Associations of sex hormone ratios with metabolic syndrome and inflammation in US adult men and women.

Background: Sex hormones play a critical role in sex differences and cardiovascular disease risk associated with metabolic syndrome (MS) and inflammation. However, the associations of sex hormone ratios with metabolic and inflammatory markers are unclear according to sex and age differences. We evaluated the associations of sex hormone ratios with MS and inflammation among males and females. Methods: A retrospective cross-sectional study was conducted by including all adults from the National Health and Nutrition Examination Survey cycles 2013-2016 and excluding any pregnant women, heart disease, diabetes, and those currently taking insulin. MS was defined using the National Cholesterol Education Program criteria and a high-sensitivity C-reactive protein (CRP) level>3 mg/L was defined as a high CRP. Measures of MS components and CRP concentrations were also analyzed. The primary exposures were testosterone to estradiol (excess androgen index), testosterone to sex hormone-binding globulin (free androgen index), and estradiol to sex hormone-binding globulin (free estradiol index). The adjusted associations were summarized with a relative risk (RR) and 95% confidence interval (CI). Results: This study included 9167 subjects with 4360 males and 4807 females. Increases in free estradiol index were positively associated with MS (RR=1.48; 95%CI: 1.39, 1.58; RR=1.31; 95%CI: 1.22, 1.40) and high CRP (RR=1.49; 95%CI: 1.25, 1.77; RR=1.26; 95%CI: 1.06, 1.50) in men with age<50 years and age≥50 years, respectively. Similarly, higher free estradiol index was also robustly associated with increased prevalence of MS (RR=1.22; 95%CI: 1.15, 1.28) and high CRP (RR=1.68; 95%CI: 1.48, 1.90) in women with age ≥50 years. Among women with age<50 years, a higher free androgen index was associated with MS (RR=1.34; 95%CI: 1.25, 1.42) and high CRP (RR=1.13; 95%CI: 1.02, 1.25). These associations were unchanged even after adjusting for all sex hormones. Conclusion: Free estradiol index was consistently and positively associated with MS and high CRP in males of all ages and older females. Free androgen index was positively associated with MS and high CRP in females with age<50 years.

Oestrogens, adipose tissues and environmental exposures influence obesity and diabetes across the lifecycle.

Endogenous oestrogens regulate essential functions to include menstrual cycles, energy balance, adipose tissue distribution, pancreatic ß-cell function, insulin sensitivity and lipid homeostasis. Oestrogens are a family of hormones which include oestradiol (E2), oestrone (E1) and oestriol (E3). Oestrogens function by binding and activating oestrogen receptors (ERs). Phytoestrogens are plant-derived compounds which exhibit oestrogenic-like activity and can bind to ERs. Phytoestrogens exert potential oestrogenic-like benefits; however, their effects are context-dependent and require cautious consideration regarding generalised health benefits. Xenoestrogens are synthetic compounds which have been determined to disrupt endocrine function through binding to ERs. Xenoestrogens enter the body through various routes and given their chemical structure they can accumulate, posing long-term health risks. Xenoestrogens interfere with endogenous oestrogens and their functions contributing to conditions like cancer, infertility, and metabolic disorders. Understanding the interplay between endogenous and exogenous oestrogens is critical in order to determine their potential health consequences and requires further investigation. This manuscript provides a summary of the role endogenous oestrogens have in regulating metabolic functions. Additionally, we discuss the impact phytoestrogens and synthetic xenoestrogens have on biological systems across various life stages. We highlight their mechanisms of action, potential benefits, risks and discuss the need for further research to bridge gaps in understanding and mitigate exposure-related health risks.

