Association of Life's Essential 8 cardiovascular health with breast cancer incidence and mortality according to genetic susceptibility of breast cancer: a prospective cohort study.

BACKGROUND: Accumulating evidence suggests that cardiovascular diseases and breast cancer share a number of common risk factors, however, evidence on the association between cardiovascular health (CVH) and breast cancer is limited. The present study aimed to assess the association of CVH, defined by Life's Essential 8 (LE8) and genetic risk with breast cancer incidence and mortality among premenopausal and postmenopausal women. METHODS: We used data from the UK Biobank and conducted the multivariate Cox proportional-hazards models to examine associations of LE8 score and genetic risk with breast cancer incidence and mortality. Date on LE8 score was collected between 2006 and 2010 and composed of eight components, including behavioral metrics (diet, tobacco or nicotine exposure, physical activity, and sleep health), and biological metrics (body mass index, blood lipids, blood glucose, and blood pressure). The polygenic risk score (PRS) was calculated as the sum of effect sizes of individual genetic variants multiplied by the allele dosage. RESULTS: A total of 150,566 premenopausal and postmenopausal women were included. Compared to postmenopausal women with low LE8 score, those with high LE8 score were associated with 22% lower risk of breast cancer incidence (HR: 0.78, 95% CI: 0.70-0.87) and 43% lower risk of breast cancer mortality (HR: 0.57, 95% CI: 0.36-0.90). By contrast, we did not observe the significant association among premenopausal women. Further analyses stratified by PRS categories showed that high LE8 score was associated with 28% and 71% decreased risk of breast cancer incidence (HR: 0.72, 95% CI: 0.60-0.87) and mortality (HR: 0.29, 95% CI: 0.10-0.83) compared to low LE8 score among high genetic risk groups, but no significant associations were found among low genetic risk groups. Furthermore, compared with postmenopausal women with high LE8 score and low genetic risk, those with low LE8 score and high genetic risk were associated with increased risk of breast cancer incidence (HR: 6.26, 95% CI: 4.43-8.84). CONCLUSIONS: The present study suggests that better CVH is a protective factor for both breast cancer incidence and mortality among postmenopausal women. Moreover, the risk of developing breast cancer caused by high genetic susceptibility could be largely offset by better CVH.

Genome-wide polygenic risk score for rheumatoid arthritis prediction in postmenopausal women.

BACKGROUND: Rheumatoid arthritis (RA), a common autoimmune disease, exhibits a vital genetic component. Polygenic risk scores (PRS) derived from genome-wide association studies (GWAS) offer potential utility in predicting disease susceptibility. The present study aimed to develop and validate a PRS for predicting RA risk in postmenopausal women. METHODS: The study developed a novel PRS using 225,000 genetic variants from a GWAS dataset. The PRS was developed in a cohort of 8967 postmenopausal women and validated in an independent cohort of 6269 postmenopausal women. Among the development cohort, approximately 70% were Hispanic and approximately 30% were African American. The testing cohort comprised approximately 50% Hispanic and 50% Caucasian individuals. Stratification according to PRS quintiles revealed a pronounced gradient in RA prevalence and odds ratios. RESULTS: High PRS was significantly associated with increased RA risk in individuals aged 60-70 years, ≥ 70 years, and overweight and obese participants. Furthermore, at age 65 years, individuals in the bottom 5% of the PRS distribution have an absolute risk of RA at 30.6% (95% confidence interval = 18.5%-42.6%). The risk increased to 53.8% (95% confidence interval = 42.8%-64.9%) for those in the top 5% of the PRS distribution. CONCLUSIONS: The PRS developed in the present study is significantly associated with RA risk, showing the potential for early screening of RA in postmenopausal women. This work demonstrates the feasibility of personalized medicine in identifying high-risk individuals for RA, indicating the need for further studies to test the utility of PRS in other populations.

Ductal carcinoma in situ and cause-specific mortality among younger and older postmenopausal women: the Women's Health Initiative.

