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Frontiers in Endocrinology 2023Natural menopause is an inevitable biological process with significant implications for women's health. However, the molecular mechanisms underlying menopause are not...
INTRODUCTION
Natural menopause is an inevitable biological process with significant implications for women's health. However, the molecular mechanisms underlying menopause are not well understood. This study aimed to investigate the molecular and cellular changes occurring in the ovary before and after perimenopause.
METHODS
Single-cell sequencing data from the GTEx V8 cohort (30-39: 14 individuals; 40-49: 37 individuals; 50-59: 61 individuals) and transcriptome sequencing data from ovarian tissue were analyzed. Seurat was used for single-cell sequencing data analysis, while harmony was employed for data integration. Cell differentiation trajectories were inferred using CytoTrace. CIBERSORTX assessed cell infiltration scores in ovarian tissue. WGCNA evaluated co-expression network characteristics in pre- and post-perimenopausal ovarian tissue. Functional enrichment analysis of co-expression modules was conducted using ClusterprofileR and Metascape. DESeq2 performed differential expression analysis. Master regulator analysis and signaling pathway activity analysis were carried out using MsViper and Progeny, respectively. Machine learning models were constructed using Orange3.
RESULTS
We identified the differentiation trajectory of follicular cells in the ovary as ARID5B+ Granulosa -> JUN+ Granulosa -> KRT18+ Granulosa -> MT-CO2+ Granulosa -> GSTA1+ Granulosa -> HMGB1+ Granulosa. Genes driving Granulosa differentiation, including RBP1, TMSB10, SERPINE2, and TMSB4X, were enriched in ATP-dependent activity regulation pathways. Genes involved in maintaining the Granulosa state, such as DCN, ARID5B, EIF1, and HSP90AB1, were enriched in the response to unfolded protein and chaperone-mediated protein complex assembly pathways. Increased contents of terminally differentiated HMGB1+ Granulosa and GSTA1+ Granulosa were observed in the ovaries of individuals aged 50-69. Signaling pathway activity analysis indicated a gradual decrease in TGFb and MAPK pathway activity with menopause progression, while p53 pathway activity increased. Master regulator analysis revealed significant activation of transcription factors FOXR1, OTX2, MYBL2, HNF1A, and FOXN4 in the 30-39 age group, and GLI1, SMAD1, SMAD7, APP, and EGR1 in the 40-49 age group. Additionally, a diagnostic model based on 16 transcription factors (Logistic Regression L2) achieved reliable performance in determining ovarian status before and after perimenopause.
CONCLUSION
This study provides insights into the molecular and cellular mechanisms underlying natural menopause in the ovary. The findings contribute to our understanding of perimenopausal changes and offer a foundation for health management strategies for women during this transition.
Topics: Female; Humans; Adult; Middle Aged; Ovary; Transcriptome; HMGB1 Protein; Serpin E2; Menopause; Transcription Factors
PubMed: 37564980
DOI: 10.3389/fendo.2023.1004245 -
Nursing Open Jan 2024The aim of the study was to explore and understand the organizational culture of a workplace in terms of support and well-being for staff experiencing perimenopausal and... (Review)
Review
AIM
The aim of the study was to explore and understand the organizational culture of a workplace in terms of support and well-being for staff experiencing perimenopausal and menopausal symptoms at work.
DESIGN
It is widely acknowledged that perimenopause and menopause symptoms are experienced by a large percentage of the female workforce. There is a lack of research into how nurses are supported through menopause (Cronin et al. Issues in Mental Health Nursing, 42, 2021, 541-548). The perimenopause and menopause transition can be a challenging time where many may require symptom management and support (RCN, The Menopause and Work: Guidance for RCN Representatives, 2020). This paper presents a case study research (CSR) approach to examine one healthcare organization.
