Decline In Estrogen Levels Research Articles

The Effects of Polyphenols on Bone Metabolism in Postmenopausal Women: Systematic Review and Meta-Analysis of Randomized Control Trials.

Osteoporosis is a condition favored by the postmenopausal decline in estrogen levels and worsened by oxidative stress (OS). Polyphenols are natural compounds abundantly found in fruits and vegetables, and they exert antioxidant and hormonal effects that could be useful in osteoporosis prevention, as suggested by epidemiological studies showing a lower incidence of fractures in individuals consuming polyphenol-rich diets. The aim of our meta-analysis is to evaluate the effects of polyphenols on bone mineral density (BMD, primary endpoint) and bone turnover markers (BTMs, secondary endpoint) in postmenopausal women. Twenty-one randomized control trials (RCTs) were included in our analysis after in-depth search on PubMed, EMBASE, and Scopus databases. We found that supplementation with polyphenols for 3-36 months exerted no statically significant effects on BMD measured at lumbar spine (sMD: 0.21, 95% CI [-0.08 to 0.51], p = 0.16), femoral neck (sMD: 0.16, 95% CI [-0.23 to 0.55], p = 0.42), total hip (sMD: 0.05, 95% CI [-0.14 to 0.24], p = 0.61), and whole body (sMD: -0.12, 95% CI [-0.42 to 0.17], p = 0.41). Subgroup analysis based on treatment duration showed no statistical significance, but a significant effect on lumbar BMD emerged when studies with duration of 24 months or greater were analyzed separately. On the other hand, we found a significantly slight increase in bone-specific alkaline phosphatase (BALP) levels (sMD: 1.27, 95% CI [1.13 to 1.42], p < 0.0001) and a decrease in pyridinoline (PD) levels (sMD: -0.58, 95% CI [-0.77 to -0.39], p < 0.0001). High heterogeneity among studies and unclear risk of bias in one third of the included studies emerged. A subgroup analysis showed similar effects for different duration of treatment and models of dual-energy X-ray absorptiometry (DXA) scanner. More robust evidence is needed before recommending the prescription of polyphenols in clinical practice.

Effect of Vitamin D on the Proliferation and Barrier of Atrophic Vaginal Epithelial Cells.

Atrophic vaginitis is very common in postmenopausal women due to declining estrogen levels. Vitamin D plays an important role in promoting epithelial cell proliferation, migration and adhesion. We established a rat model of ovariectomy (OVX) induced atrophic vaginitis with the aim of investigating the effects of Vitamin D supplementation on the vaginal epithelial barrier. The results showed that ovariectomised rats had significantly higher vaginal pH, reduced Lactobacillus, significantly lower uterine and vaginal weights, and lower vaginal epithelial PCNA, occludin, and E-cadherin mRNA expression compared with sham-operated rats. Vitamin D supplementation could reduce the vaginal pH, promote the proliferation and keratinization of vaginal epithelial cells, enhance the expression of PCNA mRNA in vaginal tissues, and improve the vaginal and uterine atrophy. Vitamin D can also increase the expression of E-cadherin and occludin proteins in vaginal tissues, maintain the integrity of the vaginal epithelium, increase the number of Lactobacillus, and reduce pathogenic bacterial infections. In vitro experiments demonstrated that 1,25(OH)2D3 could promote the proliferation and migration of VK2/E6E7 vaginal epithelial cells and increase the expression of E-cadherin protein. In conclusion, we demonstrated that Vitamin D can regulate the expression of vaginal epithelial tight junction proteins, promotes cell proliferation, and improves vaginal atrophy due to estrogen deficiency.

Beyond hot flashes: Exploring the role of estrogen therapy in postmenopausal women for myocardial infarction prevention and recovery.

Myocardial infarction (MI) commonly known as "heart attack" results from the blockage of blood flow to the heart. Postmenopausal women face an elevated risk of MI due to declining estrogen levels, a hormone pivotal in maintaining cardiovascular health. It promotes vasodilation, reduce inflammation, and improves lipid profiles. While estrogen therapy shows promise in mitigating MI risk for postmenopausal woman, its efficacy in prevention and recovery remains a subject of debate. This review provides a critical assessment of existing evidence on estrogen therapy's cardioprotective effects for postmenopausal women. It delves into estrogen's role in vascular function enhancement, inflammation reduction, and lipid metabolism modulation. Additionally, it addresses the various forms of estrogen therapy, administration methods, dosage considerations, safety implications, and associated risks. The review highlights the existing controversies and knowledge gaps related to estrogen therapy for MI prevention. It underscores the urgency for in-depth research to decipher the nexus between estrogen therapy and MI risk, especially concerning primary prevention and specific postmenopausal subgroups. Future studies should investigate optimal formulations, doses, and administration routes of estrogen therapy as well as assess treatment timing and duration. Comparative studies and long-term follow-up are necessary to inform clinical decision-making and improve patient care. Addressing these research gaps will empower clinicians to make more judicious choices about estrogen therapy for MI prevention and recovery in postmenopausal women, aiming for enhanced patient outcomes.

