Non-obese Postmenopausal Women Research Articles

Abstract PO3-11-08: High Risk of Metabolic Dysfunction in Non-Obese Breast Cancer Survivors

Abstract Much literature already depicts the relationship between metabolic syndrome (MS), obesity, and breast cancer. Despite that, up to one-third of non-obese individuals may exhibit undiagnosed MS or metabolic dysfunction, posing an independent cancer risk and worse outcomes even for those with a body mass index (BMI) < 30kg/m². In that manner, our study aims to evaluate the metabolic profile of non-obese women with postmenopausal breast cancer compared to non-obese women without breast cancer. In this cross-sectional clinical study at the State University of São Paulo Medical School - UNESP. The study group (n=130) included women aged ≥ 45 and < 75 years, in amenorrhea for at least 12 months, BMI ≤ 30kg/m2, histological diagnosis of breast cancer, without metastatic disease, and without established cardiovascular disease (CVD). The control group (n=130) comprised women with all the same criteria except for breast cancer diagnosis. The groups were matched by age and menopause time in a ratio of one case to one control (1:1). We aimed to analyze their clinical, biochemical, and oncological data to establish relationships between these groups. We presented the data in tables 1 - 3. The groups showed homogeneity in age, time since menopause, BMI, waist circumference (WC), and cholesterol levels. There was a higher occurrence of MS and hypertension (HTN) among women treated for breast cancer compared to the control group (30.8% vs. 20.0% and 25.4% vs.14.6%, respectively) (p< 0.05). Similarly, a higher percentage of women treated for breast cancer had abnormal values for total cholesterol and glucose (56.2% vs. 43.1% and 29.2% vs. 15.4%, respectively) (p< 0.05). In the analysis of metabolic profile risk-adjusted for age time since menopause and BMI, women treated for breast cancer showed an increased risk for MS (OR=2.76, 95% CI 1.48-5.15), elevated glucose (OR=2.69, 95% CI 1.46-4.96), and HTN (OR=3.03, 95% CI 1.51-6.10). In the evaluation of factors influencing the metabolic profile, women with breast cancer had significantly higher mean values of WC (82.6±8.5 vs. 79.9±6.4 cm, p=0.048), systolic and diastolic blood pressure (129.2±17.1 and 77.7±8.8 mmHg vs. 118.2±15.1 and 73.6±8.8 mmHg, p=0.0002 and p=0.01, respectively), and glucose (99.7±32.5 vs. 86.6±7.6 mg/dL, p=0.0002) compared to control group. We conducted a sub-analysis among women with BMI < 25kg/m² from both groups. Women with breast cancer (n=64) had a higher occurrence of MS compared to women without breast cancer (n=53) (17.2% vs. 1.9%, respectively). Even though this sub-analysis did not reach the minimum number of patients with BMI < 25 kg/m² to achieve p value < 0,05, this analysis reveals a significant difference in MS incidence between the groups (p=0.007). This reinforces the hypothesis that oncological diagnosis substantially affects metabolic health, and therefore, breast cancer patients should receive special attention regarding their metabolic profile, regardless of their BMI. Conclusion: Non-obese women with breast cancer showed a higher risk of MS, HTN, and diabetes, with a worse metabolic profile than non-obese postmenopausal women without breast cancer. These findings suggest that postmenopausal women diagnosed with breast cancer, even in the absence of obesity, exhibit significant metabolic dysfunction characterized by a higher occurrence of MS and its components. The findings highlight the importance of a comprehensive assessment of metabolic health in women with breast cancer, regardless of their body mass index, to ensure appropriate and individualized care for these patients. Table 1 - Comparison of clinical and laboratory characteristics among 130 non-obese postmenopausal women with breast cancer and 130 non-obese postmenopausal women (control) (average values ± standard deviation). Table 2 - Comparison of categorized clinical and laboratory characteristics that influence the metabolic profile between 130 non-obese postmenopausal women with breast cancer and 130 non-obese postmenopausal women (control). Values expressed as number and percentage in parentheses. CA, cancer; WC, waist circumference; MS, metabolic syndrome; HDL, high-density lipoprotein, LDL, low-density lipoprotein; TG, triglycerides. *Significant difference p<0.05 (Chi-square Test). Table 3. Association between the presence of Metabolic Syndrome, and its clinical and laboratory components, among the 130 non-obese postmenopausal women with breast cancer and the 130 non-obese postmenopausal women (control). Values expressed as number and percentage in parentheses. CA, cancer; BP, blood pressure; WC, waist circumference; TG, triglycerides. *Odds ratio (OR) adjusted for age, menopause duration and BMI. **Significant difference if p<0.05 (Logistic Regression). Citation Format: Pedro Paulo Perroni Filho, Daniel Buttros, Eliana Aguiar Petri Nahas. High Risk of Metabolic Dysfunction in Non-Obese Breast Cancer Survivors [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-11-08.

