Cohort Of Postmenopausal Women Research Articles

Circulating miR-340-5p and miR-506-3p as Two Osteo-miRNAs for Predicting Osteoporosis in a Cohort of Postmenopausal Women.

An increasing risk of developing osteoporosis which is characterized by bone production weakness and microarchitectural deterioration is found among postmenopausal women. MicroRNAs (miRNAs) are secreted into the circulation from cells of various tissues in response to local disease severity including bone diseases. Herein, we set out to identify candidate miRNAs predictable for osteoporosis incidence in postmenopausal elderly women. The circulating miRNA expression profiles deposited in the dataset accessioned as GSE201543 were downloaded from the GEO database. The study included 176 postmenopausal women who underwent BMD testing, including 96 women reporting osteoporosis and 70 women reporting normal BMD. All subjects were submitted their serum samples for measurements of bone metabolism markers. The miRNA expression profiles of the GSE201543 dataset were differentially analyzed and found 97 miRNAs being upregulated concomitantly with 31 miRNAs being downregulated in the serum samples between osteoporotic postmenopausal women and postmenopausal women with normal BMD. Osteoporotic postmenopausal women were demonstrated with elevated serum levels of miR-340-5p and miR-506-3p when compared to normal postmenopausal women. Pearson correlation analysis demonstrated that circulating miR-340-5p and miR-506-3p expressions were increased as BAP, β-CTx, and PINP levels increased, but osteocalcin and 25-(OH)VitD levels are declined in osteoporotic postmenopausal women. Results of the receiver operating characteristic (ROC) curve and the area under the ROC curve (AUC) showed circulating miR-340-5p and miR-506-3p expressions alone or combined together produced 0.843 AUC, 0.851 AUC, and 0.935 AUC, respectively, when used to predict the incidence of osteoporosis in postmenopausal women. Our work suggested that circulating miR-340-5p and miR-506-3p function as osteo-miRNAs in postmenopausal women and may serve as potential noninvasive biomarkers for the incidence of osteoporosis in postmenopausal women.

Sociodemographic, Anthropometric, Body Composition, Nutritional, and Biochemical Factors Influenced by Age in a Postmenopausal Population: A Cross-Sectional Study.

Postmenopausal aging has become relevant for understanding health during the transition life stages-the aging process being involved in several disturbances of the human condition. The present study aimed to investigate the relationship between postmenopausal aging and sociodemographic, anthropometric, body composition, nutritional, and biochemical (i.e., protein and lipid profiles, phosphorous-calcium metabolism, and antioxidant status) factors in postmenopausal women. This cross-sectional study enrolled 78 healthy postmenopausal women (44-76 years). The anthropometrical data showed no differences by age. Biochemical parameters, especially those involved in the protein and phosphorous-calcium metabolism, were influenced by age in our cohort of postmenopausal women. In contrast, no associations were found when considering lipid and antioxidant parameters. Height, fiber intake, blood glucose, protein profile and phosphorous-calcium metabolism markers seem to be the most affected nutritional-related factors by age in our cohort of healthy postmenopausal women. Primary prevention strategies focused on parameters at risk of disruption with postmenopausal aging are necessary to ensure the quality of life in older ages.

Mortality Associated with Healthy Eating Index Components and an Empirical-Scores Healthy Eating Index in a Cohort of Postmenopausal Women

Studies of diet and chronic disease include a recent important focus on dietary patterns. Patterns are typically defined by listing dietary variables and by totaling scores that reflect whether consumption is encouraged or discouraged for listed variables. However, precision may be improved by including total energy consumption among the dietary variables and by scoring dietary variables empirically. To relate Healthy Eating Index (HEI)-2010 components and total energy intake to all-cause and cause-specific mortality in Women's Health Initiative (WHI) cohorts and to define and evaluate an associated Empirical-Scores Healthy Eating Index (E-HEI). Analyses are conducted in WHI cohorts (n = 67,247) of healthy postmenopausal women, aged 50-79 y, when enrolled during 1993-1998 at 40 US clinical centers, with embedded nutrition biomarker studies. Replicate food-frequency assessments for HEI-2010 ratio variables and doubly labeled water total energy assessments, separated by ∼6 mo, are used as response variables to jointly calibrate baseline dietary data to reduce measurement error influences, using 2 nutrition biomarker studies (n = 199). Calibrated dietary variables are associated with mortality risk, and an E-HEI is defined, using cross-validated HR regression estimation. Of 15 dietary variables considered, all but empty calories calibrated well. Ten variables related significantly (P < 0.05) to total mortality, with favorable fruit, vegetable, whole grain, refined grain, and unsaturated fat associations and unfavorable sodium, saturated fat, and total energy associations. The E-HEI had cross-validated total mortality HRs (95% CIs) of 0.87 (0.82, 0.93), 0.80 (0.76, 0.86), 0.77 (0.72, 0.82), and 0.74 (0.69, 0.79) respectively, for quintiles 2 through 5 compared with quintile 1. These depart more strongly from the null than do HRs for HEI-2010 quintiles, primarily because of total energy. Mortality among US postmenopausal women depends strongly on diet, as evidenced by a new E-HEI that differs substantially from earlier dietary pattern score specifications.

