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American Journal of Obstetrics and... Mar 2024Identifying risk factors for Alzheimer disease in women is important as women compose two-thirds of individuals with Alzheimer disease. Previous work links vasomotor...
BACKGROUND
Identifying risk factors for Alzheimer disease in women is important as women compose two-thirds of individuals with Alzheimer disease. Previous work links vasomotor symptoms, the cardinal menopausal symptom, with poor memory performance and alterations in brain structure, function, and connectivity. These associations are evident when vasomotor symptoms are monitored objectively with ambulatory skin conductance monitors.
OBJECTIVE
This study aimed to determine whether vasomotor symptoms are associated with Alzheimer disease biomarkers.
STUDY DESIGN
Between 2017 and 2020, the MsBrain study enrolled 274 community-dwelling women aged 45 to 67 years who had a uterus and at least 1 ovary and were late perimenopausal or postmenopausal status. The key exclusion criteria included neurologic disorder, surgical menopause, and recent use of hormonal or nonhormonal vasomotor symptom treatment. Women underwent 24 hours of ambulatory skin conductance monitoring to assess vasomotor symptoms. Plasma concentrations of Alzheimer disease biomarkers, including amyloid β 42-to-amyloid β 40 ratio, phosphorylated tau (181 and 231), glial fibrillary acidic protein, and neurofilament light, were measured using a single-molecule array (Simoa) technology. Associations between vasomotor symptoms and Alzheimer disease biomarkers were assessed via linear regression models adjusted for age, race and ethnicity, education, body mass index, and apolipoprotein E4 status. Additional models adjusted for estradiol and sleep.
RESULTS
A total of 248 (mean age, 59.06 years; 81% White; 99% postmenopausal status) of enrolled MsBrain participants contributed data. Objectively assessed vasomotor symptoms occurring during sleep were associated with significantly lower amyloid β 42/amyloid β 40, (beta, -.0010 [standard error, .0004]; P=.018; multivariable), suggestive of greater brain amyloid β pathology. The findings remained significant after additional adjustments for estradiol and sleep.
CONCLUSION
Nighttime vasomotor symptoms may be a marker of women at risk of Alzheimer disease. It is yet unknown if these associations are causal.
Topics: Female; Humans; Middle Aged; Menopause; Hot Flashes; Alzheimer Disease; Amyloid beta-Peptides; Sweating; Biomarkers; Estradiol
PubMed: 37939982
DOI: 10.1016/j.ajog.2023.11.002 -
Journal of Pineal Research Jan 2024Endometrial cancer (EC) is a reproductive system disease that occurs in perimenopausal and postmenopausal women. However, its etiology is unclear. Melatonin (MT) has...
Endometrial cancer (EC) is a reproductive system disease that occurs in perimenopausal and postmenopausal women. However, its etiology is unclear. Melatonin (MT) has been identified as a therapeutic agent for EC; however, its exact mechanism remains unclear. In the present study, we determined that GATA-binding protein 2 (GATA2) is expressed at low levels in EC and regulated by MT. MT upregulates the expression of GATA2 through MT receptor 1A (MTNR1A), whereas GATA2 can promote the expression of MTNR1A by binding to its promoter region. In addition, in vivo and in vitro experiments showed that MT inhibited the proliferation and metastasis of EC cells by upregulating GATA2 expression. The protein kinase B (AKT) pathway was also affected. In conclusion, these findings suggest that MT and GATA2 play significant roles in EC development.
Topics: Humans; Female; Melatonin; GATA2 Transcription Factor; Endometrial Neoplasms; Cell Proliferation; Cell Line, Tumor
PubMed: 37814536
DOI: 10.1111/jpi.12918 -
Climacteric : the Journal of the... Feb 2024Cardiovascular disease (CVD) represents the leading cause of death and accounts for almost 50% of all deaths in women worldwide. The menopausal transition is associated... (Review)
Review
Cardiovascular disease (CVD) represents the leading cause of death and accounts for almost 50% of all deaths in women worldwide. The menopausal transition is associated with central body fat accumulation, a decrease in energy expenditure, weight gain, insulin resistance and a pro-atherogenic lipid profile. Moreover, menopause is independently associated with an adverse effect on functional and structural indices of subclinical atherosclerosis. Women with premature ovarian insufficiency have heightened CVD risk compared to women of natural age at menopause. Furthermore, women with severe menopausal symptoms may have a more adverse cardiometabolic profile than those without symptoms. We reviewed the latest evidence on the cardiovascular management of perimenopausal or postmenopausal women. Clinicians should aim for cardiovascular risk stratification, followed by dietary and lifestyle advice as required based on individual needs. The medical management of cardiometabolic risk factors at midlife should always be individualized, focusing on hypertension, diabetes and dyslipidemia. Menopausal hormone therapy, when prescribed for the management of bothersome menopausal symptoms or for the prevention of osteoporosis, has also a beneficial effect on cardiometabolic risk factors. This narrative review aims to summarize the cardiometabolic alternations occurring during the menopausal transition and to outline the appropriate prevention strategies to prevent future cardiovascular adverse outcomes.