Bacterial Vaginosis in Postmenopausal Women.

Bacterial vaginosis (BV) is the most common vaginal infection worldwide, but most research has been conducted in premenopausal women. After menopause, endogenous estrogen production decreases, often leading to the genitourinary syndrome of menopause (GSM), characterized by vulvovaginal dryness and irritation. The estrogen-deficient postmenopausal state results in an elevated vaginal pH and depletion of vaginal lactobacilli. Use of traditional BV diagnostics (Amsel criteria, Nugent score) is difficult in post-menopausal women, especially those not on estrogen replacement therapy, as these methods were originally developed in premenopausal women. In this review, we discuss recent clinical data on BV in postmenopausal women, difficulties in diagnosis using traditional methods, the role of BV molecular diagnostics, and our current expert opinion for managing BV in this population. BV prevalence has been found to range between 2%-57% among postmenopausal women per Amsel and Nugent criteria. This is likely an over-estimate of the true prevalence due to limitations in these criteria which were only validated in pre-menopausal women. Despite increasing diagnostic options for BV in recent years, including highly sensitive and specific BV nucleic acid amplification tests (NAATs), the physiologic changes of menopause and limited inclusion of postmenopausal women in clinical studies, diagnosis is difficult in this population. Recent studies utilizing 16s rRNA gene sequencing suggest that the vaginal microbiota of premenopausal and postmenopausal women is quite different, even if BV is not present. Data also suggest that obese postmenopausal women have significantly lower rates of BV compared to non-obese postmenopausal women, although further research is needed in this area. Multiple treatment options exist for vaginal atrophy and BV in this population. Data are limited regarding optimal diagnostic approaches for BV in postmenopausal women; BV NAATs and 16s rRNA gene sequencing may have a role for diagnosing BV in symptomatic women although further studies are needed. Menopausal women with characteristic vaginal symptoms and an elevated vaginal pH should be initially treated for estrogen deficiency prior to considering a diagnosis of BV; subsequent treatment for BV should be driven by symptoms.

Comparison of Mat Pilates training-induced changes on climateric symptoms in hypertensive and normotensive postmenopausal women

IntroductionPhysical exercise has been used to improve the physiological, metabolic and psychological factors of women. Objective: the aim of this study was to compare the 12-week Mat Pilates training-induced effect on climacteric symptoms in hypertensive and normotensive, non-obese postmenopausal women. Methods: Forty-seven irregularly active, non-obese postmenopausal women participated in the study: 24 normotensive (58 ± 4 years) and 23 hypertensive (58 ± 4 years). They underwent 36 sessions of Mat Pilates in nonconsecutive days during 12 weeks. Climacteric symptoms were assessed by the Cervantes Scale (CER), Menopause Rating Scale (MRS) and Blatt-Kupperman Menopause Index (B–K). The unpaired t-test compared the clinical characteristics between the groups. For the analysis of the questionnaires, the Spearman correlation and Mann-Whitney U test were used to compare the means between the groups for non-parametric data. The generalized estimates equation (GEE) was used to compare the groups and time to score the three general and domain questionnaires. The significance level adopted was ɑ = 0.05. Results: No difference in the Mat Pilates training-induced changes were found between normotensive and hypertensive women, but there was a significant reduction in the scores of the B–K and MRS and in the percentage of disappearance of symptoms by the B–K after training in both groups. Regarding the CER, there was a reduction in symptoms in the total value and the psychological, menopause and health domains. Conclusion: The presence of hypertension did not change the 12-week Mat Pilates training-induced benefits on the climacteric symptoms of non-obese postmenopausal women.

