Ospemifene and vulvovaginal atrophy: an update of the clinical profile for post-menopausal women.

INTRODUCTION: The demand for effective and safe treatments of genitourinary syndrome (GSM) in post-menopausal women (PMW) is growing. Published data on the efficacy and safety of ospemifene (OSP) prompt an updated literature review to enlighten possible improvements in the GSM treatment. AREA COVERED: We searched articles published in English from 2010 to 2023 through Medline (PubMed) and Embase databases with Boolean terms: OSP, PMW, GSM, endometrium, breast cancer, cardiometabolic syndrome, bone metabolism, adherence to treatment, and patient satisfaction. We selected randomized controlled trials (RCTs) and observational and cross-sectional studies and completed the search manually. EXPERT OPINION: Of the 157 retrieved records, 25 primary studies met the inclusion criteria (15 regarding efficacy and safety, two for additional effects, and four for adherence and satisfaction with the OSP treatment). Seven RCTs involved nearly 5,000 patients, 10 out of 18 prospective observational studies 563, and six retrospective analyses 356,439. Evidence of OSP treatment in PMW with GSM relies on RCTs and remarkable real-world data. The 25 primary studies showcased the high clinical response to symptoms, the favorable safety profile of OSP with very few adverse events, a neutral impact on the endometrium, breast, bone, and thrombosis, and the possible improvement of cardiovascular risk factors.

CA-125:CA72-4 ratio - towards a promising cost-effective tool in ovarian cancer diagnosis and monitoring of post-menopausal women under hormone treatment.

Ovarian cancer (OC) is the most lethal gynecological cancer in the developed world. Most cases are diagnosed at late stage III-IV with a very low 5-year overall survival rate. Several studies revealed an elevated risk of OC in users of hormone treatment (HT) compared with non-users. The extended duration of HT is a statistically significant risk factor. Carbohydrate antigen or cancer antigen 125 (CA-125) remains the best screening tool for OC; however, its value is limited due to low specificity, leading to unnecessary interventions, surgeries, and psychological harm. Additionally, the variability of ultrasound interpretation highlights the urgent need to develop a univariate index with higher sensitivity and specificity for early diagnosis of OC in women under HT. Herein we critically review the limitations of biomarkers for the detection of OC aiming to suggest an accurate and cost-effective diagnostic ratio that eliminates the impact of body mass index, age, HT, smoking, and benign ovarian diseases on measurements. Numerous studies combine biomarkers such as CA-125, human epididymis protein 4, and thymidine kinase 1 into diagnostic algorithms. Data suggest that the expression of estrogen receptors may have diagnostic and prognostic value, as the estrogen receptor α (ERα):estrogen receptor ß (ERß) ratio is significantly higher in OC than in normal tissue due to ERß downregulation. A high positive correlation between expression of CA-125 and carbohydrate antigen or cancer antigen 72 - 4 (CA72-4) with ERα and ERß, respectively, poses that a novel ratio CA-125:CA72-4 could be nodal for monitoring post-menopausal women under HT.

A Rare Case of Postmenopausal Hirsutism Associated With a Serous Cystadenofibroma of the Ovary.

Hirsutism in females is most commonly associated with polycystic ovarian syndrome, but can also result from congenital adrenal hyperplasia and ovarian tumors like granulosa cell tumors, Sertoli-Leydig cell tumors, and hilus cell tumors. We present a case of a 54-year-old female with hirsutism, diagnosed with ovarian cystadenofibroma. She had a history of premature ovarian failure at the age of 35 and presented with new onset chin and upper lip hair, and scalp hair loss. Labs showed elevated total testosterone, normal dehydroepiandrosterone (DHEA) and sex hormone-binding globulin (SHBG), low estradiol, and postmenopausal range anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin. Cytogenetic testing showed a normal XX karyotype. Initial transvaginal ultrasound revealed a thickened endometrial stripe and unremarkable ovaries. Repeat ultrasound and MRI noted persistent endometrial thickening and a solid-cystic structure in the left ovary. The patient underwent total hysterectomy, bilateral salpingo-oophorectomy, and sentinel lymph node dissection. Endometrial biopsy showed FIGO grade 1 endometrioid carcinoma, and the left ovary biopsy revealed benign serous cystadenofibroma and endometriosis. Postoperatively, hirsutism resolved and testosterone levels normalized. Hirsutism in postmenopausal women should prompt evaluation for adrenal or ovarian sources, including tumors. Ovarian tumors cause about 1% of hirsutism cases. Our case highlights the need for thorough evaluation, as benign ovarian tumors can also cause androgen excess and associated conditions like endometrial cancer.

