Postmenopausal Women Research Articles

Metformin improves HPRT1-targeted purine metabolism and repairs NR4A1-mediated autophagic flux by modulating FoxO1 nucleocytoplasmic shuttling to treat postmenopausal osteoporosis.

Osteoporosis is a major degenerative metabolic bone disease that threatens the life and health of postmenopausal women. Owing to limitations in detection methods and prevention strategy awareness, the purpose of osteoporosis treatment is more to delay further deterioration rather than to fundamentally correct bone mass. We aimed to clarify the pathogenesis of postmenopausal osteoporosis and optimize treatment plans. Our experiments were based on previous findings that oxidative stress mediates bone metabolism imbalance after oestrogen deficiency. Through energy metabolism-targeted metabolomics, we revealed that purine metabolism disorder is the main mechanism involved in inducing oxidative damage in bone tissue, which was verified via the use of machine-learning data from human databases. Xanthine and xanthine oxidase were used to treat osteoblasts to construct a purine metabolism disorder model. The activity and differentiation ability of osteoblasts decreased after X/XO treatment. Transcriptomic sequencing indicated that autophagic flux damage was involved in purine metabolism-induced oxidative stress in osteoblasts. Additionally, we performed serum metabolomics combined with network pharmacology to determine the pharmacological mechanism of metformin in the treatment of postmenopausal osteoporosis. HPRT1 was the potential target filtered from the hub genes, and FoxO1 signalling was the key pathway mediating the effect of metformin in osteoblasts. We also revealed that SIRT3-mediated deacetylation promoted the nuclear localization of FoxO1 to increase the expression of HPRT1. HPRT1 upregulation promoted purine anabolism and prevented the accumulation of ROS caused by purine catabolism to reverse oxidative damage in osteoblasts. We propose that purine metabolism disorder-induced oxidative stress is important for the pathogenesis of postmenopausal osteoporosis. The therapeutic mechanism of metformin should be confirmed through subsequent drug optimization and development studies to improve bone health in postmenopausal women.

Combined effects of high-intensity focused electromagnetic therapy and pelvic floor exercises on pelvic floor muscles and sexual function in postmenopausal women. A randomized controlled trial.

This study aimed to explore the impact of high-intensity focused electromagnetic therapy (HIFEMT) on the pelvic floor muscles (PFM), sexual function, and quality of life (QoL) among postmenopausal women. Fifty postmenopausal women with PFM weakness and sexual dysfunction were randomly allocated into two equal groups. The HIFEMT group participated in the PFM training program in addition to HIFEMT, whereas the control group performed PFM training only. For 12 weeks, HIFEMT was scheduled two times a week, while PFM training was performed daily. At baseline and after 12 weeks, PFM strength and endurance were assessed using a perineometer and sexual function was examined using the female sexual function index (FSFI) and menopause-specific quality of life questionnaire (MENQOL). The HIFEMT and control groups showed significant increases in PFM strength and endurance and FSFI scores, and significant declines in MENQOL compared with baseline measures (P<0.05). Compared to the control group, the HIFEMT group showed substantial improvements in all measured variables after 12 weeks (P<0.05). Addition of HIFEMT to PFM training improved the PFM strength, endurance, sexual function, and QoL in postmenopausal women with PFM weakness and sexual dysfunction.

Perceived lack of behavioral control is a barrier to a healthy lifestyle in post-menopause: a qualitative study.

Menopause is a natural phase in a woman's life, but the quality of life and health of postmenopausal women are often compromised by unhealthy lifestyles. Therefore, it is crucial to identify the factors that influence their well-being. The main objective of this study is to explore the barriers to a healthy lifestyle among Iranian postmenopausal women. Qualitative exploratory research was conducted among postmenopausal women aged 45-65 years in three different health centers located in urban areas with varying economic level in a central city of Iran. These areas represented upscale, downtown, and downscale areas with different economic statuses (wealthy, relatively wealthy, and less wealthy). Nine focus group discussions were held, focusing on managing menopausal symptoms, physical activity, and healthy nutrition. Each topic was discussed separately in a different health center, with 10 women participating in each session. Data analysis was conducted using Graneheim and Lundman's method. The study revealed a prominent theme, "perceived lack of behavioral control as a barrier to a healthy lifestyle in post-menopause." Two categories, "False attitudes" and "Perceived inability to engage in behavior," were derived from 26 codes related to managing menopausal symptoms. Furthermore, a category, "Perceived inability to engage in behavior," was formed from 11 to 13 codes related to physical activity and healthy nutrition, respectively. The theme highlighted that the perceived lack of behavioral control prevented the women from adopting a healthy lifestyle. Improving perceived behavioral control through the modification of attitudes and abilities is essential for maintaining a healthy postmenopausal lifestyle.

