Cardioprotective effects of GPER agonist in ovariectomized diabetic rats: reversing ER stress and structural changes.

The incidence of diabetic cardiomyopathy (DCM) significantly increases in postmenopausal women, suggesting protective roles of estrogen. Excessive endoplasmic reticulum (ER) stress alters myocardial structure, which plays a crucial role in DCM. The G protein-coupled estrogen receptor (GPER) has been demonstrated to have cardioprotective effects, but it remains unclear whether these effects involve the amelioration of structural changes induced by ER stress. The objective of this study was to determine whether GPER can prevent cardiac structural changes by attenuating ER stress. Female ovariectomized (OVX) rats were divided into three groups: OVX, OVX + T2D, and OVX + T2D + G1. T2D was induced by a high-fat diet, and streptozotocin and G1, a GPER agonist, were administered for 6 weeks. Finally, histological changes of the myocardium were examined and the expression of sarcoplasmic reticulum calcium ATPase (SERCA2α), GRP78 as an ER stress marker, and apoptotic signalings were determined by Western blot. We observed that the induction of T2D resulted in an increased cardiac weight index, left ventricular wall thickness, and myocyte diameter. However, GPER activation reversed these changes. T2D increased cardiac protein levels of GRP78, caspase-12, and Bax, while decreasing levels of SERCA2α and Bcl-2. Nevertheless, GPER activation reduced the expression of GRP78 in OVX + T2D rats. Furthermore, GPER activation significantly reduced cardiac caspase-12 and Bax levels and increased SERCA2α and Bcl-2 expression. In conclusion, our data suggest that GPER activation ameliorates DCM by inhibiting ER stress-induced cardiac structural changes. These findings provide a new potential target for therapeutic intervention and drug discovery specifically tailored for postmenopausal diabetic women.

SIRT1 and FOXO1 role on MASLD risk: effects of DHA-rich n-3 PUFA supplementation and exercise in aged obese female mice and in post-menopausal overweight/obese women.

Sirtuins 1 (SIRT1) and Forkhead box protein O1 (FOXO1) expression have been associated with obesity and metabolic dysfunction-associated steatotic liver disease (MASLD). Exercise and/or docosahexaenoic acid (DHA) supplementation have shown beneficial effects on MASLD. The current study aims to assess the relationships between Sirt1, Foxo1 mRNA levels and several MASLD biomarkers, as well as the effects of DHA-rich n-3 PUFA supplementation and/or exercise in the steatotic liver of aged obese female mice, and in peripheral blood mononuclear cells (PBMCs) of postmenopausal women with overweight/obesity. In the liver of 18-month-old mice, Sirt1 levels positively correlated with the expression of genes related to fatty acid oxidation, and negatively correlated with lipogenic and proinflammatory genes. Exercise (long-term treadmill training), especially when combined with DHA, upregulated hepatic Sirt1 mRNA levels. Liver Foxo1 mRNA levels positively associated with hepatic triglycerides (TG) content and the expression of lipogenic and pro-inflammatory genes, while negatively correlated with the lipolytic gene Hsl. In PBMCs of postmenopausal women with overweight/obesity, FOXO1 mRNA expression negatively correlated with the hepatic steatosis index (HSI) and the Zhejiang University index (ZJU). After 16-weeks of DHA-rich PUFA supplementation and/or progressive resistance training (RT), most groups exhibited reduced MASLD biomarkers and risk indexes accompanying with body fat mass reduction, but no significant changes were found between the intervention groups. However, in PBMCs n-3 supplementation upregulated FOXO1 expression, and the RT groups exhibited higher SIRT1 expression. In summary, SIRT1 and FOXO1 could be involved in the beneficial mechanisms of exercise and n-3 PUFA supplementation related to MASLD manifestation.

Menopause and its impact on the effectiveness of fremanezumab for migraine prophylaxis: post-hoc analysis of a prospective, real-world Greek registry.

