UNASSIGNED: Four years after the start of the pandemic, there is limited evidence on the impact of COVID-19 on the women\'s health regardless of their reproductive status.
UNASSIGNED: The aim was to analyze the prevalence and associated factors of menstrual-related disturbances in formerly menstruating women following SARS-CoV-2 infection.
UNASSIGNED: A retrospective observational study of adult women in Spain was conducted during the month of December 2021 using an online survey (N = 17,512). The present analysis includes a subpopulation of SARS-CoV-2-infected and formerly menstruating women (n = 72). The collected data included general characteristics, medical history, and specific information on COVID-19. Chi-square and Mann-Whitney U-tests were performed. Bivariate logistic regression analysis was then performed to investigate possible associations between the occurrence of menstrual-related disturbances after SARS-CoV-2 infection.
UNASSIGNED: 38.8% of participants experienced menstrual-related disturbances following COVID-19. Among these, unexpected vaginal bleeding (20.8%) was the most common event, followed by spotting (11.1%) ( Table 1). Other reported changes were in the length (shorter = 12.5%) and flow (heavier = 30.3%) of menstrual bleeding in comparison to their previous experience. Regression analysis revealed that being a perimenopausal woman [adjusted odds ratio (AOR) 4.721, CI 95%, 1.022-21.796, p = 0.047] and having a previous diagnosis of menorrhagia (AOR 5.824 CI 95%, 1.521-22.310, p = 0.010) were factors associated with the event.
UNASSIGNED: These findings could help health professionals provide their patients with up-to-date scientific information to empower them to actively manage their reproductive health, especially in societies where menstrual health is still taboo.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.

Menopausal women may experience symptoms of depression, sometimes even progressing clinical depression requiring treatment to improve quality of life. While varying levels of estrogen in perimenopause may contribute to an increased biological vulnerability to mood disturbances, the effectiveness of estrogen replacement therapy (ERT) in the relief of depressive symptoms remains controversial. Menopausal depression has a complex, multifactorial etiology, that has limited the identification of optimal treatment strategies for the management of this psychiatric complaint. Nevertheless, clinical evidence increasingly supports the notion that estrogen exerts neuroprotective effects on brain structures related to mood regulation. Indeed, research using preclinical animal models continues to improve our understanding of menopause and the effectiveness of ERT and other substances at treating depression-like behaviors. However, questions regarding the efficacy of ERT in perimenopause have been raised. These questions may be answered by further investigation using specific animal models of reduced ovarian function. This review compares and discusses the advantages and pitfalls of different models emulating the menopausal stages and their relationship with the onset of depressive-like signs, as well as the efficacy and mechanisms of conventional and novel ERTs in treating depressive-like behavior. Ovariectomized young rats, middle-to-old aged intact rats, and females treated with reprotoxics have all been used as models of menopause, with stages ranging from surgical menopause to perimenopause. Additionally, this manuscript discusses the impact of organistic and therapeutic variables that may improve or reduce the antidepressant response of females to ERT. Findings from these models have revealed the complexity of the dynamic changes occurring in brain function during menopausal transition, reinforcing the idea that the best approach is timely intervention considering the opportunity window, in addition to the careful selection of treatment according to the presence or absence of reproductive tissue. Additionally, data from animal models has yielded evidence to support new promising estrogens that could be considered as ERTs with antidepressant properties and actions in endocrine situations in which traditional ERTs are not effective.

Perimenopausal depression (PMD) is a psychological disorder that occurs in women during perimenopause. In addition to the common clinical symptoms of depression, it often manifests as a perimenopausal complication, and its notable cause is the decline in estrogen levels. Despite numerous studies and trials confirming the benefits of estrogen replacement therapy (ERT) for PMD, ERT remains unapproved for treating PMD. Therefore, we conducted a literature search using selected keywords in PubMed and Google Scholar to write a review discussing the feasibility of using ERT for PMD. This review examines the potential of ERT for PMD in terms of its underlying mechanisms, efficacy, safety, and time window. These four aspects suggest that ERT is a viable option for PMD treatment. However, the risk of thrombosis and stroke with ERT is a matter of contention among medical experts, with a paucity of clinical data. Consequently, further clinical trial data are required to ascertain the safety of ERT.

