Normal Weight Postmenopausal Women Research Articles

Association of a Healthy Lifestyle Index with Risk of Breast Cancer among Women with Normal Body Mass Index in the UK Biobank.

A high healthy lifestyle index (HLI), a composite score based on good diet quality, low alcohol consumption, no smoking, moderate to high physical activity, and waist circumference <80 cm, has been consistently associated with a reduced risk of breast cancer. Recently, high levels of body fat were found to be associated with an elevated risk of breast cancer in postmenopausal women with a normal body mass index (BMI; 18.5-<25 kg/m2). Whether the HLI is associated with breast cancer risk in women with normal BMI is unknown. We studied 102,572 women aged 40 to 69 years with a normal BMI at enrollment into the UK Biobank cohort study. The HLI was created by assigning to each component higher scores for healthier behaviors and then summing the scores. The HLI was categorized by tertiles and age- and multivariable-adjusted HRs for the association of the HLI with breast cancer risk by menopausal status were estimated using Cox proportional hazards models. In postmenopausal women, compared with a low HLI, higher scores were associated with a reduced risk of breast cancer [HRHLI-3rd tertile = 0.76; 95% confidence interval (CI), 0.64-0.91]. Findings were similar for premenopausal women, although they did not reach statistical significance, except when smoking status was excluded from the HLI score (HLIwithout smoking: HR3rd tertile = 0.71; 95% CI, 0.56-0.90). In normal BMI postmenopausal women, a high HLI score was associated with a reduced risk of breast cancer. Following a healthy lifestyle may reduce the risk of breast cancer among normal weight postmenopausal women.

Increased trunk fat is associated with altered gene expression in breast tissue of normal weight women

Increased trunk fat is associated with an elevated risk of breast cancer in normal-weight postmenopausal women. The main objective of this study was to determine whether levels of trunk fat are associated with changes in breast gene expression in normal-weight women. Non-tumorous breast tissue was collected from 32 normal BMI women who underwent mastectomy for breast cancer risk reduction or treatment. Body composition was measured by dual-energy x-ray absorptiometry. High levels of trunk fat were associated with a large number of differentially expressed genes and changes in multiple pathways and processes potentially linked to breast cancer pathogenesis. High levels of trunk fat were also associated with an elevated immune score and increased levels of leptin, CCL2, VEGF-C, IL6, and aromatase. Collectively, these results help to explain why high levels of trunk fat are associated with an increased risk of breast cancer in normal BMI women.

The association of prediagnostic circulating levels of cardiometabolic markers, testosterone and sex hormone-binding globulin with risk of breast cancer among normal weight postmenopausal women in the UK Biobank.

Emerging evidence suggests that normal weight postmenopausal women with a relative excess of body fat are at increased breast cancer risk. However, little is known about the associations between obesity-related blood markers and risk of breast cancer among these individuals. In this prospective study comprising 58 629 normal weight postmenopausal women (body mass index between 18.5 kg/m2 and 24.9 kg/m2 ) who were enrolled in the UK Biobank cohort between 2006 and 2010, we examined the associations of glycated hemoglobin, triglycerides, high-density lipoprotein cholesterol, C-reactive protein (CRP), testosterone and sex hormone-binding globulin (SHBG) with risk of breast cancer. A total of 1268 postmenopausal breast cancer cases were ascertained during a median follow-up period of 7 years. Women with CRP, total testosterone and free testosterone (FT) levels in the highest quintile had increased risk of breast cancer compared to those in the lowest quintile (HRQ5 vs Q1 : 1.35, 95% confidence interval [CI]: 1.12-1.63, HR Q5 vs Q1 : 1.47, 95% CI: 1.20-1.80 and HR Q5 vs Q1 : 1.53, 95% CI: 1.23-1.90, respectively), whereas those with SHBG in the highest quintile had reduced risk (HR Q5 vs Q1 : 0.70, 95% CI: 0.56-0.88). These associations were attenuated but persisted after additional adjustment for BMI, fat mass index (whole body fat mass [kg]/height [m2 ]) or waist circumference and after mutual adjustment for testosterone, CRP and/or SHBG. Our study suggests that the risk of postmenopausal breast cancer among normal weight women is increased in association with relatively high levels of CRP and testosterone and with relatively low levels of SHBG.