Total testosterone, sex hormone-binding globulin, and free testosterone concentrations and risk of primary liver cancer: A prospective analysis of 200,000 men and 180,000 postmenopausal women.

In most countries, males have ~2-3 times higher incidence of primary liver cancer than females. Sex hormones have been hypothesized to contribute to these differences, but the evidence remains unclear. Using data from the UK Biobank, which included ~200,000 males and ~180,000 postmenopausal females who provided blood samples at recruitment, we estimated hazard ratios (HR2) and 95% confidence intervals (CI) for a doubling in hormone concentration from multivariable adjusted Cox regression for circulating total testosterone, sex-hormone binding globulin (SHBG), and free testosterone concentrations and risk of primary liver cancer. After a median of 11.8 years of follow-up, 531 cases of primary liver cancer were observed, of which 366 occurred in males and 165 occurred in females. Total testosterone and SHBG were shown to be positively associated with liver cancer risk in both males and females (Total testosterone HR2: 3.42, 95% CI:2.42-4.84 and 1.29, 0.97-1.72, respectively; SHBG HR2: 5.44, 4.42-6.68 and 1.52, 1.09-2.12, respectively). However, free testosterone was inversely associated with primary liver cancer in males (HR2: 0.42, 0.32-0.55) and no association was observed in females. When analyses compared two main liver cancer subtypes, hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), there was evidence of heterogeneity; associations for total testosterone and SHBG concentrations were only positively associated with HCC in both males (HR2: 3.56, 2.65-4.79 and 7.72, 6.12-9.73, respectively) and females (HR2: 1.65, 1.20-2.27 and 6.74, 3.93-11.5, respectively) but not with ICC. Further research understanding the mechanisms of how sex-steroids may influence liver cancer risk is needed.

Menopausal status-dependent alterations in the transcript levels of genes encoding ERα, ERβ, PR and HER2 in breast tumors with different receptor status.

Breast cancer has distinct causes and prognoses in patients with premenopausal and postmenopausal status. The expression status of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) are analyzed by immunohistochemistry (IHC) to classify molecular subtypes of breast cancer among which large differences in prognosis exist. The mRNA expression of ESR1 (encoding ERα), ESR2 (encoding ERβ), PGR (encoding PR), and ERBB2 (encoding HER2) was analyzed based on menopausal status (pre- vs post-menopausal) in tumors from breast cancer patients with different receptor status, in R programming environment, using transcriptomics data from TCGA-BRCA project. In ER-positive or PR-positive or HER2-negative breast tumors, ESR1 transcript levels were found to be higher in tumors from postmenopausal women than those from premenopausal women; in contrast, ESR2 transcript levels were lower in tumors from postmenopausal women than those from premenopausal women. Furthermore, PGR mRNA expression was lower in breast tumors from postmenopausal women than those from premenopausal women, only in those with ER + or PR + status. The expression of these genes between tumors from pre- and post-menopausal patients with breast cancer was also analyzed based on the combination of status of three receptors. Together, the results suggest that mRNA expression of ESR1, ESR2, and PGR might differ depending on menopausal status in breast tumors with certain receptor status. More importantly, the change in the expression of ESR1 and ESR2 following menopause is in the opposite directions in breast cancer patients showing the need to identify particular molecular mechanisms regulating the expression of ER isoforms post-menopause in different directions in breast cancer patients, considering the high clinical importance of these receptors in terms of the prognosis of patients with breast cancer.

Hyaluronic acid and erbium laser for the treatment of genitourinary syndrome of menopause.