METHODS
CSR design was used: A survey distributed to all staff employed, a review of the available documentation on menopause and interviews with managers from different levels of the organization. The COREQ consolidated criteria was used for reporting the qualitative research reported this study.
RESULTS
The case study generated both quantitative and qualitative data using surveys, interviews and documentation. Data from the organization (n = 6905) showed a majority female workforce of 81.9% with 40.6% aged between 41 and 55 years old, meaning a third of the organization working through perimenopause and menopause. Survey responses (n = 167) collected biographical and psychometric data on the prevalence of perimenopausal and menopausal symptoms. Seven managers were interviewed highlighting two themes: Access to support and culture of menopause and 13 documents from the organization on menopause were analysed for content. The study design permitted an iterative approach to data collection and providing an in-depth understanding of the needs and support for those experiencing perimenopause and menopause. The findings help healthcare organizations to understand their workforce and take in to account the larger numbers of female employees particularly nurses with the need to provide person-centred support mechanisms and an organizational approach for all employees.
Topics: Female; Humans; Adult; Middle Aged; Menopause; Perimenopause; Case-Control Studies; Workforce; Research Design
PubMed: 38268277
DOI: 10.1002/nop2.2058 -
Biomedicines Jan 2024Perimenopausal depression, occurring shortly before or after menopause, is characterized by symptoms such as emotional depression, anxiety, and stress, often accompanied... (Review)
Review
Perimenopausal depression, occurring shortly before or after menopause, is characterized by symptoms such as emotional depression, anxiety, and stress, often accompanied by endocrine dysfunction, particularly hypogonadism and senescence. Current treatments for perimenopausal depression primarily provide symptomatic relief but often come with undesirable side effects. The development of agents targeting the specific pathologies of perimenopausal depression has been relatively slow. The erratic fluctuations in estrogen and progesterone levels during the perimenopausal stage expose women to the risk of developing perimenopausal-associated depression. These hormonal changes trigger the production of proinflammatory mediators and induce oxidative stress, leading to progressive neuronal damage. This review serves as a comprehensive overview of the underlying mechanisms contributing to perimenopausal depression. It aims to shed light on the complex relationship between perimenopausal hormones, neurotransmitters, brain-derived neurotrophic factors, chronic inflammation, oxidative stress, and perimenopausal depression. By summarizing the intricate interplay between hormonal fluctuations, neurotransmitter activity, brain-derived neurotrophic factors, chronic inflammation, oxidative stress, and perimenopausal depression, this review aims to stimulate further research in this field. The hope is that an increased understanding of these mechanisms will pave the way for the development of more effective therapeutic targets, ultimately reducing the risk of depression during the menopausal stage for the betterment of psychological wellbeing.
PubMed: 38255289
DOI: 10.3390/biomedicines12010184 -
Neurobiology of Disease Mar 2022Traumatic brain injury (TBI) is a leading cause of death and disability and a global public health challenge. Every year more than 50 million people suffer a TBI, and it... (Review)
Review
Traumatic brain injury (TBI) is a leading cause of death and disability and a global public health challenge. Every year more than 50 million people suffer a TBI, and it is estimated that 50% of the global population will experience at least one TBI in their lifetime. TBI affects both men and women of all ages, however there is a male bias in TBI research as women have frequently been left out of the literature despite irrefutable evidence of male and female dimorphism in several posttraumatic measures. Women uniquely experience distinct life stages marked by levels of endogenous circulating sex hormones, as well as by physiological changes that are nonexistent in men. In addition to generalized sex-specific differences, a woman's susceptibility, neurological outcomes, and treatment success may vary considerably depending upon when in her lifespan she incurred a traumatic insult. How women impacted by TBI might differ from other women as a factor of age and physiology is not well understood. Furthermore, there is a gap in the knowledge of what happens when TBI occurs in the presence of certain sex-specific and sex-nonspecific variables, such as during pregnancy, with oral contraceptive use, in athletics, in cases of addiction and nicotine consumption, during perimenopause, postmenopause, in frailty, among others. Parsing out how hormone-dependent and hormone-independent lifespan variables may influence physiological, neurodegenerative, and functional outcomes will greatly contribute to future investigative studies and direct therapeutic strategies. The goal of this review is to aggregate the knowledge of prevalence, prognosis, comorbid risk, and response of women incurring TBI at differing phases of lifespan. We strive to illuminate commonalities and disparities among female populations, and to pose important questions to highlight gaps in the field in order to further the endeavor of targeted treatment interventions in a patient-specific manner.