Associations of Fat Mass and Fat Distribution With Bone Mineral Density in Non-Obese Postmenopausal Chinese Women Over 60 Years Old.

BackgroundBone mineral density (BMD) loss is a major complication of menopause, and this loss is closely associated with Fat mass (FM). The relationship between FM, fat distribution (FD), and BMD in postmenopausal women, however, remains incompletely understood. The present study was thus developed to explore these associations between body fat accumulation, FD, and BMD among non-obese postmenopausal women over the age of 60.MethodsThis was a cross-sectional analysis of 357 healthy postmenopausal women between the ages of 60.2 and 86.7 years. Dual-energy X-ray absorptiometry (DXA) was utilized to measure total and regional BMD as well as fat-related parameters including total FM, android and gynoid fat, body fat percentage (BF%), and total lean mass (LM) for all subjects. The android-to-gynoid fat ratio (AOI) was used to assess FD. Pearson’s correlation testing and multiple regression analyses were used to explore relationships among AOI, LM, FM, and BMD.ResultsBoth LM and FM were positively correlated with total and regional BMD in univariate analysis (all P < 0.01), whereas BMD was not significantly associated with AOI in any analyzed site other than the head. Multivariate linear regression models corrected for age, height, and years post-menopause, revealed a sustained independent positive relationship between FM and BMD (standard β range: 0.141 – 0.343, P < 0.01). The relationship between FM and BMD was unaffected by adjustment for LM (standard β range: 0.132 – 0.258, P < 0.01), whereas AOI had an adverse impact on BMD at most analyzed skeletal sites (total body, hip, femoral neck, arm, leg, and head) (standard β range: −0.093 to −0.232, P < 0.05). These findings were unaffected by using BF% in place of FM (standard β range: −0.100 to −0.232, P < 0.05).ConclusionsIn this cohort of non-obese postmenopausal women over the age of 60 from China, total FM was positively associated with BMD, while AOI was negatively correlated with BMD. As such, a combination of proper weight gain and the control of central obesity may benefit the overall bone health of women after menopause.

Association of adiposity evaluated by anthropometric, BIA, and DXA measures with cardiometabolic risk factors in nonobese postmenopausal women: the CoLaus/OsteoLaus cohort.

After menopause, body composition changes with body fat accumulation, and an increase in cardiometabolic risk factors. Total fat mass, regional fat mass, and visceral adipose tissue (VAT) may be estimated with anthropometric measures, bioelectrical impedance analysis (BIA), and dual-energy X-ray absorptiometry (DXA). The aim of our study was to assess which measurement correlated best with cardiometabolic risk factors in healthy nonobese postmenopausal women. The CoLaus/OsteoLaus cohort included 1,500 postmenopausal women (age range 50-80). We analyzed correlations between: 1) measurements of body composition assessed by anthropometric measures, BIA, and DXA and 2) these measurements and different selected cardiometabolic risk factors, such as blood pressure, lipid markers (cholesterol subtypes and triglycerides), and metabolic markers (glucose, insulin, adiponectin, and leptin). Spearman correlation coefficient, stepwise forward regression, and linear regression analyses were used to determine association between anthropometric measurements and cardiometabolic risk factors. In the 803 included participants (mean age 62.0 ± 7.1 y, mean body mass index 25.6 kg/m2 ± 4.4), correlations between total fat mass measured by BIA and total fat mass, android fat, gynoid fat, or VAT measured by DXA are very strong (from r = 0.531, [99% confidence interval (CI), 0.443-0.610] to r = 0.704, [99% CI, 0.640-0.758]). Body mass index and waist circumference have a higher correlation with VAT (r = 0.815, [99% CI, 0.772-0.851] and r = 0.823 [99% CI, 0.782-0.858], respectively) than BIA (r = 0.672 [99% CI, 0.603-0.731]). Among the anthropometric measurement and the measurements derived from DXA and BIA, VAT is the parameter most strongly associated with cardiometabolic risk factors. VAT better explains the variation of most of the cardiometabolic risk factors than age and treatment. For example, nearly 5% of the variability of the diastolic blood pressure (9.9 vs 4.9), nearly 15% of the variability of high-density lipoprotein cholesterol (20.3 vs 3.8) and triglyceride (21.1 vs 6.5), 25.3% of the variability of insulin (33.3 vs 8.1), and 37.5% of the variability of leptin (37.7 vs 1.1) were explained by VAT. BIA seems not to be a good tool to assess VAT. At the population level, waist circumference and body mass index seem to be good tools to estimate VAT. VAT measured by DXA is the parameter most correlated with cardiometabolic risk factors and could become a component of the cardiometabolic marker on its own.