BACKGROUND: Whether DCIS is associated with higher breast cancer-specific and all-cause mortality is unclear with few studies in older women. Therefore, we examined DCIS and breast cancer-specific, cardiovascular (CVD)-specific, and all-cause mortality among Women's Health Initiative (WHI) Clinical Trial participants overall and by age (< 70 versus ≥ 70 years). METHODS: Of 68,132 WHI participants, included were 781 postmenopausal women with incident DCIS and 781 matched controls. Serial screening mammography was mandated with high adherence. DCIS cases were confirmed by central medical record review. Adjusted multivariable Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI). Kaplan Meier (KM) plots were used to assess 10-year and 20-year mortality rates. RESULTS: After 20.3 years total, and 13.2 years median post-diagnosis follow-up, compared to controls, DCIS was associated with higher breast cancer-specific mortality (HR 3.29; CI = 1.32-8.22, P = 0.01). The absolute difference in 20-year breast cancer mortality was 1.2% without DCIS and 3.4% after DCIS, log-rank P = 0.026. Findings were similar by age (< 70 versus ≥ 70 years) with no interaction (P interaction = 0.80). Incident DCIS was not associated with CVD-specific mortality (HR 0.77; CI-0.54-1.09, P = 0.14) or with all-cause mortality (HR 0.96; CI = 0.80-1.16, P = 0.68) with similar findings by age. CONCLUSIONS: In postmenopausal women, incident DCIS was associated with over three-fold higher breast cancer-specific mortality, with similar findings in younger and older postmenopausal women. These finding suggest caution in using age to adjust DCIS clinical management or research strategies.

Randomized placebo-controlled, double-blind clinical trial of nanoemulsion curcumin in women with aromatase inhibitor-induced arthropathy: an Alliance/NCORP pilot trial.

PURPOSE: Aromatase inhibitor (AI) therapy reduces risk of recurrence and death for postmenopausal women with breast cancer (BC); however, AI-induced arthralgia (AIIA) can lead to discontinuation of treatment. Curcumin, a bioactive polyphenolic substance, may help ameliorate inflammation-related conditions including osteoarthritis and pain. METHODS: We conducted a multisite randomized placebo-controlled, double-blind pilot trial (Alliance A22_Pilot9) to evaluate the effects of nanoemulsion curcumin (NEC, 200 mg/day) in postmenopausal women experiencing AIIA for ≥ 3 months. The primary objective was to determine the feasibility of using Functional Assessment of Cancer Treatment-Endocrine Symptoms (FACT-ES) to detect changes from 0 (T0) to 3 months (T3) of NEC treatment in AI-induced symptoms and well-being; secondary objectives included evaluation of changes in Disabilities of the Shoulder, Arm, and Hand (DASH), Brief Pain Inventory-short form (BPI-SF), grip strength, and biomarkers at T0 and T3. RESULTS: Forty-two patients were randomized to NEC or placebo; 34 women completed the 3-month study. Patient-reported outcome measures (PROMs: FACT-ES, DASH, BPI-SF) and biospecimens were collected at T0-T3 in > 80% of participants. Adherence was ≥ 90% for both arms. PROMs and grip strength did not differ significantly by treatment arm. Plasma curcumin was detected only in NEC arm participants. Serum estradiol and estrone levels were below detection or low on study agent. Gastrointestinal adverse effects were commonly reported in both arms. CONCLUSION: NEC versus placebo in a multisite randomized trial is feasible and well-tolerated. Additional studies with larger sample size are needed to further evaluate the efficacy and safety of NEC in treatment of AIIA. CLINICALTRIALS: gov Identifier: NCT03865992, first posted March 7, 2019.

Isoflavone intervention and its impact on bone mineral density in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials.