Topics: Age Factors; Brain Injuries, Traumatic; Female; Humans; Longevity; Pregnancy; Prognosis
PubMed: 34995753
DOI: 10.1016/j.nbd.2022.105613 -
Journal of Menopausal Medicine Aug 2021The levonorgestrel-releasing intrauterine system (LNG-IUS) is a highly effective contraceptive method that has several noncontraceptive benefits. It has been used in... (Review)
Review
The levonorgestrel-releasing intrauterine system (LNG-IUS) is a highly effective contraceptive method that has several noncontraceptive benefits. It has been used in various gynecological conditions, such as heavy menstrual bleeding, dysmenorrhea, and endometrial hyperplasia. During the perimenopausal period, hormonal fluctuations occur, and there is a high tendency for the development of several benign gynecologic diseases. Therefore, the use of LNG-IUS in perimenopausal women might be more beneficial than in women belonging to other age groups. Moreover, the insertion of LNG-IUS during the perimenopausal period could confer endometrial protection during estrogen replacement therapy. In this review, we discuss the use of LNG-IUS in perimenopausal women.
PubMed: 34463068
DOI: 10.6118/jmm.20038 -
Menopause (New York, N.Y.) Jun 2023Distressing sexual problems are a common complaint of menopausal women. In 2013, a Cochrane review assessed the effect of hormone therapy on sexual function in... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Distressing sexual problems are a common complaint of menopausal women. In 2013, a Cochrane review assessed the effect of hormone therapy on sexual function in menopausal women; however, new evidence has since been published, which should be considered.
OBJECTIVE
This systematic review and meta-analysis aims to update the evidence synthesis on the effect of hormone therapy, compared with control, on sexual function in perimenopausal and postmenopausal women.
EVIDENCE REVIEW
Thirteen databases and clinical trial registries (Cochrane Central Register of Controlled Trials, EMBASE, Medical Literature Analysis and Retrieval System Online, PsycINFO, Web of Science, Cumulative Index to Nursing and Allied Health Literature, Literatura Latino-Americana e do Caribe em Ciéncias da Saúde, Database of Abstracts of Reviews of Effects, ClinicalTrials.gov , International Clinical Trials Registry Platform, Iranian Registry of Clinical Trials, Chinese Clinical Trial Registry, ISRCTN) were searched from December 2012 to March 30, 2022. Backward reference searching on all retrieved full texts was also performed. Study quality was assessed using the Cochrane ROB.2 tool. Data were pooled in random-effect model meta-analyses, which included all studies identified in the present search and all studies previously included in the 2013 Cochrane review.
FINDINGS
Forty-seven randomized controlled trials (35,912 participants) were included in the systematic review, and 34 randomized controlled trials (15,079 participants) were included in the meta-analysis. The meta-analysis revealed that, in comparison to control, estrogen therapy (standardized mean difference [SMD], 0.16; 95% confidence interval [CI], 0.02 to 0.29; I2 = 59%; 2,925 participants, 16 studies), estrogen plus progestogen therapy (SMD, 0.11; 95% CI, -0.07 to 0.29; I2 = 65%; 2,432 participants, 7 studies), tibolone (SMD, 0.15; 95% CI, 0.02 to 0.28; I2 = 0%; 916 participants, 2 studies), and selective estrogen receptor modulators (SMD, 0.18; 95% CI, 0.06 to 0.30; I2 = 0%; 1,058 participants, 4 studies) may result in no effect to small benefit on sexual function composite score.