Effects of combined exercise on salivary oxidative stress in hypertensive and normotensive postmenopausal women

Aim: This study evaluated the effects of 10 weeks of combined exercise training on the salivary oxidative profile of hypertensive and normotensive postmenopausal women. Methods: Twenty-six non-obese postmenopausal women were divided into two groups: the hypertensive group (HT; n = 13; 58.9 ± 3.9 years; and BMI of 27.7 ± 4.6 kg/m2) or the normotensive group (NT; n = 13; 52.7 ± 5.2 years; and BMI of 26.9 ± 2.9 kg/m2). They performed 30 sessions of combined exercises over 10 weeks: 45 min per session, three times a week. Resting saliva samples were collected after an overnight fast to evaluate salivary nitrite levels and oxidative stress markers before and after training. Results: Two-way ANOVA showed that there was no difference in the responses over time between the hypertensive and normotensive groups in catalase, superoxide dismutase salivary activity, total antioxidant capacity, or lipid peroxidation. However, superoxide dismutase activity (δHT -0.87 ± 14.53 SOD/mg protein; δNT: 7.13 ± 9.39 SOD/mg protein; p < 0.01) and nitrite levels (δHT 10.32 ± 60.83 mM; δNT 101.92 ± 149.57 mM; p = 0.03) were higher overall in the hypertensive group compared to the normotensive group. Moreover, salivary nitrite levels increased over time (p = 0.04) in both groups. Conclusion: 10 weeks of combined exercise training did not change salivary oxidative stress markers in either normotensive or hypertensive postmenopausal women, although, after exercise training, nitrite levels increased in both groups, even with higher baseline salivary nitrite levels in hypertensive women. Thus, recurrent exercise seems to be a safe strategy after menopause from the standpoint of oxidative stress, regardless of the presence of hypertension.

Postmenopausal Chinese-Singaporean Women Have a Higher Ratio of Visceral to Subcutaneous Adipose Tissue Volume than Caucasian Women of the Same Age and BMI.

Central fat accumulation is a significant determinant of cardio-metabolic health risk, known to differ between ethnically distinct human populations. Despite evidence for preferential central adiposity in Asian populations, the proportional distribution between the subcutaneous and visceral compartments in Chinese postmenopausal women has not been thoroughly investigated. For this analysis, volumetrically quantified subcutaneous and visceral adipose tissue (SAT, VAT) in the pelvic and abdominal regions of postmenopausal Asian (Chinese-Singaporean) and Caucasian (German) women matched for age and Body Mass Index (BMI) was undertaken, to examine such differences between the two groups. Volumes were calculated from segmentations of magnetic resonance imaging datasets of the abdomen and pelvis. Despite SAT, VAT, and the corresponding total adipose tissue (TAT) being similar between the groups, VAT/SAT and VAT/TAT were higher in the Asian group (by 24.5% and 18.2%, respectively, each p = 0.02). Further, VAT/SAT and VAT/TAT were positively correlated with BMI in the Caucasian group only (p = 0.02 and p = 0.01, respectively). We concluded that VAT is proportionally higher in the non-obese Asian women, compared to the Caucasian women of matched age and BMI. This conclusion is in agreement with existing literature showing higher abdominal adiposity in Asian populations. Additionally, in the Asian group, BMI did not correlate with visceral adiposity on a significant level. Further analysis is required to examine the extent to which this increased VAT may impact cardio-metabolic health. There is, however, a need to emphasize healthy lifestyle behaviors in non-obese post-menopausal women of Chinese ancestry.

