Cohort Of Postmenopausal Women Research Articles

The impact of irritant challenge on the skin barrier and myeloid resident immune cells in post-menopausal women is modulated by hormone replacement therapy.

Sex hormone changes during menopausal transition contribute to declining skin health. However, how menopause and its treatment by hormone replacement therapy (HRT) impact the skin barrier and immune system is unclear. Therefore, we examined how menopause and HRT affect skin barrier and immune cell composition in post-menopausal women following irritant challenge. Two cohorts of post-menopausal women were recruited to the study, one untreated (HRT-; n = 10; mean age 56.5 yrs [range 48-63 yrs]) and the other receiving HRT (n = 8; mean age 54 yrs [range 48-63 yrs]). Skin irritation was induced by applying 1.25% topical Sodium Lauryl Sulfate (SLS) to occluded buttock skin for 48 hours. Clinical assessment was conducted after 24 hours, followed by biopsy of both SLS-challenged and unchallenged skin for analysis of skin barrier proteins and immune cell distribution using immunofluorescence. Clinically, there were no significant differences in skin irritant responses between those taking or not taking HRT (including increased skin redness and blood flow). In response to SLS challenge a significant increase in trans-epidermal water loss (p<0.05), filaggrin deposition and keratin-10-positive cell layers (p<0.01) was observed in individuals receiving HRT compared to the HRT- group. Following SLS challenge in individuals taking HRT, a significant (p<0.01) reduction of CD207+ cells in the epidermis was observed, accompanied by an increase of CD207+ cells in the dermis, indicative of migrating Langerhans' cells (LCs). Significantly fewer migrating LCs were observed in those not receiving HRT (p<0.01). Furthermore, the number of dermal dendritic cells (DCs), macrophages, and CD11c+CD206- and CD68+CD206- subsets were found to be significantly (p<0.05) higher in those taking HRT following SLS challenge. Individuals receiving HRT displayed enhanced skin barrier response to SLS challenge with thicker filaggrin and increased keratin-10-positive epidermal cell layers. Following challenge, HRT users exhibited elevated counts of LCs, inflammatory DCs, and macrophages in the dermis. These may render skin both, more prone to inflammation and more capable of resolving it, while also promoting skin repair.

In-Depth Analysis of Diet Diary and Urine pH Measurements Improved Food Diet Reporting in Postmenopausal Women with RUTI.

We proceeded with an in-depth review of diet diaries for nutrient analysis from a cohort of women suffering from uncomplicated recurrent urinary tract infection (RUTI) to validate the accuracy of our current food diet record (FDR) form and evaluate possible domains of improvement. As part of an IRB-approved study, this previously published cohort of NHANES-comparable women was analyzed for consistency of the nutrient intake over 3 days, the influence of the time between meals and urine pH, the effect of nutrient intake over interval time between meals, and seasonal and before/during the COVID-19 pandemic changes. Intrarater reliability for nutrient analysis and intrapatient variability for urine pH were computed to test for consistency. Intrarater reliability for diet analysis was 91% accurate for foods and beverage matching and nutrient analysis. Mean standard deviation of urine pH readings within study participants was 0.4 (95% CI: 0.4, 0.5). An association was noted between total calories and fat consumed at breakfast and an increase in time to lunch. Calories consumed were unaffected across seasons or during the COVID-19 pandemic. Water intake during summer was significantly lower than that during fall and winter (both, p < 0.001). The patients who reported drinking water had a significantly lower average urine pH than women who did not report drinking water (5.8 vs. 6.2; p = 0.026). In this cohort of postmenopausal women with RUTIs, in-depth analysis of our current FDR findings led to several actionable items, which will improve our current food diet self-reporting process by our patients.

Long-term outcomes of neoadjuvant endocrine therapy versus chemotherapy in luminal HER2-breast cancer

