There was no relationship between isoflavone intake and reported problems becoming pregnant. 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). Overall, a trend toward improvement can be appreciated but further studies are necessary to confirm the beneficial effect. 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. 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. The same authors admitted that they had no information on the type of soy used and about the last ingestion. Find company research, competitor information, contact details & financial data for Lucky Twins Distribution of Rancho Cucamonga, CA. They evaluated the hormonal variations during menstrual cycle through the composite construct that considered the cumulative information of the day of menstrual cycle for specimens. Likewise, equol-producers showed lower AMH levels in the whole cohort as well as in participants in PCOS or control groups. 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. Soy contains phytoestrogen, a plant-derived estrogen, known as isoflavones. 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). 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. In the first of the two papers by Lu and colleagues(Reference Lu, Anderson and Grady26), the intake of 36 Oz/d of soy milk (~200mg/d IF) for 1 month caused a reduction in mean estradiol levels of 31% at days 57, P=009; 81% at days 1214, P=003; 49% at days 2022, P=002, compared with the baseline. Get the latest business insights from Dun & Bradstreet. hasContentIssue true, Proposed mechanisms of isoflavones action, This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (, Copyright The Author(s), 2022. How soy isoflavones help to induce ovulation Soy isoflavones have been found effective in inducing ovulation in women with irregular ovulation or anovulation. Keywords were searched in titles and abstracts and combined with MeSH terms, where available, adapting the query format based on the search engine used. The article processing charge was funded by the Baden-Wuerttemberg Ministry of Science, Research and Art and the University of Freiburg in the funding programme Open Access Publishing. 2022. 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). 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. 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. Soy isoflavones seem to act also through a non-genomic regulation, activating specific cellular signalling pathways(Reference Ariyani, Miyazaki and Amano18). Regarding isoflavones, the equol metabolite derives from the precursor daidzein by the action of intestinal bacteria. Based on this cross-sectional study, high consumption of soy isoflavones was identified (94% of participants). Has data issue: true In particular, among selected studies, only the intervention study by Haudum and colleagues explored the stratification of participants for equol-competence(Reference Haudum, Lindheim and Ascani46). The study must be considered exploratory, because of the limited number of luteal phase deficiency cycles and a small number of fertility-related outcomes. However, the association between soy and isoflavones with the reduction of luteal phase seems weak. 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(Reference Choung, Baek and Kang49). However, urinary phytoestrogen levels were only detected at baseline and this increased the correlation uncertainty. Moreover, urinary concentrations seem to reflect the isoflavone intakes in a short time window. (As part of this process, a group of eggs matures so that one will be ready for release during ovulation .) Regarding observational studies, in 2015 Andrews and colleagues conducted a prospective cohort study on 246 American women with normal menstrual cycle, aged 1844 and with 13% of participants of Asian ethnicity, for a follow-up of 12 whole menstrual cycles(Reference Andrews, Schliep and Wactawski-Wende41). Furthermore, the individuals recruited were seeking for a pregnancy and this could have changed their behaviour. After the soy intervention, the length of menstrual cycle marginally increased (from 28319 to 31851d, P=006). However, the specific effect of soy intake on women's fertility has not yet been systematically evaluated. From the sub-analysis by ethnic stratification, follicular SHBG levels were higher in non-Asians. was a pilot study without a characterisation of diet among participants and without data on soy composition (isoflavone or antioxidant contents). Review the D&B Business Directory at DandB.com to find more. Participants were divided into four categories: non-consumers and tertiles of soy intake. 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). FSH levels were not significantly changed after genistein intervention. PMID: 35320928. Legumes, particularly soybeans, are the richest . 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. Furthermore, the use of spot urine samples could generate an underestimation of urinary isoflavones quantification. A total of 834 entries were obtained following search engine queries (PubMed: 381; ScienceDirect: 392; Cochrane Library Trials: 30 and ClinicalTrials.gov: 31). 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). Main cellular mechanism for isoflavones. Women who also have the problem of irregular periods can consume these isoflavones to get much-needed relief. These aspects were poorly characterised by self-reporting of the participants. Individuals who are not equol-producers have likely limited response to isoflavone intake(Reference Iino, Shimoyama and Iino16). 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) . Furthermore, there was no evaluation of metabolic utilisation capacity of isoflavones and their absorption by measuring serum and urinary levels. Longer, not clinically relevant duration of menstrual bleeding (adjusted MD: 037d, 95% CI 006, 068), without differences in severity of menstrual flow was observed. Phytoestrogens can modulate endogenous hormones at micromolar concentrations by influencing the expression of the enzymes cytochrome P450 19 aromatase (Cyp19), 17-hydroxysteroid dehydrogenase (17-HSD) and 3-hydroxysteroid dehydrogenase (3-HSD), steroid sulfatases (STS) and sulfotransferases (SULTs), enzymes of steroid biosynthetic pathway(Reference Rice and Whitehead80Reference Whitehead and Rice82). Studies have also shown that soybeans contribute towards lower levels of cholesterol, less risk of heart disease, breast cancer, and osteoporosis and fewer menopausal symptoms. On the other hand, many perplexities have been raised about possible negative mechanisms leading to endocrine disruptor effects(Reference Bar-El and Reifen20). Most women taking soy isoflavones to induce ovulation take around 150-200 mg a day on cycle day 3 -7 or 5-9. In response, your body starts a cascade of events to boost estrogen production. 