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Objectives: Polycystic ovary syndrome (PCOS) is a complex endocrine disorder that often coexists with cardiometabolic risk factors. Women with PCOS have a two-fold increased risk of developing type 2 diabetes and substantially elevated risk for cardiovascular disease (CVD) events later in life. PCOS patients may require more comprehensive metabolic screening to identify populations at higher risk of developing CVD and dyslipidemia. It is recommended to evaluate lipid profile, glucose tolerance and of women with PCOS every 2-3 years. Simple, short, and easy methods for the assessment of CVD risk in women with PCOS may be useful tools for implementing CVD prevention strategies by doctors or nutritionists. The aim of this study was to investigate the usefulness of anthropometric indices in the assessment of cardiometabolic risk based on lipid profile in patients with PCOS. Material and methods: The study involved 49 of Caucasian women aged 18-39 who were diagnosed with PCOS based on the Rotterdam criteria and divided into two groups with normal lipid profile (N=14) and dyslipidemia (N=35). Biochemical parameters were tested in the morning while fasting. Anthropometric parameters such as Body Mass Index (BMI), Body Adiposity Index (BAI), Waist-to-Hip Ratio (WHR), and Waist-to-Height Ratio (WHtR) were calculated, while the Percent of Body Fat was measured using a body analyzer. Results: The study demonstrated that women with dyslipidemia were older than the control group, 33 years (27-37) vs 24 years (21-26), p<0.01. Neither BMI nor BAI (%) correlated with total cholesterol (p=0.63 and p=0.27). Other lipid parameters, such as serum HDL cholesterol (R=-0.68, p<0.01; R=-0.58, p<0.01), LDL cholesterol (R=0.34, p=0.02; R=0.37, p=0.01), non-HDL cholesterol (R=0.40, p<0.01; R=0.42, p<0.01), and triglycerides (R=0.56, p<0.01; R=0.51, p<0.01) correlated with BMI and BAI (%). ROC analysis demonstrated a high predictive value for age in identifying dyslipidemia. ROC analysis demonstrated poor predictive value for BMI, BAI, WHR, WHtR in identifying dyslipidemia. Conclusions: Analysis of simple and rapid parameters used to assess body fat, such as BMI, BAI, WHR, and WHtR, has shown that they are poor predictors of dyslipidemia in women with PCOS. In young women with PCOS, age appears to be a more reliable predictor of dyslipidemia. [ABSTRACT FROM AUTHOR]

Metabolic syndrome (MetS) is associated with a high risk of cardiovascular disease, a leading cause of death among women. MetS is a diagnosis of at least 3 of the following: high blood pressure, high fasting glucose, high triglycerides, high waist circumference, and low high-density lipoprotein cholesterol. Epidemiological studies suggest that endocrine disrupting chemical (EDC) exposure is positively associated with individual components of MetS, but evidence of an association between EDCs and MetS remains inconsistent. In a cross-sectional analysis within the Multiethnic Cohort Study, we evaluated the association between 4 classes of urinary EDCs (bisphenol A [BPA], triclosan, parabens, and phthalates) and MetS among 1728 women. Multivariable logistic regression was used to estimate odds ratios and 95% CI for the association between tertiles of each EDC and MetS adjusting for age, body mass index (BMI), racial and ethnic group, and breast cancer status. Stratified analyses by race and ethnicity and BMI were conducted. MetS was identified in 519 (30.0%) women. We did not detect statistically significant associations of MetS with BPA, triclosan, or phthalate metabolite excretion. MetS was inversely associated with total parabens (P trend =.002). Although there were suggestive inverse associations between EDCs and MetS among Latino and African American women, and women with BMI < 30 kg/m2, there was no statistically significant heterogeneity in associations by race and ethnicity or BMI. These findings suggest an inverse association between parabens and MetS in larger multiethnic studies. Prospective analyses to investigate suggested differences in associations by race, ethnicity, and BMI are warranted. [ABSTRACT FROM AUTHOR]