Association between body fat and bone mineral density in non-obese post-menopausal women over 60 years old.

Background:Loss of bone mineral density is one of the most important complications of menopause. The results of studies about the relation between body fat and bone mineral density are controversial. The aim of this study was to determine the association between fat mass and bone mineral density on non-obese post-menopausal elderly women.Methods:This cross-sectional study is a part of the second phase of the Amirkola Health and Ageing Project (AHAP) that has been done on 356 elderly women with BMI of 18.5-30. Bone mineral density (BMD) and total body fat were measured using the Hologic Horizon-WI densitometer. Statistical tests were ANOVA, Pearson’s correlation coefficient and multiple linear regression and a p- value less than 0.05 was considered significant.Results:The mean age of the participants was 70.22±7.34 and the mean age of menopause was 47.68±5.05. Women with highest fat mass had a greater spine, femur and whole-body BMD (p<0.0001). In this study, we observed a direct and positive significant correlation between body fat mass and BMD at spine (r=0.308), femur (r=0.420) and whole body (r=0.312) (p<0.0001). Adjusted linear regression showed positive effect of fat mass on BMD on all three anatomical sites especially in total femur (β=0.254, p<0.0001).Conclusion:This study showed a positive correlation between fat mass and bone mineral density at all sites in post-menopausal women.

Isoflavone Supplementation Does Not Potentiate the Effect of Combined Exercise Training on Resting and Ambulatory Blood Pressure in Non-Obese Postmenopausal Women: A Randomized Double-Blind Controlled Trial-A Pilot Study.

Physical exercise and isoflavone supplementation are potential strategies to prevent and treat cardiovascular diseases in postmenopausal women. The aim of this study was to investigate whether there are additive effects of isoflavone supplementation when associated with combined aerobic and resistance exercise on resting and ambulatory blood pressure monitoring (ABPM) and in blood pressure variability (BPV). Thirty-one non-obese postmenopausal women were randomly allocated into two groups: placebo and exercise (Placebo n = 19); and isoflavone supplementation (100 mg/day) and exercise (isoflavone n = 19). ABPM and BPV were evaluated before and after 10 weeks of moderate combined (aerobic and resistance) exercise training. Generalized Estimating Equation (GEE) with Bonferroni correction and intention-to-treat analysis was used to compare the effects of interventions on resting BP, ABPM and BPV. Combined exercise training decreased resting systolic (SBP) and diastolic blood pressure (DBP) and reduced 24 h and awake ambulatory SBP, DBP and mean blood pressure over time, with no additional effects of isoflavone supplementation. No changes were observed in sleep period, or in BPV indexes (Standard Deviation of 24 h (SD), daytime and nighttime interval (SDdn) and average real variability (ARV) in both groups. We conclude that isoflavone supplementation does not potentiate the effects of combined training on resting and ambulatorial systolic and diastolic blood pressure in non-obese postmenopausal women.

Physical activity is associated with lower arterial stiffness in normal-weight postmenopausal women.

The impact of physical exercise, as preventative measure, to control the progression of cardiovascular disease in midlife remains under investigation. We aimed to investigate the effect of different levels of intensity of physical activity on metabolic and vascular profile in healthy postmenopausal women. A total of 625 healthy postmenopausal women (mean age 57.7±7.6years) were evaluated using the short IPAQ questionnaire for quantification of physical activity. The energy expenditure was estimated in metabolic equivalent of energy (MET) hours per week. Pulse wave velocity (PWV) was measured as an index of arterial stiffness. Intima-media thickness of both right and left common carotid artery, carotid bulb and internal carotid artery, and combined carotid IMT were also assessed by non-invasive and well-validated methods. Mean values of PWV decreased linearly with increasing intensity of physical activity (classes of physical activity: sedentary vs walking vs moderate vs vigorous activity: 9.07±1.22m/s vs 9.12±1.72m/s vs 8.47±1.31m/s vs 7.94±0.40m/s, ANOVA P for linear trend .003). In non-obese postmenopausal women, PWV values associated with: (a) the total number of METs (b-coefficient=-0.261, P=.002) as well as with SBP; (b) or with the number of moderate METs (b-coefficient=-0.192, P=.025) as well as with age and SBP. No significant associations were observed between the intensity of physical exercise and arterial stiffness in the overweight-obese group. Physical activity is negatively associated with arterial stiffness in postmenopausal women with normal weight. This association was not observed in overweight or obese women.

