Protective Effect Of Estrogen Research Articles

Therapeutic effects of platelet-derived extracellular vesicles on viral myocarditis correlate with biomolecular content.

Extracellular vesicles (EVs) can potently inhibit inflammation yet there is a lack of understanding about the impact of donor characteristics on the efficacy of EVs. The goal of this study was to determine whether the sex and age of donor platelet-derived EVs (PEV) affected their ability to inhibit viral myocarditis. PEV, isolated from men and women of all ages, was compared to PEV obtained from women under 50 years of age, which we termed premenopausal PEV (pmPEV). Because of the protective effect of estrogen against myocardial inflammation, we hypothesized that pmPEV would be more effective than PEV at inhibiting myocarditis. We injected PEV, pmPEV, or vehicle control in a mouse model of viral myocarditis and examined histology, gene expression, protein profiles, and performed proteome and microRNA (miR) sequencing of EVs. We found that both PEV and pmPEV significantly inhibited myocarditis; however, PEV was more effective, which was confirmed by a greater reduction of inflammatory cells and proinflammatory and profibrotic markers determined using gene expression and immunohistochemistry. Proteome and miR sequencing of EVs revealed that PEV miRs specifically targeted antiviral, Toll-like receptor (TLR)4, and inflammasome pathways known to contribute to myocarditis while pmPEV contained general immunoregulatory miRs. These differences in EV content corresponded to the differing anti-inflammatory effects of the two types of EVs on viral myocarditis.

Potential Regulation of the Long Non-Coding RNA Metastasis-Associated Lung Adenocarcinoma Transcript1 by Estrogen in Parkinson’s Disease

Parkinson’s disease (PD) is the second-leading cause of death among neurodegenerative disease after Alzheimer’s disease (AD), affecting around 2% of the population. It is expected that the incidence of PD will exceed 12 million by 2040. Meanwhile, there is a recognized difference in the phenotypical expression of the disease and response to treatment between men and women. Men have twice the incidence of PD compared to women, who have a late onset and worse prognosis that is usually associated with menopause. In addition, the incidence of PD in women is associated with the cumulative estrogen levels in their bodies. These differences are suggested to be due to the protective effect of estrogen on the brain, which cannot be given in clinical practice to improve the symptoms of the disease because of its peripheral side effects, causing cancer in both males and females in addition to the feminizing effect it has on males. As PD pathophysiology involves alteration in the expression levels of multiple LncRNAs, including metastatic-associated lung adenocarcinoma transcript 1 (MALAT1), and as estrogen has been illustrated to control the expression of MALAT1 in multiple conditions, it is worth investigating the estrogen–MALAT1 interaction in Parkinson’s disease to mimic its protective effect on the brain while avoiding its peripheral side effects. The following literature review suggests the potential regulation of MALAT1 by estrogen in PD, which would enhance our understanding of the pathophysiology of the disease, improving the development of more tailored and effective treatments.

Estrogen administration enhances the adverse effects of cigarette smoking on the heart in cycling female mice

Smoking, particularly chronic smoking (CS), is a threat to global health, contributing to increased mortality and morbidity associated with cardiovascular disease (CVD). CS induces oxidative stress and endothelial dysfunction, which has a profound impact on cardiac structure and function. While the protective effects of estrogen, particularly 17β-estradiol (E2), on cardiovascular health are well-documented in premenopausal women, the interaction between estrogen and CS remains poorly understood. The aim of this study is to investigate the impact of chronic cigarette smoking on cardiac health in relation to ethinylestradiol (EE) oral contraceptive (OC) usage in premenopausal females. Female mice were exposed to chronic cigarette smoke and co-administered EE. Cardiac structural and functional parameters were assessed alongside inflammatory markers, oxidative stress indicators, and histological changes. Results revealed that the combination of EE and CS led to adverse cardiac remodeling characterized by increased left ventricular end-diastolic volume and elevated left ventricular mass. In addition, an inflammatory state was evident, marked by increased expression of IL-4, IL-1β, IL-13, IL-10, and PARP-1, as well as increased interstitial collagen deposition. These findings suggest a progression towards adverse cardiac remodeling resembling dilated cardiomyopathy. Furthermore, our observations highlight the complexity of the inflammatory response triggered by smoking, potentially exacerbated by estrogen supplementation. The main finding of this study is that the combination of CS and EE enhanced adverse cardiac remodeling, which was shown structurally, histologically, and biochemically.