Topics: Female; Humans; Menopause; Menopause, Premature; Cardiovascular Diseases; Primary Ovarian Insufficiency; Hormone Replacement Therapy; Risk Factors
PubMed: 37224871
DOI: 10.1080/13697137.2023.2202809 -
Journal of Personalized Medicine Feb 2024Sex hormones and migraine are closely interlinked. Women report higher levels of migraine symptoms during periods of sex hormone fluctuation, particularly during... (Review)
Review
Sex hormones and migraine are closely interlinked. Women report higher levels of migraine symptoms during periods of sex hormone fluctuation, particularly during puberty, pregnancy, and perimenopause. Ovarian steroids, such as estrogen and progesterone, exert complex effects on the peripheral and central nervous systems, including pain, a variety of special sensory and autonomic functions, and affective processing. A panel of basic scientists, when challenged to explain what was known about how sex hormones affect the nervous system, focused on two hormones: estrogen and oxytocin. Notably, other hormones, such as progesterone, testosterone, and vasopressin, are less well studied but are also highlighted in this review. When discussing what new therapeutic agent might be an alternative to hormone therapy and menopause replacement therapy for migraine treatment, the panel pointed to oxytocin delivered as a nasal spray. Overall, the conclusion was that progress in the preclinical study of hormones on the nervous system has been challenging and slow, that there remain substantial gaps in our understanding of the complex roles sex hormones play in migraine, and that opportunities remain for improved or novel therapeutic agents. Manipulation of sex hormones, perhaps through biochemical modifications where its positive effects are selected for and side effects are minimized, remains a theoretical goal, one that might have an impact on migraine disease and other symptoms of menopause. This review is a call to action for increased interest and funding for preclinical research on sex hormones, their metabolites, and their receptors. Interdisciplinary research, perhaps facilitated by a collaborative communication network or panel, is a possible strategy to achieve this goal.
PubMed: 38392617
DOI: 10.3390/jpm14020184 -
BMC Women's Health Nov 2023To measure symptoms and health-related quality of life in a cross-sectional cohort of menopausal-aged women in China.
OBJECTIVE
To measure symptoms and health-related quality of life in a cross-sectional cohort of menopausal-aged women in China.
METHOD
A cross-sectional survey was conducted in a general population cohort of 2,000 Chinese females over the age of 45 years. Patients completed the Chinese version of the EuroQol-5D five level (EQ5D5L) health-related quality of life instrument via Personal Digital Assistant. Raw scores were converted to utility tariffs using value sets for China. Statistical analysis included Pearson's chi-square test, z test for multiple comparisons with adjustment by the Bonferroni method, independent-sample t-test, ANOVA, and adjustment by the Tukey method for multiple comparison. Results were considered statistically significant when p < 0.05 and the study was reported according to the STROBE recommendations.
RESULTS
In a cohort of 2000 women, 732 (37%) were premenopausal, 798 (40%) were perimenopausal and 470 (23%) were postmenopausal. Perimenopausal women reported significantly more symptoms (91%) compared to premenopausal (77%) and postmenopausal (81%) women. Health-related quality of life was significantly lower in symptomatic perimenopausal women compared to premenopausal (0.919, p < 0.05) and postmenopausal (0.877, p < 0.05) women. Within each group there was a statistically significant difference between the health-related quality of life of women with symptoms compared to without symptoms.
CONCLUSION
The perimenopausal phase of menopause is associated with significantly more symptoms and significantly lower HRQoL compared to premenopausal and postmenopausal phases.
Topics: Humans; Female; Aged; Middle Aged; Male; Cross-Sectional Studies; Perimenopause; Quality of Life; Menopause; Premenopause
PubMed: 37915020
DOI: 10.1186/s12905-023-02728-y -
Journal of Oncology Pharmacy Practice :... Apr 2024Despite the relatively high cure rates in early-stage breast cancer, advanced and metastatic breast cancer cases are associated with more inauspicious patient outcomes.... (Review)
Review
OBJECTIVE
Despite the relatively high cure rates in early-stage breast cancer, advanced and metastatic breast cancer cases are associated with more inauspicious patient outcomes. Fortunately, with the advent of cyclin-dependent kinase (CDK)4/6 inhibitors (e.g. palbociclib, ribociclib, and abemaciclib) with endocrine therapy, survival in advanced and metastatic breast cancer has appreciably improved. In the current review, we discuss these distinctions and the concomitant implications associated with the individual CDK4/6 inhibitors.
