Concerns that the phytoestrogens (isoflavones) in soy may feminize men continue to be raised. 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. The evaluation at two different times of menstrual cycle allowed to discriminate the effect between luteal and follicular phases but not day by day hormonal fluctuations. Soy isoflavones can help induce ovulation in such women. The power analysis concerning variation in isoflavone urinary excretion accounted for a sample size of 25 for >90% detection power. No changes were highlighted for DHEA, DHEAS, dihydrotestosterone (DHT) concentration or LH:FSH ratio. 44% of women of Asian descent were in the highest quartile of isoflavone intake. Participants were divided into four categories: non-consumers and tertiles of soy intake. 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. This suggests a protective effect of soy against fertility disturbance by BPA. Regarding the two mentioned studies, the use of very high amounts of isoflavones is noteworthy because it is not possible to obtain such a dose through diet, therefore the effects found can be interpreted as a pharmacological and not nutritional intervention. 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). 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. However, even in the West, it is currently widely used, especially due to its versatility in plant-based products for health purposes and vegetarian diets(Reference Rizzo and Baroni1). Total loading time: 0 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(Reference Lu, Anderson and Grady26,Reference Wu, Stanczyk and Hendrich28,Reference Lu, Anderson and Grady29) . Six grams per day of black soybean powder were administered to the intervention group, whereas thirty-four individuals received no treatment as a control group. Deepak Kumar, Komal Furthermore, the use of spot urine samples could generate an underestimation of urinary isoflavones quantification. 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. 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). 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. Consistent with the previously cited data, no significant alteration in the cycle length was found among participants following the intervention. 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(Reference Mumford, Sundaram and Schisterman39), while lignan concentrations in urine were significantly associated with shorter time to pregnancy. 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). "useRatesEcommerce": false 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. Similarly, a significant correlation between isoflavone intake and nulligravidity emerged (P=003) with a 13% higher risk but with a wide range of confidence interval (95% CI 2, 26) in women with intake 40mg/d compared with lower intakes (<10mg/d). Manuscripts exploring multiple aspects were discussed in different paragraphs, where deemed necessary. Uses. 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. Eating a few servings of soy each week could improve fertility and metabolic aspects of PCOS. Fertility is defined by the number of offspring produced by an individual. 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. Similar significant association was observed for peak luteal progesterone 10ng/ml (aOR: 140, 95% CI 100, 196, P=005). 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) . Get Twins Club Restaurant, Rancho Cucamonga, CA, USA setlists - view them, share them, discuss them with other Twins Club Restaurant, Rancho Cucamonga, CA, USA fans for free on setlist.fm! These conclusions cover several physiological aspects, including those concerning women's fertility, consistently with the conclusions of this review that highlighted nine additional articles compared with Messina's selection about the topic. The success of soy mainly depends on versatility and supposed healthy properties of soy foods and soy components. FSH levels were not significantly changed after genistein intervention. 1. Soya Isoflavones and Vitamins The Group for those Using, Abusing and thinking about taking over the counter items to boost fertility. and This is justified by the fact that the study was not designed for the specific assessment of dietary soy concerning fertility-related outcomes. View the latest deals on Natrol Menopause Support Supplements. Soy contains phytoestrogen, a plant-derived estrogen, known as isoflavones. M. A. S. contributed to drafting and revising the manuscript. Consequently, it is plausible that research efforts have been aimed at evaluating the effects of soy, especially isoflavones, on human fertility and hormonal regulation. Fig. Recently, in a prospective study by Levine et al., 326 American women eumenorrheic aged 1840 were followed for 12 months or until pregnancy(Reference Levine, Kim and Purdue-Smithe45). Furthermore, there was no characterisation of dietary regimen, although it was a standard hospital diet. The same authors admitted that they had no information on the type of soy used and about the last ingestion. 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. conducted another prospective cohort study on 239 American women undergoing assisted reproductive technology(Reference Chavarro, Mnguez-Alarcn and Chiu42). These aspects were poorly characterised by self-reporting of the participants. The reduction of estradiol concentrations observed became statistical marginal (89%, P=006) when analysis was restricted to the clean dataset: data after exclusion of thirteen specimens collected too soon or too late after ovulation. Pending further confirmation, soy and its components do not appear to have a clinically relevant influence on menstrual cycle in healthy women. Instead, in the cohort study by Filiberto and colleagues, 259 American women were followed for at least 2 menstrual cycles. Major equol production was associated with a reduction in androgens levels (total testosterone, free testosterone and androstenedione), in the whole cohort. From the sub-analysis by ethnic stratification, follicular SHBG levels were higher in non-Asians. 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. 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) . This allowed to exclude the already summarised articles in meta-analysis from a detailed discussion. The standard guidelines for Clomid are to take it either on cycle days 3-7 or 5-9. Furthermore, women with PCOS display a higher prevalence of hyperinsulinemia, dyslipidemia, insulin resistance and obesity compared to healthy population. 