Due to estrogen deficiency, postmenopausal women may suffer from an imbalance in bone metabolism that leads to bone fractures. Isoflavones, a type of phytoestrogen, have been suggested to improve bone metabolism and increase bone mass. Therefore, isoflavones are increasingly recognized as a promising natural alternative to hormone replacement therapy for postmenopausal women who face a heightened risk of osteoporosis and are susceptible to bone fractures. PURPOSE: This study aimed to evaluate the efficacy of isoflavone interventions on bone mineral density (BMD) in postmenopausal women by means of systematic review and meta-analysis. METHODS: The electronic database searches were performed on PubMed, Embase, Scopus, and Cochrane Library databases, covering literature up to April 20, 2023. A random-effects model was used to obtain the main effect estimates, with a mean difference (MD) and its 95% confidence interval (CI) as the effect size summary. The risk of bias assessment was conducted using the Risk of Bias 2 (RoB2) tool. RESULTS: A total of 63 randomized controlled trials comparing isoflavone interventions (n = 4,754) and placebo (n = 4,272) were included. The results indicated that isoflavone interventions significantly improved BMD at the lumbar spine (MD = 0.0175 g/cm2; 95% CI, 0.0088 to 0.0263, P < 0.0001), femoral neck (MD = 0.0172 g/cm2; 95% CI, 0.0046 to 0.0298, P = 0.0073), and distal radius (MD = 0.0138 g/cm2; 95% CI, 0.0077 to 0.0198, P < 0.0001) in postmenopausal women. Subgroup analysis showed that the isoflavone intervention was effective for improving BMD when the duration was ≥ 12 months and when the intervention contained genistein of at least 50 mg/day. CONCLUSION: This systematic review and meta-analysis suggests that isoflavone interventions, especially those containing genistein of at least 50 mg/day, can effectively enhance BMD in postmenopausal women.

The association of vasomotor symptoms with fracture risk and bone mineral density in postmenopausal women: a systematic review and meta-analysis of observational studies.

BACKGROUND/AIMS: Vasomotor symptoms (VMS) adversely affect postmenopausal quality of life. However, their association with bone health has not been elucidated. This study aimed to systematically review and meta-analyze the evidence regarding the association of VMS with fracture risk and bone mineral density (BMD) in peri- and postmenopausal women. METHODS: A literature search was conducted in PubMed, Scopus and Cochrane databases until 31 August 2023. Fracture, low BMD (osteoporosis/osteopenia) and mean change in lumbar spine (LS) and femoral neck (FN) BMD were assessed. The results are presented as odds ratio (OR) and mean difference (MD), respectively, with a 95% confidence interval (95% CI). The I2 index quantified heterogeneity. RESULTS: Twenty studies were included in the qualitative and 12 in the quantitative analysis (n=49,659). No difference in fractures between women with and without VMS was found (n=5, OR 1.04, 95% CI 0.93-1.16, I2 16%). However, VMS were associated with low BMD (n=5, OR 1.54, 95% CI 1.42-1.67, I2 0%). This difference was evident for LS (MD -0.019 g/cm2, 95% CI -0.03 to -0.008, I2 85.2%), but not for FN BMD (MD -0.010 g/cm2, 95% CI -0.021 to 0.001, I2 78.2%). These results were independent of VMS severity, age and study design. When the analysis was confined to studies that excluded menopausal hormone therapy use, the association with BMD remained significant. CONCLUSIONS: The presence of VMS is associated with low BMD in postmenopausal women, although it does not seem to increase fracture risk.

Prevalence of and risk factors for endometrial polyps among asymptomatic postmenopausal women with uterovaginal prolapse.

BACKGROUND: The prevalence of endometrial polyps among asymptomatic, postmenopausal women is not well defined. There is no clear clinical consensus on how to manage endometrial polyps in this population and whether these polyps truly are cause for clinical concern. OBJECTIVE: To estimate the prevalence of endometrial polyps among asymptomatic (without bleeding), postmenopausal women, and evaluate risk factors associated with their presence. STUDY DESIGN: This cross-sectional study assessed the prevalence of endometrial polyps among asymptomatic, postmenopausal women undergoing hysterectomy for uterovaginal prolapse. Patients were excluded if undergoing hysterectomy for other indications including postmenopausal bleeding. Chart review included eligible patients who received care at a single-site in Washington state from 2009 to 2018. The primary outcome was presence of endometrial polyps on pathology. Risk factors associated with polyp prevalence were subsequently assessed using univariate analysis and multivariate regression. RESULTS: Of the 317 eligible women identified, endometrial polyps were identified in 106 women (33.4%). The average polyp size and endometrial thickness was 13 +/- 10mm and 1.4 +/- 1.5mm. Most cases, 78%, had solitary polyps. Premalignant and malignant lesions were found in 2 cases (1.89%); one had endometrial carcinoma and one had endometrial intraepithelial neoplasia. Baseline clinical and demographic characteristics were similar between patients with and without endometrial polyps, including the presence of fibroids, endometriosis and adenomyosis. Multivariate logistic regression showed that presence of polyps was independently associated with high body mass index (OR 1.06, 95%-CI 1.01-1.12, p-value 0.02) and use of menopausal hormone therapy (OR 1.67, 95%-CI 1.02 - 2.72, p-value 0.04). CONCLUSION: Asymptomatic postmenopausal women undergoing hysterectomy for uterovaginal prolapse exhibit a high prevalence of endometrial polyps. Those with use of menopausal hormone therapy and high body mass index are at a higher risk of developing endometrial polyps. While the malignant risk seems to be low, more investigation is warranted to truly quantify the lifetime risk. For now, expectant management may be a reasonable approach for incidentally found, asymptomatic polyps.

