Niveles de actividad física, condición física y tiempo en pantallas en escolares de Bogotá, Colombia: Estudio FUPRECOL

Examina la relación entre los niveles de actividad física (AF) de forma objetiva, la condición física (CF) y el tiempo de exposición a pantallas en niños y adolescentes de Bogotá, Colombia.

Socioeconomic inequalities in weight status among mid-aged adults : the contribution of perceptions of weight status and weight-control behaviours

Background Socioeconomically-disadvantaged adults in developed countries experience a higher prevalence of a number of chronic diseases, such as cardiovascular disease, type 2 diabetes, osteoarthritis and some forms of cancer. Overweight and obesity are major risk factors for these diseases. Lower socioeconomic groups have a greater prevalence of overweight and obesity and this may contribute to their higher morbidity and mortality. International studies suggest that socioeconomic groups may differ in their self-perceptions of weight status and their engagement in weightcontrol behaviours (WCBs). Research has shown that lower socioeconomic adults are more likely to underestimate their weight status, and are less likely to engage in WCBs. This may contribute (in part) to the marked inequalities in weight status observed at the population level. There are few, and somewhat limited, Australian studies that have examined the types of weight-control strategies people adopt, the barriers to their weight control, the determinants of their perceived weight status and WCBs. Furthermore, there are no known Australian studies that have examined socioeconomic differences in these factors to better understand the reasons for socioeconomic inequalities in weight status. Hence, the overall aim of this Thesis is to examine why socioeconomically-disadvantaged group experience a greater prevalence of overweight and obesity than their more-advantaged counterparts. Methods This Thesis used data from two sources. Men and women aged 45 to 60 years were examined from both data source. First, the longitudinal Australian Diabetes, Obesity and Lifestyle (AusDiab) Study were used to advance our knowledge and understanding of socioeconomic differences in weight change, perceived weight status and WCBs. A total of 2753 participants with measured weights at both baseline (1999-2000) and follow-up (2004-2005) were included in the analyses. Percent weight change over the five-year interval was calculated and perceived weight status, WCBs and highest attained education were collected at baseline. Second, the Candidate conducted a postal questionnaire from 1013 Brisbane residents (69.8 % response rate) to investigate the relationship between socioeconomic position, determinants of perceived weight status, WCBs, and barriers and reasons to weight control. A test-retest reliability study was conducted to determine the reliability of the new measures used in the questionnaire. Most new measures had substantial to almost perfect reliability when considering either kappa coefficient or crude agreement. Results The findings from the AusDiab Study (accepted for publication in the Australian and New Zealand Journal of Public Health) showed that low-educated men and women were more likely to be obese at baseline compared to their higheducated respondents (O.R. = 1.97, 95 % C.I. = 1.30-2.98 and O.R. = 1.52, 95 % C.I. = 1.03-2.25, respectively). Over the five year follow-up period (1999-2000 to 2004- 05) there were no socioeconomic differences in weight change among men, however socioeconomically-disadvantaged women had greater weight gains. Participants perceiving themselves as overweight gained less weight than those who saw themselves as underweight or normal weight. There was no relationship between engaging in WCBs and five-year weight change. The postal questionnaire data showed that socioeconomically-disadvantaged groups were less likely to engage in WCBs. If they did engage in weight control, they were less likely to adopt exercise strategies, including moderate and vigorous physical activities but were more likely to decrease their sitting time to control their weight. Socioeconomically-disadvantaged adults reported more barriers to weight control; such as perceiving weight loss as expensive, requiring a lot of cooking skills, not being a high priority and eating differently from other people in the household. These results have been accepted for publication in Public Health Nutrition. The third manuscript (under review in Social Science and Medicine) examined socioeconomic differences in determinants of perceived weight status and reasons for weight control. The results showed that lower socioeconomic adults were more likely to specify the following reasons for weight control: they considered themselves to be too heavy, for occupational requirements, on recommendation from their doctor, family members or friends. Conversely, high-income adults were more likely to report weight control to improve their physical condition or to look more attractive compared with those on lower-incomes. There were few socioeconomic differences in the determinants of perceived weight status. Conclusions Education inequalities in overweight/obesity among men and women may be due to mis-perceptions of weight status; overweight or obese individuals in loweducated groups may not perceive their weight as problematic and therefore may not pay attention to their energy-balance behaviours. Socioeconomic groups differ in WCBs, and their reasons and perceived barriers to weight control. Health promotion programs should encourage weight control among lower socioeconomic groups. More specifically, they should encourage the engagement of physical activity or exercise and dietary strategies among disadvantaged groups. Furthermore, such programs should address potential barriers for weight control that disadvantaged groups may encounter. For example, disadvantaged groups perceive that weight control is expensive, requires cooking skills, not a high priority and eating differently from other people in the household. Lastly, health promotion programs and policies aimed at reducing overweight and obesity should be tailored to the different reasons and motivations to weight control experienced by different socioeconomic groups. Weight-control interventions targeted at higher socioeconomic groups should use improving physical condition and attractiveness as motivational goals; while, utilising social support may be more effective for encouraging weight control among lower socioeconomic groups.