Introduction. Neoadjuvant endocrine therapy (NET) is an effective treatment modality that can downsize breast tumors in a cohort of postmenopausal women with HR-positive HER2-negative breast cancer. A lack of data regarding efficacy of NET vs neoadjuvant cytotoxic chemotherapy (NCT) leads to limited usage of NET despite its favorable toxicity profile. Perioperative endocrine therapy is mainly used for the elderly or patients with comorbidities that limit their access to NCT. The COVID-19 pandemic led to increased data of NET efficacy. Nevertheless, long-term outcomes of NET application are underrepresented in literature. Objective. Assessment of long-term outcomes in patients treated with neoadjuvant endocrine therapy (NAT) versus neoadjuvant cytotoxic chemotherapy in a cohort of postmenopausal women with HR-positive HER2-negative breast cancer. Materials and methods. We retrospectively evaluated the results of treatment of 154postmenopausal patients with luminal HER2-breast cancer who were treated with neoadjuvant systemic therapy (NET or NCT) at the State Medical Institution «St. Petersburg Clinical Scientific and Practical Center for Specialized Types of Medical Care (Oncological)» from 01.01.2019 to 31.11.2020. We analyzed data on radiological, pathomorphological and long-term treatment outcomes (rate of locoregional and overall recurrence) in two groups.Results. 154 patients received neoadjuvant hormone therapy (n=78) or neoadjuvant chemotherapy (n=76). The clinical response was evaluated according to the RECIST criteria after 12 weeks and after study treatment using MMG. Partial or complete radiological response was achieved in 41.0% (n=32) in the NET group vs 69.7% (n=53) in the NCT group (p&lt;0.001). All patients included in the study underwent surgery. A complete pathologic response was observed in 9.2% (n=7) of patients in the chemotherapy group, and in 0% of patients in the endocrine therapy group (p=0.006). Median follow-up was 46.2 months. Progression was recorded in 23.2% (n=29) of participants, with no significant benefit of NCT over NET in the frequency of locoregional relapses (NET n=8 (10.3%) vs NCT n=4 (5.3%)) (p= 0.369) or the occurrence of distant metastases NAT n=8 (10.3%) vs NCT n=13 (17.1%)) (p=0.216). Multivariate analysis showed that only pathologic lymph node status (ypN2–3) was an independent predictor of progression (p=0.007, OR=3.2; 95%CI: 1.380-7.422). Conclusions. Long-term outcomes after neoadjuvant hormone therapy are comparable with chemotherapy in the group of postmenopausal women with luminal HER2-breast cancer. The small sample size and limited follow-up period are significant limitations of our work.

Automatic segmentation of skeletal muscles from MR images using modified U-Net and a novel data augmentation approach.

Rapid and accurate muscle segmentation is essential for the diagnosis and monitoring of many musculoskeletal diseases. As gold standard, manual annotation suffers from intensive labor and high inter-operator reproducibility errors. In this study, deep learning (DL) based automatic muscle segmentation from MR scans is investigated for post-menopausal women, who normally experience a decline in muscle volume. The performance of four Deep Learning (DL) models was evaluated: U-Net and UNet++ and two modified U-Net networks, which combined feature fusion and attention mechanisms (Feature-Fusion-UNet, FFU, and Attention-Feature-Fusion-UNet, AFFU). The models were tested for automatic segmentation of 16-lower limb muscles from MRI scans of two cohorts of post-menopausal women (11 subjects in PMW-1, 8 subjects in PMW-2; from two different studies so considered independent datasets) and 10 obese post-menopausal women (PMW-OB). Furthermore, a novel data augmentation approach is proposed to enlarge the training dataset. The results were assessed and compared by using the Dice similarity coefficient (DSC), relative volume error (RVE), and Hausdorff distance (HD). The best performance among all four DL models was achieved by AFFU (PMW-1: DSC 0.828 ± 0.079, 1-RVE 0.859 ± 0.122, HD 29.9mm ± 26.5mm; PMW-2: DSC 0.833 ± 0.065, 1-RVE 0.873 ± 0.105, HD 25.9mm ± 27.9mm; PMW-OB: DSC 0.862 ± 0.048, 1-RVE 0.919 ± 0.076, HD 34.8mm ± 46.8mm). Furthermore, the augmentation of data significantly improved the DSC scores of U-Net and AFFU for all 16 tested muscles (between 0.23% and 2.17% (DSC), 1.6%-1.93% (1-RVE), and 9.6%-19.8% (HD) improvement). These findings highlight the feasibility of utilizing DL models for automatic segmentation of muscles in post-menopausal women and indicate that the proposed augmentation method can enhance the performance of models trained on small datasets.