Computed tomography-based paravertebral muscle density predicts subsequent vertebral fracture risks independently of bone mineral density in postmenopausal women following percutaneous vertebral augmentation.

The risk of subsequent vertebral fractures (SVF) after the primary vertebral fracture cannot be explained by lower bone mineral density (BMD) alone. Computed tomography (CT) measurements of paravertebral muscle density (PMD) are recognized radiographic markers used to predict physical function, fragile fractures. This study aims to investigate the relationship between PMD and the risk of SVF in cohorts of postmenopausal women, and to determine if combining both PMD and BMD measures derived from CT can improve the accuracy of predicting SVF. This study enrolled 305 postmenopausal women between the ages of 50 and 88 for 3years of follow-up studies. Trabecular attenuation (Hounsfield units, HU) was measured at L1 level and muscle attenuation of paravertebral muscle at L3 level on preoperative lumbar CT scans to determine the L1 BMD and L3 PMD. Kaplan-Meier analysis was applied to evaluate SVF-free survival. The hazard ratios (HRs) of PMD for SVF events were estimated with the Cox proportional hazards model. The predictive values of L1 BMD and L3 PMD for SVF were quantified using the Receiver-Operating Characteristic (ROC) curve. During the 3years of follow-up studies, 88 patients (28.9%) suffered an SVF. ROC curve analysis demonstrated that an L3 PMD threshold of 32 HU had a sensitivity of 89.8% and a specificity of 62% for the prediction of SVF. Kaplan-Meier analysis showed that L3 PMD ≤ 32 HU was significantly associated with lower SVF-free survival (p < 0.001; log-rank test). After adjusting for age, BMI, diabetes, postoperative osteoporosis treatment, handgrip strength, L1 BMD, multivariate analyses also indicated a persistent modest effect of L3 PMD on SVF-free survival. The area under the ROC curve of L3 PMD and L1 BMD, combined to predict the risk of SVF, was 0.790, which was significantly higher than the value for L1 BMD alone (0.735). L3 PMD and L1 BMD significantly improved the accuracy of SVF risk prediction compared with L1 BMD alone, which was confirmed by reclassification improvement measures. The inclusion of handgrip strength and postoperative osteoporosis treatment in the model further improved SVF prediction accuracy, and PMD remained significant in the model. Decreased L3 PMD is an independent risk predictor of SVF. Combined CT-based L1 BMD and L3 PMD can significantly improve the accuracy of predicting the risk of SVF in postmenopausal women who have suffered prior osteoporotic vertebral fractures.

Biomarker-Calibrated Red and Combined Red and Processed Meat Intakes with Chronic Disease Risk in a Cohort of Postmenopausal Women

The associations of red and processed meat with chronic disease risk remain to be clarified, in part because of measurement error in self-reported diet. We sought to develop metabolomics-based biomarkers for red and processed meat, and to evaluate associations of biomarker-calibrated meat intake with chronic disease risk among postmenopausal women. Study participants were women who were members of the Women's Health Initiative (WHI) study cohorts. These participants were postmenopausal women aged 50-79 y when enrolled during 1993-1998 at 40 US clinical centers with embedded human feeding and nutrition biomarker studies. Literature reports of metabolomics correlates of meat consumption were used to develop meat intake biomarkers from serum and 24-h urine metabolites in a 153-participant feeding study (2010-2014). Resulting biomarkers were used in a 450-participant biomarker study (2007-2009) to develop linear regression calibration equations that adjust FFQ intakes for random and systematic measurement error. Biomarker-calibrated meat intakes were associated with cardiovascular disease, cancer, and diabetes incidence among 81,954 WHI participants (1993-2020). Biomarkers and calibration equations meeting prespecified criteria were developed for consumption of red meat and red plus processed meat combined, but not for processed meat consumption. Following control for nondietary confounding factors, hazard ratios were calculated for a 40% increment above the red meat median intake for coronary artery disease (HR: 1.10; 95% CI: 1.07, 1.14), heart failure (HR: 1.26; 95% CI: 1.20, 1.33), breast cancer (HR: 1.10; 95% CI: 1.07, 1.13) for, total invasive cancer (HR: 1.07; 95% CI: 1.05, 1.09), and diabetes (HR: 1.37; 95% CI: 1.34, 1.39). HRs for red plus processed meat intake were similar. HRs were close to the null, and mostly nonsignificant following additional control for dietary potential confounding factors, including calibrated total energy consumption. A relatively high-meat dietary pattern is associated with somewhat higher chronic disease risks. These elevations appear to be largely attributable to the dietary pattern, rather than to consumption of red or processed meat per se.