Beneficial associations of physical activity with 2-h but not fasting blood glucose in Australian adults

OBJECTIVE - We examined the associations of physical activity with fasting plasma glucose (FPG) and with 2-h postload plasma glucose (2-h PG) in men and women with low, moderate, and high waist circumference. RESEARCH DESIGN AND METHODS - The Australian Diabetes, Obesity and Lifestyle (AusDiab) study provided data on a population-based cross-sectional sample of 4,108 men and 5,106 women aged >= 25 years without known diabetes or health conditions that could affect physical activity. FPG and 2-h PG were obtained from an oral glucose tolerance test. Self-reported physical activity level was defined according to the current public health guidelines as active (>= 150 min/week across five or more sessions) or inactive (< 150 min/week and/or less than five sessions). Sex-specific quintiles of physical activity time were used to ascertain dose response. RESULTS - Being physically active and total physical activity time were independently and negatively associated with 2-h PG. When physical activity level was considered within each waist circumference category, 2-h PG was significantly lower in active high-waist circumference women (beta-0.30 [95% CI -0.59 to -0.01], P = 0.044) and active low-waist circumference men(beta-0.25 [-0.49 to -0.02],P = 0.036) compared with their inactive counterparts. Considered across physical activity and waist circumference categories, 2-h PG levels were not significantly different between active moderate-waist circumference participants and active low-waist circumference participants. Associations between physical activity and FPG were nonsignificant. CONCLUSIONS - There are important differences between 2-h PG and FPG related to physical activity. It appears that 2-h PG is more sensitive to the beneficial effects of physical activity, and these benefits occur across the waist circumference spectrum.

A novel association of a polymorphism in the first intron of adiponectin gene with type 2 diabetes, obesity and hypoadiponectinemia in Asian Indians

Adiponectin is an adipose tissue specific protein that is decreased in subjects with obesity and type 2 diabetes. The objective of the present study was to examine whether variants in the regulatory regions of the adiponectin gene contribute to type 2 diabetes in Asian Indians. The study comprised of 2,000 normal glucose tolerant (NGT) and 2,000 type 2 diabetic, unrelated subjects randomly selected from the Chennai Urban Rural Epidemiology Study (CURES), in southern India. Fasting serum adiponectin levels were measured by radioimmunoassay. We identified two proximal promoter SNPs (-11377C-->G and -11282T-->C), one intronic SNP (+10211T-->G) and one exonic SNP (+45T-->G) by SSCP and direct sequencing in a pilot study (n = 500). The +10211T-->G SNP alone was genotyped using PCR-RFLP in 4,000 study subjects. Logistic regression analysis revealed that subjects with TG genotype of +10211T-->G had significantly higher risk for diabetes compared to TT genotype [Odds ratio 1.28; 95% Confidence Interval (CI) 1.07-1.54; P = 0.008]. However, no association with diabetes was observed with GG genotype (P = 0.22). Stratification of the study subjects based on BMI showed that the odds ratio for obesity for the TG genotype was 1.53 (95%CI 1.3-1.8; P < 10(-7)) and that for GG genotype, 2.10 (95% CI 1.3-3.3; P = 0.002). Among NGT subjects, the mean serum adiponectin levels were significantly lower among the GG (P = 0.007) and TG (P = 0.001) genotypes compared to TT genotype. Among Asian Indians there is an association of +10211T-->G polymorphism in the first intron of the adiponectin gene with type 2 diabetes, obesity and hypoadiponectinemia.