This study aimed to evaluate the effect of the vaginal erbium laser (VEL) in association with vaginal hyaluronic acid (HA) in postmenopausal women suffering from genitourinary syndrome of menopause (GSM). One hundred sexually active postmenopausal women were selected and divided into three groups using a block randomization method; 10 women declined to participate. The remaining women received three laser applications at 30-day intervals; 22 women dropped out for personal reasons or protocol violations. Group 1 (n = 25) received VEL treatment (XS Fotona Smooth®; Fotona, Slovenia) alone; Group 2 (n = 22) received daily vaginal HA tablets for 10 days after VEL treatment, followed by a twice a week administration during the follow-up period; and Group 3 (n = 21) received daily HA tablets for 10 days before the first VEL treatment and for 10 days after each laser application, followed by a twice a week administration for the follow-up period. Vaginal dryness and dyspareunia were assessed at the screening visit, before VEL treatment, after 1 and 3 months from the last laser treatment, using the visual analog scale. Data were analyzed using one-way analysis of variance and a linear mixed model for repeated measures. The post-hoc test for the interaction between time and treatment was performed using Bonferroni correction. A significant (p < 0.001) improvement in both vaginal dryness and superficial dyspareunia was evident, with greater (p < 0.001) improvement in Group 2 and Group 3. The results suggest that vaginal HA administration can improve the VEL effects on GSM in postmenopausal women.

Early Diagnosis of Subclinical Atherosclerosis in Asymptomatic Type 2 Diabetic Normotensive Menopausal Women: A Global Pulse Wave Velocity Study

AbstractArterial stiffness serves as a cardiovascular disease marker, aiding in the early identification of high-risk patients. We aimed to evaluate the prevalence of arterial stiffness, measured by global pulse wave velocity (gPWV), among diabetic normotensive menopausal women (DPMW) and its correlation with levels of glycosylated hemoglobin (HbA1c). We recruited 641 consecutive DPMW diagnosed with type 2 diabetes over 5 years. The control group (CG) consisted of 300 normotensive, normoglycemic menopausal women. Normal gPWV was defined as a velocity ≤7.1 m/s. We enrolled 641 DPMW with a mean age of 57 ± 12 years. The CG comprised 300 normotensive, normoglycemic postmenopausal women with a mean age of 56 ± 4 years. Among DPMW, 29 (4.5%) exhibited increased gPWV compared with 4 (1.3%) in the CG (p &lt; 0.01). Of the 225 (35.1%) DPMW with HbA1c &gt; 7.5%, 23 (10.2%) had increased gPWV. In contrast, among the 416 (64.9%) DPMW with HbA1c &lt; 7.5%, only 6 (1.4%) had increased gPWV (p &lt; 0.0001). Electrocardiographic (ECG) abnormalities were detected in 208 (32.4%) DPMW, with 11 (5.3%) of them exhibiting increased gPWV (p = 0.6). There was a higher prevalence of increased gPWV in asymptomatic normotensive DPMW, with a significant association between increased gPWV and elevated HbA1c levels. However, there was no correlation between increased gPWV and abnormal ECG findings, despite ECG being the sole test recommended by current guidelines for all diabetic patients. Early detection of elevated HbA1c levels and increased gPWV may identify asymptomatic DPMW at higher cardiovascular risk, highlighting the inadequacy of a simple ECG in assessing cardiovascular risk in this population.

The Administration of Resveratrol and Vitamin C Reduces Oxidative Stress in Postmenopausal Women—A Pilot Randomized Clinical Trial

In postmenopausal women, due to endocrine changes, there is an increase in oxidative stress (OS) that predisposes them to cardiovascular and metabolic alterations. Sixty-one percent of women in this stage require a primary therapeutic strategy to decrease OS. This study aimed to evaluate the effect of resveratrol and vitamin C on OS in postmenopausal women. A randomized, double-blind clinical trial was carried out. Forty-six postmenopausal women with insulin resistance (HOMA-IR &gt; 2.5) were included and divided into three treatment groups: group A: resveratrol, n = 13; group B: resveratrol + vitamin C, n = 15; and group C: vitamin C, n = 14. Between before and after the antioxidants, group B showed a decrease of 33% in lipohydroperoxides (p = 0.02), and malondialdehyde (MDA) decreased by 26% (p = 0.0007), 32% (p = 0.0001), and 38% (p = 0.0001) in groups A–C, respectively. For protein damage, group B is the most representative, with a decrease of 39% (p = 0.0001). For total antioxidant capacity (TAC), there were significant increases of 30% and 28% in groups B and C, respectively. For HOMA-IR, there were no significant differences among the study groups. Supplementation with this combination of antioxidants significantly decreases markers of OS in postmenopausal women. In addition, it increases TAC by up to 30%.

