; Accepted 2022 Feb 7. They can bind G-protein-coupled estrogen receptor 1 (GPR30), with effects driven by both genomic and non-genomic regulation involving different cellular signalling pathways, such as intracellular increase of calcium or NO levels(75), as observed in human endothelial cells after stimulation with equol 100nM(76). Stay below 60 grams per day. FOIA Romualdi and colleagues in 2008 enrolled twelve Italian women with metabolic syndrome and PCOS and with a follow-up of 6 months using 36mg/d of oral genistein as an intervention(34). Using food frequency questionnaires, researchers found that women with high isoflavone intake ( 40 mg/day) had a 3% lower lifetime probability of giving birth to a live child compared to women with a low intake (< 10mg/day). Find technical definitions and synonyms by letter for drugs/agents used to treat patients with cancer or conditions related to cancer. Isoflavones concentrations did not show significant differences between participants at baseline. Soy and soy-derived products contain isoflavones that mimic the actions of oestrogens and may exert adverse effects on male fertility. I started taking 60mg every 12 hours (120mg daily) beginning the evening of CD2 and will finish the morning of CD8. Anni and Ashot Manukyan had spent several months unsuccessfully trying to get pregnant through IVF when they received a bewildering message this April . These also included non-soy derived phytoestrogens, such as lignans. The success of soy mainly depends on versatility and supposed healthy properties of soy foods and soy components. The standard guidelines for Clomid are to take it either on cycle days 3-7 or 5-9. There was no evaluation of dietary habits and the determination of hormone levels was performed using non-validated ELISA kits, due to limited budget. Many of its components show an antioxidant activity that can at least partially explain its effectiveness(9). 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;(10) nevertheless, soy isoflavones have attracted much attention in the last years for its estrogenic as well as non-hormonal properties(11). Furthermore, the type of dietary survey carried out in the proposed environmental questionnaire was not clear. Similar to the previous trial, the number of participants was limited. Participants were classified by ethnicity; however, the population sample size did not allow to perform stratification of outcomes based on this aspect. Fig. (2020), Soy isoflavones accelerate glial cell migration via GPER-mediated signal transduction pathway, Patel RP, Boersma BJ, Crawford JH, et al. Unfortunately, the work of Kohama et al. 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(28). Additionally, isoflavones can act as antioxidants in vitro (15), but the extent to which they contribute to the antioxidant status of humans is not yet clear. 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. They contain a plant-derived estrogen called isoflavones. Servier Medical Art. 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. It is widely used in eastern traditional cuisine and it has recently diffused among self-conscious and vegetarian diets. The hormonal improvement has been followed by clinical ameliorations such as the reduction of alopecia, serum insulin levels, HOMA-B (homeostasis model of assessment-B cell function) and HOMA-IR (homeostasis model of assessment-insulin resistance) index among patients in the intervention arm. The soy isoflavones block the estrogen receptors in your brain and fool your body into thinking its natural estrogen levels are low. In the second study by Lu and colleagues(29), 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). Only three articles declared power analysis to assess adequate sample size(30,43,46). 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.). (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. (2009), The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration, Moher D, Liberati A, Tetzlaff J, et al. Meanwhile, the possible influence on endocrine system, in particular by isoflavones, raised concerns among some researchers. (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. In the first study, the authors administered soy milk to six American women aged 2229 for 1 month, comparing outcomes with baseline(26). Additional considerations regarding hormonal influences will be discussed in the next paragraph. (2018), Bacterial metabolite S-equol modulates glucagon-like peptide-1 secretion from enteroendocrine L cell line GLUTag cells via actin polymerization. ; Several studies, of both animals and humans, have shown that soy protein supplementation containing . Most women taking soy isoflavones to induce ovulation take around 150-200 mg a day on cycle day 3 -7 or 5-9. The authors wish to thank Sandra De Dominici for language revision assistance. Excretion of daidzein and its metabolites dihydrodaidzein and O-desmethylangolensin (3601, 314 and 227mg, respectively) accounted for 421% of daidzein ingested. 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). Despite the sample size and full follow-up for endpoints evaluation, the study displays limitations. Choose any of these varieties. 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. The study did not evaluate circulating or urinary levels of isoflavones to verify the ability to metabolise isoflavones. Uses. The lack of variation in gonadotropins can explain the absence of variation in menstrual cycle. Thank God we tried it. National Library of Medicine Since there are no scientific studies on the effects of soy isoflavones and ovulation, these are just general guidelines. Furthermore, considering soy as a mere source of isoflavones is extremely reductive. (2021), Health beliefs, behavior, spiritual growth, and salvation in a global population of seventh-day adventists, A brief historical overview of the past two decades of soy and isoflavone research, Mumford SL, Steiner AZ, Pollack AZ, et al. 