Association Between Osteoporosis Self-Assessment Tool for Asians and Airflow Limitation in Japanese Post-Menopausal Women.

Purpose: This study aimed to reveal the association between the osteoporosis self-assessment tool for Asians (OSTA) and airflow limitation (AL) in post-menopausal Japanese women. Participants and Methods: This cross-sectional study included 1580 participants undergoing a comprehensive health examination using spirometry and dual-energy X-ray absorptiometry. The OSTA was calculated by subtracting the age in years from the body weight (BW) in kilograms, and the result was multiplied by 0.2. The OSTA risk level was defined as low (>-1), moderate (-4 to -1), or high (<-4). AL was defined as forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) <0.7. The association between the OSTA and AL was assessed using logistic regression analysis. Results: The prevalence of AL was significantly higher in the high OSTA group (15.3%) than in the low OSTA group (3.1%) (p<0.001). In multiple linear regression analysis, the OSTA was independently associated with FEV1/FVC. In logistic regression models adjusted for smoking status, alcohol consumption, current use of medication for diabetes, hyperglycemia, rheumatoid arthritis, second-hand smoke, and ovary removal showed a significantly higher risk of AL (odds ratio: 5.48; 95% confidence interval: 2.90-10.37; p<0.001) in participants with OSTA high risk than in those with OSTA low risk. Conclusion: These results suggest that the OSTA high risk indicates reduced BMD at the femoral neck and presence of AL in Japanese post-menopausal women aged ≥45 years.

A Case of Pyocolpos in a Postmenopausal Woman With a History of Lichen Sclerosus and Postmenopausal Bleeding.

Pyocolpos refers to the buildup of pus within the vaginal cavity. Pyocolpos in the background of lichen sclerosis and postmenopausal bleeding (PMB) has not been previously described. A 69-year-old para 3 patient presented with a history of PMB with a long-standing history of lichen sclerosis. The vaginal examination was impossible due to vaginal adhesions. Vulval appearances revealed the loss of the clitoral architecture. Further imaging revealed an endometrial thickness of 4-5 mm, a focal abnormality within the posterior ectocervix compatible with a hemorrhagic cystic lesion distending the posterior fornix, and some free fluid within the pelvis. A hysteroscopy was abandoned as the vagina was completely obliterated. After a multidisciplinary assessment, the patient had a total abdominal hysterectomy, and the presence of a pyocolpos was noticed at the opening into the vault. We could not find any previous case reports of pyocolpos that are associated with lichen sclerosus. The long-standing history of lichen sclerosus may have caused an obstruction of the outflow tract, which was secondarily infected and slowly progressed into the formation of pyocolpos. Other management options could have been explored if the diagnosis of pyocolpos had been made preoperatively. Pyocolpos should be considered in patients with a history of a long-standing lichen sclerosus who present with abdominal pain and a pelvic mass on imaging.

Urdu translation, cross-cultural validation and reliability of ECOS-16 questionnaire among post-menopausal women with osteopenia.