Sexual function scores are associated with arterial stiffness in postmenopausal women.

BACKGROUND: Female sexual dysfunction (FSD) has been suggested to be correlated with the burden of cardiovascular risk factors. AIM: We aimed to evaluate the possible association between functional indices of vascular function and FSD scores in apparently healthy postmenopausal women. METHODS: This cross-sectional study included 116 postmenopausal women who underwent assessment of endothelial function with measurement of flow-mediated dilation (FMD) of the branchial artery and arterial stiffness estimation with measurement of the carotid-femoral pulse wave velocity (PWV). We used the Greene Climacteric Scale to evaluate vasomotor symptomatology, the Female Sexual Function Index (FSFI) to evaluate FSD and the Beck Depression Inventory to evaluate mood disorder. Low sexual function was defined as an FSFI score <26.55. OUTCOMES: These included FSFI and low sexual function scores as well as measures of PWV and FMD. RESULTS: Sexual function scores were associated with measures of blood pressure (normal vs low sexual function; systolic blood pressure: 120.2 ± 15.0 mm Hg vs 113.4 ± 14.6 mm Hg; analysis of covariance P = .026; diastolic blood pressure: 75.9 ± 10.5 mm Hg vs 70.3 ± 9.9 mm Hg; analysis of covariance P = .012; both adjusted for age, body mass index, current smoking, and PWV). Systolic blood pressure, but not diastolic blood pressure, was associated with FSFI (B = 0.249, P = .041) and PWV (B = 0.392, P < .001). PWV measures were associated with FSFI (B = -0.291, P = .047) and pulse pressure (B = 0.355, P = .017). FMD measures were also associated with FSFI (B = 0.427, P = .033). All models were adjusted for age, body mass index, current smoking, insulin resistance, vasomotor symptomatology, and Beck Depression Inventory. CLINICAL IMPLICATIONS: Our findings demonstrate that lower scores of sexual function are associated with deteriorated vascular function mainly manifested as arterial stiffening, further contributing to systolic blood pressure changes. STRENGTHS AND LIMITATIONS: The strength of this study is the carefully selected healthy sample of postmenopausal women, with simultaneous assessment of climacteric symptomatology and mood disorders. The limitations include the small sample size, the cross-sectional design, and the recruitment of consecutive outpatients of a university menopause clinic. CONCLUSION: Longitudinal studies and interventions to improve FSD should further assess the clinical relevance of these findings.

Effects of combined dietary intervention and physical-cognitive exercise on cognitive function and cardiometabolic health of postmenopausal women with obesity: a randomized controlled trial.

BACKGROUND: Postmenopausal women with obesity are markedly at risk of cognitive impairment and several health issues. Emerging evidence demonstrated that both diet and exercise, particularly physical-cognitive exercise are involved in cognitive and health benefits. However, the comparative effect of diet, exercise, and combined interventions in postmenopausal women with obesity on cognition and cardiometabolic health is still lacking. Identifying the effective health promotion program and understanding changes in cardiometabolic health linking these interventions to cognition would have important medical implications. This RCT aimed to examine the effect of single and combined interventions of diet and exercise on cognitive function and cardiometabolic health in postmenopausal women with obesity. METHODS: Ninety-two postmenopausal women with obesity were randomly assigned to diet group (intermittent fasting 2 days/week, 3 months), exercise group (physical-cognitive exercise 3 days/week, 3 months), combined group, or control group (n = 23/group). All cognitive outcomes and cardiometabolic outcomes were measured at baseline and post-3 months. Primary outcomes were executive functions, memory, and plasma BDNF levels. Secondary outcomes were global cognition, attention, language domain, plasma adiponectin levels, IL-6 levels, metabolic parameters, and physical function. RESULTS: At the end of the 3-month intervention, the exercise and combined group demonstrated significant memory improvement which was accompanied by significant improvements in plasma BDNF level, insulin levels, HOMA-IR, %body fat, and muscle strength when compared to controls (p < 0.05). Only the combined intervention group demonstrated a significant improvement in executive function and increased plasma adiponectin levels when compared to control (p < 0.05). Surprisingly, no cognitive improvement was observed in the diet group (p > 0.05). Significant reduction in cholesterol levels was shown in the diet and combined groups when compared to controls (p < 0.05). Among the three intervention groups, there were no significant differences in all cognitive outcomes and cardiometabolic outcomes (p > 0.05). However, all three intervention groups showed significant improvements in plasma BDNF levels, weight, BMI, WHR, fat mass, and predicted VO2 max, when compared to control (p < 0.05). CONCLUSION: These findings suggest that combined physical-cognitive exercise and dietary intervention are promising interventions to improve cognition and obesity-related complications of postmenopausal women with obesity. TRIAL REGISTRATION: NCT04768725 ( https://clinicaltrials.gov ) 24th February 2021.