Relationship between the subgingival microbiome and menopausal hormone therapy use: The Buffalo OsteoPeriostudy.

This study investigated the association between menopausal hormone therapy (HT) use and the subgingival microbiome, for which published information is limited. This cross-sectional study included 1270 postmenopausal women, aged 53-81 years, who completed clinical examinations. Detailed information on HT use (type, delivery mode, duration) was obtained from questionnaires. HT use was categorized into three groups (never, former, current). 16S rRNA sequencing was performed on subgingival plaque samples obtained during dental examinations. Operational taxonomic units were centered log2-ratio (CLR) transformed to account for the compositional data structure. Analysis of variance was used to compare mean microbial relative abundances across HT categories with Benjamini-Hochberg correction. Significantly higher alpha diversity (Shannon Index) and beta diversity (Aitchison distance) was observed in never compared with current HT users (p<0.05, each). Of the total 245 microbial taxa identified, 18 taxa differed significantly among the three HT groups, 11 of which were higher in current users and seven of which were lower in current users as compared with never users (p<0.05, each). Differences in relative abundance between never and current HT users were materially unchanged after adjustment for age, body mass index, and oral hygiene. Relative abundance of several subgingival bacteria differed significantly between never and current HT users in a cohort of postmenopausal women. Additional studies are needed to determine the extent that these relationships might account for the previously reported inverse association between HT use and periodontal disease in older women.

Abstract 5892: Factors associated with longitudinal changes in mammographic density in a multiethnic breast screening cohort of postmenopausal women

Abstract Mammographic density is an important risk factor for breast cancer and is known to differ in women by characteristics such as age and race/ethnicity. Women who experience longitudinal decreases in breast density have a reduced risk of breast cancer; however, besides age, which correlates with decreases in breast density, it is unclear what other factors contribute to changes in breast density over time. Understanding factors associated with density changes may enable a better understanding of breast cancer risk and potential strategies for prevention. This study investigated factors associated with changes in mammographic density in a cohort of 3,392 postmenopausal women (mean age=61.3±8.8 years) with no history of breast cancer who had at least two mammograms spaced at least three months apart at a University of California, Irvine Health breast imaging facility between 2011-2017. Self-reported information on demographics, breast and reproductive history, and lifestyle factors, including body mass index (BMI), alcohol intake, smoking, and physical activity, was collected by an electronic intake form, and Breast Imaging Reporting and Database System (BI-RADS) mammographic density scores were obtained from electronic medical records. 7.9% of women exhibited a longitudinal decrease in mammographic density, 6.7% exhibited an increase, and 85.4% exhibited no change. Longitudinal changes in mammographic density were statistically significantly correlated with age, race/ethnicity, and age at menopause by univariate analysis using the Fisher’s exact test. Multivariate conditional logistic regression using baseline mammographic density as strata was performed to identify factors associated with a longitudinal increase or decrease in mammographic density. Variables were selected if they were nominally significant (p &amp;lt; 0.10) in the initial univariate analyses of women who exhibited a longitudinal change in mammographic density (race/ethnicity, age at baseline, menopause age) or were otherwise selected a priori based on previous literature showing an association with mammographic density (alcohol, physical activity, BMI). Asian women were more likely to exhibit a longitudinal increase in mammographic density (OR=1.78, 95% CI=1.02-3.09, p=0.04) and less likely to exhibit a decrease (OR = 0.58, 95% CI = 0.40-0.83, p=0.003) compared to white women. On the other hand, overweight and obese women were less likely to exhibit an increase compared to normal weight women (OR = 0.52, 95% CI = 0.31-0.87, p=0.01; OR = 0.41, 95% CI = 0.23-0.75, p=0.004, respectively). Other lifestyle factors (alcohol intake, smoking, and physical activity) were not associated with longitudinal changes in mammographic density. The potential interactions of Asian race and BMI with longitudinal breast density changes in influencing breast cancer risk should be further studied. Citation Format: Roza L. Kirmizi, Christie J. Lee, Hannah Lui Park, Argyrios Ziogas, Andrea Alvarez, Rachel M. Lucia, Deborah Goodman, Kathryn M. Larsen, Richard Kelly, Hoda Anton-Culver, Stephen A. Feig. Factors associated with longitudinal changes in mammographic density in a multiethnic breast screening cohort of postmenopausal women [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5892.

Cost-Effectiveness of Denosumab for the Treatment of Postmenopausal Osteoporosis in South Korea.

