Cohort Of Postmenopausal Women Research Articles

Pathway Analysis to Identify Factors Affecting Sexual Function in Postmenopausal Women with Hypertension Not Receiving Hormone Replacement Therapy

Purpose: As women in middle age undergo the menopausal transition, they may encounter alterations in sexual function concomitantly with physical and emotional manifestations. The present research investigated the relationships between menopausal symptoms, depression, marital intimacy, and sexual function. Additionally, it aimed to identify the mediating influences of depression and marital intimacy in the relationship between menopausal symptoms and sexual function in naturally post-menopausal women with hypertension. Methods: The study included post-menopausal women aged between 45 and 60 years with hypertension who were not undergoing hormone replacement therapy. A total of 308 post-menopausal women were recruited from three provinces in Korea. Path analysis was conducted by AMOS employing maximum likelihood estimation and bootstrapping with 2000 samples. Results: The theoretical pathway model demonstrated strong alignment with empirical findings obtained from a cohort of postmenopausal women. The association between menopausal symptoms and sexual function was mediated by depression and marital intimacy. Ultimately, menopausal symptoms, depression, and marital intimacy collectively explained 64% of the overall variance in sexual function. Conclusion: This study highlights the importance of individualized interventions targeting sexual health in middle-aged women with hypertension undergoing menopause. Counseling and intervention programs focused on alleviating menopausal symptoms and improving sexual function should be integrated into clinical practice. Furthermore, a multidimensional approach is needed to address the various factors influencing sexual function in postmenopausal women.

Vector of glycated hemoglobin in the formation of dysglycemia in postmenopause: Emphasis on early diagnosis and therapy

Introduction. The close relationship of postmenopause with insulin resistance (IR) and metabolic syndrome (MetS) marks a high cardiometabolic risk of dysglycemia, determining the need for its early diagnosis and therapy. Pathogenetically substantiated criteria for the diagnosis of prediabetes and the nature of early drug therapy for type 2 diabetes mellitus (T2DM) are debated. Information on the relationship between glucose homeostasis parameters and menopausal MetS is fragmentary.Aim. To evaluate the associations of glycated hemoglobin (HbA1c) levels with indices of IR, β-cell function and MetS character- istics in a cohort of postmenopausal women with different carbohydrate metabolic states.Materials and methods. In 94 Caucasian postmenopausal women 58.0 (53.0; 63.0) years old the following were determined: HbA1c, fasting glycemia (FG), TyG and HOMA2 indices, C-peptid, BMI, waist circumference (WC), blood pressure (BP), triglycerides (TG), HDL-C levels. When classifying women by HbA1c (ADA criteria), 15 had normoglycemia, 24 prediabetes, 55 T2DM. ME (25–75%) was assessed using SPSS (version 17); intergroup differences according to the Mann – Whitney test; Spearman and partial correlation analysis were performed.Results. HbA1c age independently correlated with IR parameters: TyG (R = 0.590; p < 0.001), HOMA2-IR (R = 0.318; p < 0.05) and beta cell function: HOMA2-B (R = -0.355; p < 0.001); with lipid markers of MetS (TG, HDL-C, respectively R = 0.382; -0.448; p < 0.001), anthropometric and blood pressure levels.Conclusion. Associations of HbA1c in postmenopausal women with a spectrum of glucose homeostasis parameters and MetS mark it as a vector of formation and progression of dysglycemia due to a close connection with the functional state of β-cells and the importance of lipoglucotoxicity in the dynamics of postmenopausal IR. The obtained data pathogenetically determine the use of HbA1c in the verification of dysglycemia and the early administration of combined antihyperglycemic therapy aimed at preserving β-cell function. The potential of dipeptidyl peptidase-4 inhibitors in slowing the progression of type 2 diabetes mellitus is considered

Falls in RAC-OST-POL Study: the results from 10-year prospective longitudinal observation.

The aim of the study was presentation of the data on falls in a cohort of postmenopausal women in a 10-year prospective longitudinal observation. 640 postmenopausal women at baseline age above 55 years were included. The cohort was randomly selected from the population of the whole Racibórz district. Data on falls and fracture incidence were gathered yearly. 256 (40%) women had no falls, and in 384 (60%) subjects at least one fall was noted. The number of women with 1, 2, and 3 or more falls were 115, 62, and 207, respectively. The total number of falls was 1988. Mean baseline age in those who noted falls was 65.7 ± 7.02 years, and it was significantly higher than in the rest of the patients (64.1 ± 6.75; p<0.01). During follow-up 190 osteoporotic fractures were noted in 129 patients. Falls were proven to have a strong, significant relationship with fracture (chi-square test = 80.5; p < 0.0001). Among potential clinical factors only diabetes type 1 (chi-square test = 5.80; p < 0.05) and depression (chi-square test = 3.82; p < 0.05) influenced falls incidence. The risk of falls was increased in cases of greater numbers of clinical risk factors (chi-square test = 28.4 df = 5; p < 0.0001). In long-term follow-up in postmenopausal women, falls were frequently observed, and their occurrence increased the fracture rate. Diabetes type 1 and depression increase the fall rate, which suggests the necessity of implementation of some preventive procedures.