The association between parity and metabolic syndrome and its components in normal-weight postmenopausal women in China

BackgroundStudies analyzing the association between parity and normal-weight metabolic syndrome (MetS) in postmenopausal women of normal weight remain limited, this study aimed to explore the association between parity and MetS among Chinese normal-weight postmenopausal women.MethodsIn total, 776 normal-weight undiagnosed type 2 diabetes postmenopausal women who visited the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University for a routine health check-up between 1 January 2017 and 31 December 2019 were included in the cross-sectional study. All individuals had fully completed information records encompassing standardized electronic medical records, physical examinations, and biochemical measurements. Metabolic health was defined as fewer than 2 parameters of the MetS were present, in combination with normal weight. Continuous variables which were normally distributed were expressed as means and standard deviation. Comparisons among normally distributed continuous variables were made using one-way ANOVA while that among non-normal distribution parameters were made using Kruskal-Wallis. The association between parity and MetS was analyzed using multivariate logistic regression. All of the analyses were performed with SPSS statistical software (Version 23.0, SPSS, Inc., Chicago, IL, USA) and the statistical software package EmpowerStats (http://www.empowerstats.com, X&Y Solutions, Inc., Boston, MA).ResultsAfter adjusting for potential confounding factors including hip circumference, parity was failed to show a significantly relationship with MetS in normal-weight women(P=0.054). Women with a higher parity (≥3) had an increased OR of abdominal obesity, while the OR (95% CI) of the parity 3 group was 2.06 (1.13, 3.77) and that of the parity ≥4 group was 3.08(1.42, 6.66) the P for trend was 0.002 after adjusting for potential confounding factors. No significant differences were detected for other metabolic disorders including high levels of triglycerides (TG), blood pressure, fasting plasma glucose (FPG), and decreased high-density lipoprotein cholesterol (HDL-C) in different parity groups.ConclusionsHigher parity was not associated with a higher risk of MetS in normal weight Chinese postmenopausal women. As for the components of MetS, only waist circumference was associated with multiparity even after controlling for hip circumference.

Abstract 16937: Gender Differences in Baseline Body Composition Profiles and Improvements With Visceral Fat-Focused Weight Loss Program

Cardiovascular disease (CVD) in women remains a leading cause of death. A recent study in the Journal of the American Medical Association highlighted the significant risk that central (or visceral) obesity confers in normal-weight postmenopausal women versus normal-weight women without central obesity- a 31% increase in premature death, including death from CVD and obesity-related cancer. Strategies targeting central obesity (visceral adipose tissue or visceral fat, VF) are a promising means to reduce the risk of, and events associated with CVD. A comprehensive telehealth program (20Lighter, 20L) combining patented customizable VLCD meal plans, nutritional supplementation, and expert daily oversight significantly reduces VF. Here we present data assessing body composition (BC) improvements between female (n= 931) and male (n= 1269) participants. We found the baseline BC profiles differed, with 3 of the 4 measures varying significantly between female and male participants (shown as female versus male, mean ± SEM): BMI (33.7 ±0.722 vs 35.4 ±0.511, p=0.0548), Body Fat (45.7% ±0.754 vs 38.8% ±0.613, p&lt;0.0001), VF (15.2 ±0.664 vs 22.7 ±0.563, p&lt;0.0001), and Intracellular Fluid (38.6% ±0.539 vs 45.2% ±0.303, p&lt;0.0001) (Figure1A). Interestingly, while baseline measures differed, both women and men achieved the same magnitude of relative percentage improvements in BC measures: BMI (12.9% ±0.192 vs 13.3% ±0.228, p=0.1798), Body Fat (19.5% ±0.560 vs 19.7% ±0.634, p=0.8131), VF (24.7% ±0.643 vs 25.9% ±0.633, p=0.1837), and Intracellular Fluid (6.9% ±0.366 vs 7.9% ±0.486, p=0.0970) (Figure1B). Our data suggest that while women and men have different baseline BC profiles, they achieve equally statistically significant and clinically meaningful changes in outcomes in an expert-supervised, structured comprehensive program that are associated with risk reduction for CVD and CVD-associated events including premature death, heart attack, and stroke.