CONCLUSION AND RELEVANCE
Hormone therapy may slightly improve sexual functioning. This potential small benefit should be considered when discussing treatment options for other menopausal symptoms.
Topics: Female; Humans; Postmenopause; Perimenopause; Iran; Estrogens; Menopause
PubMed: 37159867
DOI: 10.1097/GME.0000000000002185 -
BMC Women's Health May 2022The perimenopausal period is associated with a higher risk of various mood disorders. Similarly, although resting-state electroencephalogram (rsEEG) brain oscillatory...
BACKGROUND
The perimenopausal period is associated with a higher risk of various mood disorders. Similarly, although resting-state electroencephalogram (rsEEG) brain oscillatory activity has been associated with various neuropsychological disorders and behaviours, these issues have not been assessed in perimenopausal women. This study aimed to evaluate quantitative relationships between psychometric properties and rsEEG rhythms (delta, theta, alpha, beta and gamma powers) in perimenopausal women.
METHODS
A cross-sectional correlational descriptive study was conducted to quantitatively analyze the correlations between rsEEG low-to-high band activities (delta, theta, alpha, beta, and gamma powers) and psychometric properties in 14 perimenopausal women. Participants completed a psychological inventory comprising the State Anxiety Inventory (SAI), Depression Inventory (DI), Behavioural Inhibition Scale (BIS) and short-form UPPS Impulsive Behaviour Scale (IS) before EEG recording.
RESULTS
Results showed that impulsivity was positively related to the beta power, symmetrical at most channels (frontal, temporal, central, parietal and occipital regions; p < .05); but did not related to the delta, theta, alpha and gamma powers. The brainwave low-to-high bands, delta, theta, alpha, beta and gamma power were not associated with DI, SAI or BIS scores.
CONCLUSIONS
This study's findings propose that significantly enhanced resting-state beta activity is a trait of impulsivity in perimenopausal women. Therefore, results have potential implications for the preclinical or clinical evaluation of these issues in perimenopausal women.
Topics: Anxiety; Cross-Sectional Studies; Electroencephalography; Female; Humans; Perimenopause; Psychometrics
PubMed: 35538572
DOI: 10.1186/s12905-022-01729-7 -
Journal of Clinical Medicine May 2021Migraine course is influenced by female reproductive milestones, including menstruation and perimenopause; menstrual migraine (MM) represents a distinct clinical entity.... (Review)
Review
Migraine course is influenced by female reproductive milestones, including menstruation and perimenopause; menstrual migraine (MM) represents a distinct clinical entity. Increased susceptibility to migraine during menstruation and in perimenopause is probably due to fluctuations in estrogen levels. The present review provides suggestions for the treatment of MM and perimenopausal migraine. MM is characterized by long, severe, and poorly treatable headaches, for which the use of long-acting triptans and/or combined treatment with triptans and common analgesics is advisable. Short-term prophylaxis with triptans and/or estrogen treatment is another viable option in women with regular menstrual cycles or treated with combined hormonal contraceptives; conventional prevention may also be considered depending on the attack-related disability and the presence of attacks unrelated to menstruation. In women with perimenopausal migraine, hormonal treatments should aim at avoiding estrogen fluctuations. Future research on migraine treatments will benefit from the ascertainment of the interplay between female sex hormones and the mechanisms of migraine pathogenesis, including the calcitonin gene-related peptide pathway.
PubMed: 34073696
DOI: 10.3390/jcm10112263 -
Current Psychiatry Reports Oct 2023To review recent research regarding cognitive problems during perimenopause, including which menopause-related symptoms, demographic variables, stress exposures, and... (Review)
Review
PURPOSE OF REVIEW
To review recent research regarding cognitive problems during perimenopause, including which menopause-related symptoms, demographic variables, stress exposures, and neural biomarkers are associated with cognitive problems and which interventions demonstrate efficacy at improving cognitive performance.