Unique cardiometabolic factors in women that contribute to modified cardiovascular disease risk.

Major risk factors of cardiovascular disease (CVD) include hypertension, obesity, diabetes mellitus and metabolic syndrome; all of which are considered inflammatory conditions. Women are disproportionately affected by inflammatory conditions, with sex differences emerging as early as adolescence. Hormonal fluctuations associated with reproductive events such as menarche, pregnancy and menopause, are hypothesized to promote a pro-inflammatory state in women. Moreover, women who have experienced inflammatory-type conditions such as polycystic ovarian syndrome (PCOS), gestational diabetes or pre-eclampsia, have a cardiometabolic phenotype that pre-disposes to increased risk of myocardial infarction, stroke and coronary heart disease. Women with no notable CVD risk factors are often relatively protected from CVD pre-menopause; but overtake men in risk of major cardiovascular events when the cardiovascular protective effects of oestrogen begin to wane. Sex differences and female-specific factors have long been considered challenging to study and this has led to an underrepresentation of females in clinical trials and lack of female-specific data from pre-clinical studies. However, there is now a clear prerogative to include females at all stages of research, despite inherent complexities and potential variability in data. This review explores recent advancements in our understanding of CVD in women. We summarise the underlying factors unique to women that can promote CVD risk factors, ultimately contributing to CVD burden and the emerging therapies aimed to combat this.

Estrogen receptors and vascular aging

After years of studying cardiovascular diseases (CVD) in men due to their higher incidence compared to women, attention is now being paid to female CVD and their pathophysiology. Even though premenopausal women have a lower incidence of CVD, this disparity progressively diminishes after menopause, highlighting the key role of sex hormones. Many preclinical and fundamental studies have demonstrated protective effects of estrogens on arterial endothelium, suggesting that hormone therapy could improve cardiovascular health in menopausal women. However, disappointing outcomes from a major clinical trial two decades ago questioned the cardiovascular protection by estrogens with age. In this review, we will summarize the main clinical and experimental studies reporting the effects of estrogens on CVD, with a focus on their impact on endothelial function. Then, we will present abnormalities in the expression and signaling of estrogen receptors (ERs) in the arteries, and the contribution of conventional estrogens to arterial protection during aging. Finally, we will examine how recent advances in the mechanisms of action of ERa could help to optimize hormone therapy for menopause.

Sex differences in pediatric sepsis—a systematic review protocol

BackgroundPediatric sepsis remains a leading cause of childhood morbidity and mortality worldwide. Despite advancements in modern medicine, it accounts for more than 3 million childhood deaths per year. Multiple studies have emphasized that sex and gender have an impact on the treatment and outcome of various diseases. Adult studies have revealed sex differences in pathophysiological responses to septic shock, as well as a possible protective effect of estrogens on critical illness. Sex-specific maturational and developmental differences in host immunology have been previously demonstrated for neonatal and pediatric age groups. At present, there are no studies assessing the impact of sex on outcomes of children with sepsis.MethodsThe goal of this study is to assess sex-specific differences in childhood sepsis survival outcomes. We will systematically assess associations of sex and gender with outcomes in pediatric sepsis in the literature by performing a systematic search of MEDLINE and Embase databases. We will include all English language randomized trials and cohort studies. The study population will include children > 37 weeks gestational age and < 18 years of age. Exposure will be sepsis, severe sepsis, and septic shock and the main comparison will be between male and female sex. The primary outcome will be hospital mortality. Secondary outcomes will be the pediatric intensive care unit and hospital length of stay.DiscussionResults from this review are expected to provide important information on the association of sex with the outcomes of pediatric sepsis. If an association is noted, this study may serve as a foundation for further research evaluating the pathophysiological aspects as well as potential socioeconomic factors responsible for the clinically detected sex differences.Systematic review registrationPROSPERO CRD42022315753.