BACKGROUND: Escala de Calidad de vida Osteoporosis (ECOS-16) was originally developed in Spanish to evaluate the quality of life (QoL) in post-menopausal women (PMW) with osteoporosis or osteopenia based on the osteoporosis-specific QoL instruments. ECOS-16 has been translated into several languages, but the Urdu version is not yet available. OBJECTIVE: To translate the ECOS-16 Questionnaire into Urdu and determine its validity and reliability in PMW with osteopenia. METHODS: This was a linguistic validity and reliability study. ECOS-16 was translated into Urdu using Beaton's guidelines. Content validity was examined using Waltz's four-point ordinal scale. Twenty osteopenia-afflicted PMW aged 48-70 underwent pilot testing for face validity. Discriminant validity was determined by an independent T-test between PMW women with and without osteopenia. Convergent validity was assessed using Spearman's correlation coefficient. Cronbach's alpha and Intraclass correlation coefficient (ICC2,1) assessed internal consistency and test-retest reliability. The factor analysis was used to describe the factors. RESULTS: Each question's content validity ratio (CVR) was 0.83-1.00, while the scale's S-CVR was 0.96. Each question's Likert scale content validity index (CVI) was 0.91-0.93, while the scale's S-CVI was 0.91. Significant discriminant validity was found between groups in weeks I and II (p-value < 0.001). A correlation coefficient of 0.89 and 0.96 (p-value < 0.001) between Urdu ECOS-16 total score and SF-36 and EQ-5D scores suggests convergent validity. One component explained 83.86% of Urdu ECOS-16's variance in factor analysis. Excellent test-retest reliability (ICC2,1 = 0.990, 95% CI, 0.985-0.994, p-value < 0.001). Cronbach's alpha for standardized items was 0.995. CONCLUSION: ECOS-16 translated in Urdu is a valid and reliable questionnaire to assess QoL in PMW with osteopenia. It has a simple and easy language that can be understood easily by the Urdu-speaking population.

Anatomic Reversal of Shoulder Joint After Neck of Humerus Fracture.

We report on a singular case of a unique form of post-traumatic reversal of the humeral head after humeral neck fracture, in which the pattern of collapse resulted in the formation of a native reverse polarity shoulder. In essence, the humeral head became a socket, and the glenoid rounded to become a head with well-preserved shoulder function. To our knowledge, this is the first case of an acquired shoulder deformity that bears a remarkable functional similarity to a prosthetic reverse polarity shoulder replacement.

Mechanical stimulation-induced purinome priming fosters osteogenic differentiation and osteointegration of mesenchymal stem cells from the bone marrow of post-menopausal women.

BACKGROUND: Mechanical stimulation (MS) significantly increases the release of adenine and uracil nucleotides from bone marrow-derived mesenchymal stem cells (BM-MSCs) undergoing osteogenic differentiation. Released nucleotides acting via ionotropic P2X7 and metabotropic P2Y6 purinoceptors sensitive to ATP and UDP, respectively, control the osteogenic commitment of BM-MSCs and, thus, bone growth and remodelling. Yet, this mechanism is impaired in post-menopausal (Pm)-derived BM-MSCs, mostly because NTPDase3 overexpression decreases the extracellular accumulation of nucleotides below the levels required to activate plasma membrane-bound P2 purinoceptors. This prompted us to investigate whether in vitro MS of BM-MSCs from Pm women could rehabilitate their osteogenic commitment and whether xenotransplantation of MS purinome-primed Pm cells promote repair of critical bone defects in an in vivo animal model. METHODS: BM-MSCs were harvested from the neck of femora of Pm women (70 ± 3 years old) undergoing total hip replacement. The cells grew, for 35 days, in an osteogenic-inducing medium either submitted (SS) or not (CTR) to MS (90 r.p.m. for 30 min) twice a week. Increases in alkaline phosphatase activity and in the amount of osteogenic transcription factors, osterix and osteopontin, denoted osteogenic cells differentiation, while bone nodules formation was ascertain by the alizarin red-staining assay. The luciferin-luciferase bioluminescence assay was used to quantify extracellular ATP. The kinetics of the extracellular ATP (100 µM) and UDP (100 µM) catabolism was assessed by HPLC. The density of P2Y6 and P2X7 purinoceptors in the cells was assessed by immunofluorescence confocal microscopy. MS-stimulated BM-MSCs from Pm women were xenotransplanted into critical bone defects drilled in the great trochanter of femora of one-year female Wistar rats; bone repair was assessed by histological analysis 10 days after xenotransplantation. RESULTS: MS-stimulated Pm BM-MSCs in culture (i) release 1.6-fold higher ATP amounts, (ii) overexpress P2X7 and P2Y6 purinoceptors, (iii) exhibit higher alkaline phosphatase activity and overexpress the osteogenic transcription factors, osterix and osteopontin, and (iv) form larger bone nodules, than CTR cells. Selective blockage of P2X7 and P2Y6 purinoceptors with A438079 (3 µM) and MRS 2578 (0.1 µM), respectively, prevented the osteogenic commitment of cultured Pm BM-MSCs. Xenotransplanted MS purinome-primed Pm BM-MSCs accelerated the repair of critical bone defects in the in vivo rat model. CONCLUSIONS: Data suggest that in vitro MS restores the purinergic cell-to-cell communication fostering the osteogenic differentiation and osteointegration of BM-MSCs from Pm women, a strategy that may be used in bone regeneration and repair tactics.