BackgroundOsteoporosis is a progressive skeletal disease associated with an increased risk of bone fracture. This study aimed to estimate the cost-effectiveness of denosumab for osteoporotic fracture prevention compared to bisphosphonates (alendronate, ibandronate, risedronate, and zoledronate) and selective estrogen receptor modulators (raloxifene) in a cohort of postmenopausal women with osteoporosis.MethodsA Markov model was used to evaluate the cost and effectiveness of denosumab versus comparators. The model had a cycle length of 6 months and was run from the age of 68 years to individual patients’ lifetime or the age of 100 years. The health states considered in the model were well, hip fracture, vertebral fracture, wrist fracture, other osteoporotic fracture, post-hip fracture, post-vertebral fracture, and death. Recent local data were used as inputs for the model parameters. A discount rate of 4.5% was applied to both costs and outcomes.ResultsFrom the perspective of the healthcare system, denosumab was cost-effective or cost-saving compared to all comparators, considering one unit of Korea’s gross domestic product per capita, USA dollar (USD) 34,870. Denosumab was cost-saving compared to ibandronate (oral) and raloxifene. Compared to alendronate, denosumab was cost-effective with an incremental cost-effectiveness ratio (ICER) of USD 767.10 per quality-adjusted life year (QALY). The ICER of denosumab vs. ibandronate IV, risedronate, and zoledronate was USD 685.63, USD 1,469.71, USD 4,668.53 per QALY, respectively.ConclusionsThe findings of this analysis suggest that denosumab is a cost-effective therapeutic option for preventing fractures in postmenopausal women with osteoporosis in South Korea.

Distribution of Fracture Sites in Postmenopausal Overweight and Obese Women: The FRISBEE Study.

The association between obesity and fracture sites in postmenopausal women has been little studied. We examined the most common types of fractures in obese and overweight postmenopausal women compared to subjects with a normal BMI in the FRISBEE study, a cohort of postmenopausal women followed since 9.1 (7.2-10.6) years. Chi-squared tests and logistic regressions were used to compare the percentages of fracture sites in overweight/obese subjects to subjects with a normal BMI. Their mean (± SD) age was 76.7 ± 6.9years and their mean BMI was 26.4 ± 4.4. Seven hundred seventy-seven subjects suffered at least one validated fragility fracture with a total of 964 fractures in the whole cohort. Subjects with a BMI higher than 25 had significantly more ankle fractures and less pelvic fractures than subjects with a normal BMI (OR 1.63, 95% CI 1.02-2.56, P = 0.04 and OR 0.55, 95% CI 0.34-0.89, P = 0.01, respectively). There were no significant differences between overweight and obese subjects. Among those older than 75, there were significantly fewer pelvic fractures in overweight/obese subjects (OR 0.49, 95% CI 0.27-0.87, P = 0.01), but before 75, ankle fractures were significantly more frequent in overweight/obese subjects than in subjects with a normal BMI (OR 1.89, 95% CI 1.01-3.57, P = 0.04). In conclusion, the proportion of ankle and pelvic fractures in obese and overweight subjects differs from that in subjects with a normal BMI, but these differences are age dependent. Fracture prevention strategies should take into account the differential effects of excess weight according to age and the site of fracture.

Abstract P216: Association Of Heart Rate Variability With The Risk Of Heart Failure And Its Sub-types In Post-menopausal Women: A Longitudinal Cohort Study

Background: Previously our research findings revealed that low heart rate variability, a measure of autonomic imbalance, is associated with increased incidence of coronary heart disease (CHD) and heart failure (HF) in a cohort of post-menopausal women. Since CHD is strongly associated with HF, we investigated the effect of CHD on relationship of HRV and HF subtypes, i.e., heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF), in post-menopausal women. Methods: Total of 28,603 post-menopausal women free of baseline CHD, HF and cardiac arrhythmias enrolled in Women’s Health Initiative (WHI) study, were followed for incident hospitalized CHD, HF and its subtypes (HFrEF vs HFpEF). Using multivariate cox proportional hazard model, we estimated the association of above outcomes with baseline quartiles of HRV measures; SDNN (standard deviation of normal-to-normal RR interval) and RMSSD (root mean square of successive difference of RR interval) produced by 10-second twelve-lead ECG on enrollment. We then evaluated the relationship between HRV and HF subtypes stratified by incident CHD. Results: A total of 2279 incident CHD and 1562 incident HF events occurred during a median follow-up duration of 17.5 years. After adjusting for incident CHD in a multivariate cox proportional model, association of low SDNN and RMSSD with incident HF remained significant (SDNN HR 1.19, CI 1.05 - 1.35; RMSSD HR 1.13 (1.00 - 1.29). However, in stratified analysis low SDNN was associated with increased incidence of HFpEF only among participants without incident CHD (HR 1.29, CI 1.05 - 1.58) and not in those with incident CHD (HR 1.06, CI 0.77 - 1.47). Whereas low SDNN was associated with increased incidence of HFrEF only among participants with incident CHD (HR 1.44. CI 1.05 - 1.98) and not in those without incident CHD (HR 1.18, CI 0.87 - 1.61). Conclusion: Post-menopausal women with low HRV who develop CHD have an increased risk of HFrEF while those who don’t develop CHD have an increased risk of HFpEF. The relationship between autonomic imbalance and HF subtypes is dependent on CHD status.

