Women tolerate drug therapy for coronary artery disease as well as men do,but are treated less frequently with aspirin, β-blockers,or statins

Background: Women have worse morbidity, mortality, and health-related quality-of-life outcomes associated with coronary artery disease (CAD) compared with men. This may be related to underutilization of drug therapies, such as aspirin, β-blockers, angiotensin-converting enzyme (ACE) inhibitors, or statins. No studies have sought to describe the relationship of gender with adverse reactions to drug therapy (ADRs) for CAD in clinical practice.Objective: The aim of this study was to determine the prevalence of ADRs associated with common CAD drug therapies in women and men in clinical practice.Methods: In a cohort of consecutive outpatients with CAD, detailed chart abstraction was performed to determine the use of aspirin, β-blocker, ACE inhibitor, and statin therapy, as well as the ADRs reported for these treatments. Baseline clinical characteristics were also determined to identify the independent association of gender with use of standard drug treatments for CAD.Results: Consecutive patients with CAD (153 men, 151 women) were included in the study. Women and men were observed to have a similar prevalence of cardiac risk factors and comorbidities, except that men had significantly higher prevalence of atrial fibrillation (30 [19.6%] men vs 15 [9.9%] women; P = 0.03) and significantly lower mean (SD) high-density lipoprotein cholesterol concentrations (45 [16] mg/dL for men vs 55 [19] mg/dL for women; P < 0.001). No significant differences were observed between the sexes in the prevalence of ADRs; however, significantly fewer women than men were treated with statins (118 [78.1%] vs 139 [90.8%], respectively; P = 0.003). After adjusting for clinical characteristics, women were also found to be less likely than men to receive aspirin (odds ratio [OR] = 0.164; 95% CI, 0.083–0.322; P = 0.001) and β-blockers (OR = 0.184; 95% CI, 0.096-0.351; P = 0.001).Conclusions: Women and men experienced a similar prevalence of ADRs in the treatment of CAD; however, women were significantly less likely to be treated with aspirin, β-blockers, and statins than were their male counterparts. To optimize care for women with CAD, further study is needed to identify the cause of this gender disparity in therapeutic drug use.     

Interrelations and associations of serum levels of steroids and pituitary hormones with markers of insulin resistance,inflammatory activity,and renal function in men and women aged >70 years in an 8-year longitudinal study of opposite-sex twins

Background: The physiological serum levels of steroids and pituitary hormones in older men and women have been sparsely reported in the literature.Objectives: The aims of this study were to investigate the normal variation and sex differences in steroids and pituitary hormones in those aged >70 years, and to study the interrelation between these hormones and indicators of the metabolic syndrome, inflammatory activity, and renal function.Methods: The investigation comprised a population-based sample of pairs of white opposite-sex twins from the Swedish Twin Registry. At baseline in 1996 and at the 8-year follow-uup in 2004, serum levels of progesterone, cortisol, testosterone, estradiol, follicle-stimulating hormone, luteinizing hormone, prolactin, creatinine, C-reactive protein (CRP), and urea were analyzed. Serum levels of insulin and cystatin were analyzed only at the follow-up.Results: The study sample included 219 men and 183 women aged 71 to 80 years (mean [SD], 74.5 [2.5] years) at baseline in 1996, and 127 men and 135 women at follow-uup in 2004. At baseline, in both men and women, the variation of progesterone in serum was positively correlated with that of estradiol (men: r = 0.226, P < 0.01; women: r = 0.115, P = NS), testosterone (men: r = 0.178, P < 0.01; women: r = 0.315, P < 0.001), and cortisol (men: r = 0.314, P < 0.001; women: r = 0.296, P < 0.001). The values of progesterone and other steroid hormones were associated with markers of insulin resistance (iie, insulin, waist circumference), inflammatory activity (ie, CRP) for progesterone (men: r = 0.267, P < 0.001; women: r = 0.150, P < 0.05), and renal function (ie, creatinine) for progesterone (men: r = 0.424, P < 0.001; women: r = 0.212, P < 0.01). Estradiol and prolactin were associated with insulin resistance, inflammation, and renal function. Furthermore, progesterone was associated with prolactin (men: r = 0.275, P < 0.001; women: r = 0.172, P < 0.05).. Among both men and women, there was a strong correlation between testosterone and estradiol (men: r = 0.753, P < 0.001; women: r = 0.526, P < 0.001); in women, there was also a link between testosterone and cortisol at follow-up (r = 0.340, P < 0.01). For progesterone, there was a significant correlation between the values of the co-twins (in 1996: r = 0.16, P < 0.05; in 2004: r = 0.45, P < 0.001). Higher serum levels of progesterone (2.0 [0.7] nmol/L in men and 1.7 [0.8] nmol/L in women) and prolactin (6 [5] μg/L in men and 8 [10] μg/L in women) were found among those who were deceased at follow-up compared with survivors (progesterone: 1.8 [0.5] nmol/L in men and 1.4 [0.6] nmol/L in women, P < 0.01; prolactin: 4 [3] μg/L in men and 5 [2] μg/L in women, P < 0.001).Conclusions: In this study of opposite-sex Swedish twins aged >70 years, there was a sex difference in the serum levels of steroids and pituitary hormones between men and women. Progesterone and other steroid hormones were associated with markers of insulin resistance, inflammatory activity, and renal function. Progesterone and prolactin levels were associated with increased risk of mortality in this sample.     

