Sex Differences Research Articles

Using behavioural network mapping to investigate dyadic play in girls with congenital adrenal hyperplasia.

Examining mechanisms underlying sex differences in children's play styles, we studied girls with congenital adrenal hyperplasia (CAH) who provide a test of the relative effects of prenatal androgens versus rearing, and of behavioural similarity versus gender identity and cognitions. In this exploratory study, 40 focal children (girls and boys with and without CAH), aged 3-8 years, played for 14 min with a same-sex peer in a task designed to elicit rough-and-tumble play. Time-indexed ratings of positive affect and vigour of activity were evaluated via network mapping for sex-related differences in both levels and play dynamics (temporal relations among behaviours). Results suggest influences of both gender identity-aligned social cognitions and prenatal androgens: there was greater dyadic synchrony between positive affect for girls (regardless of CAH status) than boys, but girls with CAH displayed positive affect levels and directed vigorous peer play dynamics similar to boys.

The association of sex differences in ambulatory blood pressure with cardiovascular events and mortality in dialysis patients.

Male patients with pre-dialysis chronickidneydisease(CKD) have worse ambulatory blood pressure(BP) control than females; this is associated with higher mortality. Male hemodialysis patients have higher ambulatoryBP levels than females. This analysis aimed to investigate the association of sex differences in ambulatory BP with cardiovascular events and mortality in hemodialysis individuals. 129 male and 91 female hemodialysis patients with valid 48-h BP monitoring were followed for 53.4 ± 31.1 months. The primary endpoint was cardiovascular mortality; the secondary endpointwas a composite of cardiovascular death, non-fatal myocardialinfarction, non-fatal stroke, resuscitation after cardiacarrest, heartfailure-hospitalization, coronary or peripheral revascularization. Cumulativefreedom from the primary endpoint was lower for women (logrank-p = 0.032), while cumulative-freedom from the secondary endpoint did not differ significantly between-groups (logrank-p = 0.644). The crude risk for cardiovascular mortality was significantly higher in women (HR = 1.613, 95% CI[1.037, 2.509]). The crude risk for the combined endpoint was not different between the two groups (HR = 0.918, 95% CI[0.638, 1.320]). After adjusting for major risk factors (age, diabetes, dialysis vintage, coronary disease and hemoglobin) no significant differences in the risk for both the primary and the secondary endpoint were observed between women and men (primary: HR = 1.295 (95% CI[0.808, 2.078]), secondary: HR = 0.763 (95% CI[0.521, 1.118])). After additional adjustment for 44-h systolicBP the above relationships did not alter (primary: HR = 1.329 (95% CI [0.826, 2.137]), secondary: HR = 0.808 (95% CI [0.551, 1.184])). In conclusion, female hemodialysis patients have higher crude but similar adjusted cardiovascular mortality rates compared to male counterparts. In contrast to pre-dialysis CKD, the neutral relationship between gender and adverse cardiovascular outcomes in hemodialysis is not further affected by ambulatory BP.

Identification of candidate genes and pathways involved in the establishment of sexual size dimorphism in the olive flounder (Paralichthys olivaceus) using RNA-seq