Has increasing the age for child passengers to wear child restraints improved the extent to which they are used? Results from an Australian focus group and survey study.

Acknowledgement that many children in Australia travel in restraints that do not offer them the best protection has led to recent changes in legislation such that the type of restraint for children under 7 years is now specified. This paper reports the results of two studies (observational; focus group/ survey) carried out in the state of Queensland to evaluate the effectiveness of these changes to the legislation. Observations suggested that almost all of the children estimated as aged 0-12 years were restrained (95%). Analysis of the type of restraint used for target-aged children (0-6 year olds) suggests that the proportion using an age-appropriate restraint has increased by an estimated 7% since enactment of the legislation. However, around 1 in 4 children estimated as aged under 7 years were using restraints too large for good fit. Results from the survey and focus group suggested parents were supportive of the changes in legislation. Non-Indigenous parents agreed that the changes had been necessary, were effective at getting children into the right restraints, were easy to understand as well as making it clear what restraint to use with children. Moreover, they did not see the legislation as too complicated or too hard to comply with. Indigenous parents who participated in a focus group also regarded the legislation as improving children’s safety. However, they identified the cost of restraints as an important barrier to compliance. In summary, the legislation appears to have had a positive effect on compliance levels and on raising parental awareness of the need to restrain children child-specific restraints for longer. However, it would seem that an important minority of parents transition their children into larger restraints too early for optimal protection. Intervention efforts should aim to better inform these parents about appropriate ages for transition, especially from forward facing childseats. This could potentially be through use of other important transitions that occur at the same age, such as starting school. The small proportion of parents who do not restrain their children at all are also an important community sector to target. Finally, obtaining restraints presents a significant barrier to compliance for parents on limited incomes and interventions are needed to address this.

Clinical and technical factors associated with skin intrinsic fluorescence in subjects with type 1 diabetes from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study

The Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications(EDIC) studies have established multiyear mean hemoglobin A1c (HbA1c) as predictive of microvascular complications in persons with type 1 diabetes. However, multiyear mean HbA1c is not always available in the clinical setting. Skin advanced glycation end products (AGEs) are thought to partially reflect effects of hyperglycemia over time, and measurement of skin AGEs might be a surrogate for multiyear mean HbA1c. As certain AGEs fluoresce and skin fluorescence has been demonstrated to correlate with the concentration of skin AGEs, noninvasive measurement by skin intrinsic fluorescence(SIF) facilitates the exploration of the association of mean HbA1c and other clinical/technical factors with SIF using the detailed phenotypic database available in DCCT/EDIC.

Long-term renal outcomes of patients with type 1 diabetes mellitus and microalbuminuria:an analysis of the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications cohort

Microalbuminuria is a common diagnosis in the clinical care of patients with type 1 diabetes mellitus. Long-term outcomes after the development of microalbuminuria are variable.

Increase in prevalence of obesity and diabetes and decrease in plasma cholesterol in a central Australian Aboriginal community

Objective: To document change in prevalence of obesity, diabetes and other cardiovascular diease (CVD) risk factors, and trends in dietary macronutrient intake, over an eight-year period in a rural Aboriginal community in central Australia. Design: Sequential cross-sectional community surveys in 1987, 1991 and 1995. Subjects: All adults (15 years and over) in the community were invited to participate. In 1987, 1991 and 1995, 335 (87% of eligible adults), 331 (76%) and 304 (68%), respectively, were surveyed. Main outcome measures: Body mass index and waist : hip ratio; blood glucose level and glucose tolerance; fasting total and high density lipoprotein (HDL) cholesterol and triglyceride levels; and apparent dietary intake (estimated by the store turnover method). Intervention: A community-based nutrition awareness and healthy lifestyle program, 1988-1990. Results: At the eight-year follow-up, the odds ratios (95% CIs) for CVD risk factors relative to baseline were obesity, 1.84 (1.28-2.66); diabetes, 1.83 (1.11-3.03); hypercholesterolaemia, 0.29 (0.20-0.42); and dyslipidaemia (high triglyceride plus low HDL cholesterol level), 4.54 (2.84-7.29). In younger women (15-24 years), there was a trebling in obesity prevalence and a four- to fivefold increase in diabetes prevalence. Store turnover data suggested a relative reduction in the consumption of refined carbohydrates and saturated fats. Conclusion: Interventions targeting nutritional factors alone are unlikely to greatly alter trends towards increasing prevalences of obesity and diabetes. In communities where healthy food choices are limited, the role of regular physical activity in improving metabolic fitness may also need to be emphasised.