OBJECTIVE: This post-hoc analysis of data extracted from a prospective study aimed to explore for the first time if the efficacy of fremanezumab in preventing difficult-to-treat migraine, according to ICHD-III, would differ between pre-menopausal and post-menopausal women. METHODS: A total of 171 (aged 18-70 years) fremanezumab-treated female migraine patients for six consecutive months were classified to those at pre-menopausal (n = 82) or post-menopausal (n = 89). Monthly headache days (MHD), disability, and quality of life (QOL) outcomes were assessed at baseline and at week 24 post-fremanezumab within subgroups and were then compared between them. Safety and tolerability were also assessed. RESULTS: In both groups, fremanezumab demonstrated significant reductions in MHDs, reduced disability, and higher QOL scores at week 24 post-treatment, compared to baseline. However, the between-subgroup comparison documented that pre-menopausal women and those at post-menopausal comparably benefited with significant reductions in overall MHDs (p = 0.883). Less disability, according to MIDAS (p = 0.696) and HIT-6 scores (p = 0.912), as well as higher QOL scores at week 24 post-fremanezumab, were also comparably evident in both groups. Safety was excellent across both subgroups. CONCLUSION: Fremanezumab can be considered a very effective treatment option for preventing migraines in difficult-to-treat women, aged 18-70 years, regardless of their menopausal status.

Experiences of menopausal transition among populations exposed to chronic psychosocial stress in the United States: a scoping review.

BACKGROUND: The transition to menopause is a significant event affecting health, well-being, and quality of life. Menopause typically occurs between the ages of 44-57, accompanied by symptoms such as hot flashes, mood changes, and sleep disturbances. Being postmenopausal also increases the risk of cardiovascular disease, stroke, and osteoporosis. Despite its importance, menopause is under-researched and under-discussed, particularly concerning the impact of chronic psychosocial stress. METHODS: A scoping review of qualitative, quantitative, and mixed methods research was conducted to map existing literature on the transition to menopause among populations experiencing chronic psychosocial stress in the United States. The review followed the PRISMA-ScR methodology, systematically searching literature in PubMed and SCOPUS databases using MeSH terms. Studies were included which focused on menopausal symptoms and psychosocial stressors. Data extraction and charting were performed using Covidence software. RESULTS: Fifteen studies were included, highlighting relationships between socioeconomic status, intimate partner violence, childhood abuse, and racial disparities which influenced menopausal experiences. Lower- income, higher perceived stress, and negative attitudes towards menopause were associated with increased psychological and somatic symptoms and early onset of menopause (prior to age 45). African American women were found to experience earlier onset and more severe vasomotor symptoms compared to their White counterparts. Women veterans used hormone therapy more frequently than the general population, particularly those with mood or anxiety disorders. The review also identified a geographic bias, with most studies conducted in the Northeast, Midwest, and Western regions of the United States. CONCLUSIONS: This review underscores the necessity of considering social, cultural, and environmental factors in understanding menopausal experiences and addressing health disparities. Future research should aim to include diverse populations and adopt longitudinal and qualitative study designs to capture the dynamic nature of menopausal experiences. Policies and interventions directed at improving the well-being of women experiencing menopause in the context of chronic psychosocial stress are warranted. TRIAL REGISTRATION: N/A.

Comparison of Endometrial Polyp Characteristics in Transvaginal Sonography and Hysteroscopy in Predicting Endometrial Malignancies in Premenopausal and Postmenopausal Women.

Background: Hysteroscopy is known as the gold standard for endometrial polyps diagnosis and its findings on vascularity, size, and number of polyps can indicate malignancy, but it is a relatively expensive method with some complications. Ultrasound is a common part of the gynecological examination, and with technological advances, its ability to predict pathological outcomes has increased. This study aimed to determine the accuracy of ultrasound in diagnosing the characteristics of endometrial polyps. Materials and Methods: This diagnostic value study was performed on 300 premenopausal and postmenopausal women over 40 years of age with endometrial polyps referred to Alzahra and Beheshti hospitals in Isfahan. The characteristics of endometrial polyps were evaluated by transvaginal ultrasonography and hysteroscopy and biopsy specimens were sent for pathological evaluations. Results: In this study, 103 premenopausal women and 197 postmenopausal women were evaluated. Malignancy was confirmed by pathology in 4 premenopausal women (2%) and 2 postmenopausal women (2%). In both hysteroscopy and ultrasound methods, the frequency of vascularity was significantly different in postmenopausal and premenopausal women, but the other features of the polyp were not significantly different in them. Ultrasonic sensitivity in detecting the presence of vascularity, polyps larger than 1.5 mm, more than 1 polyp, and the presence of pedicle were 39.04, 57.38%, 91.93 and 94.95%, respectively, its specificity were 98.94, 36.47, 99.57 and 98.89% respectively. Conclusion: A comparison of the characteristics of polyps in both ultrasound and hysteroscopy methods shows that hysteroscopy has been more effective in diagnosing malignancy and ultrasound has not have acceptable sensitivity in diagnosing size and vascularity.