Leukocyte telomere length as a compensatory mechanism in vitamin D metabolism.

Vitamin D deficiency is common among postmenopausal women. Telomere length can be a potential protective mechanism for age-related diseases. The objective of our study is to examine the association of vitamin D supplementation on leukocyte telomere length (LTL) in healthy postmenopausal women with vitamin D deficiency. The study was designed as a placebo-controlled study to investigate the short-term effects of vitamin D supplementation and seasonal changes on vitamin D related parameters, including 25(OH)D, 1,25(OH)2D parathormone (PTH), Vitamin D binding protein (VDBP), vitamin D receptor (VDR), and telomere length in a cohort of postmenopausal women (n = 102). The group was divided as supplementation (n = 52) and placebo groups (n = 50). All parameters were measured before and after treatment. Serum VDBP levels were measured by ELISA method and VDR, GC (VDBP) gene expressions and relative telomere lengths were measured in peripheral blood mononuclear cells (PBMC) using a quantitative real-time PCR method. The results demonstrate that baseline levels were similar between the groups. After vitamin D supplementation 25(OH)D, 1,25(OH)2D, PTH and VDBP levels were changed significantly compared to the placebo group. At the end of the study period, LTL levels were significantly increased in both groups and this change was more prominent in placebo group. The change in GC expression was significant between treatment and placebo groups but VDR expression remained unchanged. Even though the study was designed to solely assess the effects of vitamin D supplementation, LTL was significantly increased in the whole study group in summer months suggesting that LTL levels are affected by sun exposure and seasonal changes rather than supplementation. The study displayed the short-term effect of Vitamin D supplementation on vitamin D, PTH levels, LTL and vitamin D associated gene expressions. The relation between Vitamin D and LTL is not linear and could be confounded by several factors such as the population differences, regional and seasonal changes in sun exposure.

Dietary carbohydrate intake is associated with the subgingival plaque oral microbiome abundance and diversity in a cohort of postmenopausal women

Limited research exists on carbohydrate intake and oral microbiome diversity and composition assessed with next-generation sequencing. We aimed to better understand the association between habitual carbohydrate intake and the oral microbiome, as the oral microbiome has been associated with caries, periodontal disease, and systemic diseases. We investigated if total carbohydrates, starch, monosaccharides, disaccharides, fiber, or glycemic load (GL) were associated with the diversity and composition of oral bacteria in subgingival plaque samples of 1204 post-menopausal women. Carbohydrate intake and GL were assessed from a food frequency questionnaire, and adjusted for energy intake. The V3–V4 region of the 16S rRNA gene from subgingival plaque samples were sequenced to identify the relative abundance of microbiome compositional data expressed as operational taxonomic units (OTUs). The abundance of OTUs were centered log(2)-ratio transformed to account for the compositional data structure. Associations between carbohydrate/GL intake and microbiome alpha-diversity measures were examined using linear regression. PERMANOVA analyses were conducted to examine microbiome beta-diversity measures across quartiles of carbohydrate/GL intake. Associations between intake of carbohydrates and GL and the abundance of the 245 identified OTUs were examined by using linear regression. Total carbohydrates, GL, starch, lactose, and sucrose intake were inversely associated with alpha-diversity measures. Beta-diversity across quartiles of total carbohydrates, fiber, GL, sucrose, and galactose, were all statistically significant (p for PERMANOVA p < 0.05). Positive associations were observed between total carbohydrates, GL, sucrose and Streptococcus mutans; GL and both Sphingomonas HOT 006 and Scardovia wiggsiae; and sucrose and Streptococcus lactarius. A negative association was observed between lactose and Aggregatibacter segnis, and between sucrose and both TM7_[G-1] HOT 346 and Leptotrichia HOT 223. Intake of total carbohydrate, GL, and sucrose were inversely associated with subgingival bacteria alpha-diversity, the microbial beta-diversity varied by their intake, and they were associated with the relative abundance of specific OTUs. Higher intake of sucrose, or high GL foods, may influence poor oral health outcomes (and perhaps systemic health outcomes) in older women via their influence on the oral microbiome.