Diabetes and kidney cancer risk among post-menopausal women: The Iowa women’s health study

BackgroundMany studies have reported a positive association between diabetes and kidney cancer. However, it is unclear whether diabetes is a risk factor for kidney cancer independent of other risk factors, such as obesity and hypertension. We comprehensively examined the association of diabetes and its duration with incident kidney cancer in the prospective cohort Iowa Women’s Health Study (1986–2011). MethodsDiabetes status was self-reported at baseline (1986) and on five follow-up questionnaires. Cox proportional hazards regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of baseline and time-dependent diabetes with the risk of incident kidney cancer. ResultsDuring the 25 years of follow-up, 245 cases of kidney cancer occurred among 36,975 post-menopausal women. In an age-adjusted model, there was a significant association between time-dependent diabetes and the risk of kidney cancer [HR (95% CI) = 1.76 (1.26, 1.45)]; the association was attenuated after multivariable adjustment for age, body mass index (BMI), waist-to-hip ratio (WHR), hypertension, physical activity, diuretic use, pack-years of smoking, alcohol intake, and total caloric intake [HR = 1.35 (0.94, 1.94)]. However, among non-obese women or women with a waist circumference less than 34.6 in., diabetes was significantly associated with kidney cancer risk: for time-dependent diabetes, HRs (95% CIs) were 1.82 (1.10, 3.00) among those with BMI < 30 kg/m2 and 2.18 (1.08, 4.38) among those with a waist circumference <34.6 in.. ConclusionsOur results suggest that diabetes is associated with kidney cancer risk among non-obese post-menopausal women.

Association between Serum Uric Acid and Nonalcoholic Fatty Liver Disease in Nonobese Postmenopausal Women: A Cross-sectional Study

This study aimed to determine the association between serum uric acid (sUA) and nonalcoholic fatty liver disease (NAFLD) in nonobese postmenopausal women. A total of 4323 female individuals over 18 years of age participated in this cross-sectional study. The subjects were divided into four groups according to menopause status and body mass index. sUA quartiles in this female population were categorized as follows: Q1 ≤ 230 mmol/L, Q2: 231–270 mmol/L, Q3: 271–310 mmol/L and Q4: ≥ 311 mmol/L. The presence or absence of NAFLD was assessed by abdominal ultrasonography. The prevalence of NAFLD was 38.8% in the general population, and the average age was 46.5 ± 11.3 years. Among nonobese and obese subjects, the prevalence of NAFLD was lower in nonmenopausal subjects than in postmenopausal subjects (nonobese: 20.74% vs 45.26%, respectively, P < 0.0001; obese: 70.51% vs 84.35%, respectively, P < 0.0001). After adjusting for age, current smoking status, current alcohol drinking status, diabetes, hypertension disease and triglyceride, the ORs (95% CIs) for NAFLD among individuals in Q2-Q4 were 1.518 (1.062–2.169), 1.431 (1.010–2.027) and 2.054 (1.442–2.927), respectively, P value for trend <0.0001. Higher sUA levels can be used as a predictive biomarker for NAFLD in nonobese postmenopausal women.

The effects of isoflavone supplementation plus combined exercise on salivary markers of oxidative stress in postmenopausal women.

This study tested the effect of isoflavone supplementation in addition to combined exercise training in salivary oxidative stress markers in non-obese postmenopausal women. Thirty-two postmenopausal women without hormone therapy were randomly assigned to exercise + placebo (n = 15) or exercise + isoflavone supplementation (n = 17) groups. They performed 30 sessions of combined exercises (aerobic plus resistance) over ten weeks and consumed 100 mg of isoflavone supplementation or placebo. Saliva samples were collected after an overnight fast. Superoxide dismutase, total antioxidant capacity, thiobarbituric acid reactive substances, catalase, total protein and nitrite were determined before and after ten weeks of the intervention. The ANOVA two-way analysis of variance was applied with α of 5%. Both groups increase (p<0.05) superoxide dismutase activity and decrease catalase levels. There was interaction (time × group) in both nitrite and thiobarbituric acid reactive substances results, with increase (p<0.05) in placebo group and decrease (p<0.05) in isoflavone group. No difference was found for total antioxidant capacity or total protein. The combination of isoflavone supplementation and exercise training can promote an antioxidant effect through reduction of lipid peroxidation and concentrations of salivary nitrite.