Antipsychotic-induced prolactin elevation in premenopausal women with schizophrenia: associations with estrogen, disease severity and cognition

PurposeAntipsychotic-induced prolactin elevation may impede protective effects of estrogens in women with schizophrenia-spectrum disorders (SSD). Our study sought to confirm whether the use of prolactin-raising antipsychotics is associated with lower estrogen levels, and to investigate how estrogen and prolactin levels relate to symptom severity and cognition in premenopausal women with SSD.MethodsThis cross-sectional study included 79 premenopausal women, divided in three groups of women with SSD treated with prolactin-sparing antipsychotics (n = 21) or prolactin-raising antipsychotics (n = 27), and age-matched women without SSD (n = 31). Circulating 17β-estradiol was compared among groups. In patients, we assessed the relationship between prolactin and 17β-estradiol, and the relationships of these hormones to symptom severity and cognition, using correlation analyses and backward regression models.ResultsIn women receiving prolactin-raising antipsychotics, 17β-estradiol levels were lower as compared to both other groups (H(2) = 8.34; p = 0.015), and prolactin was inversely correlated with 17β-estradiol (r=-0.42, p = 0.030). In the prolactin-raising group, 17β-estradiol correlated positively with verbal fluency (r = 0.52, p = 0.009), and 17β-estradiol and prolactin together explained 29% of the variation in processing speed (β17β−estradiol = 0.24, βprolactin = -0.45, F(2,25) = 5.98, p = 0.008). In the prolactin-sparing group, 17β-estradiol correlated negatively with depression/anxiety (r = -0.57, p = 0.014), and together with prolactin explained 26% of the variation in total symptoms (β17β−estradiol = -0.41, βprolactin = 0.32, F(2,18) = 4.44, p = 0.027).ConclusionsIn women with SSD, antipsychotic-induced prolactin elevation was related to lower estrogen levels. Further, estrogens negatively correlated with symptom severity and positively with cognition, whereas prolactin levels correlated negatively with cognition. Our findings stress the clinical importance of maintaining healthy levels of prolactin and estrogens in women with SSD.

Female-specific risk factors for cardiovascular disease: an update.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. While it was previously believed that men have greater susceptibility to CVD, recent research suggests that women face an increased risk of CVD after the onset of menopause, primarily due to the loss of the protective effects of estrogens. Premature ovarian insufficiency (POI), polycystic ovarian syndrome (PCOS), and gestational factors, such as gestational diabetes mellitus (GDM), recurrent pregnancy loss, preterm delivery, and preeclampsia, are specific reproductive disorders that may contribute to an elevated risk of CVD at earlier ages, i.e., before the onset of menopause. This suggests that women with these conditions should be closely monitored for CVD risk factors even before reaching menopause. Such early intervention may help reduce the incidence of CVD and improve overall cardiovascular health in this population. The precise pathophysiological mechanism underlying the development of CVD in women with menopause, premature POI, PCOS, and gestational factors remains elusive. This review article seeks to elucidate the latest research on the relationship between these conditions and CVD in women, aiming to explore the underlying pathogenic mechanisms contributing to this association.

The impact of female sex hormones on cardiovascular disease: from mechanisms to hormone therapy.

Cardiovascular disease remains the leading cause of mortality in women, yet it has not raised the awareness from the public. The pathogenesis of cardiovascular disease differs significantly between females and males concerning the effect of sex hormones. Estrogen and progestogen impact cardiovascular system through genomic and non-genomic effects. Before menopause, cardiovascular protective effects of estrogens have been well described. Progestogens were often used in combination with estrogens in hormone therapy. Fluctuations in sex hormone levels, particularly estrogen deficiency, were considered the specific risk factor in women's cardiovascular disease. However, considerable heterogeneity in the impact of hormone therapy was observed in clinical trials. The heterogeneity is likely closely associated with factors such as the initial time, administration route, dosage, and formulation of hormone therapy. This review will delve into the pathogenesis and hormone therapy, summarizing the effect of female sex hormones on hypertension, pre-eclampsia, coronary heart disease, heart failure with preserved ejection fraction, and cardiovascular risk factors specific to women.