Previous studies demonstrated associations of endogenous sex hormones with diabetes. Less is known about their dynamic relationship with diabetes progression through different stages of the disease, independence of associations, and role of the hypothalamic-pituitary gonadal axis. The purpose of this analysis was to examine relationships of endogenous sex hormones with incident diabetes, prediabetes, and diabetes traits in 693 postmenopausal women and 1015 men aged 45 to 74 years without diabetes at baseline participating in the Hispanic Community Health Study/Study of Latinos and followed for 6 years. Baseline hormones included estradiol, luteinizing hormone (LH), follicle stimulating hormone (FSH), sex hormone-binding globulin (SHBG), dehydroepiandrosterone sulfate (DHEAS), and, in men, testosterone and bioavailable testosterone. Associations were analyzed using multivariable Poisson and linear regressions. In men, testosterone was inversely associated with conversion from prediabetes to diabetes (incidence rate ratio [IRR] for 1 SD increase in testosterone: 0.821; 95% CI, 0.676, 0.997; P=0.046), but not conversion from normoglycemia to prediabetes. Estradiol was positively associated with increase in fasting insulin and homeostatic model assessment of insulin resistance. In women, SHBG was inversely associated with change in glycosylated hemoglobin, postload glucose, and conversion from prediabetes to diabetes (IRR= 0.62; 95% CI, 0.44, 0.86, P=0.005) but not from normoglycemia to prediabetes. Relationships with other hormones varied across glycemic measures. Stronger associations of testosterone and SHBG with transition from prediabetes to diabetes than from normoglycemic to prediabetes suggest they are operative at later stages of diabetes development. Biologic pathways by which sex hormones affect glucose homeostasis await future studies. [ABSTRACT FROM AUTHOR]

Background: Considering that metformin is widely used in the treatment of diabetes, and its protective role against various malignancies, the strength and validity of the available evidence from related systematic reviews and meta-analysis were evaluated. Methods: Scopus, PubMed, Embase, Cochrane, Web of science databases, and Google Scholar and manual screening of retrieved references were systematically searched from their inception dates to 24 March 2020 by extracting the effect size (Odds ratios (OR) and relative risk (RR) in each study. To present the forest plot of effect of metformin on each cancer, Stata version 14.2 was used. Results: This study included 36 meta-analysis studies and 620 original research studies (26 randomized control trials studies and 594 observational studies (cohort, case-control)) covering 15 different cancers. Overall, metformin medication prevented different cancers, including ovarian cancer (OR = 0.76, 95% CI: 0.62,0.93), cervical cancer (OR = 0.60, 95% CI: 0.43, 0.83), endometrial cancer (OR = 1.05, 95% CI: 0.82,1.35), liver cancer (OR = 0.59, 95% CI: 0.47,0.74), pancreatic cancer (OR = 0.59, 95%CI 0.50,0.69), head and neck cancer (OR = 0.71, 95% CI: 0.61,0.83), stomach cancer (OR = 0.72, 95% CI: 0.26,1.99), colorectal cancer (OR = 0.73, 95% CI: 0.59,0.91), colorectal adenoma cancer (OR = 0.75, 95% CI: 0.65,0.86), colon cancer (OR = 0.79, 95% CI: 0.69,0.91), esophagus cancer (OR = 0.90, 95% CI: 0.83,0.98), lung cancer (OR = 0.92, CI95%:0.85,0.99), breast cancer (OR = 0.93, 95% CI: 0.84,1.02), prostate cancer (OR = 0.94, 95% CI: 0.85-1.04), and bladder cancer (OR = 0.94 95% CI: 0.64,1.38). Conclusions: Treatment with metformin can significantly decrease the chance of all cancers with larger preventive effect on hepatocellular carcinoma and smaller preventive effect on lung and breast cancers. [ABSTRACT FROM AUTHOR]