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). Notably, during manuscript preparation, Messina and colleagues published a technical review on endocrine effect of soy and isoflavones(90). Corrections for confounding factors, such as diet, demographics, lifestyle factors, age, body composition and ethnicity, indicated reliable analysis. There was no dose-response relation in either cohort. This phenomenon highlights how in literature there is greater attention to phytoestrogens and their effect, frequently underestimating the role of other components that have a marginal interest. 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(64). (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. Fertility is closely associated with menstrual cycle functions and a longer time to pregnancy is associated with shorter menstrual cycles(5658). I continued Intralipid after a positive and 2 more the next 2 months. There was a significant correlation between dietary soy consumption and fertilisation rate (77% v. 71%, P=0004), age-adjusted pregnancy (52% v. 41%, P=003) or age-adjusted live birth rate (44% v. 31%, P=0007) among soy consumers compared with non-consumers. (1998), Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta, Ropero AB, Alonso-Magdalena P, Ripoll C, et al. 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. On the other hand, many perplexities have been raised about possible negative mechanisms leading to endocrine disruptor effects(20). However, in the work of Filiberto and colleagues(37), even if the correlation between isoflavones and the increase in SHBG was highlighted, the dosage of estradiol and free estradiol did not show significant correlations, although the estimate of free estradiol was done through Sodergard's formula(61), so a direct dosage would be more reliable. (2020), Urinary phytoestrogens and relationship to menstrual cycle length and variability among healthy, eumenorrheic women, Haudum C, Lindheim L, Ascani A, et al. In the mid-1990s he was accused of transferring ova harvested from women . In particular, among selected studies, only the intervention study by Haudum and colleagues explored the stratification of participants for equol-competence(46). However, urinary phytoestrogen levels were only detected at baseline and this increased the correlation uncertainty. Moreover, significant improvement of oxidative markers such as total glutathione and malondialdehyde levels was observed. Furthermore, the intervention group showed lower rates of miscarriage (n: 2, 31% v. n: 6, 87%; P<005) and higher rates of pregnancy (n: 13, 200% v. n: 3, 44%; P<005) compared with placebo. Besides, the lack of a placebo group warrants caution. This, in turn, stimulates ovulation and can make you ready for pregnancy. These substances could play a role in the ovaries circulatory functions(50). 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. The https:// ensures that you are connecting to the The intervention period was extended only to one menstrual cycle. From the analysis of urinary excretion of isoflavones normalised for creatinine during the intervention with soy, Asian women had significantly greater excretion of isoflavones than non-Asian women. Bethesda, MD 20894, Web Policies The FFQ was not specifically designed for phytoestrogen assessment and this may have underestimated intakes. The chemical structure similarity between soy isoflavones and endogenous estrogens has always stimulated the attention for this class of compounds. An official website of the United States government. (2012), The utility of menstrual cycle length as an indicator of cumulative hormonal exposure, Vassena R, Vidal R, Coll O, et al. Soy can contain numerous other phytochemicals such as saponins, phytosterols, phytic acid, non-isoflavone flavonoids, peptides, protease inhibitors and other bioactive substances. However, in multiple regression analysis, this reduction seemed to be significantly associated with the intake of genistein and daidzein or their concentration in urine. SMART [Internet]. 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(53). It does not appear to be randomised and blinded, but the nature of outcomes should not be affected by these limitations. SHBG levels were not associated with the intake of soy foods, except in the case of miso intake on the 22nd day of cycle (r: 036, P=002). The authors declare that they have no conflicts of interest. Finally, they show antioxidant activity: a shared property among polyphenols(19). Rome, Italy, 3Department of Human Sciences and Promotion of the Quality of Life, San Raffaele Roma Open University, 00166 The obtained results were evaluated for duplicates and then screened for titles and abstracts information. There are many reasons for infertility among couples, including genetic . (2010), Non-isoflavone phytochemicals in soy and their health effects, Aulisa G, Binda C, Padua E, et al. (2016), 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, Mosallanezhad Z, Mahmoodi M, Ranjbar S, et al. 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. Messina, Italy, 2Laboratory of Cardiovascular Endocrinology, IRCCS San Raffaele Roma, 00166 Soy food and soy isoflavone intake were unrelated to sperm motility, sperm morphology or ejaculate volume. Adapted from SMART: Servier Medical Art(89). 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