Predictive value of ovarian stroma measurement for cardiovascular risk in polycyctic ovary syndrome: a case control study

<p>Abstract</p> <p>Background</p> <p>To verify the feasibility of ovarian stromal evaluation and correlate ovarian parameteres (echogenicity and volume) with hyperandrogenism, and both cardiovascular and metabolic risk factors in PCOS.</p> <p>Methods</p> <p>Twenty four young PCOS patients and twelve age-matched control women were enrolled. Diagnosis of PCOS was based on the Rotterdam criteria. Ultrasound ovarian study included ovarian volume, stromal volume, stromal area and stromal area/total ovarian area ratio (S/A). Concerning hormones, insulin, LH, FSH, estradiol, androstenedione, testosterone, DHEAS, 17-hydroxy-progesterone, and SHBG were measured during the early follicular phase (days 2-5). Cardiovascular risk factors were represented by fasting plasma levels of glucose, lipids (total and HDL-cholesterol), plasminogen activator inhibitor 1 (PAI-1), von-Willebrand factor (vWF), and adiponectin. Carotid intima-media thickness (C-IMT) was measured as a parameter of cardiovascular risk.</p> <p>Results</p> <p>A positive correlation between the S/A ratio and plasma levels of testosterone (p < 0.05) and androstenedione (p < 0.05) was found. The stromal volume, stromal area and S/A ratio were also significantly and positively correlated with PAI-1, and vWF levels, and with IMT in PCOS women (P < 0.05).</p> <p>Conclusions</p> <p>This study shows that the ultrasound measurement of ovarian stroma is a predicting factor of hyperandrogenism degree, prothrombotic factors and cardiovascular risk in patients with PCOS.</p

Obesity and Breast Cancer: Molecular Interconnections and Potential Clinical Applications

Obesity is an important risk factor for breast cancer (BC) in postmenopausal women; interlinked molecular mechanisms might be involved in the pathogenesis. Increased levels of estrogens due to aromatization of the adipose tissue, inflammatory cytokines such as tumor necrosis factor-α, interleukin-6, and prostaglandin E2, insulin resistance and hyperactivation of insulin-like growth factors pathways, adipokines, and oxidative stress are all abnormally regulated in obese women and contribute to cancerogenesis. These molecular factors interfere with intracellular signaling in the mitogen-activated protein kinase and phosphatydilinositol-3-phosphate/mammalian target of rapamycin (mTOR) pathways, which regulate the progression of the cell cycle, apoptosis, and protein synthesis. In this context, structural defects of typical genes related to both BC and obesity, such as leptin, leptin receptor, serum paraoxonase/arylesterase 1, the fat mass and obesity-associated gene and melanocortin receptor 4, have been associated with a high or low risk of BC development. The early detection of these gene alterations might be useful as risk predictors in obese women, and targeting these pathways involved in the BC pathogenesis in obese women is a potential therapeutic tool. In particular, mTOR pathway deregulation concurs in both obesity and BC, and inhibition of this might disrupt the molecular interlinks in a similar manner to that of metformin, which exerts definite anticancer activity and is currently used as an antidiabetic drug with a weight-reducing property. The identification of both genetic and pharmacological implications on the prevention and management of BC is the ultimate aim of these studies

Possible role of hyperinsulinemia and insulin resistance in lower vitamin D levels in overweight and obese patients.

A cohort of 66 healthy overweight and obese patients, 53 women and 13 men were examined. Waist circumference and fasting 25(OH)D, insulin, glucose, lipid (cholesterol, HDL cholesterol, and triglyceride), C-reactive protein (CRP), and complement 3 (C, and 4 (C serum concentrations were measured. Insulin resistance was assessed by the homeostasis model assessment (HOMA. Results. 25(OH)D levels showed a significant negative correlation with BMI (P < 0.01), waist circumference (P < 0.05), fasting insulin (P < 0.01), HOMA(P < 0.01), triglycerides (P < 0.01), CRP (P < 0.01), C(P < 0.05), and C(P < 0.05). Multiple regression analyses were performed with 25(OH)D as the dependent variable and BMI (or waist circumferences), fasting insulin (or HOMA, triglycerides, and CRP (or Cor C as independent variables. Only insulin or HOMAmaintained a significant independent association with 25(OH)D levels, whereas vitamin D did not maintain a significant independent association with CRP or Cor Cconcentrations. Conclusions. The present study, performed in overweight and obese subjects, shows that 25(OH)D levels are negatively associated with inflammatory parameters such as CRP and Cand Clevels, but not independently of BMI, body fat distribution, insulin levels, or insulin resistance. Our results suggest that hyperinsulinemia and/or insulin resistance are directly responsible for decrease of 25(OH)D levels in obesity