Predictors of metabolic disease in normal weight postmenopausal women: A cross-sectional study

Predictors of metabolic disease in normal weight postmenopausal women: A cross-sectional study

Obesity and ethnicity\xa0alter gene expression in skin

Obesity is accompanied by dysfunction of many organs, but effects on the skin have received little attention. We studied differences in epithelial thickness by histology and gene expression by Affymetrix gene arrays and PCR in the skin of 10 obese (BMI 35–50) and 10 normal weight (BMI 18.5–26.9) postmenopausal women paired by age and ethnicity. Epidermal thickness did not differ with obesity but the expression of genes encoding proteins associated with skin blood supply and wound healing were altered. In the obese, many gene expression pathways were broadly downregulated and subdermal fat showed pronounced inflammation. There were no changes in skin microbiota or metabolites. African American subjects differed from European Americans with a trend to increased epidermal thickening. In obese African Americans, compared to obese European Americans, we observed altered gene expression that may explain known differences in water content and stress response. African Americans showed markedly lower expression of the gene encoding the cystic fibrosis transmembrane regulator characteristic of the disease cystic fibrosis. The results from this preliminary study may explain the functional changes found in the skin of obese subjects and African Americans.

Association between Dietary Energy Density and Obesity-Associated Cancer: Results from the Women’s Health Initiative

BackgroundDietary energy density (DED) is the ratio of energy (kilocalories or kilojoules) intake to food weight (grams) and is a measure of diet quality. Consumption of foods high in DED has been associated with weight gain in adults. ObjectiveTo investigate the association between baseline DED and incident obesity-associated cancers in the Women’s Health Initiative. DesignProspective cohort study of clinical trial and observational study participants. Participants/settingPostmenopausal women aged 50 to 79 years (N=92,295) enrolled in the observational study or the calcium and vitamin D trial and hormone replacement therapy trials of the Women’s Health Initiative. Main outcome measuresIncident, medical record-adjudicated, obesity-related cancers during follow-up. Exposure variable was DED (kilocalories per gram for the total diet) from self-reported dietary intake at baseline using a food frequency questionnaire. Statistical analysesThe associations between DED and each incident cancer, or any obesity-related cancer, were examined using competing-risks regression models, with death as a competing risk. Body mass index-stratified models were generated to investigate body mass index as a potential modifying factor. ResultsDED was associated with higher body mass index (28.9±6.0 vs 26.3±4.9) and waist circumference (89.3±14.2 vs 82.4±12.4 cm) for DED quintiles 5 vs 1, respectively. DED was associated with a 10% increased risk of any obesity-related cancer (subhazard ratioQ5 vs Q1: 1.1, 95% CI 1.03 to 1.2; P=0.004). This increased risk appeared limited to women who were normal weight at enrollment. ConclusionsHigher DED may be a contributing factor for obesity-related cancers, especially among normal-weight postmenopausal women and, as such, could serve as a modifiable behavior for dietary interventions to reduce obesity-associated cancer risk.

Metabolic Phenotype and Risk of Colorectal Cancer in Normal-Weight Postmenopausal Women.