Factors influencing sexual interest in postmenopausal Asian women.

BACKGROUND: The sexual interest of postmenopausal women is a crucial aspect of their overall well-being. Despite its importance, factors influencing postmenopausal sexual interest, particularly in Asian women, remain understudied and poorly understood. AIMS: To investigate the various factors influencing sexual interest in postmenopausal women in Malaysia. METHODS: A cross-sectional study was conducted of postmenopausal women attending a gynecology or primary care clinic in a teaching hospital in Malaysia. OUTCOMES: We investigated how interpersonal dynamics and cultural norms-including the physical and mental health of women and their partners, as well as their sexual values-affect menopausal sexual interest as measured by the Menopausal Sexual Interest Questionnaire. RESULTS: Women in the study reported an average sexual interest, with a mean score of 32.8 (SD, 9.4) out of 70 on the Menopausal Sexual Interest Questionnaire. Multivariable analysis results showed that higher personal sexual values (odds ratio [OR], 2.65; 95% CI, 1.26-5.61) and spousal sexual values (OR, 2.68; 95% CI, 1.22-5.86) were significantly associated with higher menopausal sexual interest. There was a positive correlation between the physical fitness of spouses and menopausal sexual interest, with women who rated their spouses as very fit or fit (OR, 3.22; 95% CI, 1.15-9.00) or moderately fit (OR, 2.63; 95% CI, 1.05-6.63) showing higher menopausal sexual interest as compared with those whose spouses were very unfit or unfit. Women with normal stress levels (OR, 5.89; 95% CI, 1.03-33.62) and mild to moderate stress levels (OR, 8.13; 95% CI, 1.53-43.22) reported higher menopausal sexual interest. CLINICAL IMPLICATIONS: This study emphasizes a holistic approach to postmenopausal sexual health, highlighting the significance of promoting positive sexual values, improving physical fitness, and managing stress. Health care providers should educate, counsel, and collaborate interdisciplinarily, ensuring culturally sensitive care tailored to individual needs. STRENGTH AND LIMITATIONS: The study's strength lies in its provision of valuable insights into factors affecting sexual interest among postmenopausal Asian women, enhancing comprehension of holistic sexual health approaches. However, reliance on self-assessments may introduce response bias influenced by social desirability, and limited generalizability stems from single-site data collection. CONCLUSION: Our study highlights the significance of adopting a holistic approach to addressing sexual health in postmenopausal women, which includes promoting positive sexual values, improving physical fitness, and managing stress.

Carvacrol improves cognitive dysfunction by decreasing amyloid-ß accumulation and regulating neuroinflammation in ovariectomized renovascular hypertensive rats.

Hypertension contributes to both the development and progression of brain damage and cognitive dysfunction in the postmenopausal period in women. Carvacrol (CAR), which can easily cross the blood-brain barrier, exhibits neuroprotective properties due to its antioxidant, anti-inflammatory, and anti-apoptotic effects. In the present study, we have examined the effect of CAR treatment on learning-memory impairment in a post-menopausal hypertensive rat model that was induced by ovariectomy following two-kidney, one-clip renovascular hypertension surgery. From the third week after the establishment of renovascular hypertension in ovariectomized rats, CAR (40 mg/kg) was administered once daily for consecutive 7 weeks by gastric gavage. Systolic blood pressure was estimated by the tail-cuff method once a week. At the end of the study, cognitive functions were evaluated with behavioral tests and also neurochemical changes were measured in serum, cortex, and hippocampus by ELISA test. Blood pressure was decreased with CAR treatment in hypertensive rats. Serum estrogen levels decreased in ovariectomized rats and did not change with CAR treatment. CAR demonstrated beneficial effects on learning and memory tests as determined by increased recognition index, the number of platforms crossed, and time spent in the target quadrant. Due to CAR treatment, there was a marked reduction in the hippocampal and cortex amyloid-ß, osteopontin, interleukin-6 and tumor necrosis factor-alpha levels, and acetylcholinesterase activity, while an increment in neprilysin and interleukin-10 levels was found. In conclusion, since CAR suppressed amyloid-ß deposition and neuroinflammation in ovariectomized-hypertensive rats, it is thought that it may be protective against memory disorders in postmenopausal hypertensive women.