The effect of polycystic ovarian syndrome on fibrocystic breast changes in postmenopausal women

Background Fibrocystic breast changes (FCCs) are benign lesions thought to be caused by an increased estrogen-to-progesterone ratio. One of the most common endocrinopathies that increases this ratio is polycystic ovarian syndrome (PCOS). Although nonproliferative FCCs do not increase the risk of breast cancer, they can make mammographic detection of malignancy in postmenopausal women more difficult. The aim of this study was to investigate the effects of PCOS on the development of postmenopausal FCCs. Methods This retrospective cohort study used the TriNetX research network to identify two cohorts of postmenopausal women (Z78.0) older than 45, without a prior diagnosis of FCCs (N60.1) or hormone replacement therapy (Z79.890). One cohort included a diagnosis of PCOS (E28.2). The cohorts were balanced for age, race, ethnicity, and hormonally relevant comorbidities. The cohorts were then evaluated for the development of FCCs after menopause. Results Postmenopausal patients with PCOS were 52% more likely to develop FCCs than those without PCOS (2.2% vs. 1.4%, relative risk 1.52, 95% confidence interval 1.05, 2.22, P = 0.03). Conclusion Postmenopausal women with PCOS have a higher risk of developing FCCs. Further studies are needed to improve the differentiation of benign FCCs from malignant lesions on imaging for postmenopausal women with PCOS who develop FCCs.

Vitamin D and vitamin K status in postmenopausal women with normal and low bone mineral density.

Vitamin D and K are believed to promote bone health, but existing evidence is controversial. This study aimed to measure several metabolites of both vitamins by liquid chromatography tandem mass spectrometry (LC-MS/MS) in a cohort of postmenopausal women with low and normal bone mineral density (BMD). Vitamin metabolites (25-hydroxyvitamin D (25[OH]D), 24,25-dihydroxyvitamin D (24,25(OH)2D), phylloquinone (K1), menaquinone-4 (MK-4) and MK-7) were measured in 131 serum samples by LC-MS/MS. The vitamin D metabolite ratio (VMR) was calculated. Parathyroid hormone (PTH), type I procollagen-N-terminal-peptide (PINP) and C-terminal telopeptides of type I collagen (CTX-I) were measured by immunoassay. Dual X-ray absorptiometry was performed to identify participants with normal (T-score>-1) and low (T-score<-1) BMD. Mean age was 58.2±8.5 years. BMD was normal in 68 and low in 63 women. Median (interquartile range) for25(OH)D and total vitamin K concentrations were 53.5 (39.6-65.9) nmol/L and 1.33 (0.99-2.39) nmol/L. All vitamin metabolites were comparable in individuals with normal and low BMD. Furthermore, BMD and trabecular bone score were comparable in participants with adequate and inadequate vitamin status (at least one criterion was met: 25(OH)D <50 nmol/L, 24,25(OH)2D <3 nmol/L, VMR <4 %, total vitamin K <0.91 nmol/L). PTH, but not PINP or CTX-I, was inversely correlated with 25(OH)D, 24,25(OH)2D and VMR. Synergistic effects between vitamin D and K were not observed. Vitamin D and K status is not related to BMD and trabecular bone quality in postmenopausal women. Inverse associations were only seen between vitamin D metabolites and PTH.

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

[This retracts the article DOI: 10.1155/2023/7571696.].

Relationship between bone marrow adipose tissue and kidney function in postmenopausal women

IntroductionBone marrow adipose tissue (BMAT) is associated with aging, osteoporosis, and chronic kidney disease (CKD). To date, the association between BMAT and kidney function in postmenopausal women has not been thoroughly investigated. The main purpose of this study was to determine whether a relationship exists between proton density fat fraction (PDFF) and kidney function in postmenopausal women. MethodsWe investigated the cross-sectional association between estimated glomerular filtration rate (eGFR) – calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation – and PDFF – measured at the lumbar spine and proximal femur using Water Fat Imaging (WFI) MRI – in 199 postmenopausal women from the ADIMOS cohort study. We also performed DXA scans and laboratory measurements of sclerostin and c-terminal Fibroblast Growth Factor 23 (cFGF23). ResultsParticipants' mean age was 67.5 (standard deviation, SD 10.0) years. Their median eGFR was 85.0 (interquartile range, IQR 72.2–95.0) ml/min/1.73 cm2, and their mean lumbar spine PDFF was 57.9 % (SD 9.6). When classified by eGFR-based CKD stages, 41.7 % of the cohort had an eGFR ≥ 90 (n = 83), 47.2 % had an eGFR of 60–89.9 (n = 94), and 11.1 % had an eGFR of 30–59.9 (n = 22). Participants with eGFR ≥ 90 had a lower lumbar spine PDFF than those with eGFR 60–89.9 (mean 55.8 % (9.8) vs. 58.9 % (9.0), p = 0.031) and those with eGFR 30–59.9 (55.8 % (9.8) vs. 60.8 % (9.8), p = 0.043). However, the differences did not remain significant after adjusting for predetermined confounders, including age, diabetes, Charlson comorbidity index, recent history of fragility fracture, appendicular lean mass, and lumbar spine BMD. The inclusion of sclerostin and/or cFGF23 as suspected mediators did not alter the findings. When proximal hip imaging-based PDFF was considered, no significant differences were found between the eGFR categories in the unadjusted and adjusted analyses. ConclusionNo evidence of an association between kidney function and bone marrow adiposity was found either in the lumbar spine or proximal femur in a cohort of postmenopausal women.