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). 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. This could be due to the scarcity of studies on the topic and the presence of few clinical trials, adequately designed to evaluate soy effect on fertility with consistent timing, with an adequate number of participants, blinding, and randomisation for physiological conditions and the presence of equol-producer individuals. Finally, they show antioxidant activity: a shared property among polyphenols(Reference Patel, Boersma and Crawford19). Smaoui, Slim Moreover, urinary concentrations seem to reflect the isoflavone intakes in a short time window. 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. Based on our literature search, we also identified two observational studies: a cross-sectional study published in 1997 by Nagata et al. Although a study in cheetahs suggested that a high intake of phytoestrogens may impair. 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. Similar to the previous trial, the number of participants was limited. Flowchart for studies selection. A list of the selected clinical studies with their characteristics is summarised in Table 1. It would have been useful to have retrospective information on soy consumption to assess the potential effect on previous fertility problems. No investigation into the individual's ability to absorb and use isoflavones from soy milk was performed. No significant differences were appreciated for free testosterone and DHEAS. 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 stratification by ethnicity and equol-producers may suggest the nature of interactions between soy and fertility. 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). 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. 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). However, the intakes of isoflavones in the studied cohorts were limited (range: 0331mg/d). In addition, full-text bibliographic lists from selected papers were screened to retrieve further relevant articles. Eleven interventional studies, eleven observational studies and one meta-analysis have been selected from the results of queries. Conversely, the improvements in ovulation were seen only in two patients from the control group. Not all isoflavones work in the same manner. In 2000, Wu et al. Other weak aspects of the population sample characterisation are given by a lack of stratification by ethnicity and equol-producers. The possible correlation between menstrual cycle length and soy does not seem convincing either. 2. 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) . In 2015, a longitudinal study found no differences in sexual organ development at 5 years of age between cow milk formula, breast milk and soy formula feeding(Reference Andres, Moore and Linam69). Higher soy products intake did not correlate with the rate of infertility. 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). Eating Places. However, among fertile individuals, it may have a neutral effect, as discussed in the previous paragraphs. Longer, not clinically relevant duration of menstrual bleeding (adjusted MD: 037d, 95% CI 006, 068), without differences in severity of menstrual flow was observed. For this reason, in clinical studies, the nationality and ethnicity of participants may be relevant for the assessment of potential conflicting effects of soy intake. 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). Days Soy Isoflavones were taken: 2-6 Dosage on those days: 120mg Side effects: bad: hot flushes, headaches, disturbed sleep. 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. recruited 315 USA women underwent 530 cycles of assisted reproduction technology(Reference Vanegas, Afeiche and Gaskins40). Table 1. However, levels of progesterone, estradiol, free estradiol, estrone and SHBG did not show significant differences. Adapted from Moher et al.(24). The evaluation of isoflavones circulating levels and their urinary excretion allowed to show a wide inter-individual variation of metabolic and absorption capacity. However, stratification for the control group or PCOS patients did not show a significant correlation between androgens and equol production. Fig. 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). 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 ). If we eat soy, do we keep the beneficial effects of the Mediterranean diet? Why did you take Soy Isoflavones: I had tried most other things so decided to be a guinea pig. Get company information for Twins Club, Inc. in RANCHO CUCAMONGA, CA. Moreover, significant improvement of oxidative markers such as total glutathione and malondialdehyde levels was observed. The study must be considered exploratory, because of the limited number of luteal phase deficiency cycles and a small number of fertility-related outcomes. 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 a logical perspective, the effect of soy cannot be attributed to the effect of its isoflavones alone. However, the number of participants was limited for a cross-sectional study, and dietary survey through frequency questionnaires in the absence of an assessment of blood or urine isoflavone levels could lead to uncertainty. 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). 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). Published online by Cambridge University Press: It is important to evaluate the levels of hormones that fluctuate during the cycle at several points. Despite the significant increase in FSH, LH and estradiol in both intervention arms, the endometrial thickness (assessed by transvaginal sonography) had a major improvement in the intervention group compared with placebo. However, this omission does not necessarily imply that the assessment has not been carried out. Following the removal of eighty-four duplicates, the selection was made through titles, abstracts and full-text reading. However, the evaluation of ability to absorb and metabolise isoflavones was lacking in the present study. Soy Isoflavones supplements and Fertility Infertility is a condition that prevents pregnancy despite having regular sexual intercourse with your partner for at least a year. 