A comprehensive interventional program for promoting sexual function in postmenopausal women: Protocol for a mixed methods study.

BACKGROUND: Menopause is a natural event in women's life that leads to physical, psychological, and social consequences. A fundamental health concern in postmenopausal women is problems with their sexual function. This study aims to design an interventional program to promote sexual function in postmenopausal women. MATERIALS AND METHODS: This sequential exploratory mixed methods study will be conducted in three phases. The first phase will be a qualitative study with a content analysis approach. The participants will be selected using a purposive sampling in Isfahan, Iran. The data will be collected through in-depth interviews and field notes and analyzed using conventional content analysis. In the second phase, the intervention will be designed and finalized to promote sexual function in postmenopausal women using the results of qualitative study and literature review, asking experts' opinions, and holding specialized panels. In the third phase, the intervention will be implemented (in the form of a quasi-experimental study) and the effect of the intervention will be determined. In this phase, the data will be collected using the female sexual function index. Finally, an appropriate interventional program will be presented. CONCLUSION: It is hoped to promote sexual function in postmenopausal women by conducting this study and implementing an appropriate interventional program that is culturally sensitive. If it is proved that the intervention is effective, a basis for health policy-making to promote sexual health in postmenopausal women can be provided by presenting evidence and increasing the knowledge in this field of health.

Assessing the Factor Structure and Measurement Invariance of the Pittsburgh Sleep Quality Index Between Postmenopausal Breast Cancer Survivors and Controls.

Background and Purpose: This study evaluates the Pittsburgh Sleep Quality Index (PSQI) in terms of factor structure and measurement invariance (MI). The sample included postmenopausal breast cancer (BC) survivors (n = 101) and matched healthy controls (n = 60). Methods: Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were performed on PSQI's seven component scores. MI was tested between groups and across time using Bayes factor (BF). Results: Two factors were identified: sleep efficiency and perceived sleep quality. MI is evidenced between groups (BF < 0.007) and over time (BF > 150). Conclusions: PSQI scores with two subscales are comparable between postmenopausal BC survivors and controls over a 1-year period, providing some validation of PSQI for researching sleep quality in this population.

Midlife Women's Menopausal Transition Symptom Experience and Access to Medical and Integrative Health Care: Informing the Development of MENOGAP.

Background: Individuals with a uterus experience menopause, the cessation of menses, on average at age 51 years in the United States. While menopause is a natural occurrence for most, over 85% of women experience multiple interfering symptoms. Menopausal women face health disparities, including a lack of access to high-quality healthcare and greater disparities are experienced by women who are black, indigenous, and people of color. Some women are turning away from hormone therapy, and some seek integrative health interventions. Objective: Some menopausal women who seek healthcare do not receive it as they lack access to medical and integrative healthcare providers. A potential solution to this problem is a medical group visit (MGV), during which a provider sees multiple patients at once. The aims of this study were to gather women's opinions about the menopause, provider access, and conventional and integrative health interventions for later use to develop a menopause MGV. Methods: We conducted a Community Engagement Session and a Return of Results (RoR) with midlife women to learn about their menopause experiences, barriers and facilitators to accessing health providers, and their interest in and suggestions for designing a future integrative MGV (IMGV). Thematic qualitative research methods were used to summarize session results. Results: Nine women participated in the Session and six attended the RoR. Participants were well-educated and diverse in race and ethnicity. Themes included: an interest in this topic; unfamiliar medical terms; relevant social factors; desired whole person care; interest in integrative health; barriers and facilitators to accessing healthcare. The group expressed interest in ongoing participation in the future process of adapting an IMGV, naming it MENOGAP. Conclusion: These findings highlight the importance of stakeholder engagement before designing and implementing MENOGAP and the great need among midlife women for education about the menopausal transition, integrative self-care, and healthcare.

The effects of laser acupuncture on metabolic syndrome in obese postmenopausal women: a randomized controlled study.