Olive flounder (Paralichthys olivaceus) is a valuable mariculture fish that shows female-biased sexual size dimorphism (SSD), yet the molecular mechanisms responsible for this phenomenon remain poorly understood. In this study, the growth differences between females and males were compared, and comparative transcriptome analyses of brains/pituitaries, livers, muscles, and gonads from 13-month-old females and males were performed. The critical time window for SSD was from 13- to 14-month-old, with females reaching significantly larger sizes than males. Muscle cell size and plasma growth hormone (GH), insulin-like growth factor 1 and 2 (IGF1, IGF2), 11-ketotestosterone (11-KT), and 17β-estradiol (E2) levels had no significant differences between the sexes of 13- and 14-month-old flounders. Furthermore, the RNA-seq data revealed differential expression in the genes encoding the receptors for these hormones, suggesting that regulation may occur at the receptor level, potentially leading to SSD during the critical window. RNA-seq analysis identified 88, 645, 414, and 15,833 differentially expressed genes between females and males in brains/pituitaries, livers, muscles, and gonads, respectively. KEGG (Kyoto Encyclopedia of Genes and Genomes) and GSEA-based KEGG analyses revealed that some pathways associated with growth and development, including “prolactin signaling pathway” in brains/pituitaries, “cell cycle”, “oocyte meiosis”, and “DNA replication” in livers, “focal adhesion”, “ECM-receptor interaction”, “protein digestion and absorption”, “arginine and proline metabolism”, and “cysteine and methionine metabolism” in muscles, and “Hippo signaling pathway” and “JAK-STAT signaling pathway” in gonads may be involved in the establishment of sexual growth differences. Notably, females had lower steroid hormone synthesis abilities than males in brains/pituitaries, livers, and gonads, indicating the importance of sex steroid hormones in the establishment of SSD. Moreover, genes including frizzled3 (fzd3) and prolactin (prl) in brains/pituitaries, and growth hormone receptor (ghr), estrogen receptor (esr1), insulin-like growth factor binding protein-3 (igfbp3), bone morphogenetic protein 8 A-like (bmp8a), leptin receptor (lepr), and lipoprotein lipase-like (lpl) in livers emerge as potential candidates for the establishment of SSD. In conclusion, this study may help clarify the molecular mechanisms involved in SSD-related growth traits in flounder and provide basic data for genetic breeding of flounder.

A new sexually dimorphic Diploechiniscus species (Tardigrada: Echiniscidae) from Calvert Island (British Columbia, Canada)

An important, but generally overlooked source in intraspecific variability of characters used in tardigrades taxonomy is sexual dimorphism. Dioecious tardigrades species with unisexual or bisexual populations are common, but external sexual dimorphism is rarely observed. The discovery and integrative analysis of a Diploechiniscus species population with high sexual dimorphism from Calvert Island (Canada) has allowed its description as a new species. Diploechiniscus dimorphus n. sp. is characterized by a different chaetotaxy in males and females, and by enlarged cephalic sensory appendages in the males. The discovery of this new species shows that it is important to consider sexual dimorphism as a source of intraspecific variability in tardigrade taxonomy due to its implications on the use of traits commonly used to delineate species such as chaetotaxy. Lastly, the finding of individuals of Diploechiniscus horningi ( Schuster and Grigarick, 1971 ), a species previously synonymized with Diploechiniscus oihonnae ( Richters, 1903 ), allows us to prove that it is genetically a separate species and to reinstate it.

The Relationship of Sex and Aortic Diameter at the Time of Acute Type A Aortic Dissection

ObjectiveEvaluate sex differences in patients undergoing repair of acute type A aortic dissection (ATAAD). MethodsSex-stratified, single-center cohort study of patients undergoing ATAAD repair from 1997-2022. The primary outcome was aortic diameter at time of presentation with ATAAD. Secondary outcomes were mortality, myocardial infraction, stroke, hemodialysis, tracheostomy, re-exploration for bleeding, a composite of major adverse events (MAE), and long-term survival. ResultsIn 390 consecutive patients (150 women), men were younger than women (61.0 [(IQR)50-70] vs 70.5[IQR 59-78]; p<0.001), had higher body mass index (BMI) (28.6[IQR 25.1-32.3] vs 25.4[IQR 21.9-29.2]; p<0.001), more frequent peripheral vascular disease (11.7% vs 4.7%; p=0.03), renal insufficiency (36.7% vs 22%; p=0.003), malperfusion (34.2% vs 18.7%; p=0.007), and smoking history (65% vs 44%; p<0.001). There was no sex difference in median aortic diameter at the time of ATAAD (men:5.3cm[IQR 4.9-6.1], women:5.2cm[IQR 4.6-5.9]; p=0.12) even when adjusted for BMI (men:5.7cm[IQR 5.4-6.1], women:5.4cm[IQR 5.4-6.1]; p=0.19). There was no sex difference in mortality (4.6% vs 6.0%; p=0.70), MAEs, or ten-year survival (50.3% vs 58.5%; p=0.13). On multivariable analysis, there was no interaction between aneurysm size and sex (interaction p=0.62). Sex was not associated with MAEs (odds ratio 0.75, 95% confidence interval 0.07-7.39; p=0.81). ConclusionsThere was no sex difference in aneurysm size at the time of presentation of ATAAD, even after adjustment for BMI, and no interaction between aneurysm size and sex, suggesting that aortic diameter remains a reasonable criterion for intervention irrespective of sex.

