Miso intake was inversely associated with SHBG levels. The present study used a community-based approach with recruitment of couples seeking pregnancy. 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. Four papers were found about assisted reproduction technology, two of which were interventional studies by Unifer and colleagues, using high intakes of soy phytoestrogens as adjuvant(31,32). The disease etiology is still debated but it seems to involve inflammatory mechanisms and oxidative stress(65,66). The evaluation of isoflavones circulating levels and their urinary excretion allowed to show a wide inter-individual variation of metabolic and absorption capacity. Fig. (2001), Exposure to soy-based formula in infancy and endocrinological and reproductive outcomes in young adulthood, Unfer V, Casini ML, Costabile L, et al. 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. 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). (2006), Rapid endocrine disruption: Environmental estrogen actions triggered outside the nucleus, Rowlands DJ, Chapple S, Siow RCM, et al. The only study found about the effect of exposure to soy in childhood and reproductive functions is the retrospective study by Strom and colleagues(30). Soy contains numerous phytochemicals that can be responsible for these positive effects through multiple mechanisms. I usually. Black soy, in addition to the content of isoflavones, is known to be rich in antioxidant substances, especially in external seed integuments, which are rich in anthocyanins(49). Let me join the club of Soy babies! If you're trying to conceive, you should eat soy-based foods in moderation. 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. Recent research suggests that consumption of soy may have a more . 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. (2014), Soy isoflavone intake and the likelihood of ever becoming a mother: the adventist health study-2, Mumford SL, Sundaram R, Schisterman EF, et al. recruited 315 USA women underwent 530 cycles of assisted reproduction technology(40). A list of the selected clinical studies with their characteristics is summarised in Table 1. When it comes to heart health, soy protein is beneficial in lowering LDL cholesterol without an unfavorable effect on HDL cholesterol or triglycerides. Main cellular mechanism for isoflavones. 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%). An official website of the United States government. SMART [Internet]. Servier Medical Art. 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(43). Choose any of these varieties. (1998), Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta, Ropero AB, Alonso-Magdalena P, Ripoll C, et al. A total number of twenty-two experimental articles plus a meta-analysis was used for the final synthesis. 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(74). In addition, no significant changes in progesterone, LH or SHBG were found in the whole study sample. 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. (2020), Impact of short-term isoflavone intervention in polycystic ovary syndrome (PCOS) patients on microbiota composition and metagenomics, Fecundity and natural fertility in humans, Choung MG, Baek IY, Kang ST, et al. 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). The obtained results were evaluated for duplicates and then screened for titles and abstracts information. 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). The site is secure. Isoflavones are non-steroidal compounds with a chemical structure similar to endogenous estrogens and for this reason, they are defined as phytoestrogens: a functional classification that also includes lignans, coumestans and stilbenes(12). M. A. S. contributed to drafting and revising the manuscript. A weak, not clinically relevant effect has been highlighted on cycle length and hormonal status. Furthermore, the use of spot urine samples could generate an underestimation of urinary isoflavones quantification. This allowed to exclude the already summarised articles in meta-analysis from a detailed discussion. Among selected prospective cohort studies, in 2012 Jarrell and colleagues conducted an observational study of 323 Canadian women with late pregnancy (aged at least 35) followed from the second month of pregnancy until delivery(36). Major equol production was associated with a reduction in androgens levels (total testosterone, free testosterone and androstenedione), in the whole cohort. 1. However, ethnicity was not used for outcomes stratification. From the general linear model of the analysis of covariance, the intervention with soy reduced free androgen index (0020005 v. +0010005, P<0001), total testosterone (01005 v. +01005ng/ml, P=0008) and increased SHBG levels (+4008 v. 1408nmol/l, P<0001) compared with placebo (adjusted for baseline values). The clinical trial was limited to a small sample size, lacking of control/placebo group and there was no characterisation of equol-competence. The two observational studies also show different limitations, in particular, one of these studies uses a follow-up of only 2 months. (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. (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. The chemical structure similarity between soy isoflavones and endogenous estrogens has always stimulated the attention for this class of compounds. I continued Intralipid after a positive and 2 more the next 2 months. Similar to the previous trial, the number of participants was limited. Individuals who are not equol-producers have likely limited response to isoflavone intake(16). The authors wish to thank Sandra De Dominici for language revision assistance. These types of products contain phytoestrogens in much higher concentrations than traditional whole-food sources. Soy has been used to treat certain symptoms of menopause (such as hot flashes) and to help prevent bone loss ( osteoporosis ).Some supplement products have been found to contain possibly . Flowchart for studies selection. Isoflavones also bind to ER receptor, albeit with lower affinity. Consequently, it is plausible that research efforts have been aimed at evaluating the effects of soy, especially isoflavones, on human fertility and hormonal regulation. However, the specific effect of soy intake on women's fertility has not yet been systematically evaluated. Soy is a key food in human nutrition. (2018), Bacterial metabolite S-equol modulates glucagon-like peptide-1 secretion from enteroendocrine L cell line GLUTag cells via actin polymerization. Discuss all supplements you are taking with your care team. Live birth odds in the multivariable-adjusted analysis was higher among women in the second tertile of soy intake, consuming 264755mg/d of soy isoflavones (OR: 187; 95% CI 112, 314) and