Relationship between physical activity and abdominal obesity and metabolic markers in postmenopausal women

This study aimed to investigate the impact of physical activity indicators monitored by the POLAR accelerometer on body obesity indicators, metabolic syndrome parameters, and energy metabolism hormones in postmenopausal women. Was included 71 participants from this study program (68.8 ± 4.3 years). We divided participants into LPA and MVPA groups based on their level of moderate to vigorous physical activity per week; Physical activity levels over 7 days were assessed using a POLAR accelerometer, with daily step counts and sedentary time recorded. Measurements included waist circumference, visceral fat volume, body fat percentage, blood pressure, fasting blood glucose, triglyceride levels, HDL cholesterol, and energy metabolism hormone levels (leptin, resistin, adiponectin). The MVPA group displayed lower waist circumference, body fat percentage, abdominal fat, and BMI compared to the LPA group (p < 0.05). A significant negative correlation was observed between daily step count and obesity indicators, including waist circumference (r = -0.301), body fat percentage (r = -0.295), abdominal fat (r = -0.318), and BMI (r = -0.238). Conversely, sedentary time showed a positive correlation with obesity indicators such as waist circumference (r = 0.258), body fat percentage (r = 0.239), and abdominal fat (r = 0.244). Moreover, daily step count exhibited a significant negative correlation with leptin levels (r = -0.245), while sedentary time was positively correlated with the energy metabolic factor leptin (r = 0.279). Waist circumference demonstrated significant positive correlations with triglycerides, blood glucose, adiponectin, resistin, and leptin levels. Postmenopausal women who engage in at least 150 min of MVPA weekly show lower obesity indices. There is a significant correlation between physical activity levels and obesity indicators, which relate to metabolic syndrome and energy metabolism factors. Thus, increased physical activity may help prevent metabolic syndrome and cardiovascular diseases in this population.

The role of adjuvant endocrine treatment in ER+, PR−, HER2− early breast cancer: a retrospective study of real-world data

Purpose: Estrogen receptor-positive (ER+), progesterone receptor-negative (PR-) and human epidermal growth factor receptor 2-negative (HER2−) breast cancer (BC) often developed resistance to endocrine treatment (ET). We aimed to explore (1) the different clinicopathological features between ER+/PR+/HER2- and ER+/PR-/HER2- BC, and (2) whether ER+/PR-/HER2- early BC patients could benefit from adjuvant ET. Methods: All patients treated for ER+/HER2- early BC who underwent surgery between 2010 and 2021 from a BC database in China were retrospectively examined. The cases followed up for less than six months were excluded. Results: The records of ER+/PR+/HER2- (n = 10843) and ER+/PR-/HER2- BC (n = 1193) cases were reviewed, with median follow-up times of 35.8 and 47.0 months, respectively. Compared with ER+/PR+/HER2- cases, ER+/PR-/HER2- BC occurred more in postmenopausal women (73.1% vs. 52.9%, p = 0.000) and were more likely to be T > 2 cm (40.6% vs. 37.6%, p = 0.048) and Ki67 > 20%+ (48.1% vs. 36.9%, p = 0.000). However, ER+/PR-/HER2- cases had fewer nodal involvement (32.9% vs. 36.9%, p = 0.000). Approximately 82.2% (981/1193) of ER+/PR-/HER2- patients received ET, while approximately 17.8% (212/1193) did not. Compared to patients did not receive adjuvant ET, the ET group had similar disease-free survival (DFS) (HR = 1.33, 95% confidence interval (CI): 0.68–2.59, p = 0.444) and overall survival (OS) (HR = 1.17, 95%CI: 0.37–3.68, p = 0.799). 65.7% of recurrent ER+/PR-/HER2- patients experienced distant relapse (65.7% vs. 48.2% (for ER+/PR + cases), p = 0.011). By comparison, recurrent ER+/PR+/HER2- patients were more likely to experience only local relapse (31.6% vs. 14.9% (for ER+/PR- cases), p = 0.007). Conclusions: ER+/PR-/HER2- BC was a special subtype with aggressive clinicopathological features and more tend to have distant metastasis rather than nodal involvement or local relapse. ER+/PR-/HER2- early BC did not seem to benefit from adjuvant ET.