The predictive value of albumin to alkaline phosphatase ratio for vertebral refractures in postmenopausal women.

INTRODUCTION: To investigate the clinical value of serum albumin to alkaline phosphatase ratio (AAPR) in predicting the risk of osteoporotic vertebral refractures group (OVRFs) after percutaneous vertebral augmentation (PVA) in postmenopausal women. MATERIALS AND METHODS: This is a retrospective case-control study including a series of postmenopausal women patients with osteoporotic vertebral fracture (OVF) and underwent PVA. Patients were divided into OVRFs and non-OVRFs. COX model was used to evaluate the correlation between preoperative AAPR and OVRFs after PVA. The receiver operating characteristic (ROC) curve and Kaplan-Meier method were used to analyze the predictive value of AAPR for the incidence of OVRFs. RESULTS: A total of 305 patients were included in the final study, and the incidence of postoperative OVRFs was 28.9%. Multivariate COX analysis showed that advanced age (HRs = 1.062, p = 0.002), low BMI (HRs = 0.923, p = 0.036), low AAPR (HRs = 0.019, p = 0.001), previous fall history (HRs = 3.503, p = 0.001), denosumab treatment (HRs = 0.409, p = 0.007), low L3 BMD (HRs = 0.977, p = 0.001) and low L3 paravertebral muscle density (PMD)value (HRs = 0.929, p = 0.001)) were closely related to the incidence of OVRFs. The area under the curve (AUC) of AAPR for predicting OVRFs was 0.740 (p < 0.001), and the optimal diagnostic cut-off value was 0.49. Kaplan-Meier curve analysis showed that low AAPR group (< 0.49) was significantly associated with lower OVRFs-free survival (p = 0.001; log-rank test). CONCLUSION: AAPR is an independent risk factor for OVRFs after PVA in postmenopausal women, and it can be used as an effective index to predict OVRFs.

Association between estrogen replacement therapy and heart failure in postmenopausal women: A systematic review and meta-analysis.

BACKGROUND: Based on past epidemiological investigations, the cardiovascular role of estrogen replacement therapy (ERT) in postmenopausal women has always been controversial. The real efficacy of ERT for heart failure (HF) among postmenopausal women remains to be further investigated. This article is based on research into European and American populations. PURPOSE: To determine the impact of estrogen replacement therapy on HF using meta-analysis. METHODS AND MATERIAL: Electronic literature was searched on Web of Science, PubMed, and Embase databases to identify randomized controlled trials (RCTs) comparing the hospitalization for heart failure between ERT users and non-users among postmenopausal women. Pairs of reviewers screened eligible articles independently, extracted data, and evaluated the risk of bias. Summary relative risks were estimated for the composite endpoint of first hospitalized heart failure and admission to the hospital for heart failure. RESULTS: A pooled study of five randomized controlled trials found that estrogen replacement therapy had no significant effect on the composite endpoint in postmenopausal women, with a relative risk of 1.02 (95% CI 0.94-1.10). CONCLUSION: This systematic review demonstrated that estrogen replacement therapy did not significantly change the risk of first hospitalized heart failure and admission to the hospital for heart failure in postmenopausal women.

Joint effects between cadmium exposure and dietary antioxidant quality score on osteoporosis and bone mineral density.