among women in the third tertile of soy intake, consuming 7562789mg/d of isoflavones (OR: 177; 95% CI 103, 303) compared with no consumption, but without a significant linear trend. The urinary or serum levels of isoflavones did not affected progesterone levels in the multiple regression analysis. Nynca A, Sadowska A, Orlowska K, et al. However, the association between soy and isoflavones with the reduction of luteal phase seems weak. 2 highlights the main cellular mechanisms attributed to isoflavones. On the other hand, many perplexities have been raised about possible negative mechanisms leading to endocrine disruptor effects(20). Ricardo Hector Asch (born 26 October 1947) is an obstetrician, gynecologist, and endocrinologist.He worked with reproductive technology and pioneered gamete intrafallopian transfer (GIFT), as well as working on research linking fertility and marijuana usage, and investigated the use of GnRH analogues with Andrew Schally. [cited 2021 Jul 26]. Isoflavones concentrations did not show significant differences between participants at baseline. Reduced E2 levels in follicular phase but not in the luteal phase. 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). (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. Finally, twelve entries were identified and ten additional articles were obtained after the consultation of full-text bibliographic lists. The FFQ was not specifically designed for phytoestrogen assessment and this may have underestimated intakes. Thank God we tried it. No restrictions were applied using filters and results were collected from search engines by the inception through 4 April 2021. 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). Finally, they show antioxidant activity: a shared property among polyphenols(19). Regarding isoflavones, the equol metabolite derives from the precursor daidzein by the action of intestinal bacteria. (2000), Effects of soy foods on ovarian function in premenopausal women, Lu LJ, Anderson KE, Grady JJ, et al. In addition, other studies investigated the urinary concentrations of isoflavones and metabolites, including equol(39,45). 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. Fertility is defined by the number of offspring produced by an individual. Genistein treatment reduced LDL cholesterol and triglycerides levels. Notably, these latter compounds are present in several foods such as legumes, cereals and seeds, whereas soy is almost the only source of isoflavones in human diet. Only three articles declared power analysis to assess adequate sample size(30,43,46). 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 is especially true for vegetarian women. Uses. Eating a few servings of soy each week could improve fertility and metabolic aspects of PCOS. 1. These clinical trials had several strengths including the presence of a placebo group, randomisation, double-blinding and recruitment of a wide number of participants. Participants recruited were seeking for pregnancy and this could have been a source of confounders. For example, it should be identified whether the interest is related to pharmacological effect, thus implying the use of high concentrations of soy components, or if the aim is to investigate soy functional effects that can be obtained mimicking eating habits, thus providing soy foods with realistic intake levels. However, soy diet reduced progesterone (45%, P<00001) and estradiol levels (23%, P<001), compared with baseline. FOIA I started taking 60mg every 12 hours (120mg daily) beginning the evening of CD2 and will finish the morning of CD8. In addition, non-English papers could have provided relevant data on the topic, especially those from countries with a more consistent history of soy consumption. In the ten women who participated in the second study(29), there were no significant changes in the levels of luteinizing and follicle-stimulating hormones. Besides, the lack of a placebo group warrants caution. The standard guidelines for Clomid are to take it either on cycle days 3-7 or 5-9. From the data obtained, diet isoflavones do not seem to have a direct effect on fertility, whether positive or negative. Despite the sample size and full follow-up for endpoints evaluation, the study displays limitations. 2023-03-29. 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). Isoflavones also show effects that do not imply ER and ER involvement. Furthermore, phytoestrogens appear to act on SHBG synthesis by altering mRNA levels in hepatocarinoma human cells treated with genistein 20M(85), and modulating the balance between bound and free steroids or competing with endogenous sex hormones for the active site binding of the carrier(86). Although isoflavones can be found in many foods, not soy foods can be considered negligible sources of these compounds. 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). However, urinary phytoestrogen levels were only detected at baseline and this increased the correlation uncertainty. Among the six women in the first clinical trial(26), the intervention with soy also led to a significant reduction in dehydroepiandrosterone sulphate (DHEAS) levels (23%, P=003), an intermediary in estradiol synthesis. (1999), Xenoestrogen interaction with human sex hormone-binding globulin (hSHBG), Inhibition of tumor promoter-induced hydrogen peroxide formation in vitro and in vivo by genistein, Morton MS, Arisaka O, Miyake N, et al. 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. 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. 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. The role of soy and soy isoflavones on women's fertility and related outcomes: an update eCollection 2022. 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. government site. 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 lack of variation in gonadotropins can explain the absence of variation in menstrual cycle. The authors defined the unusual estradiol increase as erratic. Authors Gianluca Rizzo 1 , Alessandra Feraco 2 3 , Maximilian Andreas Storz 4 , Mauro Lombardo 3 Affiliations 1 Independent Researcher, Via Venezuela 66, 98121 Messina, Italy. It would have been useful to have retrospective information on soy consumption to assess the potential effect on previous fertility problems. Interest in soy is particularly driven by its possible beneficial effects on human health. Conversely, the improvements in ovulation were seen only in two patients from the control group. (2000), Decreased ovarian hormones during a soya diet: Implications for breast cancer prevention, Strom BL, Schinnar R, Ziegler EE, et al. One in vitro study reveals that genistein (a soy isoflavone) increases the growth of estrogen-dependent breast cancer cells. 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