Serum Endocan Levels in Postmenopausal Women with Metabolic Syndrome.

Aim: Studies that explored endocan (as a novel marker of endothelial dysfunction) in relation to metabolic syndrome (MetS) are scarce and show discordant results. Importantly, no study has yet examined serum endocan levels in exclusively postmenopausal women with MetS and free of diabetes. Oxidative stress and inflammation are the key features of MetS and consequently cardiovascular diseases. Hence, we aimed to explore the potential relationship between endocan, oxidative stress [i.e., determined by total antioxidant status, total oxidant status, and pro-oxidant/antioxidant balance (PAB)], inflammation, and MetS in a cohort of postmenopausal women. Methods: A total of 126 postmenopausal women were included consecutively. MetS was diagnosed following the International Diabetes Federation criteria. Results: Higher serum endocan levels were found in MetS group as compared with MetS-free counterparts [6.03 (3.47-10.37) pg/mL vs. 2.27 (1.49-3.50) pg/mL, P < 0.001]. Endocan showed good discriminatory ability toward MetS [area under the curve (AUC) = 0.809]. Besides age, the inclusion of oxidative stress and inflammation biomarkers, such as PAB and high-sensitivity C-reactive protein (hsCRP), the AUC for discrimination postmenopausal women with MetS from MetS-free women was 0.845. Conclusion: Postmenopausal women with MetS exhibited almost 2.7 times higher serum endocan level as compared with MetS-free middle-aged women. Endocan showed good discriminatory ability toward MetS and could be a diagnostic marker in MetS. Similar results were confirmed when added an age, oxidative stress, and inflammation biomarkers (i.e., PAB and hsCRP) were included for the discrimination of postmenopausal with MetS from MetS-free women.

Abstract 3011: Psychosocial stress, social support, and incident breast cancer by estrogen receptor status

Abstract Introduction: Chronic stress affects immune function and hormonal signaling and has been hypothesized to be associated with breast cancer, although results from the few prior studies are mixed and have not examined potential differences by estrogen receptor (ER) status. We investigated the relationship between stressful life events and incident breast cancer by ER status among postmenopausal women. We further evaluated whether this association is modified by social support. Methods: Our analysis included 76,951 postmenopausal women enrolled in the Women’s Health Initiative. Participants were followed for events for up to 26 years (median, 16.7). We generated Cox proportional hazards models adjusting for demographic, clinical, lifestyle/behavioral, and social factors to estimate hazard ratios (HR) and 95% confidence intervals (95%CI) for associations between baseline self-reported stressful life events and incident breast cancer by ER status. Results: The mean age was 63 (SD 7.3), and majority of participants were White race (83.5%) and married or in a marriage-like relationship (63.0%). In analyses stratified by ER status, there was no relationship between stressful life events and ER-positive breast cancer. In contrast, compared to women in the lowest quartile, those in higher quartiles had an increased risk of ER-negative breast cancer, where those in quartile 4 had the highest risk (Quartile 4 vs Quartile 1; HR=1.30; 95%CI 1.01-1.68; Ptrend=0.050). Additionally, associations were stronger for the highest versus lowest quartile of stressful life events among widowed women (HR=2.39; 95%CI 1.29-4.44; Pinteraction&amp;lt;0.001). Moreover, while the interaction was not statistically significant, we observed an elevated risk for ER-negative breast cancer among women in the highest quartile of stressful life events reporting lower social support. Conclusion: In this cohort of postmenopausal women, higher experiences of pre-diagnostic stressful life events were associated with increased risk of ER-negative breast cancer. Citation Format: Wayne R. Lawrence, Jasmine A. McDonald, Faustine Williams, Meredith S. Shiels, Neal D. Freedman, Ziqiang Lin, Jared W. Magnani. Psychosocial stress, social support, and incident breast cancer by estrogen receptor status [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3011.