To study the laser acupuncture (LA) effects on postmenopausal obese women's metabolic syndrome. Randomized controlled trial. Benha university hospital. Thirty postmenopausal women were randomized into two equal groups. Group A received a diet regimen and Group B received LA treatment for 30 min three times a week for two months beside the diet regimen. Included weight (W), body mass index (BMI), waist (WC), hip (HC), waist-hip ratio (WHR), systolic blood pressure (SBP), diastolic blood pressure (DBP), serum level of total cholesterol (TC), triglycerides (TG), high density lipoprotein (HDL), low density lipoprotein (LDL), fasting blood glucose (FBG), fasting blood insulin (FBI), homeostatic model assessment-insulin resistance (HOMA-IR) before and after the end of treatment. The study's findings showed that both groups experienced a highly statistically significant decrease in the post-testing mean value of W, BMI, WC, HC, WHR, SBP, DBP, TC, TG, LDL, FBG, FBI, and HOMA-IR, while both groups experienced a significant increase in the post-treatment mean value of HDL (p 0.0001). The posttreatment SBP, DBP, TC, TG, LDL, FBS, FBI and insulin resistance were significantly lower while HDL was significantly higher in women who received combined LA and diet regimen compared to those who received dietary regimen only. LA beside the nutritional intervention is a physical therapy technique that may be used safely, easily, and effectively to minimize metabolic syndrome features during menopause.

Alcohol use at midlife and in menopause: a narrative review.

Alcohol use disorder stands as a prevalent global issue, contributing to 140,000 annual deaths in the United States and causing numerous adverse health and socioeconomic outcomes. Despite being a natural physiological process, menopause often leads to troublesome symptoms that affect women's quality of life and exposes them to increased health risks. Our review delves into the intricate relationship between alcohol use disorder and the menopausal experience. We examine the impact of heightened alcohol consumption on the onset, severity, and burden of menopausal symptoms, particularly vasomotor symptoms. Additionally, we explore its effects on commonly experienced menopausal symptoms such as mood disturbances, sleep problems, and sexual dysfunction. Considering the chronic health conditions associated with both menopause and alcohol use disorder, our study also investigates the influence of alcohol use disorder on bone density. This is especially important due to the elevated risks and mortality linked to bone mineral density loss in menopausal women.

Effect of estradiol with or without micronized progesterone on cholinergic-related cognitive performance in postmenopausal women.

Introduction: Women are at a higher risk of developing Alzheimer's disease (AD), and the decline in estrogens post-menopause is thought of as a factor increasing this risk. Estradiol (E2) is important in supporting cholinergic neuronal integrity, and cholinergic functioning may be negatively impacted following the loss of E2 post-menopause. The use of exogenous E2 has been observed to enhance cholinergically mediated cognitive performance in healthy post-menopausal women, which indicates a potentially protective mechanism. However, E2 is often co-administered with progestin or progesterone to prevent endometrial proliferation. Progesterone/progestins have previously been shown to have a detrimental effect on E2-mediated biological and cognitive effects mediated by cholinergic systems in preclinical models, therefore the present study aimed to assess whether progesterone would modify the effect of E2 to influence cognition during cholinergic blockade. Methods: Twenty participants completed 3-months of oral E2 treatment with micronized progesterone (mPRO) or with placebo (PLC) in a repeated-measures within-subjects crossover design, in which they also completed five anticholinergic challenge days per hormone treatment condition. During the challenge participants were administered low or high doses of the nicotinic cholinergic antagonist mecamylamine, the muscarinic cholinergic antagonist scopolamine, or placebo. Following drug administration participants performed cognitive tests sensitive to cholinergic tone, assessing attention, episodic memory, and working memory. Results: Significant decrements were found on some tasks when participants were taking E2+mPRO compared to E2 alone. Specifically, under more challenging task conditions and larger anticholinergic doses, participants showed poorer performance on the Critical Flicker Fusion task and the Stroop test and responded more conservatively on the N-back working memory task. Other tasks showed no differences between treatments under cholinergic blockade. Discussion: The findings show that mPRO when taken in concert with E2, was detrimental to effortful cognitive performance, in the presence of cholinergic blockade. These results are important for assessing the impact of combined postmenopausal hormone treatment on cognitive performance that is dependent on cholinergic functioning after menopause.

Does Urodynamic Stress Incontinence Increase After the Menopause?: Results from 2,994 Urodynamic Studies in Australian Women.