Incidental endometrial cancer detected on FDG PET/CT imaging for melanoma.

This case report follows a 66-year-old female who originally presented with malignant melanoma in the left knee and recurrence in the left inguinal region. This prompted a whole body FDG PET/CT scan which showed incidental focal hypermetabolism in the uterus. The diagnosis of endometrial cancer was confirmed at biopsy, and the patient was treated with total abdominal hysterectomy. Melanoma patients are at increased risk of second primary malignancy, and endometrial cancer is a common second primary often diagnosed in cancer survivors. Incidental endometrial focal hypermetabolism should be investigated further for a synchronous malignancy, especially in a post-menopausal woman.

Evaluation of oral health, taste perception, nutritional status and emotional well-being in post-menopausal women.

BACKGROUND: In postmenopausal women (PMW), vasomotor symptoms, emotional oscillations and sleep disturbances can affect physiological and psychological functioning. However, the effect of menopause on oral health-related parameters is not been thoroughly studied. OBJECTIVE: To evaluate oral health, taste perception, eating habits, nutritional status and emotional well-being in PMW compared with a group of young and healthy pre-menopausal women (PrMW). MATERIALS AND METHODS: Two groups (Group I: PMW and Group II: PrMW) with 30 participants each, participated in the cross-sectional study. The study proforma contained measures of oral health, taste perception, nutritional status and anxiety levels of the women in both groups using validated and previously used tools were designed and implemented. The data were analysed with student t, Mann-Whitney U, and chi-squared tests to evaluate the differences between the two groups. RESULTS: The cross-sectional study indicates no major differences in oral health, taste perception, nutritional and emotional status between PMW and PrMW. Nonetheless, there was a significant difference in perception of 'front teeth lengthening in size' and change in hot and cold sensations between the groups. Furthermore, the study group with PMW tends to have fewer natural teeth than the reference group. CONCLUSION: Overall, menopause does not appear to affect oral health, taste perception, nutrition or emotional health. It is suggested that oral health and taste perception, as well as nutritional and emotional status, are associated with gradual aging processes that may or may not be affected by menopause.

Physical Activity, Self-Care, and Menopausal Symptoms among Women in Al-Ahsa, Saudi Arabia: Adherence to Postmenopausal Guidelines (PMGs).

Menopause is a physiological change in which the menstrual period permanently ends. Every woman experiences this transition in different ways between the ages of 40 and 55. Women may have menopausal symptoms as a result of low estrogen levels. Self-care is a practice which women can use to maintain their wellness. This study aimed to assess physical activity, self-care, and menopausal symptoms and their associations with selected variables. The results showed that women should adhere to postmenopausal guidelines (PMGs). A cross-sectional study was conducted among 212 menopausal women randomly selected from health centers in Al-Ahsa, Saudi Arabia. The international physical activity tool, a self-care questionnaire, and the Kupperman menopausal index scale were used to assess women's physical activity, self-care, and menopausal symptoms, respectively. The chi-square and Pearson correlation tests were used for analysis. The women were 55.01 ± 6.87 years old, and 40.6% reached menopause between the ages of 46 and 50 years; 57.1% of the women had low physical activity, which was associated with menopausal symptoms (p < 0.022). The highest mean score (29.63 ± 5.83) was obtained for physical health, while the lowest (11.92 ± 3.58) was found in self-care screening tests. Regarding menopausal symptoms, 25.9% had mild, 69.8% had moderate, and 4.3% had severe symptoms. A significant association was found between menopausal symptoms and age, menopausal age, education, body mass index, and PMGs awareness at p < 0.001. Self-care positively correlated with menopausal symptoms (p < 0.001). Therefore, attention should be given to women's adherence to PMGs so that they can enjoy healthier lives after menopause.

Menopausal hormone therapy and risk of venous thromboembolism: The story so far.

