Sex Differences

Postoperative delirium is a common and serious complication after surgery, affecting 10-40% of older patients undergoing non-cardiac procedures. It is characterized by sudden changes in attention, awareness, and thinking that fluctuate throughout the day. Delirium is associated with longer hospital stays, higher mortality, worse long-term brain function, and substantially increased healthcare costs. While several risk factors are known, it remains unclear whether a patient's sex independently influences the risk of developing postoperative delirium, as existing studies have produced conflicting results and were often not designed to specifically examine sex differences.Family visitation is a promising non-drug approach to preventing delirium. Studies in intensive care patients have shown that those who receive family visits have a significantly lower risk of developing delirium. However, it is unknown whether men and women receive different amounts of family visits after surgery, and whether any such difference could help explain sex-based disparities in delirium risk. Given that traditional gender roles in caregiving persist, women - who often serve as primary caregivers in their families - may receive fewer visits when they themselves become patients.This prospective observational study led by the University of Zurich will enroll 471 patients aged 65 years or older undergoing non-cardiac surgery lasting at least 2 hours under general or spinal anesthesia. The primary aim is to determine whether female patients have a higher risk of developing postoperative delirium within three days after surgery compared to male patients. Delirium will be assessed twice daily using the 4 A's Test (4AT), a validated and standardized screening tool. The secondary aim is to evaluate whether female patients receive fewer family visits than male patients and whether any difference in visitation mediates the sex-dependent delirium risk. Family visits will be recorded using an anonymous sign-in sheet placed in the patient's room. The study does not involve any experimental interventions; all patients receive standard clinical care. Participation is voluntary, and withdrawal is possible at any time without affecting medical treatment.

Red blood cell (RBC) transfusions are selected based upon matching donor and recipient blood group: donor and recipient sex are not considered when selecting blood for transfusion. Hence, transfused patients can currently receive sex-matched and/or unmatched RBCs when transfusions are given. Sex-matched stem cell transplants, and some solid organ transplants, have shown that sex-matching donor to recipient improves patient outcomes. Recent exploratory studies have also suggested that patient outcomes could be improved by sex-matching for RBC transfusion. There is emerging evidence of underlying biologic mechanism(s) to support these observations. This study is designed as a randomized controlled trial and will explore the impact on patients who receive RBC transfusions from donors of the same sex ("sex-matched") compared with donors of the opposite sex ("sex-mismatched"). The trial will study adult patients admitted to the Intensive Care Unit who require an RBC transfusion. Patients will be assigned (through a process called randomization) to receive sex-matched RBCs or sex-mismatched RBCs to determine if there is a difference in mortality between those receiving matched versus mismatched RBCs. The results of this trial could have direct implications on resources, blood inventory, and RBC transfusion ordering practices.

This study will test whether biological sex influences how the body responds to circadian misalignment-a mismatch between the internal body clock and the timing of sleep and eating (as can occur with shift work or jet lag). Researchers will examine how circadian misalignment affects appetite regulation (hunger/fullness) and glucose metabolism (blood sugar control), and whether these effects differ between females and males. Findings may help inform more personalized shift work schedules and targeted strategies to reduce metabolic health risks and sex-related differences in clinical care.

Due to historical exclusion of females from research, there are gaps in the understanding of female physiology, how it differs from males, and how sex-specific hormones contribute. As a result, many diagnoses and treatments are based on male physiology and may not be appropriate or effective for females. Females consistently experience greater risk and report worse neurological outcomes in many diseases, including stroke, cardiac arrest, and dementia. As research in females progresses, differences between sexes and changes throughout the lifespan (e.g., puberty, menopause) highlight the importance of understanding the effects of sex and sex-specific hormones on the body. The brain is arguably the most important organ in the body, consuming 20% of the body's total energy. Previous research supports higher blood flow to the brain in females, and research in animals suggests hormones such as estrogen, progesterone, and testosterone are responsible. However, it is extremely difficult to isolate these hormones in humans, due to natural fluctuations (i.e., menstrual cycle). Therefore, the investigators plan to explore the direct role of these sex-specific hormones in regulating blood flow to the brain by blocking hormone production in healthy males and females and giving back testosterone and estrogen, respectively. The investigators will then conduct a range of tests to look at blood flow to the brain at rest and during various stressors. This research will provide crucial insight into how males and females differ in regulation of brain blood flow and inform new treatments and therapies to a wide range of brain injuries and diseases, improving outcomes and reducing the sex disparity in clinical pathways.

The goal of this study is to learn whether insufficient sleep affects glucose metabolism differently in healthy men and women.

This study investigates the effects of transcutaneous auricular vagus nerve stimulation (taVNS) on cognitive performance in healthy adults. The study uses a sham-controlled, cross-over design in which each participant receives both active taVNS and sham stimulation in separate sessions. Each participant completes both conditions (active and sham) in a randomized order using a crossover design. Cognitive performance will be assessed before and after each session using standardized tests. The study also explores whether males and females respond differently to taVNS, in order to identify potential sex-related differences in cognitive outcomes.

The purpose of this study is to determine how anabolic sensitivity, in response to the ingestion of a liquid protein meal, differs across the lifespan, between biological sexes, and with varying physical activity levels.

Cardiovascular disease, and especially myocardial infarction, is the most common cause of death globally, and is particularly common in older individuals. Practical measures that can reduce both the prevalence and incidence of cardiovascular disease are of great value. It is well known that regular physical activity has a protective effect against the development of cardiovascular diseases such as acute myocardial infarction. It has been shown that physical activity can improve the function of the heart and blood vessels, but it is less well known how physical activity can affect the risk of formation of dangerous blood clots, and thus the risk of heart attack and stroke. In a cross-sectional study it has been shown that a physically active lifestyle can reduce the risk of blood clot formation, but experimental evidence for the importance of a period of physical activity for the risk of blood clot formation is lacking. New methods have been set up for measuring the coagulation profile. The analyzes are performed on a blood sample and allow a thorough determination of platelet reactivity as well as an innovative measure of how the microstructure of a possible blood clot would develop. In this project, these methods is used to examine how physical activity, in the form of team sports, affects the coagulation profile of elderly men and women. The increasing age-related risk of cardiovascular disease is associated with endothelial dysfunction and decrease in capillary density, and it has been shown that initiation of capillary growth is a successful method to treat cardiovascular disease. Therefore, this project will also investigate how a longer period of physical activity, in the form of team sports, affects capillary density and endothelial function in men and women aged 60-70 years. Both men and women will be recruited, as it is still unknown whether men and women respond differently to physical activity in relation to coagulation profile, susceptibility to blood clots and capillary density.