Polycystic ovary syndrome (PCOS), a hormonal and metabolic disorder manifested in women of reproductive age, is still being treated using drugs with side effects. As an alternative to these drugs, isoflavone, also identified as phytoestrogen, has anti-PCOS activity. Isoflavone can help relieve PCOS symptoms by lowering the level of testosterone, which causes hyperandrogenism, thereby normalizing the menstrual cycle and restoring normal ovarian morphology. Furthermore, isoflavone influences the improvement of the metabolic profile, which changes because of PCOS, as well as the reduction of inflammatory markers and oxidative stress. However, both significant and non-significant results have been generated on the activity of isoflavones in PCOS. The present review aims to discuss the existing literature on the effect of isoflavone on PCOS symptoms based on in vivo and clinical trial studies.

BACKGROUND: Epidemiological studies that focus on the relationship between dietary isoflavone intake and the risk of breast cancer still lead to inconsistent conclusions. Herein, we conducted a meta-analysis of the latest studies to explore this issue.
METHODS: We performed a systematic search using Web of Science, PubMed, and Embase from inception to August 2021. The robust error meta-regression (REMR) model and generalized least squares trend (GLST) model were used to establish dose-response relationships between isoflavones and breast cancer risk.
RESULTS: Seven cohort studies and 17 case-control studies were included in the meta-analysis, and the summary OR for breast cancer was 0.71 (95% CI 0.72-0.81) when comparing the highest to the lowest isoflavone intake. A subgroup analysis further showed that neither menopausal status nor ER status has a significant influence on the association between isoflavone intake and breast cancer risk, while the isoflavone intake doses and study design does. When the isoflavones exposure was less than 10 mg/day, no effects on breast cancer risk were detected. The inverse association was significant in the case-control studies but not in the cohort studies. In the dose-response meta-analysis of the cohort studies, we observed an inverse association between isoflavone intake and breast cancer: a 10 mg/day increase in isoflavone intake was related to reductions of 6.8% (OR = 0.932, 95% CI 0.90-0.96) and 3.2% (OR = 0.968, 95% CI 0.94-0.99) in breast cancer risk when using REMR and GLST, respectively. In the dose-response meta-analysis of the case-control studies, the inverse association for every 10 mg/day isoflavone intake was associated with breast cancer risk reductions by 11.7%.
CONCLUSIONS: present evidence demonstrated that taking in dietary isoflavone is helpful in reducing the breast cancer risk.

We examined the association between soy isoflavone intake and risk of cardiovascular disease (CVD) outcomes in adults. We searched the online databases for relevant studies published up to September 2021. In total, 13 publications were included in the systematic review and 12 in the meta-analysis. We found that a high intake of soy isoflavones was significantly associated with a lower risk of coronary heart disease (CHD) among whole populations (Pooled RR: 0.92, 95% CI: 0.85-0.99, I2 = 41.0%, Pheterogeneity = 0.10) and a lower risk of overall CVD (Pooled RR: 0.91, 95% CI: 0.84-0.98, I2 = 30.7%, Pheterogeneity = 0.19) and CHD (Pooled RR: 0.89, 95% CI: 0.83-0.96, I2 = 14.4%, Pheterogeneity = 0.32) among Western population. In the linear dose-response analysis, a 3 mg/day increase in soy isoflavone intake was associated with 16% and 14% lower risks of overall CVD and CHD, respectively, among Western population. In conclusion, we found that soy isoflavone intake was associated with a lower risk of overall CVD and CHD in adults, particularly among Western population.

Estrogen deprivation is one of the major factors responsible for many age-related processes including poor wound healing in postmenopausal women. However, the reported side-effects of estrogen replacement therapy (ERT) have precluded broad clinical administration. Therefore, selective estrogen receptor modulators (SERMs) have been developed to overcome the detrimental side effects of ERT on breast and/or uterine tissues. The use of natural products isolated from plants (e.g., soy) may represent a promising source of biologically active compounds (e.g., genistein) as efficient alternatives to conventional treatment. Genistein as natural SERM has the unique ability to selectively act as agonist or antagonist in a tissue-specific manner, i.e., it improves skin repair and simultaneously exerts anti-cancer and chemopreventive properties. Hence, we present here a wound healing phases-based review of the most studied naturally occurring SERM.

OBJECTIVE: Menopause symptoms affect the various dimensions of women\'s lives and they can lead to reduction of their quality of life. Phytoestrogens can be used as an approach to diminish these symptoms. The aim of this systematic review was to investigate the effect of phytoestrogens on the treatment of urogenital menopause symptoms.
METHODS: PubMed, EMBASE, Web of Science, Cochrane library,Scopus and ProQuest were systematically searched from 2000-2020. All randomized clinical trials were included. The quality of the selected papers was evaluated by the CONSORT checklist.
RESULTS: 33 eligible high-quality papers were reviewed. Various forms of phytoestrogens such as Pueraria Mirifica, fennel, Hop plant(Humuluslupulus L.), Glycine Max (L.) Merr, soy, red clover, black cohosh, ginsing, cimicifugaracemosa, genistein, diadzein, glycitein and isoflavone in the form of oral capsules and pill, food supplement, enriched powder, vaginal gel, cream and suppository could improve menopausal urogenital symptoms. The recovery rate in vaginal use of these phytoestrogens was greater than other consumptions.
CONCLUSIONS: After using a variety of phytoestrogens in different forms indicators of urogenital atrophy and urinary disorders improved and women\'s sexual function improved after treatment. The use of phytoestrogens as a safe, low-risk compared to hormone therapy and almost accessible method for women can relieve urogenital symptoms and promote the sexual satisfaction and quality of life.