Assessment of age-dependent sexual dimorphism in paediatric vertebral size and density using a statistical shape and statistical appearance modelling approach

This work focuses on the growth patterns of the human fourth lumbar vertebra (L4) in a paediatric population, with specific attention to sexual dimorphism. The study aims to understand morphological and density changes in the vertebrae through age-dependent statistical shape and statistical appearance models, which can describe full three-dimensional anatomy. Results show that the main growth patterns are associated with isotropic volumetric vertebral growth, a decrease in the relative size of the vertebral foramen, and an increase in the length of the transverse processes. Moreover, significant sexual dimorphism was demonstrated during puberty. We observe significant age and sex interaction in the anterior vertebral body height (P = 0.005), where females exhibited an earlier increase in rates of vertebral height evolution. Moreover, we also observe an increase in cross-sectional area (CSA) with age (P = 0.020), where the CSA is smaller in females than in males (significant sex effect P = 0.042). Finally, although no significant increase in trabecular bone density with age is observed (P = 0.363), a trend in the statistical appearance model suggests an increase in density with age.

Comorbidity and sex differences in functional disorders and internalizing disorders

ObjectiveIn the current exploratory study we estimate comorbidity rates between FDs [fibromyalgia (FM), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and irritable bowel syndrome (IBS)]—and IDs—[major depressive disorder (MDD) and generalized anxiety disorder (GAD)] by using self-reported diagnostic criteria. MethodWe analyzed data from 107,849 participants (mean age = 49.3 (SD = 13.0), 58.6% women) of the Lifelines Cohort Study. Lifelines is a prospective population-based cohort study in the northeast of the Netherlands. Current IDs were assessed using the Mini-International Neuropsychiatric Interview. Current FM, ME/CFS, and IBS were assessed according to the 2010 American College of Rheumatology criteria, the 1994 Centers for Disease Control and Prevention criteria and the ROME IV criteria, respectively. We estimated tetrachoric correlations between diagnoses and tested for sex differences. Additionally, we estimated the ratio of observed-to-expected frequency for combinations of diagnoses. ResultsFDs and IDs are highly comorbid (odds ratios: 3.2–12.6) with associations stronger among men. Participants with at least three disorders/diagnoses were more prevalent than expected by chance. ConclusionStudies that aim to explain sex differences and the comorbidity of specific combinations of IDs and FDs will be an important contribution to understanding the etiology of these conditions.

Presbyopia, Dry Eye, and Retinal Thickness in the Middle-Aged Population: Focusing on Sex Differences.

Risk factors for presbyopia have not been fully determined although previous studies suggested presbyopia was associate with age, dry eye, and retinal ganglion cell complex thickness (GCC). We accessed these signs and common ocular symptoms in the middle-aged population focusing on sex differences when women have drastic hormonal change. This cohort study consecutively enrolled 2743 patients aged 36-45 years (n=1000), 46-55 years (n=1000), and 56-65 years (n=743). All underwent ocular surface tests and had near add power and GCC measured. Common ocular symptoms were asked using questionnaire. Among female participants, visual symptoms (eye strain and photophobia) were more prevalent in the age group 46-55, whereas non-visual symptoms (dryness, irritation, and pain) were not. We identified symptomatic presbyopia (near add power ≥ 1.5D) in 14.4%, 73.8%, and 97.8%, positive corneal staining in 29.1%, 23.8%, and 23.9%, and a mean GCC of 98.2 μm, 105.3 μm, and 89.6 μm in the age groups 36-45, 46-55, and 56-65, respectively. Mean tear break-up time were 3.3, 3.5, and 3.3 seconds, respectively. Results indicated a large progression of presbyopia (P<0.01) from the period of 36-45 years onward and significantly increased GCC (P<0.01) in women of age group 46-55. No notable tendency was observed in symptoms and GCC for male participants. Visual symptoms in women were worse between 46 and 55 years than before or after these ages. The increase of symptomatic presbyopia and GCC may be contributing to visual symptoms in addition to menopausal transition symptoms in this age group.

