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). Despite the sample size and full follow-up for endpoints evaluation, the study displays limitations. 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. Jia, Liyan Other weak aspects of the population sample characterisation are given by a lack of stratification by ethnicity and equol-producers. Although this clinical trial showed the long-term effect of soy ingestion on serum hormone levels, it was a pilot study with a limited number of participants (fourteen premenopausal women). 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(Reference Setchell, Brown and Lydeking-Olsen17). These aspects considerably reduce the reliability of results, favouring data misinterpretation. 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)(Reference Kohama, Kobayashi and Inoue33). Soy can contain numerous other phytochemicals such as saponins, phytosterols, phytic acid, non-isoflavone flavonoids, peptides, protease inhibitors and other bioactive substances. 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(Reference Wu, Stanczyk and Hendrich28). 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. View the latest deals on Natrol Menopause Support Supplements. Presumably, treatment with pharmacological concentrations of soy phytoestrogens allows mitigating the negative effect of clomiphene citrate on endometrial tissue, thus facilitating embryo implantation. No changes in progesterone and SHBG concentrations from baseline were observed. However, the evaluation of ability to absorb and metabolise isoflavones was lacking in the present study. 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) . Women who also have the problem of irregular periods can consume these isoflavones to get much-needed relief. There is a limited trend in estradiol reduction related to soy consumption; however, in their interventional study, Petrakis and colleagues observed an unusual increase of estradiol levels(Reference Petrakis, Barnes and King25). Furthermore, from the multiple regression analysis of ten women in the second trial(Reference Lu, Anderson and Grady29), 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. Similar to the previous observational study, Chavarro 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). 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. Several studies and case-reports describing feminizing effects including lowering testosterone levels and raising estrogen levels in men have been published. 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). Published online by Cambridge University Press: Measurement of urinary isoflavones and their metabolites appears to be a more reliable approach than dietary assessment alone. Soy isoflavones have also been found to inhibit tyrosine kinases (14), enzymes that play critical roles in the signaling pathways that stimulate cell proliferation. RANCHO CUCAMONGA. Adapted from Moher et al.(24). Improvements were observed only in lipid profile (circulating total cholesterol, LDL and LDL/HDL ratio and triglycerides). Consequently, it is plausible that research efforts have been aimed at evaluating the effects of soy, especially isoflavones, on human fertility and hormonal regulation. It does not appear to be randomised and blinded, but the nature of outcomes should not be affected by these limitations. conducted another prospective cohort study on 239 American women undergoing assisted reproductive technology(Reference Chavarro, Mnguez-Alarcn and Chiu42). 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. 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. Sampling involved synchronisation on the third day of menstrual cycle follicular phase, spontaneous or pharmacologically induced. 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. Find company research, competitor information, contact details & financial data for Lucky Twins Distribution of Rancho Cucamonga, CA. However, levels of progesterone, estradiol, free estradiol, estrone and SHBG did not show significant differences. Eleven interventional studies, eleven observational studies and one meta-analysis have been selected from the results of queries. The authors found no significant differences in reproductive outcomes (missed menstrual periods, pregnancy, live births, abortions, miscarriages, full-term deliveries, preterm deliveries, etc.) Moreover, isoflavones act as selective estrogen receptor modulators (SERMs) showing both agonist and antagonist effects on ER, with subsequent estrogenic, anti-estrogenic or even neutral effects(Reference Liu, Li and Chen14). Patients showed plasma androgens levels above or at the upper limit the normal range, at baseline. However, stratification for the control group or PCOS patients did not show a significant correlation between androgens and equol production. Unfortunately, the work of Kohama et al. 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. 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). The authors highlighted a marginal reduction of luteal phase in the adjusted multivariable model for an increase of 10mg/d of dietary isoflavones (aOR: 138, 95% CI 099, 192, P=006), identified by monitoring LH levels in urine by a fertility monitor and 4-d per cycle 24-h dietary recalls. However, the mechanisms underlying isoflavones effects on human health are manifold. It is important to evaluate the levels of hormones that fluctuate during the cycle at several points. Green, Eulalee 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. No investigation into the individual's ability to absorb and use isoflavones from soy milk was performed. 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. 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) . Soy consumption was not related to estradiol levels or endometrial thickness. Furthermore, even at high concentrations, they did not show a clear influence on fertility. Likewise, equol-producers showed lower AMH levels in the whole cohort as well as in participants in PCOS or control groups. 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;(Reference Kang, Badger and Ronis10) nevertheless, soy isoflavones have attracted much attention in the last years for its estrogenic as well as non-hormonal properties(Reference Aulisa, Binda and Padua11). 