The Impact of Menopause on Cardiovascular Aging: A Comprehensive Review of Androgen Influences.

Menopause represents a critical life stage in women, characterized by hormonal changes that significantly impact cardiovascular health. While the decline in estrogen levels has long been recognized as a major contributor to cardiovascular aging in menopausal women, the role of androgens, particularly testosterone, has gained increasing attention in recent years. This comprehensive review aims to provide a thorough understanding of the impact of menopause on cardiovascular aging, with a specific focus on the influences of androgens. A literature search was conducted to gather relevant studies and clinical evidence exploring the relationship between menopause, androgens, and cardiovascular health. The review integrates findings from various studies to present a holistic view of the topic. The review outlines the changes in hormone levels during menopause and discusses the cardiovascular risk factors associated with this transition. Furthermore, it explores the impact of menopause on cardiovascular structure and function, elucidating the underlying mechanisms that contribute to cardiovascular aging. Androgens' significance in maintaining cardiovascular homeostasis is discussed, followed by exploring the effects of androgen decline during menopause on lipid profiles, insulin sensitivity, vascular function, and other cardiovascular parameters. The review delves into the mechanisms of androgen action on the cardiovascular system, emphasizing the role of androgen receptors and the intricate interplay between androgens, estrogens, and other hormones. Clinical evidence supporting the effects of androgens on cardiovascular aging is presented, including studies investigating the association between androgen levels and cardiovascular outcomes. Additionally, the impact of androgen replacement therapy (ART) on cardiovascular risk markers and events in menopausal women is examined, along with controversies and conflicting findings surrounding the use of androgen therapy in cardiovascular aging. This structured review provides a comprehensive understanding of the impact of menopause on cardiovascular aging, with a specific focus on the role of androgens. By highlighting the significance of androgens in cardiovascular health during menopause, this review aims to create an initial impression and interest among readers, inviting potential citations in the future. The findings underscore the need for further research and offer insights into managing cardiovascular aging in menopausal women, including lifestyle interventions, pharmacological approaches, and the potential role of personalized medicine and precision therapies.

Linkage of premature and early menopause with psychosocial well-being: a moderated multiple mediation approach

PurposeMenopause occurring before the age of 40 is premature and between 40 and 44 years age is early, since the natural age of menopause lies between 45 and 50. The endocrine changes that come with menopause include an erratic decline in estrogen levels which affects the brain. Thus, leading to changes in cognitive function in the longer term due to the menopausal transition. The study aims to explore the effect of premature and early menopause on cognitive health, and psychosocial well-being. The moderated multiple mediation hypothesis of the study is that the effect of premature or early menopause is mediated by depression and insomnia, while all the pathways are moderated by smoking habits.Data and MethodsThe study utilized Longitudinal Aging Study in India (LASI), 2017–2018, Wave 1 data. The sample of 31,435 women were aged 45 and above and did not undergo hysterectomy. A moderated multiple mediation model was used to understand the association between premature or early menopause (X), insomnia (M1), depression (M2), moderator (W), and cognitive health (Y), while controlling for possible confounders.ResultsPremature menopause was negatively associated with cognition (β:-0.33; SE:0.12; p < 0.05), whereas positively associated with insomnia (β:0.18; SE:0.03; p < 0.001) and depression (β:0.25; SE:0.04; p < 0.001). There is a moderating effect of smoking or tobacco consumption has a significant moderating effect on the pathways among premature menopause, depression, insomnia and cognition. When the same model was carried out for early menopause (40–44 years), the results were not significant.ConclusionsThe findings emphasize the fact that smoking is associated with premature menopause, depression and insomnia. Women who experienced premature menopause has lower cognitive scores, depressive symptoms and insomnia symptoms, which were higher among those who consumed tobacco. The study, strongly recommends the dissemination of information on the negative effects of tobacco consumption and making more informed choices to maintain a healthy life. More research into various methods and therapy is needed to determine the relationship between the age of early menopause and their psychosocial well-being.