Postnatal Skull Development Reveals a Conservative Pattern in Living and Fossil Vizcachas Genus Lagostomus (Rodentia, Chinchillidae).

The plains vizcacha, Lagostomus maximus, is the only living species in the genus, being notably larger than fossil congeneric species, such as Lagostomus incisus, from the Pliocene of Argentina and Uruguay. Here, we compare the skull growth allometric pattern and sexual dimorphism of L. maximus and L. incisus, relating shape and size changes with skull function. We also test whether the ontogenetic trajectories and allometric trends between both sexes of L. maximus follow the same pattern. A common allometric pattern between both species was the elongation of the skull, a product of the lengthening of rostrum, and chondrogenesis on the spheno-occipitalis synchondrosis and coronalis suture. We also detected a low proportion of skull suture fusion. In some variables, older male specimens did not represent a simple linear extension of female trajectory, and all dimorphic traits were related to the development of the masticatory muscles. Sexual dimorphism previously attributed to L. incisus would indicate that this phenomenon was present in the genus since the early Pliocene and suggests social behaviors such as polygyny and male-male competition. Ontogenetic changes in L. incisus were similar to L. maximus, showing a conservative condition of the genus. Only two changes were different in the ontogeny of both species, which appeared earlier in L. incisus compared to L. maximus: the development of the frontal process of the nasals in a square shape, and the straight shape of the occipital bone in lateral view. Juveniles of L. maximus were close to adult L. incisus in the morphospace, suggesting a peramorphic process. The sequence of suture and synchondroses fusion showed minor differences in temporozygomatica and frontonasalis sutures, indicating major mechanical stress in L. maximus related to size. We suggest a generalized growth path in Chinchillidae, but further analyses are necessary at an evolutionary level, including Lagidium and Chinchilla.

Sex differences and role of lysyl oxidase-like 2 in angiotensin II-induced hypertension in mice.

Hypertension, a disease with known sexual dimorphism, accelerates aging-associated arterial stiffening, partly because of the activation of matrix remodeling caused by increased biomechanical load. In this study, we tested the effect of biological sex and the role of the matrix remodeling enzyme lysyl oxidase-like 2 (LOXL2) in hypertension-induced arterial stiffening. Hypertension was induced by angiotensin II (ANG II) infusion via osmotic minipumps in 12- to 14-wk-old male and female mice. Blood pressure and pulse wave velocity (PWV) were measured noninvasively. Wire myography and uniaxial tensile testing were used to test aortic vasoreactivity and mechanical properties. Aortic wall composition was examined by histology and Western blotting. Uniaxial stretch of cultured cells was used to evaluate the effect of biomechanical strain. LOXL2's catalytic function was examined using knockout and inhibition. ANG II infusion-induced hypertension in both genotypes and sexes. Wild-type (WT) males exhibited arterial stiffening in vivo and ex vivo. Aortic remodeling with increased wall thickness, intralamellar distance, higher LOXL2, and collagen I and IV content was noted in WT males. Female mice did not exhibit increased PWV despite the onset of hypertension. LOXL2 depletion improved vascular reactivity and mechanics in hypertensive males. LOXL2 depletion improved aortic mechanics but worsened hypercontractility in females. Hypertensive cyclic strain contributed to LOXL2 upregulation in the cell-derived matrix in vascular smooth muscle cells (VSMCs) but not endothelial cells. LOXL2's catalytic function facilitated VSMC alignment in response to biomechanical strain. In conclusion, in males, arterial stiffening in hypertension is driven both by VSMC response and matrix remodeling. Females are protected from PWV elevation in hypertension. LOXL2 depletion is protective in males with improved mechanical and functional aortic properties. VSMCs are the primary source of LOXL2 in the aorta, and hypertension increases LOXL2 processing and shifts to collagen I accumulation. Overall, LOXL2 depletion offers protection in young hypertensive males and females.NEW & NOTEWORTHY We examined the effect of sex on the evolution of angiotensin II (ANG II)-induced hypertension and the role of lysyl oxidase-like 2 (LOXL2), an enzyme that catalyzes matrix cross linking. While ANG II led to hypertension and worsening vascular reactivity in both sexes, aortic remodeling and stiffening occurred only in males. LOXL2 depletion improved outcomes in males but not females. Thus males and females exhibit a distinct etiology of hypertension and LOXL2 is an effective target in males.