Romosozumab following denosumab improves lumbar spine bone mineral density and trabecular bone score greater than denosumab continuation in postmenopausal women.

Romosozumab following anti-resorptive can be an effective sequential treatment strategy to improve bone strength. However, whether the transition to romosozumab after denosumab is associated with greater improvement in bone mineral density (BMD) and trabecular bone score (TBS) compared to denosumab continuation remains unclear. In this propensity score-matched cohort study, we analyzed data from postmenopausal women who initiated denosumab between 2017 and 2020. Individuals who were transited to 12months of romosozumab after denosumab were 1:1 matched to those who continued an additional 12months of denosumab (n = 86 for each group; denosumab-romosozumab [DR] and denosumab-denosumab [DD]). Mean BMD gain by denosumab treatment in matched DR and DD groups from denosumab initiation to transition (median 4 times [range 2 to 8]) was +4.8% and + 2.0% in the lumbar spine and total hip. DR group showed greater LS BMD gain compared to the DD group (+6.8 vs. +3.3% point, P<.001) for 12months post-transition independent of the duration of prior denosumab treatment, yielding greater overall LS BMD gain in DR compared to DD (+11.6% vs. +8.0%, P<.001). DD group showed continued improvement of hip BMD, whereas hip BMD was maintained but not improved in the DR group. DR group was associated with greater TBS improvement than the DD group (2.9% vs 1.0%, P=.042). One month after the transition to romosozumab from denosumab, P1NP immediately increased above the level of denosumab initiation with relatively suppressed CTx, creating a transient anabolic window. For 12months follow-up, one incident morphometric vertebral fracture and one patella fracture were observed in DD, whereas one ankle fracture was observed in the DR group. Romosozumab following denosumab improved lumbar spine BMD and TBS greater than denosumab continuation in postmenopausal women.

Camizestrant, a next-generation oral SERD, versus fulvestrant in post-menopausal women with oestrogen receptor-positive, HER2-negative advanced breast cancer (SERENA-2): a multi-dose, open-label, randomised, phase 2 trial