Neuroprotective Potential of Raloxifene via G-Protein-Coupled Estrogen Receptors in Aβ-Oligomer-Induced Neuronal Injury.

Amyloid-β (Aβ) is one of the causes of Alzheimer's disease (AD), damaging nerve membranes and inducing neurotoxicity. AD is more prevalent in female patients than in male patients, and women are more susceptible to developing AD due to the decline in estrogen levels around menopause. Raloxifene, a selective estrogen receptor modulator, exhibits protective effects by activating the transmembrane G-protein-coupled estrogen receptor (GPER). Additionally, raloxifene prevents mild cognitive impairment and restores cognition. However, the influence of raloxifene via GPER on highly toxic Aβ-oligomers (Aβo)-induced neurotoxicity remains uncertain. In this study, we investigated the GPER-mediated neuroprotective effects of raloxifene against the neurotoxicity caused by Aβo-induced cytotoxicity. The impact of raloxifene on Aβo-induced cell damage was evaluated using measures such as cell viability, production of reactive oxygen species (ROS) and mitochondrial ROS, peroxidation of cell-membrane phospholipids, and changes in intracellular calcium ion concentration ([Ca2+]i) levels. Raloxifene hindered Aβo-induced oxidative stress and reduced excessive [Ca2+]i, resulting in improved cell viability. Furthermore, these effects of raloxifene were inhibited with pretreatment with a GPER antagonist. Our findings suggest that raloxifene safeguards against Aβo-induced neurotoxicity by modifying oxidative parameters and maintaining [Ca2+]i homeostasis. Raloxifene may prove effective in preventing and inhibiting the progression of AD.

The role of vitamin D in menopausal women's health.

Vitamin D (VD) is known to play an important role in the maintenance of calcium homeostasis and bone metabolism. In recent years, there has also been a growing interest in Vitamin D for health issues beyond the bones. Menopausal women are at risk of reduced bone density and increased risk of fracture due to a decline in estrogen levels. There is also an increased risk of cardiovascular disease, diabetes and hyperlipidaemia due to impaired lipid metabolism. The menopausal and emotional symptoms due to menopause are also increasingly prominent. This article summarizes the role of Vitamin D in menopausal women's health, including the effects of Vitamin D on skeletal muscle, cardiovascular disease, Genitourinary Syndrome of Menopause (GSM), cancer and emotional symptoms. Vitamin D regulates the growth of vaginal epithelial cells and alleviates genitourinary tract problems in menopausal women. Vitamin D also modulates immune function and influences the production of adipokines. Vitamin D and its metabolites also have an anti-proliferative effect on tumour cells. This narrative review, by summarizing recent work on the role of Vitamin D in menopausal women and in animal models of menopause, aims to provide a basis for further development of the role of Vitamin D in the health of menopausal women.

Estrogen-regulated miRs in bone enhance osteoblast differentiation and matrix mineralization

Estrogen signaling is critical for the development and maintenance of healthy bone, and age-related decline in estrogen levels contributes to the development of post-menopausal osteoporosis. Most bones consist of a dense cortical shell and an internalmesh-like network of trabecular bone that respond differently to internal and external cues such as hormonal signaling. To date, no study has assessed the transcriptomic differences that occur specifically in cortical and trabecular bone compartments in response to hormonal changes. To investigate this, we employed a mouse model of post-menopausal osteoporosis (ovariectomy, OVX) and estrogen replacement therapy (ERT). mRNA and miR sequencing revealed distinct transcriptomic profiles between cortical and trabecular bone in the setting of OVX and ERT. Seven miRs were identified as likely contributors to the observed estrogen-mediated mRNA expression changes. Of these, four miRs were prioritized for further study and decreased predicted target gene expression in bone cells, enhanced the expression of osteoblast differentiation markers, and altered the mineralization capacity of primary osteoblasts. As such, candidate miRs and miR mimics may have therapeutic relevance for bone loss resulting from estrogen depletion without the unwanted side effects of hormone replacement therapy and therefore represent novel therapeutic approaches to combat diseases of bone loss.