INTRODUCTION AND HYPOTHESIS: Most studies attempting to estimate the age-related prevalence of urinary incontinence (UI) have used questionnaires. In the present study we analysed a consecutive series of urodynamic test results to determine the distribution of the different types of UI in pre- and post-menopausal women. We hypothesised that the prevalence of urodynamic stress incontinence (USI) would be significantly greater in pre-menopausal than in post-menopausal women. METHODS: All women from a large tertiary urogynaecology department, who underwent urodynamic tests during the years 2000-2015 were included. Patient history and test results were collected. A sample size of 1,475 was calculated, based on the hypothesis that the prevalence of USI will be 20% larger in the pre- versus the post-menopausal group. RESULTS: A total of 2,994 women with UI on urodynamics were available. There was a significant difference between pre- and post-menopausal status for each of the three diagnoses: USI 483 (59.3%) versus 912 (41.8%), detrusor overactivity (DO) 125 (15.4%) versus 399 (18.3%) and USI with concomitant DO 206 (25.3%) versus 869 (39.9%). A bimodal pattern of age was seen in women with USI, with a peak in the 46-50 and 61-65 age group, before decreasing with age. DO generally increased with age. USI with concomitant DO increased steadily after the menopause, becoming the predominant type after the age of 66. CONCLUSIONS: In this large cohort of women attending urodynamics, we have shown that USI is the predominant type of incontinence in pre-menopausal women; however, USI with concomitant DO increases after menopause, eventually predominating.

Effect of ovariectomy and high-fat diet on the expression of estrogen receptors and adipose tissue metabolism in wistar rats.

This study addresses the increasing prevalence of obesity, especially among postmenopausal. Estrogen plays a crucial role in regulating adipose tissue in women, with its absence after menopause associated with metabolic complications. The study aimed to determine the lipolytic activity in different adipose tissue depots of ovariectomized rats submitted to a high-fat diet. Also, to analyze the expression of estrogen receptors in adipose tissues and perform histological and morphometric analyzes of these deposits. Female rats were ovariectomized (O) or sham operated (S). The animals were divided into groups: ovariectomized with high-fat diet (OF), sham-operated with high-fat diet (SF), ovariectomized with control diet (OC) or sham-operated with control diet as the control group (SC). After 24 weeks of consuming the diets, rats were killed and adipose tissue deposits were removed. Polymerase chain reaction was performed to analyze the expression of estrogen receptors in adipose tissues, lipolysis assay and histological analysis. Both the high-fat diet and ovariectomy increased body weight and adiposity. There was hypertrophy of adipocytes. Estrogen replacement therapy modulate lipolytic activity in different adipose depots, with different responses in relation to estrogen receptors. Estrogen receptor expression varied between fat depots. Mesenteric adipose tissue showed greater sensitivity to estrogen compared with others. Estrogen increased lipolytic activity in some fat depots, reducing in others. Expression of ERs depends of hormonal status and adipose tissue location, which may explain distinct actions of estrogen on the metabolism of adipose tissue and on the production of adipokines by them.

Precision Nutrition for Management of Cardiovascular Disease Risk during Menopause.

BACKGROUND: Women can spend up to 40% of their lives in the postmenopausal state. As women begin to transition into menopause, known as perimenopause, changes in hormonal concentrations and body composition dramatically increase overall cardiometabolic risk. Dietary patterns and interventions can be utilized to prevent and treat cardiovascular disease (CVD) and some dietary patterns over others may be more beneficial due to their specific effects on the health aspects of menopause. In this narrative review, we summarize key cardiovascular alterations that occur during the menopause transition and explore current dietary recommendations to address CVD risk as well as explore the new frontier of precision nutrition and the implications for nutrition prescription during menopause. SUMMARY: Popular dietary interventions for CVD such as the Dietary Approaches to Stop Hypertension (DASH) diet and the Mediterranean diet (MED) have limited data in women following menopause. However, both diets improve CVD risk biomarkers of total cholesterol and low-density lipoprotein cholesterol as well as lower oxidative stress and inflammation and improve endothelial function. As the menopause transition increases the risk for developing metabolic syndrome, insulin insensitivity, and dyslipidemia, the DASH diet and MED may be impactful dietary strategies for mediating CVD risk in menopausal women. However, these are "one-size-fits-all" approaches that neglect individual characteristics such as genetic predisposition and environmental factors. Precision nutrition considers individual factors for nutrition prescription, spanning from evaluating food intake preferences and behaviors to deep phenotyping. Data from a large-scale investigation of the menopause transition suggests nutritional strategies that address postprandial glycemic responses, and the gut microbiome may attenuate some of the unfavorable effects of menopause on CVD risk factors. KEY MESSAGES: Considering menopause, women are a clinical population that would greatly benefit from precision nutrition. Future research should explore the use of machine learning and artificial intelligence in a precision nutrition framework to modify the DASH diet and MED to address adverse effects that occur during the menopause transition are vital for supporting women's health as they age.