Resistance to endocrine therapies in hormone receptor-positive breast cancer is challenging. We aimed to assess the next-generation oral selective oestrogen receptor degrader (SERD) and complete oestrogen receptor antagonist, camizestrant, versus the first-approved SERD, fulvestrant, in post-menopausal women with oestrogen receptor-positive, HER2-negative, advanced breast cancer. SERENA-2 is an open-label, randomised, phase 2 trial that is being conducted at 74 study centres across Asia, Europe, the Middle East, and North America. Female patients aged 18 years or older who were post-menopausal with histologically or cytologically confirmed metastastic or locoregional oestrogen receptor-positive, HER2-negative breast cancer, an Eastern Cooperative Oncology Group or WHO performance status of 0 or 1, and disease recurrence or progression on at least one line of endocrine therapy, and no more than one previous endocrine therapy in the advanced setting. Patients were initially randomly assigned (1:1:1:1) to receive oral camizestrant once daily at 75 mg, 150 mg, or 300 mg (until the 300 mg group was closed), or fulvestrant intramuscularly at 500 mg (per label). Randomisation was managed through an interactive web-based system and stratified by previous treatment with CDK4/6 inhibitors and presence of liver and/or lung metastases. The primary objective was to determine clinical efficacy of camizestrant versus fulvestrant at each dose level using the primary endpoint of investigator-assessed progression-free survival, per Response Evaluation Criteria in Solid Tumours (version 1.1), assessed by intention to treat in all randomly assigned patients (full analysis set). No formal statistical comparison for the efficacy analysis of the camizestrant 300 mg dose versus fulvestrant was to be performed. Safety analyses included all randomly assigned patients who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT04214288, and is ongoing. Between May 11, 2020, and Aug 10, 2021, 240 patients were randomly assigned to receive camizestrant 75 mg (n=74), 150 mg (n=73), 300 mg (n=20), or fulvestrant (n=73), and were included in the full analysis set. All patients received at least one dose of study drug. Median follow-up was 16·6 months (IQR 12·9-19·4) for the camizestrant 75 mg group, 16·3 months (12·9-18·3) for the camizestrant 150 mg group, and 14·7 months (12·7-20·1) for the fulvestrant 500 mg group. Median progression-free survival was 7·2 months (90% CI 3·7-10·9) with camizestrant 75 mg, 7·7 months (5·5-12·9) with camizestrant 150 mg, and 3·7 months (2·0-6·0) with fulvestrant. The hazard ratio for camizestrant 75 mg versus fulvestrant was 0·59 (90% CI 0·42-0·82; p=0·017), and the hazard ratio for camizestrant 150 mg versus fulvestrant was 0·64 (0·46-0·89; p=0·0090). Treatment-related adverse events occurred in 39 (53%) of 74 patients in the camizestrant 75 mg group, 49 (67%) of 73 patients in the camizestrant 150 mg group, 14 (70%) of 20 patients in the camizestrant 300 mg group, and 13 (18%) of 73 patients in the fulvestrant group. No single grade 3 or worse treatment-emergent adverse event occurred in more than two (3%) patients in any group. Serious treatment-emergent adverse events occurred in six (8%) patients in the camizestrant 75 mg group, seven (10%) patients in the camizestrant 150 mg group, two (10%) patients in the camizestrant 300 mg group, and four (5%) patients in the fulvestrant group. No treatment-related deaths occurred. Camizestrant at 75 and 150 mg showed a significant benefit in progression-free survival versus fulvestrant. These results support further development of camizestrant for the treatment of oestrogen receptor-positive, HER2-negative breast cancer. AstraZeneca.

Association Between Dietary Fiber Intake and Sleep Disorders: Based on the NHANES Database.

Utilizing data from the National Health and Nutrition Examination Survey (NHANES) database, the primary objective of this investigation was to examine the relationship between dietary fiber intake (DFI) and sleep disorders. For analysis, data from three consecutive cycles of NHANES (2009-2014) were pooled. The independent variable of interest was DFI, while the dependent variable was sleep disorders. Weighted logistic regression was employed to model the relationship between the two variables. Subgroup analyses were conducted, stratified, and adjusted to explore the association between DFI and sleep disorders. This study encompassed a cohort of 14,360 samples. Logistic regression results revealed a significant inverse association between higher DFI and the risk of sleep disorders (OR: 0.99, 95% CI: 0.98-1.00, p = 0.005). Stratified analysis demonstrated significant interactive effects of gender and physical activity on the association between DFI and sleep disorders (interaction p = 0.017, p = 0.061). Quartile-stratified analysis of DFI showed that in the crude model, Q4 exhibited a significant protective impact against sleep disorders (OR: 0.76, 95% CI: 0.59-0.97, p = 0.026). In model I, which adjusted for demographic characteristics only, Q3 (OR: 0.74, 95% CI: 0.56-0.98, p = 0.036) and Q4 (OR: 0.70, 95% CI: 0.55-0.90, p = 0.006) had significant protective effects on sleep disorders. Additionally, gender subgroup analysis revealed that DFI had a significant impact on the female population, particularly in postmenopausal women, and was more pronounced in subjects with BMI > 30kg/m2 (p = 0.011). Within the physical activity subgroup, there was a certain effect of DFI on improving sleep disorders in individuals with low activity intensity. Increasing DFI had a protective effect in reducing the risk of sleep disorders. This protective effect may be more pronounced in the female population and individuals with low physical intensity.

Adapted physical activity programs for the prevention and treatment of musculoskeletal pain induced by aromatase inhibitors in non-metastatic breast cancer patient: a scoping review.