Background: Disruption in androgen profiles and testicular adrenal rest tumors in males with congenital adrenal hyperplasia (CAH) can negatively affect sexual activity and fertility. Adrenal hyperandrogenism suppresses gonadotropin secretion and testicular adrenal rest tumors (TARTS), despite being noncancerous lesions, cause obstructive azoospermia and impaired testosterone (T) production. Circulating T in men with uncontrolled CAH is often predominantly adrenal in origin, which is reflected in high androstenedione/testosterone ratios (A4/T). Therefore, decreased luteinizing hormone (LH) levels and an increased A4/T are markers of impaired fertility in these individuals. Methods: Oral tildacerfont 200 to 1000 mg once daily (QD) (n=10) or 100 to 200 mg twice daily (n=9 and 7) for 2 weeks (Study 201), and 400 mg QD (n=11) for 12 weeks (Study 202). Outcomes measured changes from baseline in A4, T, A4/T, and LH. Results: Mean T levels increased in Study 201 from 375.5 ng/dL to 390.5 ng/dL at week 2 (n=9), 485.4 ng/dL at week 4 (n=4) and 420.7 ng/dL at week 6 (n=4). In Study 202, T levels fluctuated in the normal range from 448.4 ng/dL at baseline to 412.0 ng/dL at week 12. Mean LH levels increased in Study 201 from 0.68 IU/L to 1.59 IU/L at week 2 (n=10), 1.62 IU/L at week 4 (n=5) and 0.85 IU/L at week 6 (n=4). In Study 202, mean LH levels increased from 0.44 IU/L at baseline to 0.87 IU/L at week 12. Mean A4/T decreased across both studies. In Study 201, the mean A4/T changed from a baseline of 1.28 to 0.59 at week 2 (n=9), 0.87 at week 4 (n=4), and 1.03 at week 6 (n=4). In Study 202, the A4/T decreased from baseline of 2.44 to 0.68 at week 12. Four men were hypogonadal at baseline; all experienced improved A4/T and 3/4 (75%) reached levels <1. Conclusion: Tildacerfont treatment demonstrated clinically meaningful reductions in A4 levels, and A4/T with concomitant increased LH levels indicating increased testicular T production. The data suggests improvement in hypothalamic-pituitary-gonadal axis function, but more data is required to confirm favorable male reproductive health outcomes. [ABSTRACT FROM AUTHOR]

Objective: The aim of the present study was to determine whether polycystic ovarian morphology (PCOM) is related to insulin resistance in women with polycystic ovary syndrome (PCOS). Methods: A total of 147 Korean women aged 18 to 35 years and diagnosed with PCOS were included in this study. Fasting blood tests and standard 2-hour 75-g oral glucose tolerance tests were performed for all participants. PCOM-related parameters including total antral follicle count (TFC) and total ovarian volume (TOV) were assessed using transvaginal or transrectal ultrasonography. Correlation analysis was conducted to assess the relationships of TFC and TOV with insulin resistance-related clinical and biochemical parameters using Spearman rank correlation coefficients and linear regression analysis, with partial correlations used to control for the effects of confounding covariates. Results: Fasting insulin levels, low-density lipoprotein levels, and insulin sensitivity assessment indices (ISAIs) were significantly correlated with TFC, but neither postprandial blood glucose levels nor insulin levels were significantly associated with TFC. No insulin resistance-related parameter was significantly correlated with TOV. These results did not change after adjustments for other anthropometric covariates. Fasting insulin and some ISAIs differed significantly between groups categorized by the median TFC value (TFC =54 and TFC >54). Conclusion: TFC, but not TOV, was found to be related to fasting insulin resistance-related parameters in women with PCOS. [ABSTRACT FROM AUTHOR]