Para- and perirenal ultrasonographic fat thickness is associated with 24-hours mean diastolic blood pressure levels in overweight and obese subjects

BACKGROUND: Renal sinus fat (RSF) has been recognized as a risk factor for arterial hypertension. This study was addressed to examine whether also para- and perirenal fat accumulation is associated to higher 24-h mean systolic (SBP) and/or diastolic blood pressure (DBP) levels in overweight and obese subjects. METHODS: A cohort of 42 overweight and obese patients, 29 women and 13 men, aged 25-55 years, not treated with any kind of drug, was examined. Body mass index (BMI), waist circumference (WC), fasting insulin and glucose serum levels, insulin resistance (assessed by using the homeostasis model assessment [HOMAIR]), and 24-h aldosterone urine levels were measured. Ambulatory blood pressure monitoring (ABPM) was measured with 15 min intervals from 7.0 a.m. to 11.0 a.m. and with 30 min intervals from 23.0 to 7.0 for consecutive 24 h, starting from 8:30 AM. Measurement of para- and perirenal fat thickness was performed by ultrasounds by a duplex Doppler apparatus. RESULTS: Para- and perirenal ultrasonographic fat thickness (PUFT) was significantly and positively correlated with WC (p &lt; 0.01), insulin (p &lt; 0.01), HOMAIR (p &lt; 0.01), and 24-h mean DBP levels (p &lt; 0.05). 24-h mean DBP was also significantly and positively correlated with 24-h aldosterone urine concentrations (p &lt; 0.001). A multivariate analysis by multiple linear regression was performed; the final model showed that the association of 24-h mean DBP as dependent variable with PUFT (multiple R = 0.34; p = 0.026) and daily aldosterone production (multiple R = 0.59; p = 0.001) was independent of other anthropometric, hormone and metabolic parameters. DISCUSSION AND CONCLUSIONS: This study shows a positive independent association between PUFT and mean 24-h diastolic blood pressure levels in overweight and obese subjects, suggesting a possible direct role of PUFT in increasing daily diastolic blood pressure

A Dose–Response Study on the Relationship between White Meat Intake and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) in Southern Italy: Results from the Nutrihep Study

(1) Background: Metabolic dysfunction-associated liver disease (MASLD) is one of the most important causes of liver disease worldwide. Meat consumption is a growing trend and white meat has been shown to have beneficial effects on cardiometabolic risk factors. The aim of this study was to investigate the dose–response relationship between white meat intake and MASLD at survey level in a Southern Italy setting. (2) Methods: This cross-sectional study encompassed 1192 subjects (509 males, 42.7%) without missing data from the second wave of the NUTRIHEP cohort (2014–2016). Adjusted dose–response modeling was employed for statistical analysis; (3) Results: There were 587 subjects with MASLD (49.2%), i.e., 278 males (54.6%) and 309 females (45.2%). By increasing the intake, an unfavorable influence of white meat on MASLD was significantly revealed in females, whereas a protective effect of white meat was detectable in males. Male sex was shown to be involved in other associations in this study, such as influencing the preference for specific foods such as poultry and chicken skin. (4) Conclusions: Our data suggest that white meat does not have a clear-cut independent dose–response effect on MASLD, but sex may be a trigger moderator for age and BMI, with an increasing unfavorable effect of white meat in women, and a favorable effect in me

Anteroposterior diameter of the infrarenal abdominal aorta is higher in women with polycystic ovary syndrome