Association of polycystic ovary syndrome with cardiovascular disease among female hospitalizations in the United States.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is a complex disorder characterized by a wide range of symptoms related to ovulatory dysfunction and androgen overproduction. Although PCOS is associated with multiple cardiovascular disease (CVD)-risk factors, previous studies have reported controversial associations between PCOS and different types of CVD events. We sought to determine the association of PCOS with various CVD outcomes among hospitalized women. METHODS: All women hospitalizations between the ages of 15 and 65 years recorded in the National Inpatient Sample database, 2017 were analyzed with sampling-weighted logistic regression analysis. The International Classification of Diseases, 10th revision, codes were used to define outcomes including composite CVD, major adverse cardiovascular events (MACEs), coronary heart disease (CHD), stroke/cerebrovascular accident (CVA), heart failure (HF), arterial fibrillation (AF) or arrhythmia, pulmonary heart disease (PHD), myocardial infarction, cardiac arrest, and diabetes. RESULTS: Among the total hospitalizations of women, 13 896 (0.64) had a PCOS diagnosis. Polycystic ovary syndrome was found to be associated with most CVD outcomes, including composite CVD (adjusted odds ratio [aOR] = 1.73, 95% CI, 1.55-1.93, P < .001), MACE (aOR = 1.31, 95% CI, 1.12-1.53, P < .001), CHD (aOR = 1.65, 95% CI, 1.35-2.01, P < .001), stroke/CVA (aOR = 1.46, 95% CI, 1.08-1.98, P = .014), HF (aOR = 1.30, 95% CI, 1.07-1.57, P = .007), AF/arrhythmia (aOR = 2.20, 95% CI, 1.88-2.57, P < .001), and PHD (aOR = 1.58, 95% CI, 1.23-2.03, P < .001) among hospitalized women with an age of ≤40 years. However, the associations between PCOS and CVD outcomes were mediated by obesity and metabolic syndrome conditions. CONCLUSIONS: Polycystic ovary syndrome is associated with CVD events and the association is mediated by obesity and metabolic syndrome conditions, particularly among hospitalized women aged ≤40 years in the United States.

A systematic review and meta-analysis of the association between maternal polycystic ovary syndrome and neuropsychiatric disorders in children.

There is emerging evidence demonstrating an association between maternal polycystic ovary syndrome (PCOS) and autism spectrum disorder (ASD) in children, however, the cumulative effect of maternal PCOS on the development of ASD or other neuropsychiatry disorders (NPD) in children and separately for males and females has not been examined. We sought to systematically evaluate the influence of maternal PCOS on a wide range of NPD including ASD, attention deficit hyperactivity disorder (ADHD), chronic tic disorder (CDT), other behavior disorders, anxiety, depression, bipolar disorder, schizophrenia in children as well as in women of reproductive age only. We queried electronic databases including PubMed, EMBASE, and Google Scholar, until March 2021. We used DerSimonian and Laird (D-L) random effects method to compute pooled effect size in terms of odds ratio (OR). Nineteen studies (1667851 mothers, 2260622 children) were included in this study. Mothers with PCOS had an increased odds of children diagnosed with ASD (OR = 1.40, p < 0.001), ADHD (OR = 1.42, p < 0.001), CTD (OR = 1.44, p = 0.001), anxiety (OR = 1.33, p < 0.001), as well as other behavioral symptoms (OR = 1.45, p < 0.001) in the adjusted analysis. The association between maternal PCOS and ASD (OR: 1.43 vs. 1.66), ADHD (OR: 1.39 vs. 1.54), and CTD (OR: 1.42 vs. 1.51) was found to be significantly consistent between males and females, respectively. Our data do not suggest increased fetal testosterone exposure is associated with increased autistic traits in children. However, PCOS was significantly associated with increased odds of a wide range of NPD in women themselves. Maternal PCOS is a risk factor for various NPD with a similar extent in their children regardless of their underlying comorbidities. Managing PCOS is essential for women's health as well as for their children's health. More research is needed to determine the mechanisms and links between maternal PCOS and NPD in children.

Effect of Nutritional Supplementation on Oxidative Stress and Hormonal and Lipid Profiles in PCOS-Affected Females.