Bone mineral density in diabetes and impaired fasting glucose.

Individuals with diabetes have a higher or normal bone mineral density (BMD) compared with those without diabetes. However, paradoxically, they also have a higher fracture risk. It is not clear whether those with IFG also have altered BMD. This study aimed to determine whether individuals with IFG have elevated or normal BMD. Women (n = 858) and men (n = 970) (aged 20-80years) from the Geelong Osteoporosis Study were included. IFG was defined as fasting plasma glucose (FPG) 5.5-6.9mmol/L and diabetes as FPG ≥ 7.0mmol/L, use of antihyperglycaemic medication and/or self-report. Using multivariable linear regression, the relationships between glycaemia and BMD at the femoral neck and lumbar spine were examined, and adjusted for age, body mass index (BMI), and other variables. In women, two interaction terms were identified: menopause × glycaemia and BMI × glycaemia, and thus, the analyses were stratified by menopause and obesity status (BMI cut point ≥ 30kg/m2). There were no associations between glycaemic status and BMD for pre-menopausal women. For non-obese post-menopausal women, there was no association between FNBMD and glycaemic status, but women with IFG or diabetes had higher LSBMD than those with normoglycaemia (7.1% and 9.7%, respectively, both p < 0.01). Obese post-menopausal women with diabetes had a higher FNBMD (8.8%, p = 0.008) and LSBMD (12.2%, p < 0.001), but those with IFG were not different from the normoglycaemia group. There were no associations detected between glycaemic status and BMD in men. In this study, we report that compared with normoglycaemia, post-menopausal women (non-obese and obese) with diabetes had higher LSBMD. FNBMD was higher in obese post-menopausal women with diabetes. Only non-obese post-menopausal women with IFG had a higher LSBMD than normoglycaemia. No other associations with IFG were observed.

Free Fatty Acids Rewire Cancer Metabolism in Obesity-Associated Breast Cancer via Estrogen Receptor and mTOR Signaling.

Obesity is a risk factor for postmenopausal estrogen receptor alpha (ERα)-positive (ER+) breast cancer. Molecular mechanisms underlying factors from plasma that contribute to this risk and how these mechanisms affect ERα signaling have yet to be elucidated. To identify such mechanisms, we performed whole metabolite and protein profiling in plasma samples from women at high risk for breast cancer, which led us to focus on factors that were differentially present in plasma of obese versus nonobese postmenopausal women. These studies, combined with in vitro assays, identified free fatty acids (FFA) as circulating plasma factors that correlated with increased proliferation and aggressiveness in ER+ breast cancer cells. FFAs activated both the ERα and mTOR pathways and rewired metabolism in breast cancer cells. Pathway preferential estrogen-1 (PaPE-1), which targets ERα and mTOR signaling, was able to block changes induced by FFA and was more effective in the presence of FFA. Collectively, these data suggest a role for obesity-associated gene and metabolic rewiring in providing new targetable vulnerabilities for ER+ breast cancer in postmenopausal women. Furthermore, they provide a basis for preclinical and clinical trials where the impact of agents that target ERα and mTOR signaling cross-talk would be tested to prevent ER+ breast cancers in obese postmenopausal women. SIGNIFICANCE: These findings show that obesity-associated changes in certain blood metabolites rewire metabolic programs in cancer cells, influence mammary epithelial cell tumorigenicity and aggressiveness, and increase breast cancer risk.

