The post-menopausal period reportedly can be associated with some consequences such as glucose tolerance and increase insulin resistance. Approximately 20% of women in the age range of 55 to 65 years are suffering from impaired glucose tolerance and diabetes mellitus that face this group with developing cardiovascular disease (CVD) [1]. The impaired quality of life and even subsequently mortality can occur following the glucose metabolism disorders [2]. One of the most widely used therapeutic approaches in this regard is hormone replacement therapy (HRT) that has been always accompanied with determined adverse effects such as CVD, weight loss, elevated insulin-sensitivity and impaired blood lipid profiles [13]. Many women in treatment now decided to discontinue HRT due to a general misconception about the relationship between hormones and cancer, as well as many of the benefits of phytoestrogens advertised by trading companies relying on minimal scientific information. Hence, the increasing tendency of postmenopausal women toward compounds containing phytoestrogens as complementary and alternative medicine is clearly visible in this backward trend [4]. There are four main classes in various phytoestrogen compounds, including isoflavonoids, flavonoids, coumestans, and mammalian lignans [5]. The structure and chemical nature of the isoflavones are closely similar to estradiol (E2) as the phytoestrogens are able to match with estrogen receptors [4], but their effects physiologically are greatly less than E2 [5]. Previous systematic reviews and meta-analyses have found controversial results regarding the effect of isoflavones on the glucose metabolism [126]. Therefore, there is further need for overview of systematic reviews to draw a definite conclusion.

Process of selecting review is showed in Figure 1. Table 1 showed characteristic of 4 meta-analysis include in over view. Table 2 also showed methodological quality assessment of systematic reviews using the AMSTAR rating.

The purpose of the current overview was to summarize and critically assess the effect of isoflavones and genistein on glucose metabolism among peri- and post-menopausal women. HOMA-IR value and fasting insulin levels were significantly lower in studies used either isoflavones or genistein compared to placebo. Two meta-analyses showed that treatment with isoflavones could not alter fasting blood glucose [26]. However, one of meta-analyses suggested that isoflavones significantly improved blood glucose levels in non-Asian post-menopausal women [8]. We found a discrepancy between mrta anlysis and meta-analyses included to current study. One of the reasons can be attributed to the differences in various methodological and statistical aspects to report findings among the selected trials conducted on non-Asian versus mixed populations reviewed in our meta-analysis.

Several studies have been performed to detect potential mechanisms of the effect of isoflavones on glucose metabolism. For example, the soy in diet can improve the insulin sensitivity due to incremental glucose uptake by skeletal muscles [9]. In-vitro studies showed that several mechanisms of action may involve in the effect of soy on the glucose metabolism, such as an inhibitory action of tyrosine kinase, changes in the number of insulin receptor, impaired glucose transport and intracellular phosphorylation [6]. Villa et al. [10] divided 54 postmenopausal women into two groups of receiving 54 mg/day of genistein and placebo. Genistein affected significantly the glycoinsulinemic metabolism. They also performed a subgroup analysis in the patients of genistein group based on hyperinsulinemic and normoinsulinemic subjects. Their results revealed that glycemic indexes were improved in hyperinsulinemic group [10].

The current overview has several limitations that should be discussed. There were moderate to high heterogeneities in all reviews included to our overview. Based on AMSTAR criteria, at least two databases must be searched, and graphical plot should be drown in combination with statistical test when reporting publication bias. One of the studied reviews only searched one database and some of meta-analyses evaluated neither Begg's nor Egger's tests in combination with graphical plot. Hence, the publication bias might affect their studies. List of included and excluded studies were not reported in two out of four reviews. Moreover, none of authors of systematic reviews stated whether they include grey literature. Future systematic review and meta-analyses should be well designed to meet AMSTAR criteria.

Regardless of population, the treatment with genistein is effective on improving fasting insulin, HOMA-IR and glucose levels. Nevertheless, the high heterogeneity among studies and poor methodology of reviews make it difficult to draw a definite conclusion on the positive impacts of soy on glucose metabolism.