Menopausal hormone therapy (MHT) is known to increase the risk of venous thromboembolism (VTE), which includes deep vein thrombosis, pulmonary embolism, and less frequently cerebral vein thrombosis, but the absolute risk for a given patient is very low. After starting MHT, the risk of VTE seems to be at its highest, declining to the non-HRT user baseline level of risk after stopping. Whether estrogen-only or estrogen-progestin HRT combination is linked to a similar risk of VTE is unclear from the available evidence. The aim of this study is to evaluate the risks of developing VTE in relation to different types as well as different modes of administration of MHT through a database search including PubMed, MEDLINE, Google Scholar, Cochrane Library, and others in order to provide the women carers with the up-to-date and evidence-based guidelines and recommendations while counseling the post-menopausal women enquiring on use of hormonal therapies either to alleviate the menopausal symptoms or to prevent the long-term sequelae of estrogen deficiency.

On sait que l'hormonothérapie ménopausique (MHT) augmente le risque de thromboembolie veineuse (TEV), qui comprend la thrombose veineuse profonde, l'embolie pulmonaire et, moins fréquemment, la thrombose veineuse cérébrale, mais le risque absolu pour un patient donné est très faible. Après le début du MHT, le risque de TEV semble être à son plus haut niveau, diminuant jusqu'au niveau de risque de base des non-utilisatrices de THS après l'arrêt. Les preuves disponibles ne permettent pas de savoir si un THS à base d'œstrogène seul ou d'association œstroprogestative est lié à un risque similaire de TEV. Le but de cette étude est d'évaluer les risques de développer une TEV par rapport à différents types ainsi qu'à différents modes d'administration du MHT grâce à une recherche dans des bases de données comprenant PubMed, MEDLINE, Google Scholar, Cochrane Library et autres afin de fournir aux femmes les soignants avec les lignes directrices et recommandations à jour et fondées sur des preuves tout en conseillant les femmes ménopausées qui se renseignent sur l'utilisation de thérapies hormonales, soit pour soulager les symptômes de la ménopause, soit pour prévenir les séquelles à long terme d'une carence en œstrogènes.

Age at natural menopause and development of chronic diseases in the female population of Kharameh, Iran: A historical cohort study.

Background and Aims: Declines in estradiol levels after menopause have been reported to be associated with several health outcomes. This study aimed to determine the effect of age at natural menopause (ANM) on some of the most common chronic diseases. Methods: This historical cohort study was performed on 2636 postmenopausal women aged 40-70 years participating in phase one of the PERSIAN cohort study in Kharameh, Iran, during 2015-2017. The effect of early (<45 years), intermediate (45-53 years), and late menopause (>53 years) on chronic diseases such as hypertension, diabetes, ischemic heart diseases, stroke, thyroid diseases, and depression was assessed using classic logistic regression for diseases with an incidence rate of more than 10% and Firth's logistic regression for diseases with an incidence of less than this amount. Results: The mean age of women was 53.48 ± 8.59. Respectively, early and intermediate menopause was associated with ischemic heart disease (odds ratio [OR = 1.61, 95% confidence interval [CI]: 1.08-2.42; p = 0.020), (OR = 1.57, 95% CI: 1.13-2.21; p = 0.008) and thyroid diseases (OR = 3.10, 95% CI: 1.64-6.24; p < 0.001), (OR = 1.83, 95% CI: 1.02-3.57; p = 0.042). furthermore, early menopause was a risk factor for diabetes (OR = 1.46, 95% CI: 1.07-2.00; p = 0.018), depression (OR = 4.79, 95% CI: 2.20-11.79; p = <0.001) and stroke (OR = 3.00, 95% CI: 1.08-9.32; p = 0.034). Conclusions: In this study, women with diabetes, ischemic heart diseases, stroke, thyroid disorders, and depression had a younger ANM compared to their healthy counterparts. Therefore, applying appropriate strategies to postpone the age of menopause, can reduce the incidence of these types of chronic diseases.

Adherence to adjuvant endocrine therapy for breast cancer: a qualitative exploration of attribution of symptoms among post-menopausal women.