Heart rate variability (HRV) is a non-invasive quantitative measure of cardiac autonomic nervous activity. Due to the increase of age and the decrease of estrogen level in perimenopausal and postmenopausal women, the cardiac autonomic nervous function is abnormal, increasing the risk of cardiovascular disease. Proper exercise can increase estrogen levels, improve cardiovascular health, regulate cardiac autonomic nervous activity, and reduce the risk of cardiovascular disease. Low-moderate intensity aerobic exercise, resistance exercise, aerobic combined resistance exercise and mind-body exercise have positive effects on HRV in perimenopausal and postmenopausal women. Therefore, summarizing the effects of different exercise modes on HRV in perimenopausal and postmenopausal women, as well as the mechanism of exercise training improvement on HRV, so as to adopt better exercise strategies to improve HRV of perimenopausal and postmenopausal women, and thus reduce the risk of cardiovascular diseases and improve the health level and quality of life of perimenopausal and postmenopausal women.
心率变异性(heart rate variability，HRV)可以无创定量评估心脏自主神经活动。围绝经期和绝经后妇女由于年龄的增加和体内雌激素水平的降低，导致其心脏自主神经功能异常，心血管疾病的患病风险增加。而适当的运动可以提高雌激素水平，改善心血管健康水平，调节心脏自主神经活动，降低心血管疾病的发生风险。中低强度的有氧运动、抗阻运动、有氧结合抗阻运动和身心运动可对围绝经期和绝经后妇女HRV产生积极影响。总结不同运动方式对围绝经期和绝经后妇女HRV的影响以及运动改善HRV的机制，可为采取更佳的运动策略以改善围绝经期和绝经后妇女HRV提供依据，进而降低心血管疾病的患病风险，提高围绝经期和绝经后妇女的健康水平和生活质量。.

As both perimenopausal and menopausal periods are recognized critical windows of susceptibility for breast carcinogenesis, development of a physiologically relevant model has been warranted. The traditional ovariectomy model causes instant removal of the entire hormonal repertoire produced by the ovary, which does not accurately approximate human natural menopause with gradual transition. Here, we characterized the mammary glands of 4-vinylcyclohexene diepoxide (VCD)-treated animals at different time points, revealing that the model can provide the mammary glands with both perimenopausal and menopausal states. The perimenopausal gland showed moderate regression in ductal structure with no responsiveness to external hormones, while the menopausal gland showed severe regression with hypersensitivity to hormones. Leveraging the findings on the VCD model, effects of a major endocrine disruptor (polybrominated diphenyl ethers, PBDEs) on the mammary gland were examined during and after menopausal transition, with the two exposure modes; low-dose, chronic (environmental) and high-dose, subacute (experimental). All conditions of PBDE exposure did not augment or compromise the macroscopic ductal reorganization resulting from menopausal transition and/or hormonal treatments. Single-cell RNA sequencing revealed that the experimental PBDE exposure during the post-menopausal period caused specific transcriptomic changes in the non-epithelial compartment such as Errfi1 upregulation in fibroblasts. The environmental PBDE exposure resulted in similar transcriptomic changes to a lesser extent. In summary, the VCD mouse model provides both perimenopausal and menopausal windows of susceptibility for the breast cancer research community. PBDEs, including all tested models, may affect the post-menopausal gland including impacts on the non-epithelial compartments.

Perimenopause significantly impacts women\'s health globally, often managed with hormone replacement therapy (HRT) despite the associated risks. This study explores a novel alternative exosome therapy, aimed at stimulating estrogen production in ovarian tissues, thus offering a potential non-hormonal treatment for perimenopausal symptoms. Employing ex vivo methodologies, ovarian cortex specimens from perimenopausal women were treated with exosomes derived from human umbilical cord mesenchymal stem cells and cultured under specific conditions (patent number: PCT/US2022/073467). The exosomes were produced under cyclic guanosine monophosphate (cGMP) conditions, ensuring high safety standards. Estrogen levels were quantified using enzyme-linked immunosorbent assay (ELISA), and gene expression changes in estrogen and follicle-stimulating hormone (FSH) receptors were assessed via quantitative polymerase chain reaction (PCR). Immunohistochemistry (IHC) was utilized to evaluate cellular proliferation and apoptotic markers. The results indicated a significant increase in estrogen levels and estrogen receptor-alpha (Erα) expression in treated tissues compared to controls. Additionally, a decrease in apoptotic markers and an increase in cellular proliferation markers were observed. These findings suggest that exosome therapy can effectively enhance estrogen production and modulate receptor sensitivity in perimenopausal ovarian tissues. This approach could serve as a safer alternative to HRT, aligning with the body\'s natural regulatory mechanisms and potentially offering a more effective treatment option for managing perimenopausal symptoms.