DATA SOURCES
We conducted an extensive PubMed search comprising several review articles on the topic of advanced or metastatic breast cancer treatment, with specific terms that included CDK4/6 inhibitors, treatment, and breast cancer.
DATA SUMMARY
Palbociclib, ribociclib, and abemaciclib have exhibited superior progression-free survival differences compared to endocrine therapy alone. However, there are differences among the various CDK4/6 inhibitors with regard to overall survival, tolerability and quality of life.
CONCLUSIONS
Ribociclib may be indicated for pre/perimenopausal patients, whereas abemaciclib is potentially recommended to address endocrine-resistant or visceral disease. Alternatively, palbociclib is associated with lower discontinuation rates than abemaciclib and unlike ribociclib, QTc prolongation is not observed with palbociclib.
Topics: Humans; Breast Neoplasms; Cyclin-Dependent Kinase 6; Cyclin-Dependent Kinase 4; Female; Protein Kinase Inhibitors; Aminopyridines; Benzimidazoles; Piperazines; Neoplasm Metastasis; Purines; Quality of Life; Pyridines; Progression-Free Survival; Antineoplastic Agents
PubMed: 38404005
DOI: 10.1177/10781552241232701 -
Nutrition Reviews Sep 2023Sleep disturbances are a core symptom of menopause, which refers to the permanent cessation of menstrual periods. Nutritional interventions may alleviate...
CONTEXT
Sleep disturbances are a core symptom of menopause, which refers to the permanent cessation of menstrual periods. Nutritional interventions may alleviate menopause-related sleep disturbances, as studies have shown that certain interventions (eg, tart cherry juice, or tryptophan-rich foods) can improve relevant aspects of sleep.
OBJECTIVE
The aim of this systematic review was to examine the effect of nutritional interventions for menopause-related sleep disturbances, in order to inform the subsequent development of specific interventional trials and assess their potential as a treatment for menopause-related sleep disturbances.
DATA SOURCES
Published studies in English were located by searching PubMed and PsycArticles databases (until September 15, 2022).
DATA EXTRACTION
Following full-text review, a final total of 59 articles were included. The search protocol was performed in accordance with PRISMA guidelines.
DATA ANALYSIS
A total of 37 studies reported that a nutritional intervention improved some aspect of sleep, and 22 studies observed no benefit. Most (n = 24) studies recruited postmenopausal women, 18 recruited menopausal women, 3 recruited perimenopausal women, and 14 recruited women from multiple groups. The majority of the studies were of low methodological quality. Due to the heterogeneity of the studies, a narrative synthesis without meta-analysis is reported.
CONCLUSION
Despite the large heterogeneity in the studies and choice of intervention, the majority of the identified studies reported that a nutritional intervention did benefit sleep, and that it is mainly subjective sleep that is improved. More high-quality, adequately powered, randomized controlled trials of the identified nutritional interventions are necessary.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO registration no. CRD42021262367.
PubMed: 37695299
DOI: 10.1093/nutrit/nuad113 -
Journal of Affective Disorders Jul 2024For many women, menopause transition can be a period of emotional and physical changes, with different menopausal stages associated with varied risk for depressive... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
For many women, menopause transition can be a period of emotional and physical changes, with different menopausal stages associated with varied risk for depressive symptoms and diagnosis. This review aimed to conduct a systematic review and meta-analyses to provide an estimate for the risk of developing a) clinical depression and b) depressive symptoms at different menopausal stages.
METHODS
We searched Medline, PsycInfo, Embase and Web of Science from inception to July 2023. Seventeen prospective cohort studies with a total of 16061 women were included in the review, and risk of bias was assessed using the Quality in Prognosis Studies tool (QUIPS). Seven papers with a total of 9141 participants were included in meta-analyses, using random effects models and pooled odds ratios (OR) calculated for depressive symptoms and diagnoses.
RESULTS
Perimenopausal women were found to be at a significantly higher risk for depressive symptoms and diagnoses, compared to premenopausal women (OR = 1.40; 95 % CI: 1.21; 1.61, p < .001). We did not find a significantly increased risk for depressive symptoms or diagnoses in post-menopausal, compared to pre-menopausal women.
LIMITATIONS
Studies used different criteria to classify the menopausal stages and different measures for depression, which may have contributed to the heterogeneity seen in some models. We were unable to include a model that compared peri to post-menopause, due to a lack of longitudinal studies comparing the two stages.
CONCLUSIONS
The risk of depression in perimenopause, shown in an ethnically diverse sample; highlights the clinical need for screening and support in this potentially vulnerable group.