Sexual dimorphism in physiological responses of turbot (Scophthalmus maximus L) under acute hypoxia and reoxygenation

Dissolved oxygen (DO) is a crucial factor throughout fish life cycle. In this study, the hematology, hepatic antioxidant levels, histomorphology of the liver and gill were determined in both female and male turbot under acute hypoxia to evaluated the underlying mechanisms and potential sexual dimorphism difference. Results showed that acute hypoxia stress treatment for 3 h significantly increased plasma cortisol, glucose, hemoglobin (HGB), cholesterol (CHO), triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL) and hepatic malondialdehyde (MDA) contents, red blood cell count (RBC) number, hepatic superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), alanine-aminotransferase (ALT) and aspartate-aminotransferase (AST) activity in both male and female turbot. Male obtained higher plasma CHO, TG and LDL contents, GSH-Px and SOD activity than female under hypoxia. Meanwhile, hypoxia increased gill respiratory frequency, secondary lamellar length, secondary lamellar width, perimeter, lamellar surface area and gill surface area and decreased interlamellar distance. Acute hypoxia induced clubbing, hyperplasia, hypertrophy of gill filaments and hepatic vacuolization in both male and female turbot. The aforementioned parameters were recovered to normal levels after reoxygenation for 12 h. In conclusion, sex dimorphism difference of turbot hematological (RBC, HGB) and biochemical (glucose, CAT, GSH-Px, MDA) parameters were observed under hypoxia stress, while male demonstrated more hypoxia tolerance than female. These results help understand turbot hypoxia tolerance mechanisms and provide more data for management in captivity.

Activating transcription factor 3 (ATF3) and calcitonin gene-related peptide (CGRP) increase in trigeminal ganglion neurons in female rats after photorefractive keratectomy (PRK)-like corneal abrasion

Photorefractive keratectomy (PRK) is a type of eye surgery that involves removal of the corneal epithelium and its associated nerves, which causes intense acute pain in most people. We used a rat model of corneal epithelium removal (corneal abrasion) to examine underlying cellular and molecular mechanisms. In this study, we used immunohistochemistry of trigeminal ganglion (TG) to assess neuronal content of CGRP and ATF3, as well as orbital tightening (OT) to assess spontaneous pain behaviors. CGRP is an important neuropeptide in pain modulation and ATF3 is often used as a nerve injury marker. We found dynamic changes in CGRP and ATF3 in TG; both increased significantly at 24 h following corneal abrasion and females had a more pronounced increase at 24 h compared to males. Interestingly, there was no sex difference in OT behaviors. In addition, the number of cells containing either CGRP or ATF3 in each animal correlate significantly with their OT behavior at the assessed timepoint. Since CGRP increased most in females, we tested the effectiveness of Olcegepant, a CGRP antagonist, at reducing OT behaviors following corneal abrasion. Olcegepant (1 mg/kg) was given prior to and again at 24 h after abrasion but did not change OT behaviors at any testing time over a 1-week period. Examination of CGRP and ATF3 together in TG showed that they rarely colocalized, indicating that the cells with upregulated CGRP are distinct from the cells responding to epithelial nerve injury. The studies also show that underlying molecular responses may be sex specific.

Increasing adult-born neurons protects mice from epilepsy.