PURPOSE: Oral adjuvant endocrine therapy (AET) is an effective treatment for hormone receptor positive breast cancer to decrease recurrence and mortality, but adherence is poor. This study explored post-menopausal women's experiences with AET, with a particular focus on adherence to AET as well as distress and symptoms experienced prior to and during AET treatment. METHODS: Participants were recruited from a hospital registry, stratified by adherence to/discontinuation of AET. Telephone interviews followed a semi-structured interview guide and were recorded and transcribed verbatim. Transcripts were systematically coded using team-based coding, with analysis of themes using a grounded theory approach. RESULTS: Thirty-three participants were interviewed; ages ranged from 57 to 86 years. Participants included 10 discontinued patients and 23 patients who completed their AET course or were adherent to AET at the time of interviewing. Both adherent and discontinued patients reported symptoms throughout their AET treatment course, and both attributed symptoms to factors other than AET (e.g., older age and pre-existing comorbidities). However, discontinued patients were more likely to attribute symptoms to AET and to describe difficulty managing their symptoms, with some directly citing symptoms as the reason for discontinuing AET therapy. Conversely, adherent patients were more likely to describe the necessity of taking AET, despite symptoms. CONCLUSIONS: AET adherence was associated with beliefs about AET, symptom attribution, and symptom management. Routine symptom monitoring during AET and addressing both symptoms and patients' understanding of their symptoms may promote adherence to AET.

Assessment of Role of Bisphosphonates on Dental Implant Treatment in Post-menopausal Ladies.

Objectives: To examine the impact of bisphosphonates (BPs) on dental implant treatment and alveolar bone in post-menopausal ladies. Materials and Methods: Twenty post-menopausal ladies who had at least one dental implant within the previous 5 years participated in the current study. Ten subjects were categorized into two groups: Group A had BP medication for 1.5 years, and group B received parathyroid hormone (PTH). Both groups' bone thickness and bone mineral density (BMD) were measured. Result: Group A had 5%, and group B had 5% of dental implants failures. BMD of cortical bone was 1468 ± 136 mg/mL and 1008 ± 84 mg/mL in groups A and B, correspondingly. The cortical and cancellous bone densities in both the groups were statically significant. Cortical bone thickness was insignificant in comparison. Conclusion: Both cortical and cancellous bones' bone mineral density decreased in both groups. With continued usage of BPs, the cortical bone thickness increased.

The Heterogeneity of Post-Menopausal Disease Risk: Could the Basis for Why Only Subsets of Females Are Affected Be Due to a Reversible Epigenetic Modification System Associated with Puberty, Menstrual Cycles, Pregnancy and Lactation, and, Ultimately, Menopause?

For much of human evolution, the average lifespan was <40 years, due in part to disease, infant mortality, predators, food insecurity, and, for females, complications of childbirth. Thus, for much of evolution, many females did not reach the age of menopause (45-50 years of age) and it is mainly in the past several hundred years that the lifespan has been extended to >75 years, primarily due to public health advances, medical interventions, antibiotics, and nutrition. Therefore, the underlying biological mechanisms responsible for disease risk following menopause must have evolved during the complex processes leading to Homo sapiens to serve functions in the pre-menopausal state. Furthermore, as a primary function for the survival of the species is effective reproduction, it is likely that most of the advantages of having such post-menopausal risks relate to reproduction and the ability to address environmental stresses. This opinion/perspective will be discussed in the context of how such post-menopausal risks could enhance reproduction, with improved survival of offspring, and perhaps why such risks are preserved. Not all post-menopausal females exhibit risk for this set of diseases, and those who do develop such diseases do not have all of the conditions. The diseases of the post-menopausal state do not operate as a unified complex, but as independent variables, with the potential for some overlap. The how and why there would be such heterogeneity if the risk factors serve essential functions during the reproductive years is also discussed and the concept of sets of reversible epigenetic changes associated with puberty, pregnancy, and lactation is offered to explain the observations regarding the distribution of post-menopausal conditions and their potential roles in reproduction. While the involvement of an epigenetic system with a dynamic "modification-demodification-remodification" paradigm contributing to disease risk is a hypothesis at this point, validation of it could lead to a better understanding of post-menopausal disease risk in the context of reproduction with commonalities may also lead to future improved interventions to control such risk after menopause.

Qixian granule inhibits ferroptosis in vascular endothelial cells by modulating TRPML1 in the lysosome to prevent postmenopausal atherosclerosis.