The Association of Pelvic Bone Mineral Density and With Proximal Femoral and Spine Bone Mineral Density in Post-menopausal Women

Pelvic fragility fractures result in significant morbidity and their incidence has increased over the past 30 years. One of the main risk factors in skeletal fragility is bone mineral density (BMD). Most of the current literature has focused on understanding spine and hip BMD. We aimed to measure the BMD of pelvis in a cohort of post-menopausal women and compare it to BMD at other skeletal sites. A questionnaire regarding risk factors for osteoporosis was completed by each participant. DXA scan of the pelvis was performed using research software. Three areas of the pelvis corresponding to common fractures were defined on pelvic DXA: R1 = symphysis public, R2 = inferior public rami, R3 = superior public rami. Pelvic BMD was calculated as the average BMD of R1-3. BMD at each location was reported as mean and standard deviation (SD). ANOVA was used to compare BMD between R1-R3 and pelvis, femoral neck, total hip, and spine. Pearson correlation was used to correlate pelvic BMD to BMD of proximal femur and spine. BMD was compared in four participant groups: 1- osteoporosis in spine and hip, 2- osteoporosis in spine only, 3-osteoporosis in hip only, and 4- no osteoporosis in spine and hip. The effect of diabetes and obesity on BMD at various skeletal sites was analyzed. Among the one hundred postmenopausal women enrolled in the study, age was: 64 ± 8, 31% were obese (BMI ≥ 30), and 8% had a diagnosis of type 2 diabetes. Pelvic area R3 had significantly higher BMD than R1 or R2 (p < 0.001). Pelvic BMD (0.50 ± 0.16) was significantly lower than total hip (0.70 ± 0.20) and spine BMD (0.97 ± 0.19) (p < 0.001). Pelvic BMD correlated with BMD at other skeletal locations, with the highest correlation with total hip (total hip: R2: 0.70, femoral neck R2: 0.50, spine R2: 0.65). Pelvic BMD was significantly lower in patients with osteoporosis of both hip and spine compared to the group without osteoporosis at both locations (p = 0.02). Obesity and type 2 diabetes were both associated with significantly higher BMD at pelvis, spine, and total hip. Pelvic BMD is lower than at other skeletal sites and is highly correlated with total hip area bone density. Obesity and type 2 diabetes are associated with higher pelvic BMD. To establish guidelines for the treatment pelvic BMD, studies defining the association of pelvic BMD with pelvic fracture risk are needed.

Red blood cell fatty acids and age-related macular degeneration in postmenopausal women.

To evaluate the relationship between red blood cell (RBC) polyunsaturated fatty acid (PUFA) levels, and dietary PUFA and fish intake, with prevalent and incident age-related macular degeneration (AMD) in a US cohort of postmenopausal women. This analysis included 1456 postmenopausal women from the Women's Health Initiative (WHI) Clinical Trials. RBC PUFAs were measured from fasting serum samples collected at WHI baseline. Dietary PUFAs and fish intake were assessed via food frequency questionnaires at baseline. There were 240 women who had prevalent AMD and 138 who self-reported AMD development over 9.5years. Adjusted odds ratios and 95% confidence intervals were estimated for prevalent AMD by RBC PUFA levels, dietary PUFA intake, and frequency of fish consumption. Adjusted hazard ratios and 95% confidence intervals were estimated for incident AMD. A p-for-trend was estimated for continuous measures of dietary PUFA and fish intake. No significant association was found between prevalent or incident AMD and RBC docosahexaenoic acid (DHA) + eicosapentaenoic acid (EPA), EPA, DHA, alpha-linolenic acid (ALA), linoleic acid (LA), or arachidonic acid (AA). A positive association was found between dietary intake of AA and odds of prevalent AMD (p-for-trend for continuous AA intake = 0.02) and between intake of LA/ALA and incident AMD (p-for-trend for continuous ratio of LA/ALA intake = 0.03). No statistically significant associations were found between AMD and dietary intake of PUFAs or fish. RBC PUFAs were not associated with AMD in this cohort. Overall, dietary analyses of PUFAs supported this, excepting dietary AA intake and intake of LA in proportion to ALA of which there were trends of increased risk.

Association between diabetes status and subsequent onset of glaucoma in postmenopausal women

The purpose of this study was to analyze the risk of glaucoma based on diabetes status using a large nationwide longitudinal cohort of postmenopausal women. This study included 1,372,240 postmenopausal women aged ≥ 40 years who underwent National Health Screening Program in 2009. Subjects were classified into the following 5 categories based on diabetes status: no diabetes, impaired fasting glucose (IFG), new onset diabetes, diabetes treated with oral hypoglycemic medication, and diabetes treated with insulin. Subjects were followed from 2005 through 2018, and hazard ratios of glaucoma onset were calculated for each group. Subgroup analyses of subjects stratified by age, smoking, drinking, hypertension, and dyslipidemia were performed. During the follow up period, 42,058 subjects developed glaucoma. The adjusted hazard ratio was 1.061 (95% CI, 1.036–1.086) in the IFG group, 1.151 (95% CI, 1.086–1.220) in the new onset diabetes group, 1.449 (95% CI, 1.406–1.493) in the diabetes treated with oral hypoglycemic medication group, and 1.884(95% CI, 1.777–1.999) in the diabetes treated with insulin group compared to the no diabetes group. The results were consistent in subgroup analyses after stratifying by age, lifestyle factors (smoking and drinking), and comorbidities (hypertension and dyslipidemia). Diabetes status is associated with increased risk of glaucoma development in postmenopausal women.