Background: Women affected by polycystic ovary syndrome (PCOS) are known to be at higher risk of cardiovascular disease. The aim of this study was to identify the artery that first is affected by early pre-atherosclerotic changes in PCOS. Methods: Twenty-nine women with PCOS aged 17 to 27 years and 26 healthy nonhyperandrogenic volunteers with regular menses (control women) aged 16 to 28 years were enrolled. All PCOS patients were overweight or obese (body mass index [BMI]  25). Diagnosis of PCOS was performed in line with the 2003 Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Accordingly, PCOS was defined when at least two of the following three features were present after exclusion of other etiologies: 1) oligomenorrhea and or anovulation; 2) hyperandrogenism and/or hyperandrogenemia; and 3) polycystic ovaries visible at ultrasound. Androgen excess or related disorders were excluded. The intima-media thickness (IMT) of common carotid arteries and common femoral arteries and the anteroposterior diameter of the infrarenal abdominal aorta were measured by ultrasound. Lutenizing hormone (LH), follicle-stimulating hormone(FSH), estradiol, total testosterone, androstenedione, and sex hormone-binding globulin (SHBG) serum levels were measured between the 3rd and the 6th day of spontaneous or progestin-induced menstrual cycle. Our study was performed in the absence of any medical treatment. Results: Women with PCOS showed a higher LH to FSH ratio (p < 0.01), increased fasting insulin (p < 0.001), total testosterone (p < 0.001), and androstenedione (p < 0.001) levels, and lower SHBG concentrations (p < 0.001) compared to control women. BMI and waist-to-hip ratio were also higher in women with PCOS (p < 0.000 and p < 0.001, respectively). Women with PCOS also showed increased total cholesterol (p < 0.001), triglyceride (p < 0.001), and apolipoprotein B (p < 0.001) levels. Vascular data showed women with PCOS had a higher anteroposterior diameter than control women (p < 0.005). However, when analysis of covariance was performed and BMI was entered into the model as a covariate, anteroposterior diameter did not maintain a significant association with PCOS. Conclusion: This study shows that anteroposterior diameter of the infrarenal abdominal aorta, but not IMT of common carotid arteries or common femoral arteries, is higher in women with PCOS than in women without this disease. This represents the earliest atherosclerotic change in women with PCOS. However, this alteration seems to be due to body weight secondary to PCOS and not due to PCOS per se

COVID-19 and the Endocrine System: A Comprehensive Review on the Theme

The review aimed to summarize advances in the topic of endocrine diseases and coronavirus disease 2019 (COVID-19). Scientific and institutional websites and databases were searched and data were collected and organized, when plausible, to angle the discussion toward the following clinical issues. (1) Are patients with COVID-19 at higher risk of developing acute or late-onset endocrine diseases or dysfunction? (2) May the underlying endocrine diseases or dysfunctions be considered risk factors for poor prognosis once the infection has occurred? (3) Are there defined strategies to manage endocrine diseases despite pandemic-related constraints? Herein, the authors considered only relevant and more frequently observed endocrine diseases and disorders related to the hypothalamic-pituitary region, thyroid and parathyroid glands, calcium-phosphorus homeostasis and osteoporosis, adrenal glands, and gonads. Main. Data highlight the basis of some pathophysiological mechanisms and anatomical alterations of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)-induced endocrine dysfunctions. Some conditions, such as adrenal insufficiency and cortisol excess, may be risk factors of worse clinical progression once the infection has occurred. These at-risk populations may require adequate education to avoid the SARS-CoV-2 infection and adequately manage medical therapy during the pandemic, even in emergencies. Endocrine disease management underwent a palpable restraint, especially procedures requiring obligate access to healthcare facilities for diagnostic and therapeutic purposes. Strategies of clinical triage to prioritize medical consultations, laboratory, instrumental evaluations, and digital telehealth solutions should be implemented to better deal with this probably long-term situation

Adding liraglutide to lifestyle changes, metformin and testosterone therapy boosts erectile function in diabetic obese men with overt hypogonadism