Lower postprandial oxidative stress in women compared with men

Background: Previous studies indicate that oxidative stress is increased following intake of a high-fat meal, mediated in large part by the triglyceride (TG) response to feeding as well as fasting oxidative stress values. It has been suggested that women may process TG more efficiently after high-fat meals, based on the antilipidemic properties of estrogen. It has also been reported that women present with lower fasting oxidative stress values than do men. It is possible that women experience attenuated postprandial oxidative stress compared with men.Objective: The purpose of this study was to compare the postprandial TG and oxidative stress response after a lipid meal in healthy men and women.Methods: This study was conducted at The University of Memphis in Memphis, Tennessee, from October to December 2008. Blood samples were collected before (in a 10-hour fasted state), and at 1, 2, 4, and 6 hours after ingestion of a lipid load (heavy whipping cream at 1 g · kg^?1). Blood samples were analyzed for TG, malondialdehyde (MDA), hydrogen peroxide (H₂O₂), and nitrate/nitrite (NOx). The AUC was calculated for each variable and results were compared using a t test. Effect-size calculations were performed using Cohen's d.Results: Samples from 10 men and 10 women, aged 18 to 47 years (17 subjects aged <37 years), were compared. AUC data were not significantly different for TG (mean [SEM] 330 [48] vs 354 [34] mg · dL^?1 · 6h^?1 for men and women, respectively; effect size = 0.09) or NOx (165 [25] vs 152 [17] μmol · L^?1 · 6h^?1 for men and women; effect size = 0.09). However, significant differences were noted for MDA (10.7 [1.3] vs 6.1 [0.5] μmol · L^?1 · 6h^?1 for men and women, respectively; P = 0.002; effect size = 0.61) and H₂O₂ (154 [23] vs 86 [8] μmol · L^?1 · 6h^?1 for men and women; P = 0.013; effect size = 0.53).Conclusions: These data indicate that women experience lower oxidative stress than do men, with regard to MDA and H₂O₂, after ingestion of a lipid load in the form of heavy whipping cream. Considering the strong association between oxidative stress and cardiovascular disease, lower postprandial oxidative stress may be one mechanism associated with decreased risk of cardiovascular disease in women compared with men. Further research is needed to confirm this hypothesis.     

Symptoms of a first acute myocardial infarction in women and men

Background: Many studies have compared women and men for symptoms of acute myocardial infarction (AMI), but findings have been inconsistent, largely because of varying inclusion criteria, different study populations, and different methods.Objective: The purpose of this study was to analyze gender differences in symptoms in a well-defined, population-based sample of women and men who experienced a first AMI.Methods: Information on symptoms was collected from the medical charts of all patients with a first AMI, aged 25 to 74 years, who had taken part in the INTERGENE (Interplay Between Genetic Susceptibility and Environmental Factors for the Risk of Chronic Diseases) study. INTERGENE was a population-based research program on risk factors for cardiovascular disease. Medical charts were reviewed for each patient to determine the symptoms of AMI, and the prevalence of each symptom was compared according to sex.Results: The study included 225 patients with a first AMI: 52 women and 173 men. Chest pain was the most common symptom, affecting 88.5% (46/52) of the women and 94.8% (164/173) of the men, with no statistically significant difference between the sexes. Women had significantly higher rates of 4 symptoms: nausea (53.8% [28/52] vs 29.5% [51/173]; age-adjusted odds ratio [OR] = 2.78; 95% CI, 1.47–5.25), back pain (42.3% [22/52] vs 14.5% [25/173]; OR = 4.29; 95% CI, 2.14–8.62), dizziness (17.3% [9/52] vs 7.5% [13/173]; OR = 2.60; 95% CI, 1.04–6.50), and palpitations (11.5% [6/52] vs 2.9% [5/173]; OR = 3.99; 95% CI, 1.15–13.84). No significant gender differences were found in the proportions of patients experiencing arm or shoulder pain, diaphoresis, dyspnea, fatigue, neck pain, abdominal pain, vomiting, jaw pain, or syncope/lightheadedness. No significant differences were found in the duration, type, or location of chest pain. The medical charts listed numerically more symptoms in women than in men; 73.1% (38/52) of the women but only 48.0% (83/173) of the men reported >3 symptoms (age-adjusted OR = 3.26; 95% CI, 1.62–6.54).Conclusions: Chest pain is the most common presenting symptom in both women and men with AMI. Nausea, back pain, dizziness, and palpitations were significantly more common in women. Women as a group displayed a greater number of symptoms than did men.     