Fractures at various skeletal sites are dependent on different risk factors: the results from 10 years of prospective longitudinal observation in postmenopausal women from the RAC-OST-POL Study.

The aim of the study was to present data on risk factors for fractures in various parts of the skeleton in a cohort of postmenopausal women during a 10-year prospective observation period. It can be hypothesised that fracture risk factors should be different for spine, hip, and peripheral fractures. 640 postmenopausal women at mean baseline age was 65.0 ± 6.9 years were enrolled into the study. The cohort was randomly selected from the population of the entire Racibórz district. Data on the incidence of fractures and falls were updated annually during the 10-year follow-up period. Information on clinical risk factors for fractures was collected at baseline. During the observation period, 190 low-traumatic fractures were recorded in 129 patients. The following number of fractures was observed: hip 15, spine 30, non-hip fractures other than spine 145 (including 81 forearm fractures). The effect of falls was insignificant in the case of spine fractures (chi-square test: 3.64; p = 0.06). For all other skeletal sites, the incidence of fractures was significantly increased by falls, with the greatest effect observed for forearm fractures and non-spine and non-hip fractures (chi-square test for hip, forearm, and all non-spine, non-hip fractures was 6.43, p < 0.05; 42.7, p < 0.0001 and 66.7, p < 0.0001, respectively). To determine the factors having a significant impact on the incidence of fractures during the observation period, logistic regression was used separately in subgroups. The following risk factors were taken into account: age, height, body weight, bone mineral density (BMD) at the femoral neck as expressed by T-score, rheumatoid arthritis, steroid use, falls reported at baseline, and the total number of risk factors. Spine fractures depended only on T-score, odds ratio (OR) = 0.42 (0.23-0.76); hip fractures depended only on age, OR = 1.15 (1.07-1.24); forearm fractures depended only on age T-score, OR = 0.69 (0.51-0.92); and non-hip, non-spine on fall rate, OR = 1.86 (1.20-2.87). Fractures at various skeletal sites recorded in long-term follow-up in postmenopausal women were dependent on various risk factors. Multivariate analysis identified a single, dominant risk factor for each fracture location analysed.

Circulating Estrogen Metabolites and Risk of Breast Cancer among Postmenopausal Women in the Nurses' Health Study.

Estradiol and estrone are well-established risk factors for postmenopausal breast cancer (BC). Experimental evidence suggests that specific estrogen metabolites, produced via irreversible hydroxylation of estrone and estradiol at the 2- or 16-position may independently influence carcinogenesis. We performed a nested case-control study of BC (328 BC cases; 639 controls) among postmenopausal women within the Nurses' Health Study (NHS)to examine the role of estrogens and estrogen metabolites (jointly referred to as EM). Plasma concentrations of each EM (unconjugated+conjugated forms) were measured by liquid chromatography-tandem mass spectrometry. Multivariable conditional logistic regression, adjusting for BC risk factors, estimated relative risks (RR) and 95% confidence intervals (CI) of BC across quintiles of individual EM, EM pathways, and pathway ratios. Associations by estrogen/progesterone receptor (ER/PR) status were analyzed by unconditional logistic regression. Estradiol and estrone were strongly associated with increased BC risk [estradiol: RRQ5v.Q1 (95% CI)=2.64 (1.64-4.26), estrone: 2.78 (1.74-4.45); both p-trends<0.001]. The 2-hydroxylation pathway was strongly associated with risk [RRQ5v.Q1=3.09 (1.81-5.27), p-trend<0.001], and remained so after adjusting for unconjugated estradiol [RRQ5v.Q1=2.23 (1.25-3.96), p-trend=0.01]. While the 16-hydroxylation pathway was modestly associated with risk [RRQ5v.Q1=1.62 (1.03-2.54), p-trend=0.01], the association was attenuated after unconjugated estradiol adjustment [RRQ5v.Q1=1.24 (0.77-1.99), p-trend=0.19]. Similar positive associations with the 2-pathway and 16-pathway were observed for ER+/PR+ and ER-/PR- tumors. In this cohort of postmenopausal women, 2-hydroxylation of estrone and estradiol was associated with increased BC risk, independent of unconjugated estradiol. These results highlight the need to revisit the role of estrogen metabolism in BC etiology and prevention.