Neurogenesis occurs in the adult brain in the hippocampal dentate gyrus, an area that contains neurons which are vulnerable to insults and injury, such as severe seizures. Previous studies showed that increasing adult neurogenesis reduced neuronal damage after these seizures. Because the damage typically is followed by chronic life-long seizures (epilepsy), we asked if increasing adult-born neurons would prevent epilepsy. Adult-born neurons were selectively increased by deleting the pro-apoptotic gene Bax from Nestin-expressing progenitors. Tamoxifen was administered at 6 weeks of age to conditionally delete Bax in Nestin-CreER T2 Bax fl/fl mice. Six weeks after tamoxifen administration, severe seizures (status epilepticus; SE) were induced by injection of the convulsant pilocarpine. After mice developed epilepsy, seizure frequency was quantified for 3 weeks. Mice with increased adult neurogenesis exhibited fewer chronic seizures. Postictal depression was reduced also. These results were primarily in female mice, possibly because they were the more affected by Bax deletion than males, consistent with sex differences in Bax. The female mice with enhanced adult neurogenesis also showed less neuronal loss of hilar mossy cells and hilar somatostatin-expressing neurons than wild type females or males, which is notable because these two hilar cell types are implicated in epileptogenesis. The results suggest that selective Bax deletion to increase adult-born neurons can reduce experimental epilepsy, and the effect shows a striking sex difference. The results are surprising in light of past studies showing that suppressing adult-born neurons can also reduce chronic seizures.

Sex Differences in the Associations Between Chronic Diseases and Insomnia Symptoms Among Older Adults in India

Sex Differences in the Associations Between Chronic Diseases and Insomnia Symptoms Among Older Adults in India

Sex Differences in Impacts of Early Gestational and Peri-Adolescent Ozone Exposure on Lung Development in Rats: Implications for Later Life Disease in Humans

Air pollution exposure during pregnancy may affect fetal growth. Fetal growth restriction (FGR) is associated with reduced lung function in children that can persist into adulthood. Using an established model of asymmetrical FGR in Long-Evans rats, this study investigated sex differences in effects of early life ozone exposure on lung development and maturation. Adverse health effects for i) gestational exposure (with impacts on primary alveolarization), ii) peri-adolescent exposure (with impacts on secondary alveolarization), and iii) cumulative exposure across both periods were evaluated. Notably, female offspring were most affected by gestational ozone exposure, likely because of impaired angiogenesis and corresponding decreases in primary alveolarization. Females had diminished lung capacity, fewer mature alveoli, and medial hypertrophy of small and large pulmonary arteries. Males, especially FGR-prone offspring, were more affected by peri-adolescent ozone exposure. Males had increased ductal areas, likely due to disrupted secondary alveolarization. Altered lung development may increase risk of developing diseases, such as pulmonary arterial hypertension or chronic obstructive pulmonary disease. Pulmonary arterial hypertension disproportionately affects women. In the United States, chronic obstructive pulmonary disease prevalence is increasing, especially in women; and prevalence for both men and women is highest in urbanized areas. This investigation underlines the importance of evaluating results separately by sex, and provides biologic plausibility for later consequences of early-life exposure to ozone, a ubiquitous urban air pollutant.

Age-dependent sex differences in cofilin1 pathway (LIMK1/SSH1) and its association with AD biomarkers after chronic systemic inflammation in mice

Chronic systemic inflammation (CSI) results in neuroinflammation and neurodegeneration. Cofilin1 is a stress protein that activates microglia and induces neuroinflammation, but its role in CSI at different aging stages remains unidentified. Therefore, the study aims to identify cofilin1 and its upstream regulators LIMK1 and SSH1 after CSI in young-, middle-, and advanced-aged mice. CSI was induced by injecting the male and female mice with a sub-lethal dose of Lipopolysaccharide weekly for six weeks. The results showed that normal male mice did not show cofilin pathway dysregulation, but a significant dysregulation was observed in CSI advanced-aged mice. In females, cofilin1 dysregulation was observed in healthy and CSI advanced-aged mice, while significant cofilin1 dysregulation was observed in middle-aged mice during CSI. Furthermore, cofilin1 pathway dysregulations correlated with Alzheimer's disease (AD) biomarkers in the brain and saliva, astrocyte activation, synaptic degeneration, neurobehavioral impairments, gut-microbiota abnormalities, and circulatory inflammation. These results provide new insights into cofilin1 sex and age-dependent mechanistic differences that might help identify targets for modulating neuroinflammation and early onset of AD.