Aromatase inhibitor is associated with a high incidence of Aromatase Inhibitor-Associated Musculoskeletal Syndrome (AIMSS) in postmenopausal women with hormone-sensitive breast cancer. This scoping review aims to identify available information regarding the frameworks, models, or strategies of adapted physical activity (APA) programs implemented for the prevention and management of AIMSS. Search was realized by two independent reviewers in six databases following PRISMA-ScR guidelines. Data of included articles were extracted, and risk of bias analyzed. Finally, 14 were included. No study has examined APA in the prevention of AIMSS. There is no solid evidence supporting the impact of APA on the management of AIMSS. However, evidence suggests that an APA program can reduce the worst joint pain and improve the quality of life. Future research will enlighten clinical practices with the development of personalized APA programs in hormone-sensitive breast cancer.

Society for endocrinology guideline for understanding, diagnosing and treating female hypogonadism.

Female hypogonadism (FH) is a relatively common endocrine disorder in women of premenopausal age, but there are significant uncertainties and wide variation in its management. Most current guidelines are monospecialty and only address premature ovarian insufficiency (POI); some allude to management in very brief and general terms, and most rely upon the extrapolation of evidence from the studies relating to physiological estrogen deficiency in postmenopausal women. The Society for Endocrinology commissioned new guidance to provide all care providers with a multidisciplinary perspective on managing patients with all forms of FH. It has been compiled using expertise from Endocrinology, Primary Care, Gynaecology and Reproductive Health practices, with contributions from expert patients and a patient support group, to help clinicians best manage FH resulting from both POI and hypothalamo-pituitary disorders, whether organic or functional.

The miR-665/SOST Axis Regulates the Phenotypes of Bone Marrow Mesenchymal Stem Cells and Osteoporotic Symptoms in Female Mice

Osteoporosis is a common degenerative skeletal disease among older people, especially postmenopausal women. Bone marrow mesenchymal stem cells (BMSCs), the progenitors of osteoblasts, are essential to the pathophysiology of osteoporosis. Herein, targeting miRNAs with differential expression in dysfunctional BMSCs was accomplished by bioinformatics analysis based on public databases. Target mRNAs were predicted and applied for signaling pathway and function enrichment annotations. Invitro and invivo effects of selected miRNA on BMSC proliferation and osteogenesis were investigated, the putative binding between selected miRNA and predicted target mRNA was verified, and the co-effects of the miRNA/mRNA axis on BMSCs were determined. miRNA 665 (miR-665) was down-regulated in osteoporotic BMSCs compared with normal BMSCs and elevated in BMSCs experiencing osteogenic differentiation. In BMSCs, miR-665 overexpression promoted cell proliferation and osteogenic differentiation. miR-665 targeted the Wnt signaling inhibitor sclerostin (SOST) and inhibited SOST mRNA and protein expression. SOST overexpression inhibited BMSC cell proliferation and osteogenic differentiation. When co-transduced to BMSCs, SOST knockdown significantly reversed the effects of miR-665 on BMSCs. In ovariectomy (OVX)-induced osteoporosis model mice, OVX remarkably decreased bone mass, whereas miR-665 overexpression partially improved OVX-induced bone mass loss. miR-665 was down-regulated in osteoporotic BMSCs and up-regulated in osteogenically differentiated BMSCs. In conclusion, the miR-665/SOST axis modulates BMSC proliferation, osteogenic differentiation, and OVX-induced osteoporosis in mice, possibly through Wnt signaling.

A Multicenter Cohort Study on DNA Methylation for Endometrial Cancer Detection in Cervical Scrapings.

The increasing incidence of endometrial cancer (EC) has highlighted the need for improved early detection methods. This study aimed to develop and validate a novel DNA methylation classifier, EMPap, for EC detection using cervical scrapings. EMPap incorporated the methylation status of BHLHE22 and CDO1, along with age and body mass index (BMI), into a logistic regression model to calculate the endometrial cancer methylation (EM) score for identifying EC in cervical scrapings. We enrolled 1297 patients with highly suspected EC, including 196 confirmed EC cases, and assessed the EMPap performance in detecting EC. EMPap demonstrated robust diagnostic accuracy, with an area under the curve of 0.93, sensitivity of 90.3%, and specificity of 89.3%. It effectively detected EC across various disease stages, grades, and histological subtypes, and consistently performed well across patient demographics and symptoms. EMPap correctly identified 87.5% of the type II ECs and 53.8% of premalignant lesions. Notably, compared with transvaginal ultrasonography (TVS) in patients with postmenopausal bleeding, EMPap exhibited superior sensitivity (100% vs. 82.0%) and specificity (85.2% vs. 38.5%). In asymptomatic postmenopausal women, EMPap maintained high sensitivity (89.5%) and negative predictive value (NPV) (98.3%). This study demonstrated the potential of EMPap as an effective tool for EC detection. Despite the limited sample size, EMPap showed promise for identifying type II EC and detecting over 50% of premalignant lesions. As a DNA methylation classifier, EMPap can reduce unnecessary uterine interventions and improve diagnosis and outcomes.