The effects of tubal sterilization on menopausal age in a cohort of postmenopausal women

To evaluate whether tubal sterilization (TS) has an adverse effect on menopausal age in a cohort of postmenopausal women. The medical records on TS were gathered from 1,228 postmenopausal women in menopause clinic at a tertiary hospital. The age at menarche, the parity, smoking and secondhand smoking status and mother’s age at menopause did not show any significant difference between the groups. Likewise, marital status, educational and yearly income levels were comparable (P &gt; 0.01). Although the mean BMI (P = 0.06) and the rate of oral contraceptive use (P = 0.09) were tended to be higher in non-TS women than in TS group, the difference did not reach statistical significance. The ever use of intrauterine device rate was significantly lower in TS group than in non-TS group (P &lt;0.001). The TS women, in comparison with the non-TS women had undergone earlier natural menopause (P &lt;0.001). The age at menopause had an inverse correlation with TS, and positive correlation with mother’s age at menopause in univariate analyses. However, there was marginally significant correlation between secondhand smoking and age at menopause. Linear stepwise regression analyses revealed that TS and mother’s age at menopause were independent predictors of age at menopause (P &lt; 0.05). We found an earlier age at menopause in women with TS in this study. In this regard, this is the first report about the age at menopause in women with TS, as far as we know.

Predicting Incident Heart Failure in Women With Machine Learning: The Women’s Health Initiative Cohort

BackgroundHeart failure (HF) is a leading cause of cardiac morbidity among women, whose risk factors differ from those in men. We used machine-learning approaches to develop risk- prediction models for incident HF in a cohort of postmenopausal women from the Women’s Health Initiative (WHI). MethodsWe used 2 machine-learning methods—Least Absolute Shrinkage and Selection Operator (LASSO) and Classification and Regression Trees (CART)—to perform variable selection on 1227 baseline WHI variables for the primary outcome of incident HF. These variables were then used to construct separate Cox proportional hazard models, and we compared these results, using receiver-operating characteristic (ROC) curve analysis, against a comparator model built using variables from the Atherosclerosis Risk in Communities (ARIC) HF prediction model. We analyzed 43,709 women who had 2222 incident HF events; median follow-up was 14.3 years. ResultsLASSO selected 10 predictors, and CART selected 11 predictors. The highest correlation between selected variables was 0.46. In addition to selecting well-established predictors such as age, myocardial infarction, and smoking, novel predictors included physical function, number of pregnancies, number of previous live births and age at menopause. In ROC analysis, the CART-derived model had the highest C-statistic of 0.83 (95% confidence interval [CI], 0.81-0.85), followed by LASSO 0.82 (95% CI, 0.81-0.84) and ARIC 0.73 (95% CI, 0.70-0.76). ConclusionsMachine-learning approaches can be used to develop HF risk-prediction models that can have better discrimination compared with an established HF risk model and may provide a basis for investigating novel HF predictors.

Association between vitamin D and glycaemic parameters in a multi-ethnic cohort of postmenopausal women with type 2 diabetes in Saudi Arabia

BackgroundThe relationship between vitamin D (VitD) and insulin sensitivity and secretion in type 2 diabetes mellitus (T2D) has been shown to be different amongst different ethnic populations. In Saudi Arabia, where both T2D and VitD deficiency are highly prevalent health concerns, little is known about the relationship between VitD, insulin sensitivity, resistance and the relative importance of ethnicity. Our primary aim in this study was to investigate influence of ethnicity on VitD association with glycaemic profile and to measures of obesity as a secondary outcome, among multiethnic postmenopausal women with T2D in Saudi Arabia.MethodsA cross-sectional study was conducted at King Fahad Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia. Postmenopausal females (n = 173, age ≥ 50 years) with T2D were randomly selected in this study. Anthropometric measures and fasting blood samples were obtained for all study participants. Several biochemical parameters were measured including 25-hydroxyvitamin D (25(OH)D), glycosylated hemoglobin (HbA1c), insulin, glucose and c-peptide. Surrogate markers for insulin resistance were calculated using Homeostasis Model Assessment 2 for insulin resistance and beta cell activity (HOMA2-IR, HOMA2-β).ResultsOverall, 25(OH)D was inversely associated with fasting glucose (r=-0.165, P = 0.037), insulin (r=-0.184, P = 0.02), C-peptide (r=-0.19, P = 0.015) and HOMA2- IR C-peptide (r=-0.23, P = 0.004). Additionally, serum 25 (OH)D showed a negative correlation with body weight (r=-0.173 P = 0.028), waist and hip circumferences (r=-0.167, P = 0.033; r=-0.22, P = 0.004 respectively) but not with body mass index (BMI) or waist hip ratio (WHR).In the white ethnic group but not in black or Asian population groups, 25(OH)D level was also associated with only serum fasting C-peptide and HOMA2-IR C-peptide and BMI (P < 0.05).ConclusionsInsulin resistance and obesity were associated with VitD status in T2D in this cohort. Our findings also suggest that these VitD associations in women from white ethnic background are different than in those from black/Asian ethnic backgrounds. Whether VitD supplements are able to improve either obesity and/or insulin sensitivity should be further investigated in different ethnic population groups.