Evidence about the effect of age at menarche (AAM) on blood pressure (BP) has largely been drawn from studies in developed countries. Studies in developing countries are expanding recently but have not been summarised. To systematically explore the association between AAM and BP and the potential modifiers in developing countries. We searched PubMed, Embase, and Web of Science for publications until March 2022. A random-effects model was used to calculate the pooled relative risk (RR) with 95% confidence interval (CI). Twenty studies were eligible. In studies with participants' mean age at BP assessment <55 years, women in the oldest group as compared with the middle or the youngest group of AAM had a higher risk of hypertension in those studies without adjustment for confounders (RR 1.79, 95% CI 1.41–2.28, I2=97.0%), those with adjustment for confounders excluding adiposity (1.25,1.04–1.51, I2=84.8%), and those with adjustment for confounders including adiposity (1.38,1.03–1.86, I2=91.8%). In studies with participants' mean age at BP assessment ≥55 years, no significant differences were found for studies without adjustment for confounders (RR 1.07, 95% CI 0.78–1.47, I2=90.3%), studies with adjustment for confounders excluding adiposity (0.85, 0.78–0.92, I2=12.3%), or studies with adjustment for confounders including adiposity (0.95, 0.80–1.11, I2=45.5%). A similar association was observed between AAM and baseline systolic BP and diabolic BP. Late menarche was associated with a higher risk of BP and this association was modified by age and adiposity in developing countries. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes mellitus and pre-diabetes are associated with reduced circulating testosterone levels. However, the role of testosterone replacement therapy in these patients is still conflicting. Objectives: To summarize and critically analyze available data on the possible effect of testosterone administration in men with glucose abnormalities. Materials and methods: A comprehensive systematic review was performed. When available, meta-analytic data were preferred. To better analyze the relationship between testosterone and the pre-diabetes condition, a systematic analysis was performed and the data obtained with the latter search were used for a meta-analytic approach. Finally, clinical data derived from a consecutive series of 4682 patients seeking medical care for sexual dysfunction at the University of Florence were also considered. Results: Patients with impaired fasting glucose were characterized by a 3 nmol/L lower level of total testosterone when compared to controls. Similarly, impaired fasting glucose was associated with a 1.8-fold increased risk of hypogonadism, when compared to subjects with normal glucose levels. Waist circumference and body mass index resulted as being the best predictors of reduced total testosterone levels. Secondary hypogonadism was two times higher in subjects with impaired fasting glucose when compared to rates observed in the general population. Testosterone replacement therapy was able to improve body composition, insulin resistance, and glucose profile both in impaired fasting glucose and type 2 diabetes mellitus whereas its role on body weight, lipid profile, and sexual function was less evident. Discussion and conclusion:Weight loss and physical activities are able to improve both metabolic profile and testosterone levels. The combined approach of testosterone replacement therapy and lifestyle modifications could be suggested in symptomatic hypogonadal men to better motivate patients to perform physical activity which can eventually result in weight loss as well as metabolic profile and sexual function improvement. Whether or not these approaches can prevent the development of type 2 diabetesmellitus from pre-clinical conditions requires more studies. [ABSTRACT FROM AUTHOR]

This article reviews the main findings on anti-Müllerian hormone (AMH) and its involvement in the pathogenesis of polycystic ovary syndrome (PCOS) and its male equivalent. In women, AMH is produced by granulosa cells from the mid-fetal life to menopause and is a reliable indirect marker of ovarian reserve. AMH protects follicles from atresia, inhibits their differentiation in the ovary, and stimulates gonadotrophin-releasing hormone neurons pulsatility. AMH overexpression in women with PCOS likely contributes to the increase of the follicle cohort and of androgen levels, leading to follicular arrest and anovulation. In the male, AMH is synthesized at high levels by Sertoli cells from fetal life to puberty when serum AMH falls to levels similar to those observed in women. AMH is involved in the differentiation of the genital tract during fetal life and plays a role in Sertoli and Leydig cells differentiation and function. Serum AMH is used to assess Sertoli cell function in children with disorders of sex development and various conditions affecting the hypothalamic–pituitary–testicular axis. Although the reproductive function of male relative of women with PCOS has been poorly investigated, adolescents have elevated levels of AMH which could play a detrimental role on their fertility. [ABSTRACT FROM AUTHOR]