Age-related renal disease in female Dahl salt-sensitive rats is attenuated with 17²-estradiol supplementation by modulating nitric oxide synthase expression

Background: The incidence of chronic renal disease in women increases with aging, especially after menopause, suggesting that loss of sex hormones may contribute to the development and progression of renal disease. However, the mechanisms by which sex hormones, particularly estrogens, contribute to the disease process are unclear.Objective: The present study examined the effects of ovariectomy (OVX) with or without 17²-estradiol (E₂) supplementation (OVX+E₂) on the expression of inducible (iNOS) and endothelial (eNOS) nitric oxide synthase in the kidney.Methods: The study was performed in young (4 months [4M]) and aged (12 months [12M]) female Dahl salt-sensitive rats fed a low-sodium (0.1% NaCl) diet. At 3 months of age, the animals were either subjected to sham surgery, OVX, or OVX with implantation of an E₂ silastic pellet. The treatments were administered for either 1 or 9 months, rendering the animals 4 months of age or 12 months of age at the time of sacrifice, respectively. Renal expression of NOS isoforms was measured by Western blotting and immunohistochemistry.Results: OVX in the aged rats was associated with 35% and 25% decreases in medullary iNOS (mean [SEM] relative optical density [ROD]: 4M OVX, 1.81 [0.14] vs 12M OVX, 1.17 [0.16]; P < 0.05) and eNOS (mean ROD: 4M OVX, 1.91 [0.09] vs 12M OVX, 1.43 [0.15]; P < 0.05) protein expression, respectively, and a 25-fold increase in the abundance of CD68-positive cells, indicating macrophage infiltration (mean cells/mm²: 4M OVX, 1.18 [0.09] vs 12M OVX, 30.0 [0.74]; P < 0.001). E₂ supplementation either partially or completely attenuated these changes in iNOS (mean ROD: 4M OVX+E₂, 2.26 [0.08] vs 12M OVX+E₂, 1.70 [0.09]; P < 0.05), eNOS (mean ROD: 4M OVX+E₂, 2.03 [0.07] vs 12M OVX+E₂, 1.77 [0.11]; P = NS) and CD68 (mean cells/mm²: 4M OVX+E₂, 1.46 [0.07] vs 12M OVX+E₂, 6.87 [1.6]; P < 0.01) associated with OVX in the aging kidney.Conclusions: These data suggest that ovarian E₂ loss with aging may contribute to the development of age-related renal disease through downregulation of iNOS and eNOS protein abundance and increased renal inflammation in this animal model. Furthermore, E2 supplementation may be protective in the aging kidney by attenuating these changes.     

Predictors of depressive symptoms post-acute coronary syndrome

Objective: We examined the influence of gender on the prevalence of acute coronary syndrome (ACS) and the severity of depressive symptoms post-ACS.Methods: Patients received a Zung self-assessment questionnaire at hospital discharge for unstable angina (UA) or acute myocardial infarction (AMI) and returned it by mail. Major depressive symptoms were diagnosed based on a summed depressive symptoms (SDS) score of >50. Depressive symptomatology was modeled by stepwise multivariable logistic regression with the following predictors: gender, age, hypertension, diabetes mellitus, history of smoking, hypercholesterolemia, peripheral vascular disease, prior stroke, prior myocardial infarction (MI), and prior percutaneous coronary intervention or coronary artery bypass graft surgery. We also modeled severity of depressive symptoms via stepwise multiple linear regression with the same predictor variables.Results: A total of 944 patients were surveyed: 716 men and 228 women, mean (SD) age, 67 (13) years and 71 (12) years, respectively. Of these patients, 250 (35%) men and 103 (45%) women had depressive symptoms (P = 0.005). No significant difference was observed between men and women in rates of cardiac catheterization; severity of coronary artery disease; treatment with antiplatelet agents, β-blockers, angiotensin-converting enzyme inhibitors, or statins; or percutaneous or surgical revascularization rates during or post-ACS. Significant predictors of the presence of depressive symptoms were female gender (odds ratio [OR] = 1.64; 95% CI, 1.19-1.28), diabetes mellitus (OR = 1.42; 95% CI, 1.03-1.97), prior MI (OR = 1.56; 95% CI, 1.15-2.20), and smoking (OR = 1.41; 95% CI, 1.01-1.97). Variables significantly associated with a higher severity of depressive symptoms were female gender, prior MI, smoking, and stroke. Men with prior MI had significantly higher mean (SD) SDS scores than did men without prior MI in all age groups (48.4 [11] vs 44.6 [11], respectively; P < 0.001). In addition, significantly more men with prior MI had depressive symptoms compared with those without prior MI (45% vs 32%; P = 0.001). However, prior MI did not appear to affect SDS scores in women (49.1 [12] for prior MI vs 48.5 [12] for no prior MI; P = NS), and there was no significant difference in the percentage of women who had depressive symptoms with or without a history of prior MI. Depressive symptoms were much more severe in women with UA (SDS = 49.0 [12]) compared with women with AMI (SDS = 45.0 [12]; P = NS), or men with AMI (45.0 [12]; P = 0.004) or UA (46.0 [11]; P = 0.007) (analysis of variance, P = 0.003).Conclusions: Female gender is a significant independent predictor of depressive symptoms and their severity post-UA and post-AMI. History of prior MI is associated with a higher frequency and severity of depressive symptoms in men. These findings call for routine screening for depressive symptoms in men with prior MI and in women who present with ACS.     