This study aimed to identify hub genes and elucidate the molecular mechanisms underlying low bone mineral density (BMD) in perimenopausal women. R software was used to normalize the dataset and screen the gene set associated with BMD in perimenopausal women from the Gene Expression Omnibus database. Cytoscape software was used to identify 7 critical genes. Gene enrichment analysis and protein interaction was employed to further analyze the core genes, and the CIBERSORT deconvolution algorithm was used to perform immune infiltration analysis of 22 immune genes in the samples. Furthermore, an analysis of the immune correlations of 7 crucial genes was conducted. Subsequently, a receiver operating characteristic curve was constructed to assess the diagnostic efficacy of these essential genes. A total of 171 differentially expressed genes were identified that were primarily implicated in the signaling pathways associated with apoptosis. Seven crucial genes (CAMP, MMP8, HMOX1, CTNNB1, ELANE, AKT1, and CEACAM8) were effectively filtered. The predominant functions of these genes were enriched in specific granules. The pivotal genes displayed robust associations with activated dendritic cells. The developed risk model showed a remarkable level of precision, as evidenced by an area under the curve of 0.8407 and C-index of 0.854. The present study successfully identified 7 crucial genes that are significantly associated with low BMD in perimenopausal women. Consequently, this research offers a solid theoretical foundation for clinical risk prediction, drug sensitivity analysis, and the development of targeted drugs specifically tailored for addressing low BMD in perimenopausal women.

UNASSIGNED: Healthcare professionals and educators closely monitor the occurrence of climacteric symptoms in women\'s primes. Knowledge and perception of menopause play a crucial role in improving quality of life. This study aimed to assess the knowledge and perceptions of menopause among Saudi women and identify its predictors. This study is the first of its kind in the southern region of Saudi Arabia.
UNASSIGNED: Conducted in accordance with the STROBE guidelines, this cross-sectional study was carried out in the Jazan region from May 2022 to January 2023 and involved 480 Saudi women who provided consent. Data were collected through interviews using a validated questionnaire and random sampling. The questionnaire consisted of four parts: informed consent, demographics, 21 knowledge questions, and ten menopause perception questions. The validity of the content and the internal consistency were evaluated before data collection. Primary healthcare centers were randomly selected from four governorates with a proportional sample size to the population. Descriptive analysis, Pearson correlation, and multivariate logistic regression analyses were performed using IBM-SPSS.
UNASSIGNED: Among the participants, 64 % were under 40 years old, 80 % had experienced menarche between the ages of 10 and 15, 48 % were employed, approximately half held a bachelor\'s degree, and they had a good family income. The mean knowledge score of the participants was 48.87 ± 11.72, with a minimum score of 27 and a maximum score of 78. In terms of knowledge categories, 56.3 % of the participants (N = 270) were classified as having low knowledge, while 43.8 % (N = 210) were classified as having high knowledge. Most of the participants had positive perceptions and agreed that menopause is a natural event in women\'s lives. There was a significant positive correlation between knowledge and perception (R = 0.219, P < 0.01). Variable findings were observed regarding the role of explanatory variables in women\'s knowledge of menopause between univariate and multivariate models. The results of the multivariate model showed that age (46-50 years, OR = 0.42), having children (OR = 1.09), residence (OR = 0.45-5.73) and family income categories (medium: OR = 3.98, good: OR = 3.78, and excellent: OR = 1.95) had a significant impact on knowledge, highlighting the correlation between demographic factors and knowledge.
UNASSIGNED: Based on the study findings, we recommend implementing workplace and community-based activities to increase women\'s awareness of menopause and incorporating it as an integral part of counseling sessions for women in this age group. Therefore, the results of the study will be shared with the relevant authorities responsible for women\'s health, enabling them to effectively support and educate women.

Risk of cardiovascular disease mortality rises in women after menopause. While increased cardiovascular risk is largely attributed to postmenopausal declines in estrogens, the molecular changes in the heart that contribute to risk are poorly understood. Disruptions in intracellular calcium handling develop in ovariectomized mice and have been implicated in cardiac dysfunction. Using a mouse model of menopause in which ovarian failure occurs over 120 days, we sought to determine if perimenopause impacted calcium removal mechanisms in the heart and identify the molecular mechanisms. Mice were injected with 4-vinylcyclohexene diepoxide (VCD) to induce ovarian failure over 120 days, mimicking perimenopause. Hearts were removed at 60 and 120 days after VCD injections, representing the middle and end of perimenopause. SERCA2a function was significantly diminished at the end of perimenopause. Neither SERCA2a nor phospholamban expression changed at either time point, but phospholamban phosphorylation at S16 and T17 was dynamically altered. Intrinsic SERCA inhibitors sarcolipin and myoregulin increased >4-fold at day 60, as did the native activator DWORF. At the end of perimenopause, sarcolipin and myoregulin returned to baseline levels while DWORF was significantly reduced below controls. Sodium-calcium exchanger expression was significantly increased at the end of perimenopause. These results show that the foundation for increased cardiovascular disease mortality develops in the heart during perimenopause and that regulators of calcium handling exhibit significant fluctuations over time. Understanding the temporal development of cardiovascular risk associated with menopause and the underlying mechanisms is critical to developing interventions that mitigate the rise in cardiovascular mortality that arises after menopause.