(002) The Effects of Vaginal Testosterone versus Placebo on Female Sexual Function: Interim Analysis of the PIVoT Trial (Prevention of Recurrent Urinary Tract Infection using Vaginal Testosterone)

Abstract Introduction Post-menopasual women experience changes in vaginal flora and vaginal atrophy that have been associated with declining estrogen levels. These changes to the vaginal microenvironment often lead to significant genital pain and discomfort during sexual intercourse. Vaginal estrogen treats atrophy thereby restoring flora, which prevents UTIs and improves sexual function in post-menopausal women. While estrogen is effective, some patients have contraindications or are unwilling to use it. Vaginal testosterone cream (VT) has been shown to improve vaginal atrophy, however, its effects on overall vaginal health and sexual function have not been fully described. Objective The purpose of this study was to determine if VT is more effective than placebo cream in restoring the vaginal flora, improving the vaginal health index (VHI), and the sexual function of postmenopausal women with recurrent UTIs. Methods This is an interim analysis of a randomized, double- blind placebo-controlled pilot study enrolling postmenopausal women with recurrent UTIs. Vaginal health index (VHI) and swab to assess flora via DNA sequencing were collected. Patients were randomized to VT or placebo. Female sexual function index (FSFI) questionnaires were administered at baseline, one month, and nine months post treatment. Results A total of 44 women have been enrolled. Average VHI at enrollment was 13.66 +/− 0.4. There was no difference in baseline characteristics among the groups. Results show an improvement in female sexual function index scores in both groups from baseline. In the VT arm, improvements were seen in the desire (2.18 to 2.85), lubrication (1.74 to 2.175), orgasm (1.64 to 2.5) and pain (0.91 to 1.3) domains of the FSFI. Interestingly, improvements in all domains were seen in the placebo group, however, more patients in this group reported being sexually active. In terms of VHI, there was a statistically significant increase in VHI scores at 9 months post-treatment with VT (14.65 +/−4.20 to 17.50 +/− 4.43, p = 0.04). This increase in vaginal health index was not observed in the placebo arm. Conclusions Initial data demonstrates improvement in vaginal pH and VHI after 9 months of treatment with VT. Improvement in sexual function scores were also seen in both the treatment and the placebo groups. Higher patient enrollment and longer treatment follow up will be valuable in understanding the effects of VT versus placebo on sexual function among postmenopausal women. Disclosure No

Early Natural Menopause Is Associated With Poor Lung Health and Increased Mortality Among Female Smokers

ABSTRACT Menopause results from the decline of estrogen levels and is driven by ovarian aging. Some tissues, including the lung, may contribute to local estrogen synthesis in the postmenopausal state. Cigarette smoking is the most established factor for early menopause, and previous studies have shown that the menopause transition accelerated age-related decline of lung function following a restrictive disease pattern. In addition, studies have supported a potential synergistic effect of cigarette smoking and menopause on lung function. Delineating the effect of menopause timing and estrogen exposure on subsequent disease development may have important benefits for health maintenance and disease prevention in older women. This study aimed to assess the associations between early menopause and lung biomarkers, lung cancer risk, and cause-specific mortality. Data were obtained from the Pittsburg Lung Screening Study, a community-based research cohort of current and former smokers screened with low-dose computed tomography (CT) at baseline and 1 year later. Menstrual and reproductive history and data on respiratory symptoms were collected through questionnaires. Radiographic emphysema score was calculated from the baseline CT scan. Early menopause was defined as age at menopause of &lt;45 years. The study cohort included female Pittsburg Lung Screening Study participants who reported natural (n = 1038) or surgical (n = 628) menopause at study entry. A total of 1064 participants (63.9%) were current smokers with an average pack-years of 46.1 ± 19.8 at baseline. Early menopause was associated with several pathologies including self-reported wheezing (odds ratio [OR], 1.65; 95% confidence interval [CI], 1.18–2.30; P &lt; 0.01), chronic bronchitis (OR, 1.73; 95% CI, 1.19–2.53; P &lt; 0.01), cardiovascular diseases (OR, 1.87; 95% CI, 1.13–3.11; P = 0.02), radiographic emphysema (OR, 1.70; 95% CI, 1.25–2.31; P &lt; 0.001), and incident airway obstruction (OR, 2.02; 95% CI, 1.03–3.96; P = 0.04) in women with natural menopause, but not surgical menopause except for physician-diagnosed cardiovascular diseases (OR, 4.03; 95% CI, 1.78–9.14; P &lt; 0.001). Trend tests for each of these outcomes in women with natural menopause identified monotonically increasing risk associated with younger age at menopause. Early menopause was associated with lower measurements of the lung function measurements forced expiratory volume in 1 second (FEV1; −104.8 ± 36.7 mL/s; P &lt; 0.01), forced vital capacity (FVC; −78.6 ± 38.2 mL; P = 0.04), and FEV1-to-FVC ratio (−2.1% ± 0.8%; P = 0.01) at baseline in women with natural menopause but not surgical menopause. The use of hormone therapy at any point was associated with higher baseline FEV1 levels and higher FEV1-to-FVC ratio at baseline among women with natural menopause. Early natural menopause was associated with a 40% increased risk of all-cause death with respiratory diseases (hazard ratio [HR], 2.32; 95% CI, 1.52–3.52; P &lt; 0.001), and early menopause was associated with twice the risk of lung cancer-specific mortality (HR, 1.94; 95% CI, 1.05–3.58; P = 0.03). This association was exacerbated by continuous cigarette smoking, with HRs of 4.65 (95% CI, 2.55–8.49; P &lt; 0.001) and 4.61 (95% CI, 2.63–8.07; P &lt; 0.001) for lung cancer and cancer mortality, respectively, among continuous smokers with early menopause compared with women with noncontinuous smoking and nonearly menopause. The results of this study demonstrate that among a postmenopausal cohort of middle-aged and older smokers, natural early menopause is associated with worse lung health and accelerated lung aging.