The Role of Estrogen and Estrogen Receptors in Head and Neck Tumors.

Head and neck squamous cell carcinoma (HNSCC) is the most common histological form of head and neck tumors (HNTs), which originate from the epithelium of the lips and oral cavity, pharynx, larynx, salivary glands, nasal cavity, and sinuses. The main risk factors include consumption of tobacco in all forms and alcohol, as well as infections with high-risk human papillomaviruses or the Epstein-Barr virus. Regardless of the etiological agent, the risk of developing different types of HNTs is from two to more than six times higher in males than in females. The reason for such disparities probably lies in a combination of both biological and psychosocial factors. Therefore, it is hypothesized that exposure to female sex hormones, primarily estrogen, provides women with protection against the formation and metastasis of HNTs. In this review, we synthesized available knowledge on the role of estrogen and estrogen receptors (ERs) in the development and progression of HNTs, with special emphasis on membrane ERs, which are much less studied. We can summarize that in addition to epidemiologic studies unequivocally pointing to the protective effect of estrogen in women, an increased expression of both nuclear ERs, ERα, and ERβ, and membrane ERs, ERα36, GPER1, and NaV1.2, was present in different types of HNSCC, for which anti-estrogens could be used as an effective therapeutic approach.

Loss of ADAM15 in female mice does not worsen pressure overload cardiomyopathy, independent of ovarian hormones.

Cardiac hypertrophy is a common feature in several cardiomyopathies. We previously reported that loss of ADAM15 (disintegrin and metalloproteinase 15) worsened cardiac hypertrophy and dilated cardiomyopathy following cardiac pressure overload. Here, we investigated the impact of ADAM15 loss in female mice following cardiac pressure overload induced by transverse aortic constriction (TAC). Female Adam15-/- mice developed the same degree of cardiac hypertrophy, dilation, and dysfunction as the parallel female wild-type (WT) mice at 6 wk post-TAC. To determine if this is due to the protective effects of estrogen, which could mask the negative impact of Adam15 loss, WT and Adam15-/- mice underwent ovariectomy (OVx) 2 wk before TAC. Cardiac structure and function analyses were performed at 6 wk post-TAC. OVx similarly impacted females of both genotypes post-TAC. Calcineurin (Cn) activity was increased post-OVx-TAC, and more in Adam15-/- mice; however, this increase was not reflected in the total-to-phospho-NFAT levels. Integrin-α7 expression, which was upstream of Cn activation in male Adam15-/- -TAC mice, remained unchanged in female mice. However, activation of the mitogen-activated protein kinases (ERK, JNK, P38) was greater in Adam15-/--OVx-TAC than in WT-OVx-TAC mice. In addition, ADAM15 protein levels were significantly increased post-TAC in male but not in female WT mice. Myocardial fibrosis was comparable in non-OVx WT-TAC and Adam15-/- -TAC mice. OVx increased the perivascular fibrosis more in Adam15-/- compared with WT mice post-TAC. Our data demonstrate that loss of ovarian hormones did not fully replicate the male phenotype in the female Adam15-/- mice post-TAC. As ADAM15 levels were increased in males but not in females post-TAC, it is plausible that ADAM15 does not play a prominent role in post-TAC events in female mice. Our findings highlight the significance of factors other than sex hormones in mediating cardiomyopathies in females, which require a more thorough understanding.NEW & NOTEWORTHY Loss of ADAM15 in female mice, unlike the male mice, does not worsen the cardiomyopathy following cardiac pressure overload. Ovariectomy does not worsen the post-TAC cardiomyopathy in female Adam15-/- mice compared with female WT mice. Lack of deleterious impact of Adam15 deficiency in female mice is not because of the protective effects of ovarian hormones but could be due to a less prominent role of ADAM15 in cardiac response to post-TAC remodeling in female mice.