To explore the relationship between dietary antioxidant quality score (DAQS) and Cd exposure both alone and in combination with osteoporosis and bone mineral density (BMD) among postmenopausal women. In total, 4920 postmenopausal women from the National Health and Nutrition Examination Survey were included in this cross-sectional study. Weighted univariate and multivariate logistic regression analyses to assess the association between DAQS and Cd exposure with femur neck BMD, total femur BMD, osteoporosis among postmenopausal women, respectively, and the coexistence effect of DAQS and Cd exposure. Four hundred and ninety-nine had osteoporosis. DAQS (OR = 0·86, 95 % CI 0·77, 0·97) and high DAQS (OR = 0·60, 95 % CI 0·36, 0·99) were found to be associated with decreased odds of osteoporosis, while Cd exposure (OR = 1·34, 95 % CI 1·04, 1·72) and high Cd exposure (OR = 1·45, 95 % CI 1·02, 2·06) were related to increased odds of osteoporosis. A positive correlation was observed between high DAQS and both total femur BMD and femur neck BMD. Conversely, Cd exposure was found to be negatively correlated with total femur BMD and femur neck BMD. Additionally, taking low-Cd and high-quality DAQS group as reference, the joint effect of Cd exposure and DAQS showed greater increased odds of osteoporosis and decreased total femur BMD and femur neck BMD as Cd level and DAQS combinations worsened. There may be an interaction between Cd exposure and DAQS for femur neck BMD, total femur BMD, and osteoporosis in postmenopausal women.

L-Citrulline supplementation attenuates aortic pressure and pressure waves during metaboreflex activation in postmenopausal women.

Postmenopausal women have augmented pressure wave responses to low-intensity isometric handgrip exercise (IHG) due to an overactive metaboreflex (postexercise muscle ischaemia, PEMI), contributing to increased aortic systolic blood pressure (SBP). Menopause-associated endothelial dysfunction via arginine (ARG) and nitric oxide deficiency may contribute to exaggerated exercise SBP responses. L-Citrulline supplementation (CIT) is an ARG precursor that decreases SBP, pulse pressure (PP) and pressure wave responses to cold exposure in older adults. We investigated the effects of CIT on aortic SBP, PP, and pressure of forward (Pf) and backward (Pb) waves during IHG and PEMI in twenty-two postmenopausal women. Participants were randomised to CIT (10 g/d) or placebo (PL) for 4 weeks. Aortic haemodynamics were assessed via applanation tonometry at rest, 2 min of IHG at 30 % of maximal strength, and 3 min of PEMI. Responses were analysed as change (Δ) from rest to IHG and PEMI at 0 and 4 weeks. CIT attenuated ΔSBP (−9 ± 2 v. −1 ± 1 mmHg, P = 0·006), ΔPP (−5 ± 2 v. 0 ± 1 mmHg, P = 0·03), ΔPf (−6 ± 2 v. −1 ± 1 mmHg, P = 0·01) and ΔPb (−3 ± 1 v. 0 ± 1 mmHg, P = 0·02) responses to PEMI v. PL. The ΔPP during PEMI was correlated with ΔPf (r = 0·743, P < 0·001) and ΔPb (r = 0·724, P < 0·001). Citrulline supplementation attenuates the increase in aortic pulsatile load induced by muscle metaboreflex activation via reductions in forward and backward pressure wave amplitudes in postmenopausal women.

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

OBJECTIVES: 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). METHODS: 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. RESULTS: Mean age was 58.2±8.5 years. BMD was normal in 68 and low in 63 women. Median (interquartile range) for 25(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. CONCLUSIONS: 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.

MicroRNAs regulate the vicious cycle of vascular calcification-osteoporosis in postmenopausal women.

Menopause is a normal physiological process accompanied by changes in various physiological states. The incidence of vascular calcification (VC) increases each year after menopause and is closely related to osteoporosis (OP). Although many studies have investigated the links between VC and OP, the interaction mechanism of the two under conditions of estrogen loss remains unclear. MicroRNAs (miRNAs), which are involved in epigenetic modification, play a critical role in estrogen-mediated mineralization. In the past several decades, miRNAs have been identified as biomarkers or therapeutic targets in diseases. Thus, we hypothesize that these small molecules can provide new diagnostic and therapeutic approaches. In this review, we summarize the close interactions between VC and OP and the role of miRNAs in their interplay.