Comparison of oxidative stress and antioxidant capacity before and after running exercises in both sexes

Background: It has been difficult to determine, from the published literature, whether men or women have higher levels of exercise-induced oxidative stress.Objective: The aim of this study was to compare variations between the sexes in lipid hydroperoxide (LPO), superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), and lactate dehydrogenase (LDH) after 3 different running exercises performed at the same speed.Methods: Eligible participants were healthy university students of both sexes. The participants performed running exercise tests at distances of 800, 1500, and 3000 m at a speed of 10 km/h. Blood samples were taken from the participants just before and immediately after the running activities to determine LPO, SOD, CAT, GR, and LDH, and these measures were compared both before and after exercise and between the sexes.Results: A total of 17 young and healthy, but not physically trained, students (n = 8 men; mean age, 22.00 years; n = 9 women; mean age, 21.78 years) participated in this study. Height, weight, and maximum oxygen consumption values were significantly higher in men than in women (P = 0.01). Significant gender effects were found in LPO levels at 3000 m (F = 5.51; P = 0.03) and in SOD activity at 800 m (F = 7.92; P = 0.01) and 3000 m (F = 6.05; P = 0.03). CAT activity also differed between the sexes at 800 m (F = 15.67; P = 0.01) and 1500 m (F = 6.55; P = 0.02). However, no significant gender-time interaction effect was observed for any measurement at the 800-, 1500-, and 3000-m distances.Conclusions: Changes in LPO, SOD, and CAT activities at different running distances were not different between men and women over time because of a nonsignificant gender-time interaction. With regard to changes in oxidative stress, men and women had similar responses to exercise at the same absolute workload, despite significant differences in physical characteristics.     

Effects of gender and depression on oral medication adherence in persons with type 2 diabetes mellitus

Background: In a range of chronic conditions including diabetes, it has been observed that depressive symptoms may be associated with nonadherence to medications.Objective: The objective of the study was to determine the main effects, and interactive effect, of depression and gender on patients adherence to oral diabetes medications.Methods: A cross-sectional design was employed, in which persons with type 2 diabetes mellitus completed a questionnaire regarding medication use behaviors, depressive symptoms (measured by the 8-item Patient Health Questionnaire [PHQ-8]), health beliefs, and demographics. A 2 x 2 factorial analysis of variance was used to determine the effects of gender and depression on medication adherence after adjusting for age, education, self efficacy, social support, and number of doses of diabetes medications.Results: Of the 391 respondents who completed the questionnaire, 73 (18.7%) were categorized as having depression (ie, PHQ-8 score >10). Overall, women (n = 196) had a mean (SD) score of 6.10 (6.19) on the PHQ-8, and men (n = 195) had a lower score of 4.62 (5.28) (t = 2.75; P < 0.01). There was a significant main effect of depression, but not gender, on patients' adherence to diabetes medications in that those who were categorized as depressed had significantly worse adherence to diabetes medications (F = 4.82; P = 0.03).Additionally, there was a significant “gender x depression” interaction effect on adherence (F = 5.93; P = 0.01). Men with depression had mean adherence scores that indicated more nonadherence than did men without depression (9.44 [3.45] vs 7.47 [2.50], respectively), but adherence varied little between women with depression and women without depression (7.83 [2.69] vs 7.55 [2.58], respectively).Conclusions: The association between depression and medication adherence appears to be stronger in men than in women. Clinicians should be cognizant of the potential effect of depression on self-care for diabetes, particularly in men with depressive symptoms.     

The influence of gender on adults admitted for asthma

Background: In the United States, the prevalence of asthma is not only higher than in most other countries, it also varies greatly between diverse populations. Only limited data exist that examine the variation of outcomes by gender in patients admitted to a hospital for asthma.Objective: This study assessed outcome differences based on gender in adults who were admitted nationally with the primary diagnosis of asthma.Methods: A retrospective cohort study was conducted of all patients who were admitted to a hospital with the primary diagnosis of asthma in 2002-2005 and were reported in the Nationwide Inpatient Sample of the Healthcare Cost and Utilization Project. Patients were excluded if they were aged <18 years or had an additional diagnosis of chronic obstructive pulmonary disease.Results: A total of 590,410 patients (439,991 women, 150,419 men) were included in the study. Patients admitted for asthma were significantly more likely to be female (P < 0.05). Women were significantly older compared with men (mean [SD], 48.5 [17.4] vs 44.6 [17.0] years, respectively), had a longer length of stay (3.44 vs 2.84 days), were more likely to be white (37.9% vs 34.2%), and had a higher total cost of admission ($10,575 vs $9390) (all, P < 0.05). Women were more likely than men to need a tracheostomy (adjusted odds ratio [AOR] = 2.04; 95% CI, 1.77-2.35) and to have a bronchoscopy (AOR =1.12; 95% CI, 1.05-1.21). Men were significantly more likely than women to have arterial blood gases performed (AOR = 1.15; 95% Cl, 1.05-1.27) and to be intubated (AOR = 1.18; 95% Cl, 1.10-1.26) (both, P < 0.05). Men were significantly more likely to be admitted as an emergency admission (AOR = 1.10; 95% Cl, 1.04-1.18) and to die during hospitalization (AOR =1.69; 95% CI, 1.41-2.03).Conclusion: Although they were less likely to be admitted to a hospital, men were more likely to be admitted as an emergency and to experience worse outcomes compared with women, in this study of adults with asthma in the United States.     