Sex dimorphism controls dysbindin-related cognitive dysfunctions in mice and humans with the contribution of COMT.

Cognitive dysfunctions are core-enduring symptoms of schizophrenia, with important sex-related differences. Genetic variants of the DTBPN1 gene associated with reduced dysbindin-1 protein (Dys) expression negatively impact cognitive functions in schizophrenia through a functional epistatic interaction with Catechol-O-methyltransferase (COMT). Dys is involved in the trafficking of dopaminergic receptors, crucial for prefrontal cortex (PFC) signaling regulation. Moreover, dopamine signaling is modulated by estrogens via inhibition of COMT expression. We hypothesized a sex dimorphism in Dys-related cognitive functions dependent on COMT and estrogen levels. Our multidisciplinary approach combined behavioral-molecular findings on genetically modified mice, human postmortem Dys expression data, and in vivo fMRI during a working memory task performance. We found cognitive impairments in male mice related to genetic variants characterized by reduced Dys protein expression (pBonferroni = 0.0001), as well as in male humans through a COMT/Dys functional epistatic interaction involving PFC brain activity during working memory (t(23) = -3.21; pFDR = 0.004). Dorsolateral PFC activity was associated with lower working memory performance in males only (p = 0.04). Also, male humans showed decreased Dys expression in dorsolateral PFC during adulthood (pFDR = 0.05). Female Dys mice showed preserved cognitive performances with deficits only with a lack of estrogen tested in an ovariectomy model (pBonferroni = 0.0001), suggesting that genetic variants reducing Dys protein expression could probably become functional in females when the protective effect of estrogens is attenuated, i.e., during menopause. Overall, our results show the differential impact of functional variants of the DTBPN1 gene interacting with COMT on cognitive functions across sexes in mice and humans, underlying the importance of considering sex as a target for patient stratification and precision medicine in schizophrenia.

Abstract TP287: Estrous Cycle Stages and Cerebral Blood Flow: Implications for Ischemic Tolerance in Stroke

Introduction: Previous stroke studies in female rodents have demonstrated that the severity of ischemic damage is differentially impacted by the estrous cycle. Estrogen is considered to be neuroprotective, but it is unclear whether this protection is dependent on the vasodilator properties of estrogen. In this study, we investigated the impact of estrus cycle stage on stroke lesion volume and whether that impact was dependent on cerebral blood flow (CBF) changes during stroke. Methods: Ischemia was induced in adult ( 10 weeks) male and female Sprague-Dawley rats by 30 minutes middle cerebral artery occlusion (MCAO) using the suture model. Prior to the stroke procedure, the phases of the estrous cycle (proestrus(P), estrus(E), metestrus(M) and diestrus (D)) were determined by vaginal smear tests in female rats. Cerebral blood flow (CBF) was measured by laser doppler and infarct volume were measured by TTC staining at d2 post-stroke. Results: Females in proestrus and diestrus (P/D) stages of the estrous cycle, which have reportedly high levels of estrogen, had significantly (p&lt;0.05) smaller CBF decreases during ischemia and a trend for smaller infarcts than those in estrous and metestrus stages, which have lower estrogen levels. This suggests that the protective effects of estrogen may be related to effects on blood flow. However, when compared to male rats, females in P/D stages had significantly (p&lt;0.05) smaller brain infarcts despite having similar CBF decreases. This implies that additional mechanisms are responsible for the neuroprotection observed in females when compared to males. Conclusion: Estrous cycle stage affects CBF decrease during ischemia, but this does not account for the difference in infarct size observed between male and female rats. Our study indicates that multiple mechanisms are responsible for ischemic tolerance in specific stages of the estrous cycle. Keywords: stroke, estrous cycle, CBF, estrogen

Investigating the therapeutic potential of hesperidin targeting CRISP2 in intervertebral disc degeneration and cancer risk mitigation.