Association between metabolic phenotypes of overweight/obesity and cardiovascular diseases in postmenopausal women.

BACKGROUND AND AIM: Obesity and metabolic abnormalities were associated with an increased risk of cardiovascular disease. However, it is unclear how metabolic weight phenotypes relate to cardiovascular diseases in postmenopausal women. This study aimed to explore the relationships in postmenopausal women. METHODS AND RESULTS: We included 15,575 postmenopausal women aged 35-75 years (median age, 60.6) without cardiovascular disease at baseline from a subcohort of the China Patient-centered Evaluative Assessment of Cardiac Events Million Persons Project. Metabolically unhealthy phenotype was defined as having ≥2 risk factors of metabolic syndrome: blood pressure ≥130/85 mm Hg or current use of antihypertensive drugs, fasting glucose ≥5.6 mmol/L or current use of antidiabetic agents, triglycerides ≥1.7 mmol/L, and high-density lipoprotein cholesterol <1.3 mmol/L. Cox regression analysis was used to evaluate the risks of cardiovascular diseases. Over a median follow-up period of 3.55 (interquartile range, 2.59-4.44) years, a total of 1354 cardiovascular events occurred. Compared to metabolically healthy normal weight, the multivariate-adjusted hazard ratios and their 95% confidence intervals were 1.41 (1.16-1.72) for metabolically unhealthy normal weight, 1.42 (1.16-1.73) for metabolically healthy overweight/obesity, and 1.75 (1.48-2.08) for metabolically unhealthy overweight/obesity. Subdividing overweight/obesity into separate groups revealed higher total cardiovascular disease risk only in metabolically unhealthy individuals across body mass index categories. CONCLUSION: In postmenopausal women, both metabolically healthy overweight/obesity and metabolically unhealthy normal weight were associated with a higher risk of cardiovascular disease compared to metabolically healthy normal weight, and the greatest risk was observed in the metabolically unhealthy overweight/obesity category.

Prevalence and associated factors of depression in postmenopausal women: a systematic review and meta-analysis.

BACKGROUND: Depression is a prevalent mental health problem in postmenopausal women. Given its significant impact on the quality of life and overall well-being of postmenopausal women, there is need for a comprehensive review and meta-analysis of the existing research globally. This systematic review and meta-analysis evaluated the global prevalence of depression and potential associated factors in postmenopausal women. METHODS: The Cochrane Library, PubMed, EMBASE, Web of Science, MEDLINE, and PsycINFO databases were systematically searched from inception to March 22, 2023. The meta-analysis used the random-effects model to calculate the prevalence of depression rates and associated factors. In addition, subgroup analysis and sensitivity analysis were performed. Publication bias was assessed using funnel plots, Egger's test, and nonparametric trim-and-fill tests. RESULTS: The meta-analysis included 50 studies that involved 385,092 postmenopausal women. The prevalence of depression in postmenopausal women was 28.00% (95% CI, 25.80-30.10). Among the factors relevant to depression among postmenopausal women, marital status (OR: 2.03, 95%CI: 1.33-3.11), history of mental illness (OR: 2.31, 95%CI: 1.50-3.57), chronic disease (OR: 3.13, 95%CI: 2.20-4.44), menstrual cycle (OR: 1.42, 95%CI: 1.17-1.72), abortion numbers (OR: 1.59, 95%CI: 1.40-1.80), menopausal symptoms (OR: 2.10, 95%CI: 1.52-2.90), and hormone replacement therapy (OR: 1.76, 95%CI: 1.31-2.35) were risk factors, while physical activity (OR: 0.56, 95%CI: 0.53-0.59), number of breastfed infants (OR: 0.43, 95%CI: 0.19-0.97), menopause age (OR: 0.44, 95%CI: 0.37-0.51) were preventive factors. CONCLUSIONS: This study demonstrated that the prevalence of postmenopausal depression is high, and some risk factors and protective factors associated with it have been identified. It is necessary to improve screening and management and optimize prevention and intervention strategies to reduce the harmful effects of postmenopausal depression.

COVID-19 vaccination and postmenopausal bleeding: a retrospective cohort study.