Abstract P306: Aldosterone levels are associated with hypertension in post-menopausal women: the Study of Women’s Health Across the Nation

Introduction: Hypertension (HTN) is the leading cause of premature death in women. Apparent treatment-resistant hypertension (aTRH) is systolic blood pressure (SBP) ≥140 or diastolic BP (DBP) ≥90 mmHg despite treatment with ≥3 antihypertensive medications, or the use of ≥4 antihypertensive medications (irrespective of the BP level). aTRH occurs in approximately 17% of people with treated HTN. High aldosterone may elevate cardiovascular risk; despite causing sodium retention, aldosterone may paradoxically continue to be secreted even when dietary sodium intake is high. Little is known, however, about how aldosterone relates to BP and HTN in women, in whom significant increases in BP, carotid atherosclerosis, and arterial stiffness occur near the time of menopause. We examined the relationships of aldosterone with HTN and aTRH in a cohort of post-menopausal women. Methods: The Study of Women’s Health Across the Nation (SWAN) is a longitudinal cohort of women followed from midlife into late adulthood. This cross-sectional analysis included 999 women (30.3% of the cohort) free of congestive heart failure and with serum aldosterone measured during the 2015-2016 (15th follow-up) study visit. HTN was defined as SBP or DBP ≥140 or ≥90 mmHg, respectively, or use of antihypertensive medications. aTRH was defined as reported use of 4 or more concurrent antihypertensive medications at any visit, or 3 or more concurrent medications and SBP≥140 or DBP≥90 at two consecutive visits. Multivariable logistic regression related HTN or aTRH and aldosterone, adjusting for age, race/ethnicity, and body mass index. Results: In this cohort of women [mean age 66 years (standard deviation:2.7)], the prevalence of HTN and aTRH was 52% and 4.1%, respectively. Women with aTRH had higher median serum aldosterone [8.7 ng/dL, interquartile range (IQR) 5.0-11.7] versus those without (6.7 ng/dL, IQR 2.7-10.5). Each unit increase in aldosterone was associated with a 4% increased odds of HTN (95%CI 1.02,1.06; p&lt;0.001). Similarly, the odds ratio for aTRH in the adjusted model was 1.04 (95%CI 0.99,1.08), although the association was not statistically significant (p=0.09). Conclusion: Aldosterone was positively associated with HTN and there was a non-statistically significant trend toward an association with aTRH in this cohort of post-menopausal women. Our findings suggest that aldosterone within an ostensibly “normal” range is associated with HTN in postmenopausal women.

Fine-Scale Haplotype Mapping Reveals an Association of the FTO Gene with Osteoporosis and Fracture Risk in Postmenopausal Women.

The Fat Mass and Obesity-Associated (FTO) gene encodes a demethylase, which modulates RNA N6-methyladenosine (m6A) and plays a regulatory role in adipocyte differentiation and the pathogenesis of human obesity. To understand the potential role of FTO in osteoporosis (OP), we investigated five single nucleotide variations (SNVs) in intron 1 (rs8057044, rs8050136, rs9939609, rs62033406, and rs9930506) of the FTO gene, and a missense SNV i.e., rs3736228 (A1330V), located in exon 18 of the LRP5 gene, in a cohort of postmenopausal women (n = 188) from Central Europe. Genotyping was performed with an allele discrimination assay, while haplotypes were reconstructed in the population by PHASE 2.1. The rs9930506 was strongly associated with OP (p < 0.0035), which was supported by Bonferroni correction (p < 0.0175), and all SNVs located in the FTO gene were more strongly associated with severe OP with fragility fractures. Among seventeen haplotypes detected for the FTO gene, two haplotypes (H1 and H9) were frequent (frequency > 10%) and distributed in three main haplotypes pairs (H1/H1, H1/H9 and H9/H9, respectively). The pathogenic pair H1/H9 was associated with a leaner phenotype, increased fracture risk, and a lower bone mineral density (BMD), and carried the heterozygous GA of rs9930506, while the protective pair H9/H9 was associated with an increased obesity risk and carried AA alleles of rs9939609. Concordant associations with OP, an increased fracture risk, and a lower BMD at all skeletal sites indicate that the FTO gene is a promising candidate for OP, explaining the complex relationship with obesity and offering new perspectives for the study of the epigenetic regulation of bone metabolism.