Obesity and comorbid risk factors for cardiovascular disease among physically inactive patients with musculoskeletal disorders : a targeted intervention for this priority patient group is warranted

Introduction The benefits of physical activity are established and numerous; not the least of which is reduced risk of negative cardiovascular events. While sedentary lifestyles are having negative impacts across populations, people with musculoskeletal disorders may face additional challenges to becoming physically active. Unfortunately, interventions in ambulatory hospital clinics for people with musculoskeletal disorders primarily focus on their presenting musculoskeletal complaint with cursory attention given to lifestyle risk factors; including physical inactivity. This missed opportunity is likely to have both personal costs for patients and economic costs for downstream healthcare funders. Objectives The objective of this study was to investigate the presence of obesity, diabetes, diagnosed cardiac conditions, and previous stroke (CVA) among insufficiently physically active patients accessing (non-surgical) ambulatory hospital clinics for musculoskeletal disorders to indicate whether a targeted risk-reducing intervention is warranted. Methods A sub-group analysis of patients (n=110) who self-reported undertaking insufficient physical activity level to meet national (Australian) minimum recommended guidelines was conducted. Responses to the Active Australia Survey were used to identify insufficiently active patients from a larger cohort study being undertaken across three (non-surgical) ambulatory hospital clinics for musculoskeletal disorders. Outcomes of interest included body mass index, Type-II diabetes, diagnosed cardiac conditions, previous CVA and patients’ current health-related quality of life (Euroqol-5D). Results The mean (standard deviation) age of inactive patients was 56 (14) years. Body mass index values indicated that n=80 (73%) were overweight n=26 (24%), or obese n=45 (49%). In addition to their presenting condition, a substantial number of patients reported comorbid diabetes n=23 (21%), hypertension n=25 (23%) or an existing heart condition n=14 (13%); 4 (3%) had previously experienced a CVA as well as other comorbid conditions. Health-related quality of life was also substantially impacted, with a mean (standard deviation) multi-attribute utility score of 0.51 (0.32). Conclusion A range of health conditions and risk factors for further negative health events, including cardiovascular complications, consistent with physically inactive lifestyles were evident. A targeted risk-reducing intervention is warranted for this high risk clinical group.

Diabetes mellitus and the risk of depressive and anxiety disorders in Australian women: A longitudinal study

Background Longitudinal studies examining the risk of depressive and anxiety disorders associated with diabetes are limited. This study examined the association between diabetes and the risk of depressive and anxiety disorders in Australian women using longitudinal data. Methods Datawere froma sample of women who were part of anAustralian pregnancy and birth cohort study. Data comprised self-reported diabetes mellitus and the subsequent reporting of depressive and anxiety disorders. Mood disorders were assessed according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, obtained from participants using Composite International Diagnostic Interview (CIDI)-Auto (WHO WMH-CIDI CAPI, version 21.1.3). Multiple regression models with adjustment for important covariates were used. Results Women with diabetes had a higher lifetime prevalence of any depressive and/or anxiety disorder than women without diabetes. About 3 in 10 women with diabetes experienced a lifetime event of any depressive disorder, while 1 in 2 women with diabetes experienced a lifetime event of any anxiety disorder. In prospective analyses, diabetes was only significantly associated with a 30-day episode of any anxiety disorder (odds ratio [OR] 1.53, 95% confidence interval [CI] 1.09–2.15). In the case of lifetime disorders, diabetes was significantly associated with any depressive disorder (OR 1.37, 95% CI 1.03–1.84), major depressive disorder (OR 1.36, 95% CI 1.01–1.85), and posttraumatic stress disorder (OR 1.42, 95% CI 1.01–2.02). Conclusions The findings suggest that the presence of diabetes is a significant risk factor for women experiencing current anxiety disorders. However, in the case of depression, the association with diabetes only held for women who had experienced past episodes, there was no association with current depression. This suggests that the evidence is not strong enough to support a direct effect of diabetes as a cause of mood disorders.