Estrogens in Adipose Tissue Physiology and Obesity-Related Dysfunction.

Menopause-related decline in estrogen levels is accompanied by a change in adipose tissue distribution from a gynoid to an android and an increased prevalence of obesity in women. These unfavorable phenomena can be partially restored by hormone replacement therapy, suggesting a significant role for estrogen in the regulation of adipocytes' function. Indeed, preclinical studies proved the involvement of these hormones in adipose tissue development, metabolism, and inflammatory activity. However, the relationship between estrogen and obesity is bidirectional. On the one hand-their deficiency leads to excessive fat accumulation and impairs adipocyte function, on the other-adipose tissue of obese individuals is characterized by altered expression of estrogen receptors and key enzymes involved in their synthesis. This narrative review aims to summarize the role of estrogen in adipose tissue development, physiology, and in obesity-related dysfunction. Firstly, the estrogen classification, synthesis, and modes of action are presented. Next, their role in regulating adipogenesis and adipose tissue activity in health and the course of obesity is described. Finally, the potential therapeutic applications of estrogen and its derivates in obesity treatment are discussed.

Menopause, skin and common dermatoses. Part 4: oral disorders.

The physiological impact of declining oestrogen levels during menopause has been well documented. We conducted a literature review to assess the impact of menopause on oral health. Falling oestrogen levels are associated with adverse effects on the gingival, oral and buccal epithelia. The symptoms prevalent in perimenopausal and postmenopausal women range from dry mouth to immune-mediated mucocutaneous disease and burning mouth syndrome. Our review has highlighted the need for further research into potential treatments for oral symptoms in menopause, particularly with regard to hormone replacement therapy.

Efficacy of Non-Soy Isoflavone (Pueraria phaseoloides) on The Symptoms Severity Scoring by Kupperman Index in Menopausal Women

Introduction: Menopause is defined by a decline in estrogen levels, which causes various symptoms. Treatments based on foods or supplements enriched in phytoestrogens, notably isoflavones, plant-derived compounds with estrogenic effects, have recently become quite popular. This study aims to see how effective non-soy isoflavone supplementation is for menopausal symptoms in women. Methods: 26 menopausal women were given 67.5 mg of non-soy isoflavone, and 25 menopausal women were given a placebo daily for 12 weeks in an analytical double-blind, randomized clinical trial (RCT). Inclusion criteria were (1) RCT, (2) perimenopausal or postmenopausal women experiencing menopausal symptoms, (3) intervention with an oral non-soy isoflavone. Symptoms Severity Score (SSS) based on the Kupperman index (KI) questionnaire was administered to the patients before starting and at the end of the study. The Statistical Package for Social Sciences (SPSS) software was used to analyze the responses. Results: The difference in SSS scores between the treatment and control groups was significant (p = 0.000). Women receiving 67.5 mg of non-soy isoflavone daily, reduced myalgia, fatigue, and hot flushes by 92.3%, 77%, and 53.8%, respectively. For clinical significance rating, relative risk reduction (RRR) is used. A significant RRR value resulted from myalgia symptoms (76.6%), fatigue (55.7%), hot flushes (39.2%), and SSS (68.7%). Conclusion: Isoflavones did not bring a significant change in Kupperman Index compared to placebo but provided significantly improved Symptoms Severity Scoring in menopausal women.