ETHNOPHARMACOLOGICAL RELEVANCE: QiXian Granule (QXG) is an integrated traditional Chinese medicine formula used to treat postmenopausal atherosclerotic (AS) cardiovascular diseases. The previous studies have found that QXG inhibited isoproterenol (ISO)-induced myocardial remodeling. And its active ingredient, Icraiin, can inhibit ferroptosis by promoting oxidized low-density lipoprotein (xo-LDL)-induced vascular endothelial cell injury and autophagy in atherosclerotic mice. Another active ingredient, Salvianolic Acid B, can suppress ferroptosis and apoptosis during myocardial ischemia/reperfusion injury by reducing ubiquitin-proteasome degradation of Glutathione Peroxidase 4 (GPX4) and down-regulating the reactive oxygen species (ROS)- c-Jun N-terminal kinases (JNK)/mitogen-activated protein kinase (MAPK) pathway. AIM OF THE STUDY: The objective of this research was to assess the possible impact of QXG on atherosclerosis in postmenopausal individuals and investigate its underlying mechanisms. MATERIALS AND METHODS: Female ApoE-/- mice underwent ovariectomy and were subjected to a high-fat diet (HFD) to establish a postmenopausal atherosclerosis model. The therapeutic effects of QXG were observed in vivo and in vitro through intraperitoneal injection of erastin, G-protein Coupled Estrogen Receptor (GPER) inhibitor (G15), and silent Mucolipin Transient Receptor Potential Channel 1 (TRPML1) adenovirus injection via tail vein. UPLC-MS and molecular docking techniques identified and evaluated major QXG components, contributing to the investigation of QXG's anti-postmenopausal atherosclerotic effects. RESULTS: QXG increased serum Estradiol levels, decreased follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels, which indicated QXG had estrogen-like effects in Ovx/ApoE-/- mice. Furthermore, QXG demonstrated the potential to impede the progression of AS in Ovx/ApoE-/- mice, as evidenced by reductions in serum triglycerides (TG), total cholesterol (TC), and low-density lipoprotein-cholesterol (LDL-C) levels. Additionally, QXG inhibited ferroptosis in Ovx/ApoE-/- mice. Notably, UPLC-MS analysis identified a total of 106 active components in QXG. The results of molecular docking analysis demonstrated that Epmedin B, Astragaloside II, and Orientin exhibit strong binding affinity towards TRPML1. QXG alleviates the progression of atherosclerosis by activating TRPML1 through the GPER pathway or directly activating TRPML1, thereby inhibiting GPX4 and ferritin heavy chain (FTH1)-mediated iron pendant disease. In vitro, QXG-treated serum suppressed proliferation, migration, and ox-LDL-induced MMP and ROS elevation in HAECs. CONCLUSION: QXG inhibited GPX4 and FTH1-mediated ferroptosis in vascular endothelial cells through up-regulating GPER/TRPML1 signaling, providing a potential therapeutic option for postmenopausal females seeking a safe and effective medication to prevent atherosclerosis. The study highlights QXG's estrogenic properties and its promising role in combating postmenopausal atherosclerosis.

The Association between Hormone Replacement Therapy and Gastroparesis in Post-Menopausal Women: A Worldwide Database Analysis.

Female sex hormones have been hypothesized to influence the higher prevalence of gastroparesis in females. This study investigated the effects of hormone replacement therapy (HRT) on gastroparesis and its related symptoms, medication use, and diagnostic testing in post-menopausal women. Utilizing the TriNetX platform, we conducted a population-based cohort study involving post-menopausal women aged 50 or older, with and without HRT. One-to-one propensity score matching was performed to adjust for age, race, ethnicity, diabetes, body mass index (BMI), and hemoglobin A1c. The exclusion criteria included functional dyspepsia, cyclic vomiting syndrome, and surgical procedures. After applying the exclusion criteria, we identified 78,192 post-menopausal women prescribed HRT and 1,604,822 not prescribed HRT. Post-propensity matching, each cohort comprised 67,874 patients. A total of 210 of the post-menopausal women prescribed HRT developed an ICD encounter diagnosis of gastroparesis at least 30 days after being prescribed HRT compared to post-menopausal women not prescribed HRT (OR = 1.23, 95% CI [1.01-1.51] p-value = 0.0395). These associations persisted in sensitivity analysis over 5 years (OR = 1.65, 95% CI [1.13-2.41] p-value = 0.0086). HRT was associated with increased GI symptoms, including early satiety (OR = 1.22, 95% CI [1.03-1.45] p-value = 0.0187), domperidone use (OR = 2.40, 95% CI [1.14-5.02] p-value = 0.0163), and undergoing gastric emptying studies (OR = 1.67, 95% CI [1.39-2.01] p-value < 0.0001). HRT is linked to an increased risk of developing an ICD encounter diagnosis of gastroparesis.