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. These enzymes convert estrone and androstenedione into estrogen and testosterone(Reference Gunnarsson, Ahnstrm and Kirschner83,Reference Thompson and Siiteri84) . Although this was a randomised, placebo-controlled and double-blinded trial with a sample size appropriate to the power of detection, there was no evaluation of serum and urinary levels of isoflavones and/or metabolites. Similarly, the stratification by ethnicity and equol-producers may suggest the nature of interactions between soy and fertility. Fertility is defined by the number of offspring produced by an individual. These aspects considerably reduce the reliability of results, favouring data misinterpretation. Major equol production was associated with a reduction in androgens levels (total testosterone, free testosterone and androstenedione), in the whole cohort. Get company information for Twins Club, Inc. in RANCHO CUCAMONGA, CA. The authors found that consuming moderate amounts of traditionally . In another study, women were more likely to get pregnant if they ate soy isoflavones alongside . These alterations easily lead to hyperandrogenism and irregular menstrual cycles. The length of menstrual cycle may represent an indirect marker of ovarian function and reproductive health(Reference Mumford, Steiner and Pollack54,Reference Vassena, Vidal and Coll55) . Interest in soy is particularly driven by its possible beneficial effects on human health. In the first study, the authors administered soy milk to six American women aged 2229 for 1 month, comparing outcomes with baseline(Reference Lu, Anderson and Grady26). The advantages of observational cohort studies include longer times and wider population samples. 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) . Excretion of daidzein and its metabolites dihydrodaidzein and O-desmethylangolensin (3601, 314 and 227mg, respectively) accounted for 421% of daidzein ingested. 4 Center for Complementary Medicine, Department of Internal Medicine II, Faculty of Medicine, University of Freiburg, Freiburg, Germany. Correction for covariates included demographics, education, income, lifestyle, dietary and behavioural factors. The two observational studies also show different limitations, in particular, one of these studies uses a follow-up of only 2 months. 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. Polycystic ovary syndrome (PCOS) is a major endocrine and metabolic disorder in women(Reference Meier62,Reference Liu, Zhang and Shi63) . Despite the sample size and full follow-up for endpoints evaluation, the study displays limitations. Servier Medical Art. Soy isoflavones can help induce ovulation in such women. 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. For these reasons, results should be interpreted with caution. We use cookies to distinguish you from other users and to provide you with a better experience on our websites. The interaction between isoflavones and ER estrogen receptor results in a competitive effect which in turn blunts endogenous estrogens action(Reference Rosselli, Reinhart and Imthurn72), as suggested by estrogenic activity of biochanin A and genistein on BT-474 human breast cancer(Reference Zand, Jenkins and Diamandis73). Table 2 summarises main limitations about the studies discussed. However, among fertile individuals, it may have a neutral effect, as discussed in the previous paragraphs. 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. Finally, they show antioxidant activity: a shared property among polyphenols(Reference Patel, Boersma and Crawford19). A weak, not clinically relevant effect has been highlighted on cycle length and hormonal status. Choose any of these varieties. Adapted from SMART: Servier Medical Art(89). Fig. The power analysis concerning variation in isoflavone urinary excretion accounted for a sample size of 25 for >90% detection power. 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. As for males, a 2010 meta-analysis highlighted the safety of soy on fertility outcomes(Reference Hamilton-Reeves, Vazquez and Duval21), recently confirmed by an updated meta-analysis on this topic(Reference Reed, Camargo and Hamilton-Reeves22). No changes in progesterone and SHBG concentrations from baseline were observed. 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. Recently, Wesselink and colleagues evaluated the fertility of 7778 healthy American or Canadian women in two cohort studies that followed participants for 12 months or until pregnancy(Reference Wesselink, Hatch and Mikkelsen44). Consequently, it is plausible that research efforts have been aimed at evaluating the effects of soy, especially isoflavones, on human fertility and hormonal regulation. 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. 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. Additional considerations regarding hormonal influences will be discussed in the next paragraph. However, the number of combined participants of the two studies was very limited (n: 40). In 2000, Wu et al. A total number of twenty-two experimental articles plus a meta-analysis was used for the final synthesis. The use of surveys only through self-administered questionnaires, although validated, is easily exposed to self-reporting errors or incompleteness and misclassifications derived from the database used for food intake quantification. In October 1999, the US Food and Drug Administration (FDA) approved labeling for foods containing soy protein as protective against coronary heart disease. 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(Reference Basu and Maier12). 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) . Such shorter menstrual cycle length seemed not clinically relevant because shorter than 1d. Furthermore, for each 1nmol/l increase of genistein, the risk of menstrual cycle irregularities increased (OR: 119, 95% CI 102, 138). No changes were highlighted for DHEA, DHEAS, dihydrotestosterone (DHT) concentration or LH:FSH ratio. However, a suggestive positive influence has been shown among women with fertility issues and during assisted reproductive technologies. 1. Isoflavones also show effects that do not imply ER and ER involvement. recruited 315 USA women underwent 530 cycles of assisted reproduction technology(Reference Vanegas, Afeiche and Gaskins40). 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. Regulation, activating specific cellular signalling pathways ( Reference Gunnarsson, Ahnstrm and Kirschner83, Reference Thompson and ). The correlation uncertainty detection power and without data on soy composition ( isoflavone or antioxidant contents.! University of Freiburg, Germany, because of the two studies was limited... Group of eggs matures so that one will be ready for release during ovulation. follicular SHBG levels were detected. 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