The prevalence of metabolically unhealthy phenotype in normal-weight adults is 30%, and few studies have explored the association between metabolic phenotype and colorectal cancer incidence in normal-weight individuals. Our aim was to compare the risk of colorectal cancer in normal-weight postmenopausal women who were characterized by either the metabolically healthy phenotype or the metabolically unhealthy phenotype. A large prospective cohort, the Women's Health Initiative, was used. The analytic sample included 5,068 postmenopausal women with BMI 18.5 to <25 kg/m2 Metabolic phenotype was defined using the Adult Treatment Panel-III definition, excluding waist circumference; therefore, women with one or none of the four components (elevated triglycerides, low high-density lipoprotein cholesterol, elevated blood pressure, and elevated fasting glucose) were classified as metabolically healthy. Multivariable Cox proportional hazards regression was used to estimate adjusted HRs for the association between metabolic phenotype and risk of colorectal cancer. Among normal-weight women, those who were metabolically unhealthy had higher risks of colorectal cancer (HR, 1.49; 95% CI, 1.02-2.18) compared with those who were metabolically healthy. A metabolically unhealthy phenotype was associated with higher risk of colorectal cancer among normal-weight women. Normal-weight women should still be evaluated for metabolic health and appropriate steps taken to reduce their risk of colorectal cancer. Cancer Epidemiol Biomarkers Prev; 26(2); 155-61. ©2017 AACR.

Association of Obesity with Forearm Fractures, Bone Mineral Density and Fracture Risk (FRAX®) During Postmenopausal Period

Objective: The aim of this study was to investigate the association among obesity with bone mineral density (BMD) and subsequent fracture risk among postmenopausal women with a previous forearm fracture. Materials and Methods: The study enrolled obese (n=40) and normal-weight (n=40) postmenopausal women who had a previous forearm fracture. BMD measurements were obtained using a GE-LUNAR DPX dual energy X-ray absorptiometry scan for all subjects. FRAX® fracture risk scores were calculated taking into account former fractures and current risk factors of the subjects. Both groups were compared with respect to their BMD values, T scores, FRAX® risk scores and frequency of previous fractures. Results: No difference was observed between groups with regard to mean age, mean age of menopause onset and mean serum calcium, phosphorus and alkaline phosphatase levels (p>0.05 for all). Statistically, obese patients showed highly significantly greater mean BMD values at lumbar spine (L1-L4) and femoral neck in comparison to subjects with normal body weight (p=0.000 for all). Obese patients had a lower 10-year probability of a major osteoporotic fracture on average as determined by FRAX® fracture risk score compared to that in normalweight subjects (p<0.05). Also, obese group had a lower 10-year probability of a hip fracture versus normal-weight subjects (p<0.01). Both groups were found to have a similar frequency of previous fractures. Conclusion: Although obese patients in this study had greater BMD values and lower FRAX® risk scores, the probability of subsequent fractures predicted for the obese group was not lower when compared to that predicted for normal-weight group. It should be kept in mind that obesity may not necessarily be protective against fractures and treatment algorithms based solely on BMD might be inadequate to predict future fracture risk.

Effect of Aerobic Exercise in Water on Serum Estrogen and C - Reactive Protein and Body Mass Index Level in Obese and Normal Weight Postmenopausal Women

with progressive intensity of 50 to 70 percent of maximum heart rate for 45 minutes between 10-11 am. The blood samples were taken the day before and two days after the exercise sessions through the left brachial vein. Wilcoxon signed ranks test and Mann-Whitney test were used for data analysis. Results: In the obese and normal weight groups exercise caused significant increase in estrogen (P=0.001, P = 0.001, respectively) and decreased the BMI (P = 0.009, P = 0.003, respectively); however, CRP decreased significantly when compared to pre exercise in the normal weight group (P = 0.005), No statistically significant change was observed in the obese group (P = 0.084). There was no significant difference in estrogen (P = 0.32), BMI (P = 0.62) and CRP (P = 0.35) changes following exercise between obese and normal weight groups. Conclusions: In the present study, aquatic aerobic exercise caused similar reduction in some cardiovascular risk factors among obese and normal weight postmenopausal women. However, future studies are recommended for more clarification.