Intervertebral disc degeneration (IDD) can lead to disc herniation and spinal instability, sometimes requiring surgical intervention. Currently, estrogen has a potential protective effect on IDD, and estrogen is associated with an increased risk of some cancers, such as breast and endometrial cancer. Therefore, it is important to identify natural compounds that estrogen analogues treat IDD while reducing the risk of tumor development. This study aims to explore a natural metabolic treatment strategy by targeting CRISP2 with the natural compound Hesperidin to mimic the protective effects of estrogen on IDD and reduce the risk of tumor development. Microarray data from healthy volunteers and IDD patients were extracted from the Gene Expression Omnibus (GEO) database, and RNA sequencing and clinical data from various cancer types were analyzed. Differentially expressed genes (DEGs) were identified using the Bioconductor Limma package, followed by principal component analysis, volcano plot, and heatmap visualization. Additionally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, CIBERSORT and ssGSEA immune cell infiltration assessments, survival analysis, metabolite enrichment analysis, and molecular docking were performed. Hesperidin's interaction with CRISP2 was further validated through molecular docking and experimental studies. Hesperidin significantly reduced the expression of CRISP2, iNOS, and COX2 in IDD models, decreased reactive oxygen species (ROS) and apoptosis, and diminished inflammatory markers. CIBERSORT and ssGSEA analyses revealed a correlation between CRISP2 and immune cell infiltration. Survival analysis demonstrated that CRISP2 expression levels were associated with patient survival across various cancer types. Hesperidin was found to mimic estrogen's effects on IDD and reduce tumor progression. Cell culture and experimental validation confirmed Hesperidin's protective effects on nucleus pulposus cells (NPCs). Hesperidin, as a potential natural metabolic regulator, not only has therapeutic effects on IDD but may also synergize with estrogen therapy to promote spinal health without increasing cancer risk. This study presents a new clinical approach for IDD treatment and lays the foundation for further drug development and experimental research.

Estrogen as a guardian of auditory health: Tsp1–CD47 axis regulation and noise-induced hearing loss

Objectives This study aimed to analyze the role of estrogen in noise-induced hearing loss (NIHL) and uncover underlying mechanisms. Methods An ovariectomized Sprague-Dawley rat model (OVX) was constructed to investigate the hearing threshold and auditory latency before and after noise exposure using the auditory brainstem response (ABR) test. The morphological changes were assessed using immunofluorescence, scanning electron microscopy and transmission electron microscopy. Proteomics and bioinformatics were used to analyze the mechanism. The findings were further verified through western blot and Luminex liquid suspension chip technology. Results After noise exposure, OVX rats exhibited substantially elevated hearing thresholds. A conspicuous delay in ABR wave I latency was observed, alongside increased loss of outer hair cells, severe collapse of stereocilia and pronounced deformation of the epidermal plate. Accordingly, OVX rats with estrogen supplementation exhibited tolerance to NIHL. Additionally, a remarkable upregulation of the thrombospondin 1 (Tsp1)–CD47 axis in OVX rats was discovered and verified. Conclusions OVX rats were more susceptible to NIHL, and the protective effect of estrogen was achieved through regulation of the Tsp1–CD47 axis. This study presents a novel mechanism through which estrogen regulates NIHL and offers a potential intervention strategy for the clinical treatment of NIHL.

The Effects of Estrogen on the Risk of Developing Dementia using the UK Biobank Data

AbstractBackgroundThe incidence of dementia increases with postmenopausal women, which prompted the investigation of the role of estrogen in the development of dementia. We aimed to investigate the role of estrogen in the UK Biobank.MethodA total of 273,201 women were included in this study. Comprehensive interviews, medical history, body mass index (BMI), and the apolipoprotein E (APOE) genotype were obtained. Reproductive characteristics, including estrogen length and history of surgery, were used as exposure variables. The Cox Proportional Hazard model was used to estimate hazard ratios (HR) for the development of dementia, adjusting for age, education, the Townsend deprivation score, the APOE genotype, family history of dementia, BMI, smoking status, diabetes mellitus, hypertension, and hyperlipidemia.ResultThe mean estrogen length was 37.25 years (8.03 years). About 19% of women had a history of surgery. Compared to women with the lowest overall exposure to estrogen (Estrogen length ≤33), women with higher levels of cumulative estrogen had a decreased risk of dementia (34≤Estrogen length ≤37, HR = 0.79, 95% CI = 0.72‐0.89, p&lt;0.001; 38≤Estrogen length ≤42, HR = 0.72, 95% CI = 0.65‐0.79, p&lt;0.001; 43≤Estrogen length, HR = 0.77, 95% CI = 0.70‐0.85, p&lt;0.001). Compared to women without a history of surgery, women with a history of surgery had an increased risk of dementia (HR = 1.08, 95%CI = 1.00‐1.17, p = 0.038).ConclusionThis study found that longer estrogen length had a decreased risk for dementia and a history of surgery had an increased risk for dementia. The results of this study suggested that estrogen might have a protective role in women’s development of dementia. The exact biological mechanism of the protective effects of estrogen in the brain needs to be elucidated in the future.