Paeonol alleviates postmenopause-induced neuropsychiatric symptoms through the modulation of GPR30 in ovariectomized mice.

ETHNOPHARMACOLOGICAL RELEVANCE: The Moutan cortex (MC), the root bark of Paeonia suffruticosa Anderws (Paeoniaceae), has been historically employed in traditional herbal medicine for addressing women's ailments by replenishing kidney Yin. AIM OF THE STUDY: We aimed to explore if paeonol, an active constituent of MC, could ameliorate neuropsychiatric symptoms, such as anxiety, depression, and cognitive impairments, associated with post-menopausal syndrome (PMS) in an ovariectomized (OVX) mouse model. MATERIALS AND METHODS: The experimental design comprised 6 groups, including a sham group, OVX group, paeonol administration groups (3, 10 or 30 mg/kg, p.o.), and an estradiol (E2)-treated positive control group. Behavioral tests including the open field, novel object recognition, Y-maze, elevated plus-maze, splash, and forced swimming tests were conducted. In addition, we investigated the effets of paeonol on the phosphorylated levels of phosphatidylinositol 3-kinase (PI3K), Akt, and mammalian target of rapamycin (mTOR), as well as on the expression levels of G protein-coupled receptor (GPR30) and brain-derived neurotrophic factor (BDNF) in the prefrontal cortex and hippocampus. RESULTS: Paeonol treatment (10 and 30 mg/kg, p.o.) effectively reversed the cognitive decline in OVX mice, measured by the novel object recognition and Y-maze tests, similar to that in the positive control group. Additionally, it alleviated anxiety- and depressive-like behaviors, as evaluated by the elevated plus-maze test, splash test, and forced swimming test. Paeonol restored GPR30 expression levels in the prefrontal cortex and hippocampus, mirroring the effects of E2 administration. Furthermore, it reversed the reduced expression levels of the PI3K-Akt-mTOR signaling pathway in the prefrontal cortex and hippocampus and increased BDNF expression in the hippocampus of OVX mice. CONCLUSION: This research suggests that paeonol would be beneficial for alleviating PMS-associated cognitive impairment, anxiety and depression.

Association of neutrophil to lymphocyte ratio with bone mineral density in post-menopausal women: a systematic review and meta-analysis.

BACKGROUND: We conducted a systematic review and meta-analysis to compare the neutrophil lymphocyte ratio (NLR) levels between women with post-menopausal osteopenia or osteoporosis to those with normal bone mineral density (BMD). METHODS: We used Web of Science, PubMed, and Scopus to conduct a systematic search for relevant publications published before June 19, 2022, only in English language. We reported standardized mean difference (SMD) with a 95% confidence interval (CI). Because a significant level of heterogeneity was found, we used the random-effects model to calculate pooled effects. We used the Newcastle-Ottawa scale for quality assessment. RESULTS: Overall, eight articles were included in the analysis. Post-menopausal women with osteoporosis had elevated levels of NLR compared to those without osteoporosis (SMD = 1.03, 95% CI = 0.18 to 1.88, p = 0.017, I2 = 98%). In addition, there was no difference between post-menopausal women with osteopenia and those without osteopenia in neutrophil lymphocyte ratio (NLR) levels (SMD = 0.58, 95% CI=-0.08 to 1.25, p = 0.085, I2 = 96.8%). However, there was no difference between post-menopausal women with osteoporosis and those with osteopenia in NLR levels (SMD = 0.75, 95% CI=-0.01 to 1.51, p = 0.05, I2 = 97.5%, random-effect model). CONCLUSION: The results of this study point to NLR as a potential biomarker that may be easily introduced into clinical settings to help predict and prevent post-menopausal osteoporosis.