Gender-specific differences in bladder cancer: A retrospective analysis

Background: A higher incidence of bladder cancer has been reported in men compared with women. Clinical gender differences have been observed but are less well described.Objective: This retrospective analysis further examines clinical differences in the development and manifestation of bladder cancer between men and women.Methods: Consecutive male and female patients with bladder cancer treated between 1969 and 1997 at a single center (University Hospital of Innsbruck, Innsbruck, Austria) were included in the study. Patient characteristics regarding age, tumor classification, localization, and recurrence were compared between male and female patients. Statistical analysis was conducted using the t test, the χ² test, and the Kaplan-Meier method, with the log-rank test for subgroup analysis.Results: In the 1269 patients (876 men, 393 women) who were examined, 1744 tumors were found. The male-to-female bladder cancer incidence ratio was 2.2:1. Tumors were diagnosed at a significantly younger age in men than in women (mean age: 62 years vs 67 years, respectively; P < 0.001). No difference in the histology of tumors was observed between the sexes. Muscle-invasive tumors more frequently occurred in men than in women (39.8% vs 34.5%; P = NS). In men compared with women, primary tumors were more aggressive (grade 2, 36.6% vs 28.2%; P < 0.001) and tumor recurrences were more invasive (59.0% vs 57.8%; P = NS). Tumors were more often located in the urethra in men than in women (43 [3.4%] vs 9 [1.8%]; P = 0.034), the trigonum (246 [19.8%] vs 75 [14.9%]; P < 0.001), and the bladder dome or vault (128 [10.3%] vs 37 [7.4%]; P = 0.015). Generally, no difference in survival rate was observed between the sexes; only in the subgroup of muscle-invasive tumors (n = 455) did women have a worse overall survival rate than did men (P = 0.022).Conclusions: Clinical gender differences in bladder cancer appear to have a higher incidence in men than in women. In this analysis, women were older at the age of detection, but had less-invasive and less-aggressive tumors than did men. However, women with muscle-invasive disease had a worse overall survival rate than did men in the same subset.     

Blood oxidative stress biomarkers: influence of sex,exercise training status,and dietary intake

Background: Sex and lifestyle factors are known to influence the oxidation of protein, lipids, and DNA. Biomarkers such as protein carbonyls (PC), malondialdehyde (MDA), and 8-hydroxydeoxyguanosine (8-OHdG) have been commonly used in an attempt to characterize the oxidative status of human subjects.Objective: This study compared resting blood oxidative stress biomarkers, in relation to exercise training status and dietary intake, between men and women.Methods: Exercise-trained and sedentary men and women (with normal menstrual cycles; reporting during the early follicular phase) were recruited from the University of Memphis, Tennessee, campus and surrounding community via recruitment flyers and word of mouth. Participants were categorized by sex and current exercise training status (ie, trained or untrained). Each completed a detailed 5-day food record of all food and drink consumed. Diets were analyzed for kilocalories and macro- and micronutrient (vitamins C, E, A) intake. Venous blood samples were obtained at rest and analyzed for PC, MDA, and 8-OHdG.Results: In the 131 participants (89 men, of whom 74 were exercise trained and 15 untrained, and 42 women, of whom 22 were exercise trained and 20 untrained; mean [SD] age, 24 [4] years), PC did not differ significantly between trained men and women or between untrained men and women. However, trained participants had significantly lower plasma PC (measured in nmol · mg protein^-1) (mean [SEM] 0.0966 [0.0055]) than did untrained participants (0.1036 [0.0098]) (P < 0.05). MDA levels (measured in μmol · L^-1) were significantly lower in trained women (0.4264 [0.0559]) compared with trained men (0.6959 [0.0593]); in trained men and women combined (0.5621 [0.0566]) compared with untrained men and women combined (0.7397 [0.0718]); and in women combined (0.5665 [0.0611]) compared with men combined (0.7338 [0.0789]) (P < 0.05 for all comparisons). No significant differences were noted between any groups for 8-OHdG. Neither PC nor 8-OHdG were correlated to any dietary variable, with the exception of PC and percent of protein in untrained men (r = 0.552; P = 0.033). MDA was positively correlated to protein intake and negatively correlated to percent of carbohydrate and vitamin C intake, primarily in trained men (P ≤ 0.03).Conclusions: In this sample of young healthy adults, oxidative stress was lower in women than in men and in trained compared with untrained individuals, particularly regarding MDA. With the exception of MDA primarily in trained men, dietary intake did not appear to be correlated to biomarkers of oxidative stress.     

Female protection in progressive renal disease is associated with estradiol attenuation of superoxide production