Associations of endogenous estrogens, plasma Alzheimer's disease biomarkers, and APOE4 carrier status on regional brain volumes in postmenopausal women.

Background: Women carrying the APOE4 allele are at greater risk of developing Alzheimer's disease (AD) from ages 65-75 years compared to men. To better understand the elevated risk conferred by APOE4 carrier status among midlife women, we investigated the separate and interactive associations of endogenous estrogens, plasma AD biomarkers, and APOE4 carrier status on regional brain volumes in a sample of late midlife postmenopausal women. Methods: Participants were enrolled in MsBrain, a cohort study of postmenopausal women (n = 171, mean age = 59.4 years, mean MoCA score = 26.9; race = 83.2% white, APOE4 carriers = 40). Serum estrone (E1) and estradiol (E2) levels were assessed using liquid chromatography-tandem mass spectrometry. APOE genotype was determined using TaqMan SNP genotyping assays. Plasma AD biomarkers were measured using single molecule array technology. Cortical volume was measured and segmented by FreeSurfer software using individual T1w MPRAGE images. Multiple linear regression models were conducted to determine whether separate and interactive associations between endogenous estrogen levels, plasma AD biomarkers (Aß42/Aß40, Aß42/p-tau181), and APOE4 carrier status predict regional brain volume (21 regions per hemisphere, selected a priori); and, whether significant interactive associations between estrogens and AD biomarkers on brain volume differed by APOE4 carrier status. Results: There was no main effect of APOE4 carrier status on regional brain volumes, endogenous estrogen levels, or plasma AD biomarkers. Estrogens did not associate with regional brain volumes, except for positive associations with left caudal middle frontal gyrus and fusiform volumes. The interactive association of estrogens and APOE4 carrier status on brain volume was not significant for any region. The interactive association of estrogens and plasma AD biomarkers predicted brain volume of several regions. Higher E1 and E2 were more strongly associated with greater regional brain volumes among women with a poorer AD biomarker profile (lower Aß42/40, lower Aß42/p-tau181 ratios). In APOE4-stratified analyses, these interactions were driven by non-APOE4 carriers. Conclusion: We demonstrate that the brain volumes of postmenopausal women with poorer AD biomarker profiles benefit most from higher endogenous estrogen levels. These findings are driven by non-APOE4 carriers, suggesting that APOE4 carriers may be insensitive to the favorable effects of estrogens on brain volume in the postmenopause.

Low-dose glucocorticoid increase the risk of fracture in postmenopausal women with low bone mass: a retrospective cohort study.

Long-term glucocorticoids (GCs) treatment is associated with osteoporosis and fractures. We investigated whether low-dose GC treatment also increased the risk of osteoporotic fractures, and the results showed that even low-dose GC treatment increased the risk of osteoporotic fractures, especially spine fractures. PURPOSE: The effect of low-dose glucocorticoid (GC) therapy on the fracture risk in postmenopausal women with low bone mass was investigated. METHODS: 119,790 66-year-old postmenopausal women with low bone mass based on bone mineral density (BMD) results were included. GC group consisted of patients who had been prescribed oral GCs within 6 months of BMD testing. In GC group, GCs dosage was calculated by a defined daily dose (DDD), and divided into five groups according to GC usage (Group 1[G1]; < 11.25 DDDs, G2; ≥ 11.25, < 22.5 DDDs, G3; ≥ 22.5, < 45 DDDs, G4; ≥ 45, < 90 DDDs, G5; ≥ 90 DDDs). The risk of major osteoporotic fractures (MOF) and non-MOF was analyzed and compared with that of the control group during the 1-year follow-up. RESULTS: The risk of total fracture was higher in G3-G5 than in the control group (G3, hazard ratio (HR) 1.25, 95% confidence interval [CI] 1.07-1.46; G4, 1.37 [1.13-1.66]; G5 1.45 [1.08-1.94]). The risk of MOF was higher in all groups except G2 than in the control group (G1, 1.23 [1.05-1.45]; G3, 1.37 [1.11-1.68]; G4, 1.41 [1.09-1.83]; G5, 1.66 [1.14-2.42]). The risk of spine fracture was significantly higher in all GC groups except G2 than in the control group. The risk of non-MOF was higher only in G4 than in the control group (G4, 1.48 [1.13-1.94]). CONCLUSION: Low-dose GC therapy can increase the risk of osteoporotic fractures, particularly spine fractures, in postmenopausal women with low bone mass.