Abstract P4-04-16: Obesity-associated systemic interleukin-6 promotes pre-adipocyte aromatase expression via increased breast cancer cell prostaglandin E2 production

Abstract Introduction: Obesity is associated with a worse breast cancer prognosis, particularly in estrogen receptor alpha (ERα) positive, postmenopausal patients. Resistance to aromatase inhibitor treatment may be one mechanism mediating this effect, as obese patients have a lower response rate to this class of drugs and higher breast tissue aromatase expression. We hypothesized that obesity-associated circulating factors promote breast cancer cell cyclooxygenase-2 (COX-2) expression and prostaglandin E2 (PGE2) production, resulting in an elevation in pre-adipocyte aromatase expression that enhances breast cancer cell estrogen receptor activity and proliferation. Methods: We utilized an in vitro model of the obese patient’s tumor microenvironment in which cultured MCF-7 breast cancer cells and pre-adipocytes were exposed to pooled serum from obese (OB; BMI≥30.0 kg/m2) or normal weight (N; BMI 18.5-24.9 kg/m2) postmenopausal women. Results: Exposure to OB versus N patient sera significantly increased MCF-7 cell COX-2 expression and PGE2 production. This was coupled with 89% greater pre-adipocyte aromatase expression following culture in conditioned media (CM) from MCF-7 cells exposed to OB versus N patient sera, a difference nullified by treatment of the MCF-7 cells with the COX-2 inhibitor celecoxib during CM generation. Previous analysis of the sera revealed significantly higher interleukin 6 (IL-6) concentrations in the OB versus N patient samples. Depletion of IL-6 from the sera resulted in neutralization of the difference between OB and N CM-stimulated aromatase expression. N CM generated with the addition of IL-6 treatment at the time of N patient sera exposure also induced pre-adipocyte aromatase expression that was statistically equivalent to the OB CM condition. Finally, CM from pre-adipocyte/MCF-7 cell co-cultures exposed to OB patient sera stimulated greater MCF-7 and T47D breast cancer cell ERα activity and proliferation in comparison to N. Conclusions: This study indicates that obesity-associated systemic IL-6 indirectly enhances pre-adipocyte aromatase expression via increased breast cancer cell PGE2 production, thereby promoting greater cancer cell ERα activity and proliferation. Investigation regarding the efficacy of a COX-2 inhibitor/aromatase inhibitor combination therapy in the obese postmenopausal patient population is warranted. Citation Format: Laura W Bowers, Andrew J Brenner, Stephen D Hursting, Rajeshwar R Tekmal, Linda A deGraffenried. Obesity-associated systemic interleukin-6 promotes pre-adipocyte aromatase expression via increased breast cancer cell prostaglandin E2 production [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-04-16.

Oxidative Stress in Obese Postmenopausal Women: An Additive Burden for Atherosclerosis

Coronary Artery Disease are on the rise in the general population and is the leading cause of death in both men and women. The impact of CAD is underappreciated in younger women when compared to men. Women have unique risk factors for CAD and postmenopausal women are at higher risk of developing CAD when compared to normal menstruating women. The aim of our study was to find out the difference in oxidative stress levels between obese postmenopausal women and normal menstruating women, also to compare the same in normal weight postmenopausal women. Thirty one normal and 29 obese postmenopausal women with age more than 45 years who visited obstetrics and gynaecology outpatient department for general clinical evaluation at a tertiary care centre were recruited in this cross-sectional study. Thirty normal menstruating women were compared. Anthropometric measurements were recorded and the body mass index was calculated. Serum Malondialdehyde and superoxide dismutase was measured using a spectrophotometer. There was a significant difference in mean MDA levels in postmenopausal women (1.477 ± 0.359) when compared to normal menstruating women (0.666 ± 0.302) (p < 0.01). There was no significant difference in mean SOD levels in postmenopausal women (2.836 ± 0.899) when compared to normal menstruating women (2.986 ± 0.686) (p > 0.05). Also, there was a significant increase between mean MDA levels in obese postmenopausal women (2.48 ± 0.52) when compared to normal weight postmenopausal women (1.65 ± 0.36) (p < 0.01). There was a significant difference between mean SOD levels in obese postmenopausal women (1.36 ± 0.96) and normal weight postmenopausal women (2.56 ± 1.03) (p < 0.01). The oxidative stress was higher in obese postmenopausal women when compared to normal weight postmenopausal women and normal menstruating women.

