Sex-specific cardiometabolic responses during microgravity simulation in European Space Agency VIVALDI dry immersion

Exposure to microgravity is marked by enhanced physical inactivity, reduced gravitational loading and fluid shifts. These characteristics provide a unique model for medical research. Dry immersion is used as a ground-based model to simulate and investigate some of the physiological effects of microgravity experienced by astronauts (body fluid shifts, lack of mechanical support, unloading of the musculoskeletal system and hypokinesia). To date, there is limited knowledge about the effect of sex on cardiovascular and metabolic responses to dry immersion. This study integrates results from two 5-day dry immersion validation campaigns conducted by the European Space Agency (ESA): VIVALDI-1 (women, n = 18) and VIVALDI-2 (men, n = 19), where a wide range of physiological data was collected before, during, and after immersion. We investigated hormones changes and fluid redistribution, orthostatic tolerance, aerobic capacity, physical activity, muscle force, venous function, body composition, glucose tolerance, metabolic rate, lipid and bone turnover profiles, endothelial responses, with particular attention to sex-based differences. Our findings reveal that dry immersion induces an acute multi-system deconditioning, affecting cardiovascular, metabolic, and fluid-regulation systems, which is largely comparable between men and women, although women show lower orthostatic tolerance, greater elevation of the atherogenic index, and increase in bone resorption biomarker. These results establish dry immersion as a valuable tool for studying the physiological adaptations of astronauts to microgravity and understanding sex-specific responses, while providing a comprehensive control dataset for the development of future countermeasures. Spaceflights induce physiological changes, and understanding how men and women respond is key to keeping astronauts healthy. We used a method called dry immersion to simulate space conditions by placing participants in a water tank for five days. This study combined data from two European Space Agency campaigns to compare male and female responses. We observed similar multi-system changes in both sexes. However, women showed lower tolerance to simulated gravity stress after immersion, more signs of reduced insulin sensitivity, and stronger bone loss markers. These findings support the development of sex-specific strategies to protect astronaut health during space missions. Robin et al. use dry immersion to assess cardiovascular and metabolic responses to 5 days of simulated microgravity in healthy women and men. They find pronounced but largely similar deconditioning in both sexes, supporting dry immersion as a robust ground-based model for spaceflight-related physiological changes.