Tamoxifen in breast cancer and risk of Parkinson's disease: A meta-analysis

BackgroundTamoxifen is widely used for hormone-sensitive breast cancer, achieved by modulating the estrogen receptor activity in a tissue-specific manner. There is evidence to support the protective effects of estrogen against Parkinson's disease (PD), a common neurodegenerative condition. Some epidemiologic studies suggest the use of tamoxifen may modulate the PD risk. We conducted a meta-analysis to examine the association between tamoxifen and risk of PD. MethodsA search of PubMed using search terms synonymous with “tamoxifen” and “Parkinson's disease” was conducted. Outcomes of interest were the odds ratio (OR) of PD comparing tamoxifen-exposed to -unexposed women, as well as the incidence rate of PD in tamoxifen-exposed women. ResultsA total of 37,932 subjects with breast cancer, comprising 17,233 tamoxifen-exposed subjects and 20,699 tamoxifen-unexposed subjects, satisfied the inclusion criteria. The exposure to tamoxifen ranged from 30-96 months. Using the common-effect model, the pooled OR of PD was 2.4, with (95% CI 1.91-3.01, P < 0.0001), with high heterogeneity (I2 = 81.5%, Cochran's Q test P = 0.001). Pooling 28,640 tamoxifen-exposed patients under the common-effect model found an incidence rate of 5.86 events per 10,000 person-years (95% CI 4.82–7.12) with minimal heterogeneity (I2 = 26%, Cochran's Q test P = 0.258). ConclusionsOur meta-analysis suggests that tamoxifen use may be associated with an increased PD risk in women. However, due to heterogeneity and potential limitations of some of the studies, further clinical and functional validation will be needed. Longitudinal studies supported by imaging and biomarkers evaluation will be useful to identify the mechanisms linking tamoxifen and PD risk.

The impact of menopausal status on auditory brainstem responses

ObjectiveTo determine the effect of decreased estrogen levels due to menopause on auditory brainstem response measurements (ABR). Study designRetrospective chart review. SettingAcademic. PatientsPre- and post-menopausal females (pre-M, post-M) and age-matched males. MethodsABR measurements of wave I, III, and V latencies, and interpeak latencies; amplitudes of waves I, III, V, and V/I ratio. Outcome measureDifferences in ABR measurements between pre-M and post-M. Results164 subjects (101 female and 64 male) were included. Post-M had significantly greater latencies (msec) than pre-M of wave V. Post-M had a significantly smaller wave I amplitude (uV) than pre-M. Post-M had a significantly higher wave V/I amplitude ratio than pre-M. Pre-M had significantly shorter latencies than young males for wave III, and wave V. Post-M had significantly shorter latencies than older males at wave III, and wave V. A two-way ANOVA revealed a significant interaction between the effects of age category and gender on V/I amplitude. ConclusionPost-M group showed a significant drop in wave I amplitude compared with pre-M group, even in the absence of hearing loss, suggesting that the gender differences in hearing are related to estrogen signaling along the auditory pathway. If wave I amplitude changes between older and younger groups resulted from decreased peripheral hearing sensitivity, we would expect larger drops in amplitude in males since rates of presbycusis are higher. We observed much larger drops in wave I amplitude in females, which cannot be attributed to peripheral hearing loss. These results may assist in understanding gender differences in presbycusis and a possible protective effect of estrogen on the auditory system. Knowledge of gender differences in wave I may be important when ABR is used to assess possible synaptopathy.