Improved vascular health linked to increased physical activity levels and reduced sedentary behavior in rheumatoid arthritis.

Rheumatoid arthritis (RA) is characterized by deteriorated vascular health and increased cardiovascular risk. Physical activity (PA) is recommended for cardiovascular management in RA, but evidence on the associations between objectively-measured PA and vascular health markers in RA is limited. In this cross-sectional study, eighty-two post-menopausal women with RA (62±7 years) undertook ultrasound assessments of vascular function and structure, including brachial and superficial femoral artery (BA and SFA) flow-mediated dilation; baseline and post-hyperemia peak diameters; and carotid intima-media thickness. Participants also performed a 7-day accelerometer-based assessment of PA and sedentary behavior (SB). Fitted regression models controlled for age, body mass index and disease activity were conducted to examine associations between vascular and PA outcomes. Regression analyses revealed that prolonged SB (bouts>60min) and total sedentary time were inversely associated with both baseline and peak BA diameters, with each additional hour of SB resulting in decreases of 0.08-0.1mm in these diameters (p≤0.01). Total sedentary time also showed similar negative associations with peak SFA diameters (β=-0.14[-0.24-0.05], p<0.01). Conversely, light-intensity PA and stepping time were positively associated with both baseline and peak BA diameters, with each additional hour increasing these diameters by 0.10-0.24mm (p≤0.02). Finally, standing time was positively associated with SFA peak diameter (β=0.11[0.01-0.20], p=0.02). No associations were found between moderate-to-vigorous PA and vascular outcomes. In conclusion, in patients with RA, SB was negatively, while light PA was positively, associated with BA and SFA diameters. These findings suggest that reducing SB and increasing PA, even at light intensities, may improve vascular health in RA.

Refining Ovarian Cancer Test accuracy Scores: A multicentre, prospective cohort study investigating diagnostic accuracy among women with symptoms of suspected ovarian cancer (the ROCkeTS study): Results for post-menopausal women

Refining Ovarian Cancer Test accuracy Scores: A multicentre, prospective cohort study investigating diagnostic accuracy among women with symptoms of suspected ovarian cancer (the ROCkeTS study): Results for post-menopausal women

Prevalence and Risk Factors of Osteoporosis among Postmenopausal Women Visiting a District Hospital of Nepal: An Observational Study

Introduction: Osteoporosis and low bone mass affect millions of people worldwide, leading to severe consequences ranging from disability to mortality. This study aimed to determine the prevalence and risk factors of osteoporosis among postmenopausal women in a district of Nepal.Methods: An analytical cross-sectional study involving postmenopausal women from Nuwakot, Dhading, and Rasuwa districts in Nepal was conducted at Trishuli Hospital, Nuwakot. Ethical approval was taken from the Institutional Review Board of Nepal Health Research Council(Reference number: 1768). The prevalence of osteoporosis was determined, and the associated factors were analyzed using multivariate logistic regression. Dual-Energy X-ray Absorptiometry (GE-Lunar Prodigy) was used to measure Bone Mineral Density (g/cm2) at the proximal femur and lumbar spine. Various factors related to osteoporosis were also analyzed.Results: There were 384 postmenopausal women and the prevalence of osteoporosis was 82 (21.35%; 95% CI: 17.25%-25.45%)e. The mean age of female with osteoporosis was 67.52±8.84 years and that without osteoporosis was 55.70±7.69 years (p &lt;0.001). The multivariate logistic regression showed aOR 0.82 for body mass index.Conclusions: The study reports a lower prevalence of osteoporosis than expected in postmenopausal women. There was a significant inverse relationship between osteoporosis and body mass index. However, no significant association was observed between Bone Mineral Density, biochemical variables, smoking, and parity.