Formononetin (FORM) is an isoflavone from the group of phytoestrogens that exhibits a broad spectrum of physiological effects beneficial to health through dependent and independent mechanisms of estrogen. This article aimed to present FORM main functions and future prospects for applications in different areas. Scientific publications and patents dated between 1998 and 2019 were analyzed. FORM has potential as an active compound of interest to product development for the industries of food, medicine, and cosmetics, among others. Moreover, in the medical area, this active compound has shown potential in the prevention and treatment of several diseases, including chronic ones, such as cancer, obesity, and neurodegenerative diseases.

Milk and dairy products are important sources of nutrients in the human diet because they contain a number of essential substances and other biologically active components. Many of these substances can be modified, and thus offer opportunities to use milk and dairy products as functional food. Isoflavones are particularly important in human nutrition due to their diverse pharmacological and antioxidant properties. The clinical effectiveness of isoflavone-rich products is believed to be dependent on their ability to metabolize daidzein to equol, which may directly exert cancer preventive effects. However, only approximately 30-40% of humans are able to produce equol, while animals, in general, produce equol. Equol is the predominant product of bacterial metabolism of isoflavones and can be found in various amounts in some food of animal origin, especially in milk. Therefore, milk and dairy products can be considered to be sources of equol for humans who are not able to produce this metabolite. When the content of isoflavones in milk is to be modified, two groups of factors should be considered, i.e., dietary factors that include the source of isoflavones and the processing effects on feedstuffs and animal factors that include the intake of isoflavones, ruminal and postruminal changes, and the health and physiological status of animals. The approximate content of isoflavones in milk can be predicted using carry-over rates for different dietary sources or using a formula that describes the relationship between equol concentration in milk and formononetin intake. Processing and storage can affect the content and profile of isoflavones in milk and dairy products.

Soybeans are a rich source of isoflavones, which are classified as phytoestrogens. Despite numerous proposed benefits, isoflavones are often classified as endocrine disruptors, based primarily on animal studies. However, there are ample human data regarding the health effects of isoflavones. We conducted a technical review, systematically searching Medline, EMBASE, and the Cochrane Library (from inception through January 2021). We included clinical studies, observational studies, and systematic reviews and meta-analyses (SRMA) that examined the relationship between soy and/or isoflavone intake and endocrine-related endpoints. 417 reports (229 observational studies, 157 clinical studies and 32 SRMAs) met our eligibility criteria. The available evidence indicates that isoflavone intake does not adversely affect thyroid function. Adverse effects are also not seen on breast or endometrial tissue or estrogen levels in women, or testosterone or estrogen levels, or sperm or semen parameters in men. Although menstrual cycle length may be slightly increased, ovulation is not prevented. Limited insight could be gained about possible impacts of in utero isoflavone exposure, but the existing data are reassuring. Adverse effects of isoflavone intake were not identified in children, but limited research has been conducted. After extensive review, the evidence does not support classifying isoflavones as endocrine disruptors.

OBJECTIVE: Pro-inflammatory mediators, including serum tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), can be used as biomarkers to indicate or monitor disease. This study was designed to ascertain the effects of soy products on TNF-α and IL-6 levels.
METHODS: PubMed, EMBASE, Science Direct, Web of Science, Google Scholar and the Cochrane Central Register of Controlled Trials were searched to November 2019 for RCTs around the effects of soy-based products on TNF-α and IL-6. A random effects model was used to calculate overall effect size.
RESULTS: In total, 29 eligible publications were considered in the present systematic review, of which 25 were included in this meta-analysis. The overall effect of soy products on TNF-α and IL-6 levels failed to reach statistical significance (MD = - 0.07; 95% CI - 0.22-0.09; I2 50.9; MD = 0.03; 95% CI - 0.07-0.14; I2 42.1, respectively). According to a subgroup analysis, natural soy products led to a reduction in TNF-α concentration compared with processed soy products (MD = - 0.32; 95% CI - 0.45 to - 0.19; I2 0.0). Moreover, IL-6 reduction was stronger in participants who were affected by different diseases (MD = - 0.04; 95% CI - 0.07 to - 0.02; I2 0.0).
CONCLUSIONS: A review of RCTs published to November 2019 found that natural soy products are effective in lowering TNF-α levels. While the beneficial effects on reduction of IL-6 appeared stronger in individuals affected by different diseases, this finding cannot be generalized to all individuals affected by different diseases.

Equol (4\',7-isoflavandiol), is a phytoestrogenic compound, which is synthesized from parent molecule diadzein by intestinal bacterial flora. It is among one of the most extensively researched molecule due to its high affinity towards estrogen receptors. Its enantiomeric form S-equol has been explored in the treatment of estrogen/androgen mediated diseases. Various therapeutic applications such as anti-cancer, cardioprotective, antidiabetic, antiosteoporosis, anti-ageing, and neuroprotective efficacy are attributed to it. This review explored major studies related to biochemistry and pharmacological applications of equol for human health.