Anti-Inflammatory and Anti-oxidative Effects of Puerarin in Postmenopausal Cardioprotection: Roles of Akt and Heme Oxygenase-1.

During menopause, the sharp decline in estrogen levels leads to an increased risk of cardiovascular disease in women. The inflammatory response and oxidative stress are reportedly involved in the development of cardiovascular disorders postmenopause. In this study, we evaluated the cardioprotective effects of puerarin, a phytoestrogen derived from the root of Pueraria lobate, and investigated its underlying molecular mechanisms. Puerarin alleviated cytotoxicity and the production of reactive oxygen species (ROS) in lipopolysaccharide (LPS)- and hydrogen peroxide-stimulated H9c2 cardiomyoblasts. Puerarin scavenges free radicals and reduces apoptosis, thereby suppressing NADPH oxidase-1 and Bax activation to attenuate the production of ROS and restore Bcl-2 expression. Additionally, puerarin inhibited the expression of inducible nitric oxide synthase, cyclooxygenase-2, and nitric oxide production and decreased the hypertrophic phenotype under LPS stimulation. Treatment with puerarin reduced the levels of malondialdehyde and restored glutathione levels when facing oxidative stress. Mechanistically, puerarin inhibited both the LPS-induced Toll-like receptor 4/NF-[Formula: see text]B and mitogen-activated protein kinase signaling pathways. Furthermore, it reversed both the LPS-mediated downregulation of Akt activation and heme oxygenase-1 (HO-1) expression. The cardioprotective effects of puerarin were abolished by inhibitors of Akt and HO-1 and the estrogen receptor antagonist fulvestrant (ICI). This indicated that the estrogen receptor mediated by these two molecules plays important roles in conferring the anti-inflammatory and anti-oxidative functions of puerarin. These results demonstrate the therapeutic potential of puerarin for treating heart disease in postmenopausal women through Akt and HO-1 activation.

GPER limits adverse changes to Ca2+ signalling and arrhythmogenic activity in ovariectomised guinea pig cardiomyocytes.

Background: The increased risk of post-menopausal women developing abnormalities of heart function emphasises the requirement to understand the effect of declining oestrogen levels on cardiac electrophysiology and structure, and investigate possible therapeutic targets, namely the G protein-coupled oestrogen receptor 1 (GPER). Methods: Female guinea pigs underwent sham or ovariectomy (OVx) surgeries. Cardiomyocytes were isolated 150-days post-operatively. Membrane structure was assessed using di-8-ANEPPs staining and scanning ion conductance microscopy. Imunnohistochemistry (IHC) determined the localisation of oestrogen receptors. The effect of GPER activation on excitation-contraction coupling mechanisms were assessed using electrophysiological and fluorescence techniques. Downstream signalling proteins were investigated by western blot. Results: IHC staining confirmed the presence of nuclear oestrogen receptors and GPER, the latter prominently localised to the peri-nuclear region and having a clear striated pattern elsewhere in the cells. Following OVx, GPER expression increased and its activation reduced Ca2+ transient amplitude (by 40%) and sarcomere shortening (by 32%). In these cells, GPER activation reduced abnormal spontaneous Ca2+ activity, shortened action potential duration and limited drug-induced early after-depolarisation formation. Conclusion: In an animal species with comparable steroidogenesis and cardiac physiology to humans, we show the expression and localisation of all three oestrogen receptors in cardiac myocytes. We found that following oestrogen withdrawal, GPER expression increased and its activation limited arrhythmogenic behaviours in this low oestrogen state, indicating a potential cardioprotective role of this receptor in post-menopausal women.

The role of oestrogen in determining sexual dimorphism in energy balance.

