In humans, the combination of all sex-specific genetic, epigenetic, and hormonal influences of biologic sex produces different in vivo environments for male and female cells. We dissect how these ...influences of sex modify the pharmacokinetics and pharmacodynamics of multiple drugs and provide examples for common drugs acting on specific organ systems. We also discuss how gender of physicians and patients may influence the therapeutic response to drugs. We aim to highlight sex as a genetic modifier of the pharmacological response to drugs, which should be considered as a necessary step toward precision medicine that will benefit men and women. SIGNIFICANCE STATEMENT: This study discusses the influences of biologic sex on the pharmacokinetics and pharmacodynamics of drugs and provides examples for common drugs acting on specific organ systems. This study also discusses how gender of physicians and patients influence the therapeutic response to drugs.
Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body ...fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
•Compared to men, women with acute myocarditis were older at the time of diagnosis, presented with more severe heart failure symptoms and higher levels of NT-proBNP.•During hospitalization, women ...received more advanced therapies, experienced severe arrhythmia 3.8 times more often and were 1.9 times more likely to develop incident or worsening heart failure.•Men presented more often with chest pain, ST-elevation and showed more non-ischemic affected segments in cardiac MRI compared to women.
This study investigated sex differences in acute myocarditis patients during index hospitalization.
We included 365 patients with acute myocarditis, hospitalized with continuous monitoring at the Intensive care unit (ICU), from 2000-2023 into the Basel Myocarditis Cohort study. We compared sex differences in clinical presentation, the presenting ECG prior medical history, inflammatory and cardiac biomarkers, cardiac imaging, arrhythmia occurrence and short to midterm outcomes.
Mean age was 41.3 years and 26.3% were female. Compared to men, women were older (median 49.7 vs 38.3 years, p<0.001) at the time of diagnosis and presented more frequently with dyspnea (41 vs 26%, p=0.013) and a higher Killip class (p=0.011). In the presenting ECG, men had a higher occurrence of diffuse ST-elevation (38 vs 9%, p<0.001) and PQ-depression (31 vs 20%, p=0.042), compared to women. Women had higher NT-proBNP levels (1180 vs 387 ng/l, p=0.015), lower cardiac troponin T levels (389 vs 726 ng/l, p=0.006), less segments with non-ischemic LGE on CMR (1 vs 3, p=0.005) but similar LVEF (55 vs 55%, p=0.629), compared to men. Overall, hospital stay was longer in women compared to men (7 vs 5 days, p=0.018) with a similar length of ICU stay (2.6 vs 2.7 days, p=0.922). Women developed more often severe arrhythmia (8.3 vs 2.2%, p=0.015) and heart failure during the hospitalization (31.3 vs 16.4%, p=0.003).
Compared to men, women with acute myocarditis were older at the time of diagnosis, presented more often with heart failure and had an increased frequency of severe arrhythmia.
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Major differences between men and women exist in epidemiology, manifestation, pathophysiology, treatment, and outcome of cardiovascular diseases (CVD), such as coronary artery disease, pressure ...overload, hypertension, cardiomyopathy, and heart failure. Corresponding sex differences have been studied in a number of animal models, and mechanistic investigations have been undertaken to analyze the observed sex differences. We summarize the biological mechanisms of sex differences in CVD focusing on three main areas, i.e., genetic mechanisms, epigenetic mechanisms, as well as sex hormones and their receptors. We discuss relevant subtypes of sex hormone receptors, as well as genomic and nongenomic, activational and organizational effects of sex hormones. We describe the interaction of sex hormones with intracellular signaling relevant for cardiovascular cells and the cardiovascular system. Sex, sex hormones, and their receptors may affect a number of cellular processes by their synergistic action on multiple targets. We discuss in detail sex differences in organelle function and in biological processes. We conclude that there is a need for a more detailed understanding of sex differences and their underlying mechanisms, which holds the potential to design new drugs that target sex-specific cardiovascular mechanisms and affect phenotypes. The comparison of both sexes may lead to the identification of protective or maladaptive mechanisms in one sex that could serve as a novel therapeutic target in one sex or in both.
The purpose of this review is to discuss ways to think about and study sex differences in preclinical animal models. We use the framework of addiction, in which animal models have excellent face and ...construct validity, to illustrate the importance of considering sex differences. There are four types of sex differences: qualitative, quantitative, population, and mechanistic. A better understanding of the ways males and females can differ will help scientists design experiments to characterize better the presence or absence of sex differences in new phenomena that they are investigating. We have outlined major quantitative, population, and mechanistic sex differences in the addiction domain using a heuristic framework of the three established stages of the addiction cycle: binge/intoxication, withdrawal/negative affect, and preoccupation/anticipation. Female rats, in general, acquire the self-administration of drugs and alcohol more rapidly, escalate their drug taking with extended access more rapidly, show more motivational withdrawal, and (where tested in animal models of "craving") show greater reinstatement. The one exception is that female rats show less motivational withdrawal to alcohol. The bases for these quantitative sex differences appear to be both organizational, in that estradiol-treated neonatal animals show the male phenotype, and activational, in that the female phenotype depends on the effects of gonadal hormones. In animals, differences within the estrous cycle can be observed but are relatively minor. Such hormonal effects seem to be most prevalent during the acquisition of drug taking and less influential once compulsive drug taking is established and are linked largely to progesterone and estradiol. This review emphasizes not only significant differences in the phenotypes of females and males in the domain of addiction but emphasizes the paucity of data to date in our understanding of those differences.
•Anxiety turned out to be the most prevalent and serious issue for college students, especially for female students.•A significantly higher percentage of male students endured depression than ...females, which persisted during the four academic years.•Anxiety had a significant positive correlation with introversion. Female freshmen's anxiety levels were also associated with their body image, drinking habits, and academic performance.•It is of great significance to adopt collegiate policies reflecting the gender differentials and offer female and male students more proper guidance in freshman and sophomore years in order to promote their psychological well-being.
The objective of this longitudinal study was to examine the gender differences in college students' depression, anxiety, and stress over the four academic years, and to explore possible anxiety-related factors among first year students.
The study analyzed 1892 undergraduate students from 15 universities in China, with 898 females and 994 males. The students have been followed for four years and completed a survey containing the Depression Anxiety Stress Scale-21 questionnaire, students’ socio-demographic information, and their educational background, etc.
(1) On average, both female and male college students suffered from mild anxiety in the first three years. Female students scored significantly higher in anxiety than males in the first and second years, and there was no significant gender difference in students’ average depression and stress levels. (2) A significantly larger proportion of female students experienced anxiety above the normal threshold, whereas a higher percentage of male students endured different degrees of depression; no significant gender differences were found in stress problems. (3) Anxiety had a significant positive correlation with introversion. Female freshmen's anxiety levels were also associated with their body image, drinking habits, and academic performance.
Response bias may exist considering that self-reported data was used. Due to data unavailability, we only explored the anxiety-related factors in freshman year, which cannot sufficiently reflect the consistency of correlations over time.
Anxiety turned out to be the most prevalent and serious issue for college students, especially for female students; while a growing prevalence of depression was found among male students during college. It is of great significance to adopt collegiate policies reflecting the gender differentials.
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