OBJECTIVE: COVID-19 vaccination has been related to menstrual irregularities; however, the effect on postmenopausal women is unknown. The aim of this study was to analyze the prevalence of postmenopausal bleeding (PMB) after COVID-19 vaccination. METHODS: A retrospective study was conducted in the Department of Gynecology in Hospital del Mar. Consecutive postmenopausal women with data available and endometrial biopsy were included between February 2021 and January 2022. Patients were stratified between COVID-19 vaccinated and unvaccinated groups. PMB after 30 days from last vaccine dose was considered unrelated to vaccine. Endometrial pathology diagnoses were stratified into benign or malignant. Univariable and multivariable of regression analysis on variables potentially associated with PMB was performed. RESULTS: A total of 381 patients were included, 91 in the vaccinated group and 290 in the unvaccinated group. Prevalence of PMB in the vaccinated group was 75.8% compared to 59.0% in the unvaccinated group (p < 0.005). No increase in endometrial malignant pathology was observed among the vaccinated group (p = 0.189). Multivariable analysis that correlates factors associated with PMB suggests COVID-19 vaccine and malignant endometrial biopsy as independent risk variables. CONCLUSIONS: A higher prevalence of PMB was associated with COVID-19 vaccine. Endometrial histological results showed no association with COVID-19 vaccination, but endometrial biopsy should be performed for PMB.

Ultra-low-dose estradiol and dydrogesterone for treatment of vasomotor symptoms in Europe and China.

OBJECTIVE: Among postmenopausal women, oral, ultra-low-dose continuous combined estradiol (E0.5 mg) plus dydrogesterone (D2.5 mg) reduces vasomotor symptoms (VMS). METHODS: This study was a post hoc analysis of data from two phase 3, double-blind studies. Postmenopausal women were randomized 2:1:2 to receive E0.5 mg/D2.5 mg, E1 mg/D5 mg (not included in this analysis) or placebo for 13 weeks (European study), or randomized 1:1 to receive E0.5 mg/D2.5 mg or placebo for 12 weeks (Chinese study). Endpoints assessed in ethnicity subgroups (European and Chinese) included changes from baseline in number of hot flushes, number of moderate-to-severe hot flushes and Menopause Rating Scale (MRS) score. RESULTS: Overall, 579 women were included in the analysis (E0.5 mg/D2.5 mg, n = 288; placebo, n = 291). European and Chinese women receiving E0.5 mg/D2.5 mg experienced greater reductions from baseline in mean daily number of hot flushes and mean daily number of moderate-to-severe hot flushes at week 4, week 8 and end of treatment versus those receiving placebo. Significant improvements in the 'hot flushes, sweating' MRS item score were reported in both European and Chinese women. CONCLUSION: Oral, ultra-low-dose continuous combined 0.5 mg 17ß-estradiol and 2.5 mg dydrogesterone improved VMS compared with placebo in European and Chinese postmenopausal women, with a positive impact on health-related quality of life.

Use of an estradiol transdermal spray in women with menopausal symptoms: a non-interventional study.

OBJECTIVE: This study aimed to investigate the effectiveness, tolerability and application of estradiol metered-dose transdermal spray (EMDTS) in postmenopausal women during real-world use. METHODS: This was a prospective, non-interventional, multicenter, observational phase IV cohort study. The Menopause Rating Scale II (MRS II) was used to assess symptoms and clinical response. Safety was assessed by the occurrence of adverse events and adverse drug reactions (ADRs). RESULTS: A total of 451 postmenopausal women were enrolled at 52 gynecological practices across Germany; 383 patients were evaluated for effectiveness and 430 patients for safety. Mean age was 54.3 ± 7.4 years. In total, 228 patients (59.5%) received EMDTS monotherapy and 155 patients (40.5%) received EMDTS plus progestogens. Significant improvements (p < 0.0001) from baseline in symptom severity were recorded for all 11 items of the MRS II at 3, 6 and 12 months of treatment. At 12 months, 81.4% of patients reported improvement in hot flushes/sweating. At final visit, 73% of patients and 77% of physicians were 'satisfied/very pleased' with EMDTS. Most common ADRs were headache (n = 6), nausea (n = 4), dizziness (n = 4) and pruritus (n = 3). CONCLUSIONS: EMDTS is an effective, well tolerated and easily applied hormone replacement therapy for women experiencing postmenopausal symptoms.