Accuracy of self-reported treated hypertension in the women's health initiative: Comparisons with medication inventories.

Few studies have reported on the accuracy of self-reported hypertension history among older postmenopausal women, which was this study's objective. Participants were postmenopausal women enrolled in the Osteoporosis and Periodontal Disease (OsteoPerio) study, an ancillary investigation of the Women's Health Initiative Observational Study (WHI-OS) at the Buffalo, New York, clinical site. Participants self-reported their history of physician diagnosed hypertension treated with medication at WHI-OS enrollment (1993-1998; n=1342, mean age 63 years), then 3 years later at OsteoPerio enrollment (1997-2001; n=1342), and again at OsteoPerio Year 5 follow-up (2002-2005; n=1020). At each time point, medication inventories were recorded and served as the criterion with which self-report was compared in the present study. Physician diagnosed-treated hypertension was also self-reported annually on mailed health update questionnaires in the WHI-OS and were compared against medication inventory at the subsequent clinic exam. Of those participants who self-reported a history of hypertension at WHI enrollment, OsteoPerio enrollment, and OsteoPerio Year 5 follow-up, 41.2%, 90.3%, and 94.4%, respectively, had anti-hypertensive pills in their medication inventory. Across the three time points, sensitivity and specificity ranged from 0.72 to 0.98 and from 0.85 to 0.95, and kappa coefficients ranged from 0.52 to 0.79 when comparing self-report with medication inventory. For self-reported newly physician-diagnosed and treated hypertension on the annual health update questionnaire, 88.4% and 95.2% of those reporting hypertension had anti-hypertensive pills in the subsequent medication inventory. In general, sensitivity and kappa were lower in women aged ≥70 versus<70 years and in those with history of cardiovascular disease and diabetes compared to those without these comorbidities. In this cohort of postmenopausal women, self-reported physician diagnosed and treated hypertension demonstrated moderate to high accuracy when compared against anti-hypertensive medication use documented by pill inventory, particularly for those who were younger and managing fewer comorbidities.

The impact of irritant challenge on the skin barrier and myeloid-resident immune cells in women who are postmenopausal 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. To examine how menopause and HRT affect the skin barrier and immune cell composition in postmenopausal women following irritant challenge. Two cohorts of postmenopausal women were recruited to the study. The first cohort consisted of 10 untreated women [HRT-; mean (SEM) age 56.5 (1.6) years (range 48-63)] and the second was composed of 8 women receiving HRT [HRT+; mean (SEM) age 54.0 (2.1) years (range 48-63)]. Skin irritation was induced by applying topical sodium lauryl sulfate (SLS) 1.25% to occluded buttock skin for 48 h. Clinical assessment was conducted after 24 h, 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 transepidermal water loss (P < 0.05), filaggrin deposition and cytokeratin 10 (K10)+ cell layers (P < 0.01) was observed in individuals receiving HRT compared with the HRT- group. Following SLS challenge in individuals taking HRT, a significant (P < 0.01) reduction in 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 found in those who were not receiving HRT (P < 0.01). Furthermore, the numbers 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 K10+ epidermal cell layers. Following challenge, HRT users exhibited elevated LC, inflammatory DC and macrophage counts 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.

A novel mean shape based post-processing method for enhancing deep learning lower-limb muscle segmentation accuracy.

This study aims at improving the lower-limb muscle segmentation accuracy of deep learning approaches based on Magnetic Resonance Imaging (MRI) scans, crucial for the diagnostic and therapeutic processes in musculoskeletal diseases. In general, segmentation methods such as U-Net deep learning neural networks can achieve good Dice Similarity Coefficient (DSC) values, e.g. around 0.83 to 0.91 on various cohorts. Some generic post-processing strategies have been studied to incorporate connectivity constraints into the resulting masks for the purpose of further improving the segmentation accuracy. In this paper, a novel mean shape (MS) based post-processing method is proposed, utilizing Statistical Shape Modelling (SSM) to fine-tune the segmentation output, taking into consideration the muscle anatomical shape. The methodology was compared to existing post-processing techniques and a commercial semi-automatic tool on MRI scans from two cohorts of post-menopausal women (10 Training, 8 Testing, voxel size 1.0x1.0x1.0 mm3). The MS based method obtained a mean DSC of 0.83 across the different analysed muscles and the best performance for the Hausdorff Distance (HD, 20.6 mm) and the Average Symmetric Surface Distance (ASSD, 2.1 mm). These findings highlight the feasibility and potential of using anatomical mean shape in post-processing of human lower-limb muscle segmentation task and indicate that the proposed method can be popularized to other biological organ segmentation mission.

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.