Energy balance is determined by caloric intake and the rate at which energy is expended, with the latter comprising resting energy expenditure, physical activity and adaptive thermogenesis. The regulation of both energy intake and expenditure exhibits clear sexual dimorphism, with young women being relatively protected against weight gain and the development of cardiometabolic diseases. Preclinical studies have indicated that females are more sensitive to the satiety effects of leptin and insulin compared to males. Furthermore, females have greater thermogenic activity than males, whereas resting energy expenditure is generally higher in males than females. In addition to this, in post-menopausal women, the decline in sex steroid concentration, particularly in oestrogen, is associated with a shift in the distribution of adipose tissue and overall increased propensity to gain weight. Oestrogens are known to regulate energy balance and weight homeostasis via effects on both food intake and energy expenditure. Indeed, 17β-oestradiol treatment increases melanocortin signalling in the hypothalamus to cause satiety. Furthermore, oestrogenic action at the ventromedial hypothalamus has been linked with increased energy expenditure in female mice. We propose that oestrogen action on energy balance is multi-faceted and is fundamental to determining sexual dimorphism in weight control. Furthermore, evidence suggests that the decline in oestrogen levels leads to increased risk of weight gain and development of cardiometabolic disease in women across the menopausal transition.

Neuroprotective effects of combined therapy with memantine, donepezil, and vitamin D in ovariectomized female mice subjected to dementia model

Women older than 60 have a higher risk of dementia, aging-related cognitive decline, and Alzheimer's Disease (AD) than the rest of the population. The main reason is hormonal senescence after menopause, a period characterized by a decline in estrogen levels. Since the effectiveness of drugs currently approved for the treatment of AD is limited, it is necessary to seek the development of new therapeutic strategies. Vitamin D deficiency is prevalent in AD patients and individuals with dementia in general. The supplementation of this vitamin in dementia patients might be an interesting approach for increasing the effectiveness of pre-existing medications for dementia treatment. Thus, the present study aims to investigate the effect of vitamin D treatment associated with memantine and donepezil in female mice submitted to ovariectomy (OVX) for five months and subjected to a dementia animal model induced by intracerebroventricular injection of aggregated amyloid βeta (Aβ1–42). For this purpose, Balb/c mice were divided into five experimental groups, which received 17 days of combined therapy with vitamin D, donepezil, and memantine. Then, animals were subjected to behavioral tests. OVX groups exhibited reduced levels of estradiol (E2) in serum, which was not altered by the combined therapy. Higher levels of vitamin D3 were found in the OVX animals submitted to the triple-association treatment. Mice exposed to both OVX and the dementia animal model presented impairment in short and long-term spatial and habituation memories. Also, female mice exposed to Aβ and OVX exhibited a reduction in brain-derived neurotrophic factor (BDNF) and interleukin-4 (IL-4) levels, and an increase in tumor necrose factor-α (TNFα) levels in the hippocampus. Besides, increased levels of IL-1β in the hippocampus and cerebral cortex were observed, as well as a significant increase in immunoreactivity for glial fibrillary acidic protein (GFAP), an astrocytes marker, in the hippocampus. Notably, triple-association treatment reversed the effects of the exposition of mice to Aβ and OVX in the long-term spatial and habituation memories impairment, as well as reversed changes in TNFα, IL-1β, IL-4, and GFAP immunoreactivity levels in the hippocampus of treated animals. Our results indicate that the therapeutic association of vitamin D, memantine, and donepezil has beneficial effects on memory performance and attenuated the neuroinflammatory response in female mice subjected to OVX associated with a dementia animal model.

Dietary Supplementation With Tinospora cordifolia Improves Anxiety-Type Behavior and Cognitive Impairments in Middle-Aged Acyclic Female Rats.

The midlife transition period in women marks the progressive flattening of neurological health along with increased adiposity, dyslipidemia, frailty, and inflammatory responses mainly attributed to the gradual decline in estrogen levels. Conflicting reports of hormone replacement therapy (HRT) necessitate the exploration of novel therapeutic interventions using bioactive natural products having the least toxicity and a holistic mode of action for the preservation of metabolic homeodynamics with aging in women. The present study was planned to investigate the effects of aging and/or a high-fat diet (HFD) on cognitive impairments and anxiety and further their management by dietary supplement with the Tinospora cordifolia stem powder (TCP). Acyclic female rats were included in this study as the model system of the perimenopause phase of women along with young 3–4 months old rats as controls. Rats were fed on with and without TCP supplemented normal chow or HFD for 12 weeks. Animals fed on a TCP supplemented normal chow showed consistent management of body weight over a 12-week regimen although their calorie intake was much higher in comparison to their age-matched controls. Post-regimen, neurobehavioral tests, such as novel object recognition and elevated plus maze, performed on these animals showed improvement in their learning and memory abilities as well as the anxiety-like behavior. Furthermore, due to the presence of multiple components, TCP was observed to modulate the expression of key marker proteins to ameliorate neuroinflammation and apoptosis and promote cell survival and synaptic plasticity in the hippocampus and the prefrontal cortex (PFC) regions of the brain. These findings suggest that TCP supplementation in diet during the midlife transition period in women may be a potential interventional strategy for the management of menopause-associated anxiety and cognitive impairments and healthy aging.