The aim of this retrospective observational study was to evaluate whether adding liraglutide to lifestyle changes, metformin (Met) and testosterone replacement therapy (TRT), by means of improving weight and glycaemic control, could boost erectile function in type 2 diabetic obese men with overt hypogonadism and erectile dysfunction (ED) in a 'real-life setting'. Forty-three obese, diabetic and hypogonadal men (aged 45-59 years) were evaluated because of complaining about the recent onset of ED. They were subdivided into two groups according to whether hypogonadism occurred after puberty (G1; n = 30: 25 with dysfunctional hypogonadism and 5 with acquired hypogonadotropic hypogonadism) or before puberty (G2; n = 13: 10 with Klinefelter's syndrome and 3 with idiopathic hypogonadotropic hypogonadism). Both G1 and G2 patients were given a combination of testosterone (T) [testosterone undecanoate (TU) 1000 mg/every 12 weeks] and Met (2000-3000 mg/day) for 1 year. In the poor responders (N) to this therapy in terms of glycaemic target (G1N: n = 16; G2N: n = 10), liraglutide (L) (1.2 μg/day) was added for a second year, while the good responders (Y) to T + Met (G1Y: 14/30 and G2Y: 3/13) continued this two drugs regimen therapy for another year. All patients were asked to fill in the International Index of Erectile Function (IIEF 15) questionnaire before starting TU plus Met (T1) and after 12 months (T2) and 24 months (T3) of treatment. Patients underwent a clinical examination and a determination of serum sex hormone binding globulin (SHBG), total testosterone (T) and glycosylated haemoglobin (HbA1c) at T1, T2 and T3. At T2, each patient obtained an improvement of ED (p &lt; 0.01) and of the metabolic parameters without reaching, however, the glycaemic goals [HbA1c = &gt;7.5% (&gt;58 mmol/mol)], while T turned out to be within the range of young men. L added to TU and Met regimen in G1N and G2N allowed these patients to reach not only the glycaemic target [HbA1c = &lt;7.5% (&lt;58 nmol/mol)] and a significant reduction in body weight (p &lt; 0.01), but also a further increase in SHBG (p &lt; 0.05) and T (p &lt; 0.01) plasma levels as well as a significant increment of IIEF score (T3). Conversely, at T3 G1Y and G2Y, who received the combined therapy with TRT and Met for the second year, showed a partial failure of that treatment given that there was no improvement of the IIEF score and they showed a significant rise in serum HbA1c (p &lt; 0.05) and weight (p &lt; 0.04) compared with the assessments at T2. These results suggest that TRT could improve clinical and metabolic parameters in obese, type 2 diabetic men with ED and overt hypogonadism (independently of when T deficit occurred). Furthermore, in case of insufficient metabolic control the addition of L to TRT and Met regimen allows to achieve serum T levels in the range of healthy men, as well as to reach glycaemic target and to lower weight, leading to a considerable improvement of ED

Dehydroepiandrosterone Stimulates Glucose Uptake in Human and Murine Adipocytes by Inducing GLUT1 and GLUT4 Translocation to the Plasma Membrane

Dehydroepiandrosterone (DHEA) has been shown to modulate glucose utilization in humans and animals, but the mechanisms of DHEA action have not been clarified. We show that DHEA induces a dose- and time-dependent increase in glucose transport rates in both 3T3-L1 and human adipocytes with maximal effects at 2 h. Exposure of adipocytes to DHEA does not result in changes of total GLUT4 and GLUT1 protein levels. However, it does result in significant increases of these glucose transporters in the plasma membrane. In 3T3-L1 adipocytes, DHEA increases tyrosine phosphorylation of insulin receptor substrate (IRS)-1 and IRS-2 and stimulates IRS-1- and IRS-2-associated phosphatidylinositol (PI) 3-kinase activity with no effects on either insulin receptor or Akt phosphorylation. In addition, DHEA causes significant increases of cytosolic Ca2+ concentrations and a parallel activation of protein kinase C (PKC)-β2. The effects of DHEA are abrogated by pretreatment of adipocytes with PI 3-kinase and phospholipase Cγ inhibitors, as well as by inhibitors of Ca2+-dependent PKC isoforms, including a specific PKC-β inhibitor. Thus, DHEA increases glucose uptake in both human and 3T3-L1 adipocytes by stimulating GLUT4 and GLUT1 translocation to the plasma membrane. PI 3-kinase, phospholipase Cγ, and the conventional PKC-β2 seem to be involved in DHEA effects