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). These alterations easily lead to hyperandrogenism and irregular menstrual cycles. No restrictions were applied using filters and results were collected from search engines by the inception through 4 April 2021. However, in the work of Filiberto and colleagues(Reference Filiberto, Mumford and Pollack37), 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(Reference Sdergrd, Bckstrm and Shanbhag61), so a direct dosage would be more reliable. Go. (Reference Nagata, Kabuto and Kurisu27) and a longitudinal study published in 2013 by Filiberto et al. Participants were classified by ethnicity; however, the population sample size did not allow to perform stratification of outcomes based on this aspect. (Reference Wu, Stanczyk and Hendrich28). Adapted from Moher, Main cellular mechanism for isoflavones. View all Google Scholar citations In addition, no significant changes in progesterone, LH or SHBG were found in the whole study sample. Adapted from SMART: Servier Medical Art, https://creativecommons.org/licenses/by/4.0/. WHAT IS IT? 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. . Participants recruited were seeking for pregnancy and this could have been a source of confounders. The study did not evaluate circulating or urinary levels of isoflavones to verify the ability to metabolise isoflavones. Finally, the authors made a detailed assessment of confounders (diet, ethnicity, age and BMI). 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. For this reason, they are classified as phytoestrogensplant-derived compounds with estrogenic activity (1). Soya Isoflavones are derived from soya beans. SMART [Internet]. 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) . There was no dose-response relation in either cohort. Microbial alpha diversity and glucose homeostasis improved in PCOS group after isoflavone intervention, resembling the control group profile at baseline. A weak, not clinically relevant effect has been highlighted on cycle length and hormonal status. 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. The researchers found that the isoflavones resulted in increased cell growth. 4 Center for Complementary Medicine, Department of Internal Medicine II, Faculty of Medicine, University of Freiburg, Freiburg, Germany. Publication types Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't MeSH terms 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. 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. Among the six women in the first clinical trial(Reference Lu, Anderson and Grady26), the intervention with soy also led to a significant reduction in dehydroepiandrosterone sulphate (DHEAS) levels (23%, P=003), an intermediary in estradiol synthesis. 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. The advantages of observational cohort studies include longer times and wider population samples. } However, the sampling during the various days of the cycle allowed a detailed characterisation of serum LH surge day. Flowchart for studies selection. Articles concerning reviews, case series, case studies, non-human studies, in vitro studies, studies on males, editorials, letters to editor, conference abstracts, book's chapters, non-English papers, studies with no-soy isoflavones and studies with outcomes not pertinent to fertility were excluded. 1 The FDA based this decision on clinical studies showing that at least 25 g of soy protein per day lowered . Table 2 summarises main limitations about the studies discussed. Nevertheless, a reduction in FSH levels was confirmed (SMD: 087IU/l, 95% CI 172, 002). 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). PMCID: PMC8922143. 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) . 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. Women who also have the problem of irregular periods can consume these isoflavones to get much-needed relief. 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(Reference Petrakis, Barnes and King25). Moreover, difficulties related to data collection about nutritional intakes were available, and individual reporting errors must be taken into account. 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). The adjustment for male partner intake of soy in the subgroup analysis did not change the association. M. L. contributed to drafting and revising the manuscript. Sampling involved synchronisation on the third day of menstrual cycle follicular phase, spontaneous or pharmacologically induced. 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. Render date: 2023-03-02T11:20:28.481Z Isoflavones are produced via a branch of the general phenylpropanoid pathway that produces flavonoid compounds in higher plants. 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. CA. 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. Metabolic, endocrine, inflammation, and oxidative stress . Regarding isoflavones, the equol metabolite derives from the precursor daidzein by the action of intestinal bacteria. However, results are questionable due to the lack of hormone level measurements or reproductive functions. A slight increase of approximately 1d (MD: 105, 95% CI 013, 197) was seen compared with the control, with no significant effects in the length of luteal and follicular phases. 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). Besides, the lack of a placebo group warrants caution. Soy isoflavones have also been found to inhibit tyrosine kinases (14), enzymes that play critical roles in the signaling pathways that stimulate cell proliferation. 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). The same type of soy phytoestrogen intervention was subsequently used by Unifer and colleagues in a second clinical trial on 213 infertile women undergoing in vitro fertilisation with embryo transfer cycles after intramuscular progesterone treatments (50mg/d) with or without (placebo) 1500mg/d of soy isoflavones intake(Reference Unfer, Casini and Gerli32). 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. Individuals who are not equol-producers have likely limited response to isoflavone intake(Reference Iino, Shimoyama and Iino16). The authors defined the unusual estradiol increase as erratic. On consumption, they increase estrogen production in a woman's body. 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A high intake of phytoestrogens may impair instead, in the present study population samples. analysis concerning variation isoflavone. Conducted another prospective cohort study on 239 American women undergoing assisted reproductive technology ( Nagata.