Sex differences in the association of physical functions with hospitalization and mortality events among community-dwelling older adults with disabilities

This study aimed to investigate the role of sex in the association between physical function and the occurrence of hospitalization and mortality among community-dwelling older adults with impairments in activities of daily living (ADL). Participants included community-dwelling older adults aged ≥65 years with ADL disabilities. Physical functions (hand grip strength [HGS], knee extension muscle strength, and comfortable walking speed [CWS]) were measured at baseline and analyzed for association with hospitalization and mortality by sex using Cox regression analysis, adjusted for potential confounders. In this Cox regression analysis, HGS was significantly associated with the occurrence of hospitalization and mortality in women, whereas CWS was significantly associated with the occurrence of hospitalization and HGS with mortality in men. These findings reveal that the predictive ability of adverse events in community-dwelling older adults with disabilities differs by sex, requiring outcome- and sex-specific prognostication.

Sex Disparities in Ischemic Heart Disease Mortality in Europe

BackgroundIschemic heart disease (IHD) is the leading cause of death in the European Union (EU). Understanding variations by sex, income, and countries can help in tailoring effective public health policies. ObjectivesThe purpose of the study was to examine trends in sex differences in IHD prevalence and prognosis within the EU. MethodsWe conducted a cross-sectional analysis of IHD using the Global Burden of Disease Study Database to examine trends in sex-specific age-standardized mortality rate (ASMR)-to-age-standardized prevalence rate (ASPR) ratio (ASMR-to-ASPR index) per 100,000 inhabitants/year across the EU from 2005 to 2019. ResultsMen showed higher ASMR than women. However, the ASMR-to-ASPR index was notably higher in women than in men indicating that women who develop IHD have a higher risk of dying from the disease compared with their male counterparts. Despite a significant decline in ASMR across EU from 2005 to 2019 both among women (from 1.752 to 1.662) and men (from 3.372 to 3.135), sex disparities in ASMR-to-ASPR index (EU average: 4.96% vs 4.34%) persisted (with a women-to-men ratio ranging from 1.05 to 1.44). No significant relationship was found between country-specific ASMR or country income status and ASMR-to-ASPR index. Examples include Romania, which displayed higher ASMR (men: 219.87, women: 143.54) compared with Germany (men: 107.22, women: 60.76), yet with smaller differences in ASMR-to-ASPR index between women and men (Romania: 6.54% vs 5.85%; ratio: 1.12, and Germany: 4.79% vs 3.80%; ratio: 1.26). ConclusionsMortality from IHD has decreased substantially among EU countries. However, the declines were accompanied by a persistently higher ASMR-to-ASPR index in women, indicating significant potential for further gains in closing the gender gap in IHD mortality.

Sex Differences in Patient-Reported Depression Following Vascular Surgery Procedures

IntroductionFemale patients frequently experience worse clinical outcomes than male patients after undergoing vascular surgery procedures. However, it is unclear whether these sex-based disparities also impact mental health outcomes. This study was designed to investigate sex differences in patient-reported outcome measures of depression for patients undergoing vascular surgery. MethodsWe retrospectively analyzed 107 patients (73 males and 34 females) who underwent vascular surgery procedures between January 2016 and April 2023. These patients completed a Patient-Reported Outcome Measurement Information System (PROMIS) Item Bank v1.0-Depression assessment 90 d before surgery and at least once after surgery. After stratifying patients by sex, we analyzed changes in PROMIS depression scores using a multiple mixed-effects linear regression model. Then, logistic regression was used to compare the proportion of patients who achieved a clinically meaningful difference in PROMIS depression score within 15 mo after surgery. ResultsThere was no significant difference between female and male patients among rates of complications, length of hospital stay, or rates of nonhome discharge. However, female sex was associated with significantly improved PROMIS depression scores after surgery compared to male sex (P = 0.034). Furthermore, female patients were over 3-fold more likely than male patients to reach the minimal clinically important difference threshold for improvement in PROMIS depression scores (odds ratio 4.66, 95% confidence interval 1.39-15.61). ConclusionsThese results suggest that female sex is associated with improved patient-reported measures of depression after undergoing vascular surgery. Clinicians should consider these mental health benefits when evaluating female patients for vascular interventions.

Sex differences in placental gene expression and intraplacental variation in normotensive versus hypertensive pregnancies

Sex differences in placental gene expression and intraplacental variation in normotensive versus hypertensive pregnancies