Background: Several types of renal disease progress at a faster rate in men compared with women, but the reasons for this sex difference are not well understood. Chronic renal disease is associated with elevated levels of toxic reactive oxygen species (ROS). Superoxide, the major ROS in the kidney, is generated by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase.Objective: To determine if female protection from renal disease progression is consistent with 17β-estradiol (E₂) attenuation of superoxide production, this study was conducted to assess superoxide production in the renal cortex of male and female control and renal wrap (RW) rats, as well as in ovariectomized rats treated with vehicle or E₂.Methods: Sprague-Dawley rats were divided into 2 sham operation male (Sham-M) and female (Sham-F) control groups, and 4 RW hypertensive groups: RW-M; RW-F; RW ovariectomized females treated with vehicle (RW-OVX); and RW ovariectomized females treated with E₂, supplied as a 0.24 mg/60-day release pellet (RW-OVX+E₂). All groups were maintained on a high-sodium (4% NaCl) diet for 6 weeks.Results: Mean (SEM) markers of renal injury and oxidative stress, including urinary protein (mg/24 h: RW-M, 298 [31] vs RW-F, 169 [22]; P < 0.001), microalbuminuria (RW/Sham arbitrary units [AU]/24 h: M, 8.78 [0.58] vs F, 4.31 [1.0]; P < 0.005), and malondialdehyde (nmol/24 h: RW-M, 167 [23] vs RW-F, 117 [8.5]; P < 0.05) levels, as well as mean glomerular volume (μm³ × 10⁶: RW-M, 2.25 [0.16] vs RW-F, 1.25 [0.04]; P < 0.001) and the glomerulosclerotic index (AU: RW-M, 2.64 [0.19] vs RW-F, 1.10 [0.09]; P < 0.001) were greater in both control and RW males compared with females in the same treatment groups. Though RW surgery increased mean arterial pressure in both male and female rats, no sex difference was observed. Under these conditions, mean (SEM) renal cortical NADPH oxidase activity was 1.3-fold higher in RW males compared with RW females (relative light units [RLU]/180 sec: RW-M, 4080 [240] vs RW-F, 3200 [260]; P < 0.05). Ovariectomy increased NADPH oxidase activity by 1.4-fold (RLU/180 sec: RW-OVX, 4520 [184]; P < 0.01) under conditions in which the mean glomerular volume and glomerulosclerotic index were both increased by 1.5-fold, whereas E₂ replacement (RLU/180 sec: RW-OVX+E₂, 2745 [440]) prevented these effects. Furthermore, the effects on NADPH oxidase activity were mirrored by changes in the protein abundance of NADPH oxidase subunit p22P^phox.Conclusion: These results suggest that E₂ protects the female kidney in part by attenuating injury-induced increases in renal superoxide production.     

Disease Presentation and Remission Rate in Graves Disease Treated With Antithyroid Drugs: is Gender Really A Factor?

Objective: Male gender is considered an adverse prognostic factor for remission of Graves disease treatment with antithyroid drugs (ATDs), although published data are conflicting. This often results in early consideration of radioiodine treatment and surgery for men. Our objective was to compare disease presentation and outcome in men versus women treated with ATDs.Methods: Retrospective study of 235 patients (64 men, 171 women) with Graves disease who were evaluated for features at presentation and outcome at the end of follow-up between 2010 and 2015.Results: Disease presentation was similar in men and women for age at diagnosis (41.4 ± 14 years vs. 40 ± 15 years), duration of follow-up (6.6 ± 7 years vs. 7.7 ± 6 years), rates of comorbid autoimmune diseases, and rate of Graves ophthalmopathy. Smoking was more prevalent in males (31% vs. 15%; P = .009). Free thyroxine and triiodothyronine levels were comparable. ATDs were first-line treatment in all males and in 168 of 171 females, for a median duration of 24 and 20 months, respectively (P = .55). Remission rates were 47% in men and 58% in women (P = .14). Males had fewer adverse events (9% vs. 18%) and treatment discontinuation (5% vs. 16%). Disease recurrence was comparable (14% vs. 20%; P = .32), as was requirement for second-line treatment, either radioiodine therapy or thyroidectomy.Conclusion: Graves disease presentation is similar in men and women. Men treated with ATDs have high remission rates and similar recurrence rates compared to women, with fewer adverse events and less discontinuation of treatment. ATDs are an attractive first-line treatment for both genders.Abbreviations: ATA = American Thyroid Association; ATD = antithyroid drug; GO = Graves ophthalmopathy; T3 = triiodothyronine; T4 = thyroxine; TSH = thyroid-stimulating hormone     

Gender differences in psychosocial responses to lung cancer

Background: Although biologically based sex differences in the smoking patterns, epidemiology, biomedical markers, and survival rates associated with lung cancer are well documented, examinations of psychosocial gender differences are scarce.Objective: This cross-sectional study examined gender differences in psychosocial factors that are important in the medical management of lung cancer.Methods: A convenience sample of patients who were attending a multidisciplinary lung cancer treatment center (Markey Cancer Center, Lexington, Kentucky) were invited to complete a psychosocial needs assessment. Eligibility criteria included primary diagnosis of lung cancer, age ≥18 years, and being cognitively intact. Measures focused on psychosocial resources, treatment decision-making, social consequences of treatments, and treatment outcomes. Data were collected between the fall of 2005 and the summer of 2006.Results: A total of 47 women and 53 men (mean [SD] age, 62.81 [12.01] years; 95% white) completed the needs assessment. Gender was not found to be associated with demographic characteristics, time until diagnosis, treatment, or survival rate. Smoking histories differed significantly in the proportion of women and men who smoked or were former smokers (P = 0.01) as well as the age when they began to smoke (P = 0.02). There were no significant gender differences in social support networks, general coping, information needs, treatment decision satisfaction, functional health, life satisfaction, financial impact, or service needs. However, significant gender differences did indicate that women favored spiritual practices (P = 0.02) and religious coping (P = 0.04), and were more likely to endorse having a life mission (P = 0.03) and being part of a divine plan (P = 0.01).Conclusions: Previous research has found that religiousness and spirituality improved depressive symptoms and may ease end-of-life despair. In the present study of patients with lung cancer, gender differences in religiousness and spirituality suggest that this may be especially true for women, and that interventions should be directed toward their religious practices and coping.     