Effect of diabetes mellitus on young female patients with acute coronary syndrome

BackgroundDiabetes mellitus (DM) is one of the most important risk factors of acute coronary syndrome (ACS). There have been many studies on the relationship between DM and ACS. However, the effect of DM on young females with ACS is still unclear. ObjectiveTo explore the effect of DM on coronary arteries lesions in young females with ACS. Methods1278 young females (age ≤ 44 years) undergoing coronary angiography were divided into DM group (n = 197) and control group (n = 1081) according to whether they had diabetes. Based on whether the patient has ACS, each group was further divided into DM-ACS subgroup and Non-DM-ACS subgroup to compare the characteristics and severity of coronary artery lesions and follow-up outcomes. ResultsThe prevalence of diabetes was 15.41% (197/1278). Overweight (58.88%) and depression or anxiety (11.17%) in the DM group was significantly higher than those (32.22% and 6.20%) in the control group (P < 0.05). The prevalence of ACS (85.28%) in the DM group was significantly higher than that (25.35%) in the control group (P < 0.05). The proportion of type A lesions in the DM-ACS subgroup was lesser than that in the Non-DM-ACS subgroup (P < 0.05). The type C lesions in the DM-ACS subgroup were significantly higher than that in the Non-DM-ACS subgroup (P < 0.01). The number of stents implantation in the DM-ACS subgroup was no significant difference compared with the Non-DM-subgroup (P > 0.05). The length of stent implantation in the DM-ACS subgroup was significantly longer than that in the Non-DM-ACS subgroup (P < 0.05). The rate of MACE was not statistically significant between the two subgroups (P > 0.05), but the rate of all-cause death (2.98%) in the DM-ACS subgroup was significantly higher than that (0.36%) in the Non-DM-ACS subgroup (P < 0.05). ConclusionsDM is an important risk factor in young females with ACS. Young women with diabetes are prone to coronary heart disease. The coronary artery lesions in DM patients were more severe than those in Non-DM patients, despite the protective effect of estrogen on the cardiovascular system. Therefore, young women with DM should be treated to prevent ACS and future events activelyandpurposefully.

Emotion recognition and mood along the menstrual cycle

Previous studies have demonstrated menstrual cycle dependent changes in the recognition of facial emotional expressions, specifically the expression of fear, anger, sadness or disgust. While some studies demonstrate an improvement of emotion recognition performance during the peri-ovulatory phase, when estradiol levels peak, other studies demonstrate a deterioration of emotion recognition performance during the mid-luteal phase, when progesterone levels peak. It has been hypothesized, that these changes in emotion recognition performance mirror mood changes along the menstrual cycle. In the present study, we investigate, whether changes in emotion recognition performance along the menstrual cycle are mediated by mood changes along the menstrual cycle. In a combined cross-sectional and longitudinal study design, two large samples of women completed an emotion recognition task, as well as several mood questionnaires during their menses, peri-ovulatory or mid-luteal cycle phase. 65 women completed the task thrice, once during each cycle phase, order counterbalanced. In order to control for potential learning effects, a sample of 153 women completed the task only once in one of the three cycle phases. In both samples, results demonstrated no significant changes in emotion recognition performance along the menstrual cycle, irrespective of the performance measure investigated (accuracy, reaction time, frequency of emotion classifications) and irrespective of the emotion displayed. Bayesian statistics provided very strong evidence for the null hypothesis, that emotion recognition does not change along the menstrual cycle. There was also no moderation of emotion recognition changes along the menstrual cycle by mood changes along the menstrual cycle. Mood changes along the menstrual cycle followed the expected pattern with highest positive affect and least premenstrual symptoms around ovulation and lowest positive affect, but strongest premenstrual symptoms during menses. Interestingly, premenstrual symptoms were negatively related to estradiol, suggesting a protective effect of estrogen during the luteal cycle phase against mood worsening during the premenstrual phase.