Sex hormone binding globulin, total and HMW adiponectin and insulin resistance among normal weight postmenopausal women with metabolic syndrome

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

The adipokine profile of metabolically benign obese and at‐risk normal weight postmenopausal women: The Women's Health Initiative Observational Study

Nearly, a third of obese individuals, termed metabolically benign obese, have a low burden of adiposity-related cardiometabolic abnormalities, whereas a substantial proportion of normal-weight individuals possess risk factors. In cross-sectional analyses of 699 normal weight and 1,294 overweight/obese postmenopausal women enrolled in a nested case-control stroke study ancillary to the Women's Health Initiative Observational Study, we compared levels of adiponectin, leptin, and resistin among metabolically benign normal weight, at-risk normal weight, metabolically benign obese, and at-risk obese women using components of the ATP III definition of the metabolic syndrome (metabolically benign: ≤1 of the four components; at-risk phenotype: ≥2 components or diabetes). Overall, 382/699 normal-weight women (54.6%) and 328/1,194 overweight/obese women (27.5%) were metabolically benign. Among normal-weight women, at-risk women had higher leptin and lower adiponectin levels compared to metabolically benign women; multivariate-adjusted odds ratios were significant for having leptin (OR: 2.51; 95% CI: 1.28-5.01) and resistin (1.46; 1.03-2.07) in the top tertile and adiponectin in the bottom tertile (2.64; 1.81-3.84). Compared to metabolically benign overweight/obese women, at-risk obese women had higher odds of having leptin in the top tertile (1.62; 1.24-2.12) and adiponectin in the bottom tertile (2.78; 2.04-3.77). Overall, metabolically benign overweight/obese women had an intermediate adipokine profile (between at-risk obese and metabolically benign normal-weight women), whereas at-risk normal-weight women had a less favorable profile compared to metabolically benign normal-weight women. As adiponectin was the only adipokine independent of BMI, it may be most likely to have a role in the etiological pathway of these phenotypes.

Increased oxidative stress in normal-weight postmenopausal women with metabolic syndrome compared with metabolically healthy overweight/obese individuals

ObjectiveThe purpose of this study was to assess whether the metabolically healthy overweight/obese phenotype is associated with decreased oxidative stress compared with normal-weight individuals with metabolic syndrome (MetS). Materials/MethodsPlasma oxidized LDL (ox-LDL) and urinary 8-epi-prostaglandin F2α (8-epi-PGF2α) were analyzed in a cross-sectional study of 1846 healthy postmenopausal women. Participants were classified by presence (n=569) or absence (n=1277) of MetS and by BMI (18.5–24.9kg/m2=normal weight, n=1254; ≥25kg/m2=overweight/obese, n=592). MetS was diagnosed with the modified National Cholesterol Education Program Adult Treatment Panel III criteria. ResultsCompared to normal weight women with MetS (n=296), metabolically healthy overweight/obese women (n=319) showed lower blood pressure, triglyceride, and glucose and higher HDL cholesterol, adiponectin, and LDL particle size. Ox-LDL was higher in overweight/obese women without MetS than in normal weight women without MetS (n=958) but was lower than in women with MetS. Urinary 8-epi-PGF2α level was about 11% lower in women without MetS than in women with MetS. Normal weight women with MetS had greater odds of having ox-LDL (multivariate odds ratio [OR] 2.42, 95% CI: 1.65–3.55) and 8-epi-PGF2α (OR 1.49; CI: 1.03–2.14) levels in the top quartile compared to normal weight women without MetS after adjusting for age, drinking, smoking, total- and LDL-cholesterol, and high sensitivity C-reactive protein. Additionally, there was no significant correlation between ox-LDL and 8-epi-PGF2α. ConclusionsThe metabolically healthy overweight/obese phenotype was associated with a better overall metabolic profile and less oxidative stress than that observed in normal weight individuals with MetS. Furthermore, there was a lack of association between ox-LDL and 8-epi-PGF2α.