Hormonal predictors of metabolic obesity in non-obese postmenopausal women

Hormonal predictors of metabolic obesity in non-obese postmenopausal women

Metabolic health is strongly predicted by free Testosterone and SHBG levels in non-obese postmenopausal women

Metabolic health is strongly predicted by free Testosterone and SHBG levels in non-obese postmenopausal women

Deregulated microRNAs and Adiponectin in Postmenopausal Women with Breast Cancer

Background: Obesity is a risk factor for breast cancer (BC). Some mechanisms through which obesity can lead to cancer development are insulin-like growth factors (IGFs), adipokines, and microRNAs (miRs). The objective of the study was to determine whether miR-17-5p, miR-195-5p, and miR-221-3p expressions were deregulated in serum samples of obese and nonobese postmenopausal women with BC. In addition, insulin, adiponectin, leptin and IGFs were analyzed. Methods: Fifty postmenopausal women with newly diagnosed BC and 50 postmenopausal healthy women were evaluated. Differences in miRs between BC and healthy cases and between obese and lean participants were analyzed. Receiver operating characteristic curves for miRs for discriminating patients with or without BC were established, and relationships between the miRs, adipokines, and breast tumor characteristics were also investigated. Results: miR-17-5p and miR-195-5p were higher in patients with BC in comparison to the controls, while miR-221-3p and adiponectin were significantly lower. Increased levels of miR-195-5p allowed the differentiation of BC from controls with a sensitivity of 83.3 and a specificity of 78.3%, and were associated with lobular and poorly differentiated cancer. There was no difference in miRs levels between obese and lean groups. Conclusions: Circulating miRs and adiponectin were deregulated in postmenopausal women with BC.

Differences in foot contact times between obese and non-obese postmenopausal women when crossing obstacles

Objective: This study aimed to investigate the foot contact time differences between obese and non-obese subjects during walking when crossing obstacles.Methods: Ninety-eight postmenopausal women were assigned to four groups, and their plantar pressure temporal data were collected using a two-step protocol during walking when crossing an obstacle set at 30% height of lower limb length of each subject. The initial, final, and duration of contact of 10 foot areas were measured.Results: Leading limb: (1) the heel groups initiated foot contact using the heel, and the non-heel groups initiated contact using the metatarsals; (2) heel obese subjects showed an earlier initial contact and a longer contact duration of metatarsals 2–3; (3) non-heel obese subjects showed an earlier midfoot initial contact. Regarding the trailing limb: (4) heel obese subjects showed an earlier midfoot initial contact and a longer contact duration of metatarsal 5; (5) non-heel obese subjects showed an earlier initial contact and a longer contact duration of metatarsals 4–5.Conclusions: (1) The non-heel groups’ foot rollover pattern may result from an attempt of rapidly restoring stability; (2) the heel obese subjects seem to regulate their plantar foot muscles to overcome their overweight; (3) the overweight of the non-heel obese subjects leads to a quicker backward foot roll-over from the metatarsals to the heel; (4) the overweight of the heel obese subjects can distort their footprints and/or their higher inertia may precipitate an anticipation of the midfoot contact, which can also explain the result observed for 5.

The Effects of Isoflavone Supplementation Plus Combined Exercise on Lipid Levels, and Inflammatory and Oxidative Stress Markers in Postmenopausal Women

This study tested the effect of isoflavone supplementation in addition to combined exercise training on plasma lipid levels, inflammatory markers and oxidative stress in postmenopausal women. Thirty-two healthy and non-obese postmenopausal women without hormone therapy were randomly assigned to exercise + placebo (PLA; n = 15) or exercise + isoflavone supplementation (ISO; n = 17) groups. They performed 30 sessions of combined exercises (aerobic plus resistance) over ten weeks and consumed 100 mg of isoflavone supplementation or placebo. Blood samples were collected after an overnight fast to analyze the lipid profile, interleukin-6 (IL-6), interleukin-8 (IL-8), superoxide dismutase (SOD), total antioxidant capacity (FRAP), and thiobarbituric acid reactive substances (TBARS), before and after ten weeks of the intervention. There were no differences in the changes (pre vs. post) between groups for any of the inflammatory markers, oxidative stress markers or lipid profile variables. However, interleukin-8 was different between pre- and post-tests (p < 0.001) in both groups (Δ = 7.61 and 5.61 pg/mL) as were cholesterol levels (p < 0.05), with no interaction between groups. The combination of isoflavone supplementation and exercise training did not alter oxidative stress markers in postmenopausal women, but exercise training alone may increase IL-8 and decrease total cholesterol levels.