Endometriosis in women undergoing ovarian tissue transplantation due to premature menopause after gonadotoxic treatment or spontaneous premature ovarian failure.

Cryopreservation of ovarian tissue with subsequent transplantation is an efficient option for restoring fertility in women at risk of premature ovarian failure. The association between infertility and endometriosis is well recognized. Although endometriosis usually ends with the onset of natural or iatrogen menopause due to declining estrogen levels, endometriosis can in rare cases occur after menopause. This study aims to investigate women with premature menopause who were diagnosed with endometriosis during laparoscopy for ovarian tissue transplantation, and to address the questions of how endometriotic lesions after cytotoxic treatment and premature menopause might be explained, whether endometriosis affects pregnancy rates, and whether there is an association between endometriosis and the original cancer. Seventeen patients who had undergone ovarian tissue transplantation to restore their fertility and who were diagnosed with endometriosis during transplantation were included in this retrospective study. The endometriosis foci were completely removed and ovarian tissue was transplanted into the pelvic peritoneum. Preexisting conditions, use of hormonal preparations, endometriosis stage pain assessment, as well as pregnancy and live birth rate were evaluated. The mean age of the patients was 29.5 ± 6.3 years (range 14-39) at the time of ovarian tissue harvest and 34.6 ± 4.3 years (range 28-40) at transplantation. Prior to transplantation, four patients had taken hormone replacement therapy, four women oral contraceptives and two patients' tamoxifen. Twelve women had stage I endometriosis and five stage II endometrioses according to the rASRM classification. Four patients reported dysmenorrhea. None of the women complained of general pelvic pain or dyspareunia. The pregnancy rate in the study population was 41.2%, with a live birth rate of 35.3%. The pregnancies occurred in three cases after spontaneous conception, in four women after a natural cycle IVF/ICSI. This study highlights the under-researched association between endometriosis in women entering premature or early menopause either after gonadotoxic treatment or due to primary ovarian insufficiency. As more and more patients seek to have their cryopreserved ovarian tissue transplanted to fulfill their desire to have children, specialists will inevitably encounter women with this condition.

Follicle stimulating hormone promotes production of renin through its receptor in juxtaglomerular cells of kidney

BackgroundPost-menopausal hypertension has been attributed solely to declining estrogen levels. The purpose of the research is to elucidate the mechanism by which follicle stimulating hormone(FSH) increases renin production involved in the regulation of blood pressure.MethodsThe expression of follicle stimulating hormone receptors (FSHRs) in renal juxtaglomerular cells and a As4.1 juxtaglomerular mouse cell line was evaluated. We established a mouse model by ovariectomy (OVX). Ovariectomized mice were treated with gonadotropin-releasing hormone agonist (GnRHa) (OVX + GnRHa). Ovariectomized mice initially received physiological doses of estrogen and were then injected with recombinant FSH (OVX + E + FSH).ResultsWe found that FSHR was expressed in mouse renal juxtaglomerular cells labeled by renin antibody and in As4.1 cells. FSH promoted renin synthesis via Gsα-coupled FSHRs that activated protein kinase A, cyclic adenosine monophosphate(cAMP) response element-binding protein, extracellular signal-regulated kinase (Erk1/2), Protein kinase B(AKT), and c-Jun N-terminal kinase signaling pathways in As4.1 cells. We found increased serum FSH levels in the ovariectomized mouse with concurrent increases in renin, angiotensin II, heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial blood pressure (MAP). Additionally, increases in serum renin, angiotensin II, HR, SBP, DBP, and MAP were reduced by the additional injection of GnRHa. Exogenous FSH administration completely reversed decreases in renin, angiotensin II, HR, SBP, DBP, and MAP even in mice that received physiological doses of estrogen to maintain normal estradiol levels.ConclusionsElevated FSH stimulates renin production involving a mechanism that may be relevant to the expression of FSH receptors in renal juxtaglomerular cells.