Assessing the relationship between obesity and type II diabetes among South Asian Indians in Houston A population based study

Objective: My study aimed at determining the association between obesity and diabetes prevalence in South Asian Indian immigrants in Houston, Texas. To also compare the prevalence odds of diabetes given obesity, using WHO-BMI criteria and recommended Asian ethnic-specific BMI criteria for obesity, as well as using WHO-standard waist circumference criteria and ethnic-specific criteria for abdominal obesity, across gender and age, in this population. ^ Methods: My study was a secondary data analysis based on a cross-sectional study carried out on adult South Asian Indians who attended a local community health fair in Houston, in 2007. They recruited 213 voluntary, eligible, South Asian Indian participants aged between 18 to 79 years. Self reported history of Diabetes was obtained and height, weight, waist and hip circumference were measured. I classified BMI based on WHO-standard and ethnic-specific criteria, according to gender and age groups of 18–35 years, 36–64 years and 65 years and over. Waist circumference was also classified based on WHO-standard NCEP criteria and currently recommended ethnic-specific IDF criteria and analysis was done stratifying by gender and age groups. ^ Results: The prevalence of diabetes in this population was 14.6%, significantly higher in older age groups (25.8%) and males (19.2%). The prevalence of DM was statistically similar in individuals who were overweight/obese compared to those not overweight/obese, however in overweight/obese individuals, there was a statistically significant difference in the prevalence of DM between WHO and ethnic-specific criteria for both BMI and waist circumference. In older adults and in males, ethnic-specific criteria identified significantly more as overweight/obese compared to WHO-standard criteria. ^ Conclusions: Ethnic-specific criteria for both BMI and waist circumference give a better estimate for obesity in this South Asian Indian population. Diabetes is highly prevalent in migrant South Asian Indians even at low BMI or waist circumference levels and significantly more in males and older age groups, hence adequate awareness should be created for early prevention and intervention.^

Intake of isoflavone and lignan phytoestrogens and associated demographic and lifestyle factors in older Australian women

The purpose was to determine intake of phytoestrogens in a sample of older Australian women, and to investigate associated lifestyle factors. Subjects were an age-stratified sample of 511 women aged 40-80 y, randomly selected from the electoral roll and participating in the Longitudinal Assessment of Ageing in Women at the Royal Brisbane and Women’s Hospital. A cross-sectional study was conducted to assess isoflavone and lignan intake over the past month from food and supplements using a 112-item phytoestrogen frequency questionnaire. Data were also collected on nutrient intakes, physical activity, smoking, alcohol, non-prescription supplements, hormone therapy, education and occupation. Logistic regression was used to evaluate associations between demographic and lifestyle variables and soy/linseed consumption while controlling for age. Isoflavone intakes were significantly higher in the younger compared to older age groups (p<0.001); there were no age-related differences in lignan intake. Forty-five percent of women consumed at least one serve of a soy and/or linseed item and were defined as a soy/linseed consumer. Median (range) intakes by consumers for isoflavones and lignans (3.9 (0-172) mg/d and 2.4 (0.1-33) mg/d) were higher than intakes by non-consumers (0.004 (0-2.6) mg/d and 1.57 (0.44-4.7) mg/d), respectively (p<0.001). Consumers had higher intakes of dietary fibre (p=0.003), energy (p=0.04) and polyunsaturated fat (p=0.004), and higher levels of physical activity (p=0.006), socio-economic position (p<0.001), education (p<0.001) and supplement use (p<0.001). Women who consumed soy or linseed foods differed in lifestyle and demographic characteristics suggesting these factors should be considered when investigating associations with chronic disease outcomes.