Use of systemic glucocorticoids and risk of breast cancer in a prospective cohort of postmenopausal women

BackgroundGlucocorticoids could theoretically decrease breast cancer risk through their anti-inflammatory effects or increase risk through immunosuppression. However, epidemiological evidence is limited regarding the associations between glucocorticoid use and breast cancer risk.MethodsWe investigated the association between systemic glucocorticoid use and breast cancer incidence in the E3N cohort, which includes 98,995 women with information on various characteristics collected from repeated questionnaires complemented with drug reimbursement data available from 2004. Women with at least two reimbursements of systemic glucocorticoids in any previous 3-month period since January 1, 2004, were defined as exposed. We considered exposure as a time-varying parameter, and we used multivariable Cox regression models to estimate hazard ratios (HRs) of breast cancer. We performed a competing risk analysis using a cause-specific hazard approach to study the heterogeneity by tumour subtype/stage/grade.ResultsAmong 62,512 postmenopausal women (median age at inclusion of 63 years old), 2864 developed breast cancer during a median follow-up of 9 years (between years 2004 and 2014). Compared with non-exposure, glucocorticoid exposure was not associated with overall breast cancer risk [HR = 0.94 (0.85–1.05)]; however, it was associated with a higher risk of in situ breast cancer and a lower risk of invasive breast cancer [HRinsitu = 1.34 (1.01–1.78); HRinvasive = 0.86 (0.76–0.97); Phomogeneity = 0.01]. Regarding the risk of invasive breast cancer, glucocorticoid exposure was inversely associated with oestrogen receptor (ER)-positive breast cancer [HRER+ = 0.82 (0.72–0.94); HRER− = 1.21 (0.88–1.66); Phomogeneity = 0.03]; it was also inversely associated with the risk of stage 1 or stage 2 tumours but positively associated with the risk of stage 3/4 breast cancers [HRstage1 = 0.87 (0.75–1.01); HRstage2 = 0.67 (0.52–0.86); HRstage3/4 = 1.49 (1.02–2.20); Phomogeneity = 0.01].ConclusionThis study suggests that the association between systemic glucocorticoid use and breast cancer risk may differ by tumour subtype and stage.

ACUTE DIETARY NITRATE MAY IMPAIR CUTANEOUS VASCULAR CONDUCTANCE DURING LOCAL SKIN HEATING IN POSTMENOPAUSAL WOMEN

Declining estradiol production during menopause is linked to increased oxidative stress and reduced endothelial-dependent vasodilation. It is unknown whether supplementation with dietary nitrate may improve nitric oxide (NO) bioactivity and microvascular function in postmenopausal women. PURPOSE: To determine the effects of acute dietary nitrate ingestion on NO-mediated cutaneous vascular conductance (CVC) in a cohort of postmenopausal women. METHODS: In eight women (mean ± SD: age = 62 ± 4 y, BMI = 31 ± 2 kg/m2), two laser-Doppler flowmetry probes were affixed to the dorsal aspect of the forearm for measurement of red blood cell (RBC) flux during local skin heating to 39 °C and 44 °C. Assessments were made before and 3 h after ingesting 140 mL of beetroot juice containing 12.9 mmoL of inorganic nitrate. Fractional exhaled nitric oxide (FeNO) concentrations were measured at the same time points. Cutaneous vascular conductance (CVC) at 39 °C was calculated as RBC flux/ mean arterial pressure then normalized as a proportion of maximal CVC at 44°C. During the plateau phase at 39 °C, median spectral power of the endothelial NO-dependent frequency interval was analyzed using a Morlet wavelet transform. Pre-post comparisons were performed using within-sample t-tests. RESULTS: Following beetroot juice ingestion, FeNO concentrations (mean ± SD: 18 ± 8 ppb vs. 35 ± 16 ppb; p = 0.006, dz = 1.4) and spectral power of the NO-dependent frequency interval (0.01 - 0.02 Hz; p = 0.018, dz = 1.1) increased. Despite evidence for greater NO bioavailability, CVC at 39 °C was reduced (76 ± 12% vs. 50 ± 18%; p < 0.001, dz = 2.3). There was no change in maximal CVC at 44 °C (p = 0.287). CONCLUSION: A functional consequence of increased NO-bioavailability with acute dietary nitrate ingestion appears to be a diminished NO-mediated CVC response to local skin heating in our cohort of postmenopausal women with overweight and obesity. Future research should consider the effects of dietary nitrate coupled with an antioxidant supplement as means to further support NO-mediated endothelial function in such populations.