Polycystic ovary syndrome (PCOS) affects several reproductive and endocrine features in females and has a poorly understood etiology. Treatment strategies for PCOS are limited and are based primarily on diet and nutrient supplementation. Recent studies have recommended some nutrients such as vitamins, minerals and vitamin-like nutrients for the therapy for PCOS. Therefore, it is claimed that the cause of PCOS could be vitamin or mineral deficiency. This review provides a narrative on the effect of nutritional supplementation on oxidative stress induced in PCOS. Oxidative stress plays a formative role in PCOS pathophysiology. This article reviews oxidative stress, its markers, nutritional supplementation and clinical studies. We also aim to show the effect of nutritional supplementation on genes affecting hormonal and glucose-mediated pathways.

Prevalence of at-risk hyperandrogenism by age and race/ethnicity among females in the United States using NHANES III.

OBJECTIVE: Hyperandrogenism in females leads to multiple endocrine and metabolic disorders including polycystic ovary syndrome (PCOS) that yields adverse health outcomes across all ages. We sought to estimate the prevalence of hyperandrogenemia and at-risk hyperandrogenism among the US females of different age groups, racial/ethnic, and metabolic characteristics. MATERIALS AND METHODS: A retrospective population-based cross-sectional study of females 6 years or older having serum testosterone measures using the National Health and Nutrition Examination Surveys, 2013-2016 was conducted. Age-appropriate thresholds as per assay methods were used for evaluating high total testosterone, low sex hormone binding globulin (SHBG), and high free androgen index (FAI) levels. The weighted analysis was performed to estimate prevalence and 95 % confidence interval (CI). RESULTS: The prevalence of at-risk hyperandrogenism was estimated as 19.8 % (95 %CI: 18.6 %, 21.2 %) in the overall sample, 11.8 % (95 %CI: 9.5 %, 14.5 %) in prepubertal, 20.5 % (95 %CI: 18.9 %, 22.2 %) in premenopausal, and 21.1 % (95 %CI: 18.7 %-23.7 %) in postmenopausal females with considerable heterogeneity by racial/ethnic and metabolic characteristics. In the entire sample, hyperandrogenemia was estimated as 10.4 % and 4.3 % using total testosterone and FAI respectively while 10.7 % cases had a low SHBG. CONCLUSIONS: At-risk hyperandrogenism is equally prevalent in premenopausal and postmenopausal women with a considerable amount in prepubertal females and varied by racial/ethnic groups depending on specific ages. Regular screening of hyperandrogenism using SHBG and total testosterone measures among at-risk subjects for specific ages is critical for treating and preventing adverse consequences of abnormal hormonal parameters.

Association Between Obesity and Cardiovascular Outcomes: Updated Evidence from Meta-analysis Studies.

PURPOSE OF REVIEW: The prevalence of obesity and cardiovascular disease (CVD) has been increasing worldwide. Studies examining the association between adiposity and CVD outcomes have produced conflicting findings. The interplay between obesity and CVD outcomes in the general population and in specific subpopulations is complex and requires further elucidation. RECENT FINDINGS: We report updated evidence on the association between obesity and CVD events through a review of meta-analysis studies. This review identified that obesity or high body mass index (BMI) was associated with an increased risk of CVD events, including mortality, in the general population and that cardiac respiratory fitness (CRF) and metabolic health status appear to stratify the risk of CVD outcomes. In patients with diabetes, hypertension, or coronary artery disease, mortality displayed a U-shaped association with BMI. This U-shaped association may result from the effect of unintentional weight loss or medication use. By contrast, patients with other severe heart diseases or undergoing cardiac surgery displayed a reverse J-shaped association suggesting the highest mortality associated with low BMI. In these conditions, a prolonged intensive medication use might have attenuated the risk of mortality associated with high BMI. For the general population, a large body of evidence points to the importance of obesity prevention and maintenance of a healthy weight. However, for those with diagnosed cardiovascular diseases or diabetes, the relationship between BMI and cardiovascular outcomes is more complex and varies with the type of disease. More studies are needed to define how heterogeneity in the longitudinal changes in BMI affects mortality, especially in patients with severe heart diseases or going under cardiac surgery, in order to target subgroups for tailored interventions. Interventions for managing body weight, in conjunction with improving CRF and metabolic health status and avoiding unintentional weight loss, should be used to improve CVD outcomes.