Prevalence of low bone mass in postmenopausal Kuwaiti women residents in the largest province of Kuwait

We measured bone mineral density (BMD) in Kuwaiti women residents in the largest province of Kuwait state to highlight the BMD changes with each age, in particular when they reach the postmenopausal stage. Healthy Kuwaiti females between the ages of 10 and 89years, who were residents in the largest province of Kuwait, were included in the study. After measurements of their height and weight, their bone mineral density of L2-L4 lumbar spine and femur (neck and total) was measured using dual-energy X-ray absorptiometry. Out of the studied 903 female subjects, 811 fulfilled the inclusion criteria. Their mean ± SEM age and body mass index (BMI) were respectively 47 ± 1years and 30.8 ± 0.2kg/m(2). Out of these 811 subjects, 454 were postmenopausal, and their age and BMI were 55.0 ± 0.3years and 32.0 ± 0.3kg/m(2), respectively. We have demonstrated that osteoporotic BMD of the spine and femur neck occurred in 20.2 and 12.5% of postmenopausal Kuwaiti females, whereas osteopenic BMD of the spine and femur neck was observed at a frequency of 35.4 and 42.8% of women, respectively. When the subjects were subdivided as per BMI, it was notable that overweight and obese had significantly higher BMD than normal weight postmenopausal women. BMD of the spine, femur neck, and femur total demonstrated significant positive correlations with body weight and BMI, whereas they demonstrated significant negative correlations with age. Low BMD of the femur neck and spine, reflected by the combination of osteopenia and osteoporosis, seemed to occur in more than half (55.3-55.6%) of postmenopausal Kuwaiti women. Most of the studies on assessment of prevalence of low bone mass were focused in Caucasian population. Data on subjects of the Mediterranean area are limited. We measured bone mineral density (BMD) in Kuwaiti women residents in the largest province of Kuwait state to highlight the BMD changes with each age, in particular when they reach the postmenopausal stage. Kuwaiti female subjects of different age groups between 10 and 89years, who were residents in the largest province of Kuwait (Hawalli), were included in the study. They were included if they had been healthy over the last 12months, had no past history of bone disease, and are not taking any prescription medication that may affect bone density. Their bone mineral density of L2-L4 lumbar spine and femur (neck and total) was measured using dual-energy X-ray absorptiometry. Out of the studied 903 female subjects, 811 fulfilled the inclusion criteria and were included in the study. Their mean ± SEM age and body mass index (BMI) were respectively 47 ± 1years and 30.8 ± 0.2kg/m(2). Out of these 811 subjects, 454 were postmenopausal, and their age and BMI were 55.0 ± 0.3years and 32.0 ± 0.3kg/m(2), respectively. We have demonstrated that osteoporotic BMD of the spine and femur neck occurred in 20.2 and 12.5% of postmenopausal Kuwaiti females, respectively, whereas osteopenic BMD of the spine and femur neck was observed at a frequency of 35.4 and 42.8% of women. When subjects were subdivided as per BMI, it was notable that overweight and obese postmenopausal women had significantly higher BMD of lumbar spine, femur neck, and femur total than normal weight postmenopausal women. Bone mineral densities of the spine, femur neck, and femur total demonstrated significant positive correlations with body weight and BMI, whereas they demonstrated significant negative correlations with age. Low BMD of the femur neck and spine, reflected by the combination of osteopenia and osteoporosis, seemed to occur in more than half (55.3-55.6%) of postmenopausal Kuwaiti women residents at the largest province of Kuwait.

The Lipid Accumulation Product Is Associated With Increased Mortality in Normal Weight Postmenopausal Women