The effect of a high fat meal on postprandial arterial stiffness in men with obesity and type 2 diabetes

Context: Postprandial dysmetabolism is emerging as an important cardiovascular risk factor. Augmentation index (AIx) is a measure of systemic arterial stiffness and independently predicts cardiovascular outcome. Objective: The objective of this study was to assess the effect of a standardized high-fat meal on metabolic parameters and AIx in 1) lean, 2) obese nondiabetic, and 3) subjects with type 2 diabetes mellitus (T2DM). Design and Setting: Male subjects (lean, n = 8; obese, n = 10; and T2DM, n = 10) were studied for 6 h after a high-fat meal and water control. Glucose, insulin, triglycerides, and AIx (radial applanation tonometry) were measured serially to determine the incremental area under the curve (iAUC). Results: AIx decreased in all three groups after a high-fat meal. A greater overall postprandial reduction in AIx was seen in lean and T2DM compared with obese subjects (iAUC, 2251 +/- 1204, 2764 +/- 1102, and 1187 +/- 429% . min, respectively; P < 0.05). The time to return to baseline AIx was significantly delayed in subjects with T2DM (297 +/- 68 min) compared with lean subjects (161 +/- 88 min; P < 0.05). There was a significant correlation between iAUC AIx and iAUC triglycerides (r = 0.50; P < 0.05). Conclusions: Obesity is associated with an attenuated overall postprandial decrease in AIx. Subjects with T2DM have a preserved, but significantly prolonged, reduction in AIx after a high-fat meal. The correlation between AIx and triglycerides suggests that postprandial dysmetabolism may impact on vascular dynamics. The markedly different response observed in the obese subjects compared with those with T2DM was unexpected and warrants additional evaluation.

Sleepless nights : the effect of socioeconomic status, physical activity, and lifestyle factors on sleep quality in a large cohort of Australian women

The aims of this study were to examine: (1) the association between sociodemographic and lifestyle factors and sleep quality in a population-based cohort of Australian women and (2) possible influence of reproductive status and mental and physical health factors on these associations. Data on 3,655 women (mean age046.6 years, range 34.3–67.4) were obtained from the Mater Hospital University of Queensland Study of Pregnancy for this cross-sectional study. Self-rated sleep quality was assessed using the Pittsburgh Sleep Quality Index. For the purpose of this study, two cutoff points (scores 5 and 10) were used to divide women into three categories: normal (65.2 %), moderately poor (26.4 %), and very poor sleep quality (8.5 %). Other covariates were measured at 21-year follow-up as well. After adjusting for reproductive status, mental and physical health, there were significant associations between moderately poor sleep quality and education and between very poor sleep quality and unemployment, both measures of socioeconomic status. In addition, work-related exertion was associated with increased rates of moderately poor sleep quality, whereas those women undertaking moderate exercise were less likely to experience very poor sleep quality. Independent associations between sociodemographic factors and exercise with moderately poor and very poor sleep quality were identified. These findings demonstrate the dynamic nature of the association between exercise/exertion, socioeconomic status, and sleep quality and highlight the importance of taking these into consideration when dealing with issues of poor sleep quality in women.

A longitudinal study of the impact of chronic psychological stress on health-related quality of life and clinical biomarkers : protocol for the Australian Healthy Aging of Women Study

BACKGROUND: Despite advancements in our understanding of the importance of stress reduction in achieving good health, we still only have limited insight into the impact of stress on cellular function. Recent studies have suggested that exposure to prolonged psychological stress may alter an individual's physiological responses, and contribute to morbidity and mortality. This paper presents an overview of the study protocol we are using to examine the impact of life stressors on lifestyle factors, health-related quality of life and novel and established biomarkers of stress in midlife and older Australian women.The primary aim of this study is to explore the links between chronic psychological stress on both subjective and objective health markers in midlife and older Australian women. The study examines the extent to which exposure frightening, upsetting or stressful events such as natural disasters, illness or death of a relative, miscarriage and relationship conflict is correlated with a variety of objective and subjective health markers.Methods/design: This study is embedded within the longitudinal Healthy Aging of Women's study which has collected data from midlife and older Australian women at 5 yearly intervals since 2001, and uses the Allostastic model of women's health by Groer and colleagues in 2010. The current study expands the focus of the HOW study and will assess the impact of life stressors on quality of life and clinical biomarkers in midlife and older Australian women to explain the impact of chronic psychological stress in women. DISCUSSION: The proposed study hypothesizes that women are at increased risk of exposure to multiple or repeated stressors, some being unique to women, and the frequency and chronicity of stressors increases women's risk of adverse health outcomes. This study aims to further our understanding of the relationships between stressful life experiences, perceived quality of life, stress biomarkers, chronic illness, and health status in women.