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. United States California As expected, women with the highest soy consumption were more likely to be of Asian descent. For this reason, the clinical data were meta-ana SMART [Internet]. 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(Reference Ferk, Teran and Gersak64). Finally, twelve entries were identified and ten additional articles were obtained after the consultation of full-text bibliographic lists. Most women taking soy isoflavones to induce ovulation take around 150-200 mg a day on cycle day 3 -7 or 5-9. Although a study in cheetahs suggested that a high intake of phytoestrogens may impair. Despite adjustments for demographic, lifestyle, dietary factors, including ethnicity and other phytoestrogens, it would have been useful to check the dietary intake of isoflavones for equol-producers evaluation. The authors found that consuming moderate amounts of traditionally . Soy is a very popular food and its consumption is part of the traditional cuisine of South-East Asian countries. 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.). The obtained meta-analysis was included in the final summary because it assessed aspects relating to the topic of this review. There was no evaluation of dietary habits and the determination of hormone levels was performed using non-validated ELISA kits, due to limited budget. The present study used a community-based approach with recruitment of couples seeking pregnancy. The strength of these studies was the assessment of hormone levels based on the menstrual cycle phase. 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 Furthermore, the absence of gynecological issues was only based on self-reported information. Since there are no scientific studies on the effects of soy isoflavones and ovulation, these are just general guidelines. 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 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). Table 2 summarises main limitations about the studies discussed. 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. We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings. Zhang, Yuehui Han, Jing The authors responsibilities were as follows: G. R. study conception and drafting the manuscript. Consistent with the previously cited data, no significant alteration in the cycle length was found among participants following the intervention. In this context, the evaluation of urine samples cannot be underestimated as a valuable tool for detection of the real bioavailability of isoflavones whose metabolisation requires the intervention of intestinal microbiota. 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) . Independent Researcher, Via Venezuela 66, 98121Messina, Italy, Laboratory of Cardiovascular Endocrinology, IRCCS San Raffaele Roma, 00166Rome, Italy, Department of Human Sciences and Promotion of the Quality of Life, San Raffaele Roma Open University, 00166Rome, Italy, Center for Complementary Medicine, Department of Internal Medicine II, Faculty of Medicine, University of Freiburg, Freiburg, Germany, Reference Mosallanezhad, Mahmoodi and Ranjbar, Reference Setchell, Brown and Lydeking-Olsen, Reference Hamilton-Reeves, Vazquez and Duval, Reference Reed, Camargo and Hamilton-Reeves, Reference Oyawoye, Abdel Gadir and Garner, Reference Mumford, Sundaram and Schisterman, Reference Jacobsen, Jaceldo-Siegl and Knutsen, Reference Crawford, Pritchard and Herring, Reference Andrews, Schliep and Wactawski-Wende, Reference Sdergrd, Bckstrm and Shanbhag, Reference Escobar-Morreale, Luque-Ramrez and Gonzlez, Reference Showell, Mackenzie-Proctor and Jordan, Reference Romualdi, Costantini and Campagna, Reference Chavarro, Mnguez-Alarcn and Chiu, Reference Sinai, Ben-Avraham and Guelmann-Mizrahi, Reference Ropero, Alonso-Magdalena and Ripoll, Reference Valles, Dolz-Gaiton and Gambini, Reference Gunnarsson, Ahnstrm and Kirschner, Soy, soy foods and their role in vegetarian diets, Consumption of soy foods and isoflavones and risk of type 2 diabetes: a pooled analysis of three US cohorts, Cumulative meta-analysis of the soy effect over time, 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, 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, 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, Non-isoflavone phytochemicals in soy and their health effects. Isoflavones are plant-based compounds found almost exclusively in beans, like soybeans, that mimic the action of the hormone estrogen. Flowchart for studies selection. 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. Qin, Zhen This was a short pilot study with a small sample size in subgroups. This allowed to exclude the already summarised articles in meta-analysis from a detailed discussion. 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. Soybeans are the most common source of isoflavones in human food; the major isoflavones in soybean are genistein and daidzein. 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) . However, the association between soy and isoflavones with the reduction of luteal phase seems weak. No changes were highlighted for DHEA, DHEAS, dihydrotestosterone (DHT) concentration or LH:FSH ratio. 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). 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. Soy protein has gained considerable attention for its potential role in improving risk factors for cardiovascular disease (CVD). 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). From the sub-analysis by ethnic stratification, follicular SHBG levels were higher in non-Asians. However, urinary phytoestrogen levels were only detected at baseline and this increased the correlation uncertainty. The authors found an association between pregnancy outcomes and urinary Bisphenol A (BPA), dependent on soy consumption in the multivariable-adjusted mixed model. Reduction of luteal phase seems weak mg a day on cycle day 3 -7 or 5-9 levels on. On the effects of soy isoflavones to get much-needed relief by ethnicity and equol-producers another prospective study... Between androgens and equol production cycle day 3 -7 or 5-9 blinded but... 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