Topics: Humans; Female; Menopause; Depression; Risk Factors; Middle Aged; Perimenopause; Premenopause
PubMed: 38642901
DOI: 10.1016/j.jad.2024.04.041 -
Journal of Women's Health (2002) Mar 2024The levels of oxidative stress and proinflammatory factors in perimenopausal females increased, and they were also deeply troubled by insomnia. The occurrence of...
The levels of oxidative stress and proinflammatory factors in perimenopausal females increased, and they were also deeply troubled by insomnia. The occurrence of insomnia is related to the changes of oxidative stress and inflammation levels in the body. Perimenopausal insomnia may be related to mild systemic inflammation, and oxidative stress can promote chronic inflammation. However, the underlying mechanism behind the phenomenon is still unclear. The aim was to investigate whether the occurrence of perimenopausal insomnia disorder is related to higher levels of oxidative stress and inflammation in the body, and to explore the role of inducible nitric oxide synthase (iNOS) in perimenopausal insomnia. A total of 127 perimenopausal participants were recruited in this study. Participants with global scores of the Pittsburgh sleep quality index (PSQI) >7 were diagnosed with insomnia ( = 54). The patient health questionnaire-9 (PHQ-9) and generalized anxiety disorder-7 (GAD-7) were evaluated, and sociodemographic data were obtained. The serum concentrations of iNOS, interleukin 6 (IL6), and tumor necrosis factor α (TNFα) were measured using commercial assays. In the insomnia group, IL6 levels were positively correlated with scores of component 5 and component 7 of PSQI, respectively. PHQ-9 and GAD-7 were positively correlated with the global score of PSQI component 7 and PSQI, respectively; PHQ-9 was positively correlated with the global score of PSQI component 1. Finally, PHQ-9, iNOS, and IL6 were found to be independent predictors of perimenopausal insomnia using logistic regression. Moderate oxidative stress caused by a certain concentration of iNOS plays a protective role in perimenopausal insomnia, while proinflammation and depression are potential risk factors.
Topics: Female; Humans; Sleep Initiation and Maintenance Disorders; Perimenopause; Interleukin-6; Patient Health Questionnaire; Inflammation
PubMed: 38394165
DOI: 10.1089/jwh.2023.0316 -
International Urogynecology Journal May 2024The aim of this review is to discuss the link between menopause and nocturia and to give an overview of the increasing prevalence, risk factors, causative factors,... (Review)
Review
INTRODUCTION AND HYPOTHESIS
The aim of this review is to discuss the link between menopause and nocturia and to give an overview of the increasing prevalence, risk factors, causative factors, treatment needs and options for nocturia in peri-menopausal women.
METHODS
This opinion article is a narrative review based on the expertise and consensus of a variety of key opinion leaders, in combination with an extensive literature review. This literature search included a thorough analysis of potential publications on both the PubMed Database and the Web of Science and was conducted between November 2022 and December 2022. The following key words were used "nocturia" and "menopause" or "nocturnal frequency and menopause." Moreover, key words including "incidence," "prevalence," "insomnia," "estrogen therapy," "metabolic syndrome," and "hot flushes" were used in combination with the aforementioned key words. Last, the reference lists of articles obtained were screened for other relevant literature.
RESULTS
The perimenopause can be a trigger for inducing nocturia. Typically, obesity, body mass index (BMI), and waist circumference are risk factors for developing peri-menopausal nocturia. Presumably the development of peri-menopausal nocturia is multifactorial, with interplay among bladder, sleep, and kidney problems due to estrogen depletion after the menopause. First, impaired stimulation of estrogen receptors in the urogenital region leads to vaginal atrophy and reduced bladder capacity. Moreover, menopause is associated with an increased incidence of overactive bladder syndrome. Second, estrogen deficiency can induce salt and water diuresis through blunted circadian rhythms for the secretion of antidiuretic hormone and the activation of the renin-angiotensin-aldosterone system. Additionally, an increased incidence of sleep disorders, including vasomotor symptoms and obstructive sleep apnea signs, is observed. Oral dryness and a consequent higher fluid intake are common peri-menopausal symptoms. Higher insulin resistance and a higher risk of cardiovascular diseases may provoke nocturia. Given the impact of nocturia on general health and quality of life, bothersome nocturia should be treated. Initially, behavioral therapy should be advised. If these modifications are inadequate, specific treatment should be proposed. Systemic hormone replacement is found to have a beneficial effect on nocturia, without influencing sodium and water clearance in patients with nocturnal polyuria. It is presumed that the improvement in nocturia from hormonal treatment is due to an improvement in sleep disorders.
Topics: Humans; Nocturia; Female; Menopause; Risk Factors; Middle Aged; Prevalence; Incidence; Estrogen Replacement Therapy; Metabolic Syndrome; Obesity; Hot Flashes
PubMed: 38436669
DOI: 10.1007/s00192-024-05743-1