MP34-11 URINARY GLYCOSAMINOGLYCANS ARE ASSOCIATED WITH RECURRENT UTI AND UROBIOME ECOLOGY IN POSTMENOPAUSAL WOMEN

You have accessJournal of UrologyCME1 Apr 2023MP34-11 URINARY GLYCOSAMINOGLYCANS ARE ASSOCIATED WITH RECURRENT UTI AND UROBIOME ECOLOGY IN POSTMENOPAUSAL WOMEN Michael L. Neugent, Neha V. Hulyalkar, Philippe E. Zimmern, Kelli L. Palmer, Vladimir Shulaev, and Nicole J. De Nisco Michael L. NeugentMichael L. Neugent More articles by this author , Neha V. HulyalkarNeha V. Hulyalkar More articles by this author , Philippe E. ZimmernPhilippe E. Zimmern More articles by this author , Kelli L. PalmerKelli L. Palmer More articles by this author , Vladimir ShulaevVladimir Shulaev More articles by this author , and Nicole J. De NiscoNicole J. De Nisco More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003268.11AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The composition of urinary glycosaminoglycans (GAGs) is not fully understood. The luminal urothelial GAG layer is likely an important interface between the human host and the resident urobiome, which has been shown to be altered in postmenopausal (PM) women with history of recurrent urinary tract infection (rUTI).1 We sought to profile the urinary GAG distribution and associate urinary GAGs with the ecology of the resident urobiome in a controlled cohort of PM women designed to study rUTI. METHODS: Clean catch midstream urine was collected from a controlled cohort of PM women (n=75) who passed a set of exclusion criteria for an ongoing study of rUTI.1 GAGs were extracted from urine via macromolecular filtration and then enzymatically digested into constituent disaccharides for chondroitin Sulfate (CS), heparin Sulfate (HS), and hyaluronic Acid (HA) following a published protocol.2 The liberated disaccharides were analyzed and quantified via targeted liquid chromatography-mass spectrometry (LC-MS/MS). For whole genome metagenomics, DNA was purified from matched urine and prepared libraries were sequenced on an Illumina NextSeq500 and analyzed for taxonomic enrichment as described previously.1 RESULTS: We find that CS is the major urinary GAG in PM women and women who were experiencing an active UTI exhibited significantly higher urinary CS compared to those with no UTI (Figure 1). Lastly, we find that two urobiome bacterial species, Atopobium vaginae and Blautia obeum exhibit significant negative associations with urinary CS. CONCLUSIONS: Our findings of increased urinary CS during active UTI may be a sign of tissue damage during infection. We find negative associations between bacterial species known to be associated with vaginal dysbiosis and urinary CS levels. These associations may be indicators of bladder dysbiosis and alterations of urothelial GAG composition.

Total energy expenditure as assessed by doubly labeled water and all-cause mortality in a cohort of postmenopausal women

BackgroundThe association of TEE with all-cause mortality is uncertain, as is the dependence of this association on age. ObjectivesTo examine the association between TEE and all-cause mortality, and its age interaction, in a Women’s Health Initiative (WHI) cohort of postmenopausal United States women (1992–present). MethodsA cohort of 1131 WHI participants having DLW TEE assessment of ∼10.0 y (median) following WHI enrollment with ∼13.7 y (median) of subsequent follow-up, was used to study the EE associations with all-cause mortality. To enhance the comparability of TEE and total EI, key analyses excluded participants having >5% weight change between WHI enrollment and DLW assessment. The influence of participant age on mortality associations was examined, as was the ability of concurrent and earlier weight and height measurements to explain the results. ResultsThere were 308 deaths following the TEE assessment through 2021. TEE was unrelated to overall mortality (P = 0.83) in this cohort of generally healthy, older (mean 71 y at TEE assessment) United States women. However, this potential association varied with age (P = 0.003). Higher TEE was associated with a higher mortality rate at the age of 60 y and a lower mortality rate at the age of 80 y. Within the weight-stable subset (532 participants, 129 deaths), TEE was weakly positively related to overall mortality (P = 0.08). This association also varied with age (P = 0.03), with mortality HRs (95% CIs) for a 20% increment in TEE of 2.33 (1.24, 4.36) at the age of 60 y, 1.49 (1.10, 2.02) at 70 y of age, and 0.96 (0.66, 1.38) at 80 y of age. This pattern remained, although was somewhat attenuated, following control for baseline weight and weight changes between WHI enrollment and TEE assessment. ConclusionsHigher EE is associated with higher all-cause mortality among younger postmenopausal women, only partially explained by weight and weight change.This study is registered with clinicaltrials.gov identifier: NCT00000611.

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.