Sex-specific differences in the expression levels of estrogen receptor subtypes in colorectal cancer

Background: Altered expression of estrogen receptors alpha and beta (ERα and ERβ) has been hypothesized to play a role in carcinogenesis. However, little is known about the sex-specific differences of ER expression in colorectal cancer (CRC).Objective: This study examined ERα and ERβ protein levels in male and female patients with CRC.Methods: Using Western blot analysis, the intensity of ERα and ERβ protein levels was determined in tumor tissue and in corresponding normal colon mucosa from patients with CRC.Results: All 64 white patients (33 men, mean [SEM] age 64.1 [13.1] years, age range 26-90 years; 31 women, mean age 68.5 [14.5] years, age range 39-91 years [4 were premenopausal at time of surgery]) expressed ERα and ERβ protein in normal colon mucosa, and there were no significant differences between men and women. In tumor tissue, a significantly increased ERα protein level was observed in men (P = 0.02 vs normal tissue), whereas in women, the ERα level did not differ significantly between tumor and normal tissue. The level of ERβ protein in CRC was significantly reduced in both men and women, but more so in men (P = 0.04 vs women). Furthermore, in men, the ERβ level was significantly lower in poorly differentiated tumors than in moderately differentiated tumors (P < 0.03), whereas in women, poor differentiation of the tumor was not associated with a significant decrease of ERβ level.Conclusions: Altered levels of ER subtypes resulting in an increased ERα:ERβ ratio were found in patients with CRC. The observation of significantly greater alterations in men than in women supports the hypothesis of sex-specific differences in the pathogenesis of CRC.     

Relationship between serum progesterone concentrations and cardiovascular disease,diabetes, and mortality in elderly Swedish men and women: An 8-Year prospective study

Background: The use of synthetic progesterone-like substances in hormone replacement therapy and birth control pills has been associated with increases in cardiovascular morbidity and the prevalence of diabetes.Objectives: The primary aims of this study were to investigate whether physiologic concentrations of progesterone might also be associated with cardiovascular disease and diabetes, and to explore potential gender differences in these associations in elderly Swedish men and women.Methods: This prospective, longitudinal study was performed in a Swedish population-based sample of opposite-sex twins aged between 71 and 80 years who were not receiving sex hormone therapy. Serum concentrations of progesterone, estradiol, C-reactive protein (CRP), and urea were measured at baseline (1996) and at 8-year follow-up (2004), and serum concentrations of cystatin and insulin were measured only at follow-up. The outcomes of interest were cardiovascular morbidity (myocardial infarction, angina pectoris, peripheral arterial disease, stroke, congestive heart failure [CHF], cardiac arrhythmia, hypertension, and thromboembolism), diabetes, and mortality throughout the observation period.Results: At baseline, the study sample included 230 men and 195 women (mean [SD] age, 74.6 [2.6] years). At follow-up, 132 men and 145 women (mean age, 82.4 [2.5] years) met the inclusion criteria, of whom 128 men and 112 women did so at both baseline and follow-up. Serum progesterone concentrations, which did not differ significantly from reported concentrations for the age group, were significantly associated with mortality across the observation period (P < 0.001). At follow-up, higher serum progesterone was significantly associated with the occurrence of CHF (P < 0.01); this association remained robust after adjustment for CRP, cystatin, and insulin levels.Conclusion: In these elderly Swedish men and women, increased physiologic concentrations of progesterone were found to be associated with an increased prevalence of CHF, independent of inflammatory factors, markers of renal function, and insulin metabolism.     

Gender differences in help-seeking behavior on two internet forums for individuals with self-reported depression

Background: The published literature reflects differences between the sexes in the help-seeking behavior of individuals with depression. Professional mental health services reach men to a lesser extent than women. Internet forums are considered an option to better reach males specifically.Objective: We investigated gender differences in the active use of the Internet to access English- and German-language information on depression.Methods: Analysis differentiated contributors' sex for 200 threads (clusters of responses related to one person seeking advice) followed on 2 Internet forums, www.defeatdepression.org, originating from the United Kingdom, and www.verrueckt.de, originating from Germany. From the qualifying date of January 3, 2007, the investigated threads retrospectively reached 149 days. Using 2 variables, “sex ratio of regular Internet users” and “epidemiologically expected sex ratio,” we calculated a hypothetical value for the female-to-male (F:M) ratio of requests for help of 1.23 for the United Kingdom and 1.16 for Germany. Then we compared the actual versus the estimated gender distributions with a 2-sided x² test.Results: We included 89 queries from www.defeatdepression.org and 97 queries from www.verrueckt.de. On the English-language forum, 46 (52%) of the queries were from women and 43 (48%) from men. On the German-language forum, 67 (69%) of the queries were from women and 30 (31%) from men. The German forum had a significantly higher F:M ratio of contributors compared with the English forum (2.23 vs 1.07, respectively; x² = 5.885; P = 0.015). The actual F:M ratio of contributors for the English forum was similar to the expected calculation (1.07 actual vs 1.23 expected; x² = 0.230; P = 0.652), but was significantly lower than the actual versus the expected F:M ratio of contributors for the German forum (2.23 actual vs 1.16 expected; x² = 4.891; P = 0.027).Conclusion: Possible reasons for the German Internet forum having a higher F:M ratio of contributors compared with the English Internet forum are the differences in presentation style, language, and cultural context between the 2 Web sites.     