Lipid accumulation product (LAP) is an emerging cardiovascular risk factor, which is calculated from waist circumference (WC) and triglyceride (TG) levels. The aim of this study was to elucidate the relationship between LAP and cardiovascular mortality as well as the presence of type 2 diabetes with respect to gender-specific differences. We determined WC and fasting TG levels and the cardiovascular and metabolic phenotypes coronary artery disease (CAD), hypertension, metabolic syndrome, and diabetes mellitus in 2,279 men and 875 postmenopausal women who were routinely referred to coronary angiography. The LAP was calculated as (WC (cm)--65) × (TG (mmol/l)) for men and as (WC (cm)--58) × (TG (mmol/l)) for women. LAP levels were independently associated with congestive heart failure mortality in all postmenopausal women and with all-cause mortality in diabetic postmenopausal women but not in men. Multivariable-adjusted hazard ratios (with 95% confidence intervals) for all-cause, cardiovascular, and congestive heart failure mortality in the third compared to the first LAP tertile were 4.28 (1.94-9.44; P < 0.001), 3.47 (1.28-9.40; P = 0.015), and 10.77 (1.21-95.88; P = 0.033), respectively, in normal weight postmenopausal women, whereas no significant associations were found in men. LAP levels were highly associated with type 2 diabetes in all subjects, postmenopausal women, and men. High LAP values are predictive of mortality independently of other cardiovascular risk factors in normal weight and diabetic postmenopausal women but not in men. Type 2 diabetes (T2DM) was highly associated with LAP in women and men. Our study validates an inexpensive and simple risk profiling that may allow identifying postmenopausal women at high cardiovascular risk.

Dysregulation of subcutaneous adipose tissue blood flow in overweight postmenopausal women

A putative link between abdominal obesity and metabolic-vascular complications after menopause may be due to a decreased adipose tissue blood flow (ATBF). The present work aimed to analyze possible changes in ATBF with being overweight and menopausal and its putative link to endothelial dysfunction and autonomic nervous system balance. Forty-three healthy women were classified into four groups according to weight and menopause status. The ATBF was measured by xenon washout while fasting and after oral glucose intake. The nitric oxide synthase inhibitor asymmetric dimethylarginine was used as a marker of endothelial function and heart rate variability-estimated autonomic nervous system activity. Fasting ATBF was decreased in both overweight groups (P = 0.044 and P = 0.048) versus normal-weight premenopausal women. Normal-weight and overweight postmenopausal women exhibited lower maximum ATBF compared with normal-weight premenopausal women (P = 0.015 and P = 0.001, respectively), and overweight postmenopausal women exhibited lower maximum ATBF compared with normal-weight postmenopausal women (P = 0.003). A negative correlation was found between fasting ATBF and asymmetric dimethylarginine (P = 0.015), whereas maximum ATBF was negatively associated with sympathetic-parasympathetic nervous system balance (ratio of the power of the low frequency to the power of the high frequency; P = 0.002). Loss of ATBF flexibility in overweight postmenopausal women may contribute to the metabolic dysfunction seen in this group of women.

Tissue-Specific Increases in 11β-Hydroxysteroid Dehydrogenase Type 1 in Normal Weight Postmenopausal Women

With age and menopause there is a shift in adipose distribution from gluteo-femoral to abdominal depots in women. Associated with this redistribution of fat are increased risks of type 2 diabetes and cardiovascular disease. Glucocorticoids influence body composition, and 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) which converts inert cortisone to active cortisol is a putative key mediator of metabolic complications in obesity. Increased 11βHSD1 in adipose tissue may contribute to postmenopausal central obesity. We hypothesized that tissue-specific 11βHSD1 gene expression and activity are up-regulated in the older, postmenopausal women compared to young, premenopausal women. Twenty-three pre- and 23 postmenopausal, healthy, normal weight women were recruited. The participants underwent a urine collection, a subcutaneous adipose tissue biopsy and the hepatic 11βHSD1 activity was estimated by the serum cortisol response after an oral dose of cortisone. Urinary (5α-tetrahydrocortisol+5β-tetrahydrocortisol)/tetrahydrocortisone ratios were higher in postmenopausal women versus premenopausal women in luteal phase (P<0.05), indicating an increased whole-body 11βHSD1 activity. Postmenopausal women had higher 11βHSD1 gene expression in subcutaneous fat (P<0.05). Hepatic first pass conversion of oral cortisone to cortisol was also increased in postmenopausal women versus premenopausal women in follicular phase of the menstrual cycle (P<0.01, at 30 min post cortisone ingestion), suggesting higher hepatic 11βHSD1 activity. In conclusion, our results indicate that postmenopausal normal weight women have increased 11βHSD1 activity in adipose tissue and liver. This may contribute to metabolic dysfunctions with menopause and ageing in women.