Background: Sex hormones are strongly linked to the occurrence and development of diabetes, and influence glycated hemoglobin (HbA1c) levels in diabetic population; but, the relationship between sex hormones and HbA1c in non-diabetic population remains unknown. This study aimed to explore the extent of influence of sex hormones on HbA1c levels in non-diabetic population. Methods: A total of 1409 non–diabetic subjects, including 601 men and 808 postmenopausal women were recruited from Shanghai community. HbA1c was detected using high performance liquid chromatography, and hemoglobin level was determined by sodium lauryl sulfate colorimetry. Serum estradiol (E2), total testosterone (TT), and sex hormone binding globulin (SHBG) were measured by chemiluminescent microparticle immunoassays. Results: The level of HbA1c was 5.6 (5.4–5.9) % in all subjects, with 5.6 (5.4–5.8) % in men and 5.7 (5.5–5.9) % in postmenopausal women. After adjusting for age, body mass index (BMI), and hemoglobin, E2 was positively correlated with HbA1c in men (r = 0.122, P =.003), and SHBG was inversely correlated with HbA1c (r = − 0.125, P <.001) in women. Other hormones were not correlated with HbA1c (all P >.05). Multivariate linear regression analysis showed that, except for traditional factors, such as age, hemoglobin, and BMI, E2 was another determinant of HbA1c (standardized β = 0.137, P =.003) in men; besides, in women, SHBG was another determinant of HbA1c (standardized β = − 0.178, P <.001), except for age and systolic blood pressure. Conclusion: After controlling for confounding factors, two sex hormones, as E2 and SHBG could influence HbA1c levels in non-diabetic population. [ABSTRACT FROM AUTHOR]

Context: Although polycystic ovary syndrome (PCOS) is the most common endocrinopathy affecting women of reproductive age, risk factors that may cause the syndrome are poorly understood. Based on epidemiologic studies, PCOS is thought to cause several adverse outcomes such as cardiovascular disease; however, the common presence of comorbidities such as obesity may be responsible for such associations, rather than PCOS in and of itself. To overcome the limitations of observational studies, investigators have employed Mendelian randomization (MR), which uses genetic variants to interrogate causality between exposures and outcomes. Evidence Acquisition: To clarify causes and consequences of PCOS, this review will describe MR studies involving PCOS, both as an exposure and as an outcome. The literature was searched using the terms "Mendelian randomization," "polycystic ovary syndrome," "polycystic ovarian syndrome," and "PCOS" (to May 2021). Evidence Synthesis: MR studies have suggested that obesity, testosterone levels, fasting insulin, serum sex hormone-binding globulin concentrations, menopause timing, male-pattern balding, and depression may play a causal role in PCOS. In turn, PCOS may increase the risk of estrogen receptor-positive breast cancer, decrease the risk of endometrioid ovarian cancer, and have no direct causal effect on type 2 diabetes, coronary heart disease, or stroke. Conclusions: The accumulation of genome-wide association studies in PCOS has enabled multiple MR analyses identifying factors that may cause PCOS or be caused by PCOS. This knowledge will be critical to future development of measures to prevent PCOS in girls at risk as well as prevent complications in those who have PCOS. [ABSTRACT FROM AUTHOR]

Objective. Decreased synthesis of sex hormone-binding globulin (SHBG) related to hyperinsulinemia is one of the disturbances characteristic of polycystic ovary syndrome (PCOS). Hyperinsulinemia is a compensatory mechanism for liver insulin resistance (IR); thus, SHBG may be considered as a surrogate marker of liver IR. Therefore, this study aimed to assess the prediction of IR and impaired fasting glucose (IFG) based on SHBG levels in women with PCOS. Methods. This analysis included data retrieved from medical records of 854 patients with PCOS hospitalized in the Gynecological Endocrinology Clinic from 2012 to 2019. Data including anthropometric parameters, fasting plasma glucose, insulin, and SHBG levels were analyzed. BMI and HOMA-IR were calculated with standard formulas. Results. IFG and IR assessed based on HOMA-IR values > 2.0 were found in 19.5% and 47.8% of the study group, respectively. Empirical optimal cutoff values for SHBG levels were ≤41.5 nmol/L typical for IR (AUC 0.711, sensitivity 61.1%, specificity 71.6%, positive predictive value (PPV) 70.7%, and negative predictive value (NPV) 62.1%). The probability of insulin resistance occurrence for SHBG concentration 26.1 nmol/L (the lower normal range) was 61.6% (95% CI: 57.4%–65.8%). The SHBG concentration of 36.4 nmol/L and 8.1 nmol/L was related to a 10% and 20% probability of IFG, respectively. Conclusion. In conclusion, this is the first study estimating the probability of liver IR and IFG occurrence based on SHBG levels in women with PCOS. Despite the low sensitivity, SHBG level below 42 nmol/L should cause closer monitoring for the fatty liver and prediabetes. [ABSTRACT FROM AUTHOR]