RECENT FINDINGS
Cognitive problems are common during perimenopause and have a significant impact on a substantial proportion of women. Evidence continues to indicate that verbal learning and verbal memory are the cognitive functions that are most negatively affected during perimenopause, and new research suggests that perimenopause may also be associated with deficits in processing speed, attention, and working memory. Recent research suggests that the cognitive profiles of women transitioning through perimenopause are heterogenous - with some showing strengths and others demonstrating weaknesses in particular cognitive domains. Depression, sleep problems, and vasomotor symptoms in perimenopause may be associated with cognitive difficulties. Recent neuroimaging studies are identifying changes in activity patterns within brain regions that correlate with cognitive performance in perimenopause, but future causal studies are needed to understand the neural mechanisms of cognitive problems during this time. Although clinical treatment studies for cognitive concerns have historically focused on postmenopause, some small trials in perimenopausal samples have been conducted recently but are frequently underpowered. Current guidelines from the North American Menopause Society do not support the use of hormone therapy at any age for cognitive problems. Animal research demonstrates that estradiol and levonorgestrel combined may alleviate working memory problems. Much progress has been made in understanding how perimenopause impacts cognition, and more research is needed to better identify who is at highest risk and how to meaningfully prevent and alleviate cognitive problems during this reproductive stage. Larger-scale randomized intervention trials specifically during perimenopause are urgently needed to address cognitive concerns in this population of women. More consistent reproductive staging, inclusion of covariates, and analyses examining perimenopause specifically would improve study quality and the ability to draw clear conclusions from this research.
Topics: Female; Humans; Perimenopause; Menopause; Postmenopause; Estradiol; Cognition
PubMed: 37755656
DOI: 10.1007/s11920-023-01447-3 -
Scientific Reports May 2024This cross-sectional study aimed to explore the knowledge, attitude and practice (KAP) toward sleep disorders and sleep hygiene among perimenopausal women, who were...
This cross-sectional study aimed to explore the knowledge, attitude and practice (KAP) toward sleep disorders and sleep hygiene among perimenopausal women, who were enrolled in Dezhou region of Shandong Province between July and September 2023. A total of 720 valid questionnaires were collected (mean age: 51.28 ± 4.32 years old), and 344 (47.78%) reported experiencing insomnia. The mean scores for knowledge, attitude, practice, and Dysfunctional Beliefs and Attitudes about Sleep (DBAS) were 15.73 ± 7.60 (possible range: 0-36), 29.35 ± 3.15 (possible range: 10-50), 28.54 ± 4.03 (possible range: 10-50), and 6.79 ± 1.90 (possible range: 0-10), respectively. Path analysis showed that knowledge had direct effects on attitude (β = 0.04, 95% CI 0.01-0.07, P = 0.001), and DBAS (β = 0.04, 95% CI 0.02-0.05, P < 0.001). Knowledge had direct effects (β = 0.11, 95% CI 0.08-0.15, P < 0.001) and indirect (β = 0.02, 95% CI 0.00-0.03, P = 0.002) effect on practice. Moreover, attitude also had a direct impact on practice (β = 0.34, 95% CI 0.25-0.43, P < 0.001). In conclusion, perimenopausal women exhibited insufficient knowledge, negative attitude, inactive practice toward sleep disorders and sleep hygiene, and unfavorable DBAS, emphasizing the need for targeted healthcare interventions.
Topics: Humans; Female; Middle Aged; Health Knowledge, Attitudes, Practice; Sleep Hygiene; Perimenopause; Cross-Sectional Studies; Sleep Wake Disorders; Surveys and Questionnaires; China; Sleep Initiation and Maintenance Disorders; Adult
PubMed: 38777871
DOI: 10.1038/s41598-024-62502-4