Age-Dependent Influence of Gender on the Association Between Obesity and a Cluster of Cardiometabolic Risk Factors

BackgroundObesity is a main risk factor in metabolic syndrome. Gender is known to influence the risk of obesity and other cardiovascular risk factors. However, it remains to be determined whether there is a gender-specific difference in the relationship between obesity and accumulation of other cardiometabolic risk factors such as hypertension, dyslipidemia, and diabetes.ObjectiveThe aim of this study was to determine whether the association between obesity and a cluster of other cardiometabolic risk factors is modified by gender.MethodsThe subjects were 17,791 Japanese men and women who were divided into younger (35–40 years) and older (60–70 years) age groups. The relationships between obesity (body mass index [BMI] ≥25 kg/m² or waist-to-height ratio [WHtR] ≥0.5) and multiple cardiometabolic risk factors (≥2 of the risk factors of high blood pressure, dyslipidema, and hyperglycemia) were compared between men and women in each age group.ResultsIn the younger group, the crude odds ratios (ORs) for multiple cardiometabolic risk factors in obese versus nonobese subjects were significantly higher in women than in men (BMI: 6.23 [range, 5.53–7.02] in men vs 16.63 [range, 12.37–22.37] in women, P < 0.01; WHtR: 6.04 [range, 5.36–6.81] in men vs 9.77 [range, 7.14–13.37] in women, P < 0.01), whereas this difference was not found in the older group (BMI: 3.03 [range, 2.69–3.42] in men vs 2.92 [range, 2.33–3.67] in women P = 0.076; WHtR: 3.11 [range, 2.78–3.47] in men vs 2.50 [range, 2.02–3.09] in women, P < 0.05). On multivariate logistic regression analysis, the ORs for multiple cardiometabolic risk factors after adjusting for age, smoking, alcohol consumption, and regular exercise in subjects with versus subjects without a large waist circumference tended to be higher in women than in men in the younger group but not in the older group. The ORs of the interaction term consisting of gender and each adiposity index for multiple cardiometabolic risk factors were significantly higher than a reference level of 1.00 in the younger group (BMI: 2.68 [range, 1.95–3.69], P < 0.01; WHtR: 1.62 [range, 1.16–2.27], P < 0.01) but not in the older group (BMI: 0.95 [range, 0.74–1.23], P = 0.712; WHtR: 0.80 [range, 0.63–1.02], P = 0.066).ConclusionThe results suggest that the association between obesity and a cluster of cardiometabolic risk factors is stronger in women than in men, and this gender-specific difference exists in younger (35–40 years) but not in older (60–70 years) individuals.     

Gender differences in self-rated health,quality of life,quality of care,and metabolic control in patients with diabetes

Background: Because the projected increase in the number of diabetic patients is expected to strain the capabilities of health care providers worldwide, we are challenged to find ways of reducing the burden of diabetes. Maintaining and improving health-related quality of life (QoL) for diabetic patients may be viewed as public health goals.Objective: The aim of this cross-sectional study was to compare different aspects of health, QoL, and quality of care (QoC) between men and women with diabetes as a basis for planning and managing diabees care.Methods: All patients in 2 age groups (aged 20–30 years [younger age group] and aged 50–60 years [middle-aged group]) who were registered with the Department of Endocrinology, Metabolism, and Diabetes at Karolinska University Hospital, Stockholm, Sweden, in October 2004, were recruited for a survey. Questions were included about self-rated health (SRH), QoL, QoC, diabetes-related worries, occupational status, physical activity level, living arrangements, and educational background. Glycosylated hemoglobin (HbA_1c) values were obtained from medical records.Results: Of the 223 eligible patients (109 men, 114 women) in the younger age group, 49 men and 74 women responded to the questionnaire; of the 300 eligible patients (170 men, 130 women) in the middle-aged group, 120 men and 93 women responded. Middle-aged women rated their mental well-being and QoL as worse compared with men (P < 0.001 and P < 0.05, respectively). In both age groups, women reported more diabetes-related worries and less ability to cope (P < 0.05 for the younger age group and P < 0.001 for the middle-aged group for both variables), thus the differences were more marked for middleaged women. Although there were no gender differences in metabolic control, middle-aged women reported less satisfaction with diabetes care (P < 0.001). Higher HbA_1c was related to worse SRH in both men and women when analyzing the age groups together (P < 0.05). This association was most prominent in young women, in whom having more diabetes-related worries was also related to higher HbA_1c (P < 0.01).Conclusion: In this study, women with diabetes appeared to have worse QoL and mental well-being compared with men with diabetes. Therefore, identifying strategies to improve SRH and QoL among diabetic patients, especially among women, is of great importance.