Pyometra Puzzler: Unraveling Senile Endometritis in an Unconventional Presentation.

Pyometra is a very uncommon condition in postmenopausal women that rarely improves with standard antibiotic treatments. It is usually overlooked as the patient presents with vague symptoms. Our case presented a postmenopausal woman with sepsis due to a huge pyometra. Swabs for sensitivity, tubercular gene testing, and basic blood workup were done, and the patient was started on intravenous antibiotic therapy. Pyometra drainage could not be done due to thin, friable uterine walls. When the patient had improved, a clinically total abdominal hysterectomy was done after ruling out malignant causes. Delay in the diagnosis of this condition may lead to perforation, which may, in turn, cause peritonitis, which may gravely affect the patient.

Short and long-term effect of polycarbophil vaginal gel on vaginal atrophy of peri- and post-menopausal women. The TRIPLE study.

OBJECTIVES: This TRIPLE study was aimed to evaluate the efficacy of polycarbophil vaginal gel (PCV) in treating symptoms of vaginal atrophy (VA) of peri- and post-menopausal women. MATERIALS AND METHODS: Sexually active women in peri- (n = 29) and post-menopause (n = 54) suffering from VA, were progressively enrolled and treated for 30 days with PCV. Those wishing to continue (n = 73) were treated for additional 180 days. PCV was administered as one application twice a week. The vaginal health index (VHI; range 5 to 25) and the visual analogue score (VAS range for 0 to 100 mm for each item) for vaginal dryness, irritation, and pain at intercourse, along with the global symptoms score (GSS; range 1 to 15) and treatment safety, were evaluated at baseline and after 30 days. In those continuing the treatment an evaluation was performed after additional 180 days. RESULTS: Women in peri and post-menopause were of 48.7 ± 3.3 years and 57.5 ± 5.7 years old., respectively. At baseline all outcomes were significantly worse (p<0.002) in postmenopausal group, except the VHI (p < 0.056). After 30 days VHI increased (p < 0.001) of 4.1 ± 0.5 (mean ± SE), and 5.1 ± 0.4 in peri- and post-menopausal women respectively. VAS of vaginal dryness decreased (p < 0.001) of -24.4 ± 3.6, and -52.7 ± 2.6 (p < 0.001), VAS of irritation decreased (p<0.001) of -18.6 ± 4.4 and -47.8 ± 3.2, VAS of pain decreased (p < 0.001) of -26.2 ± 4.3 and -55.6 ± 3.1 and the GSS decreased (p < 0.001) of -3.9 ± 0.3, and -4.9 ± 0.2, in peri and post-menopausal women, respectively. All the modifications were significantly greater (p < 0.001)(p < 0.032 for GSS) in postmenopausal women, and after 30 days all outcomes were similar in the two groups of women. In comparison to baseline, after 210 days of treatment VHI increased of 7.7 ± 0.3 (p < 0.001), VAS of vaginal dryness decreased of -53.6 ± 1.9 (p < 0.001) VAS of irritation of -42.6 ± 1.4 (p < 0.001) VAS of pain of -46.7 ± 2.3 (p < 0.001) and the GSS of -6.5 ± 0.2 ± 0.2 (p < 0.001). All outcomes improved (p < 0.001) over the values observed after 30 days of treatment (p < 0.001). No side effect was reported. CONCLUSIONS: In peri- and post-menopausal women PCV administration rapidly improves VA symptoms, and its prolongation up to 6 months further increases its efficacy.