Sex Differences in Cardiovascular Responses to Head-Up Tilt in Middle-Aged Healthy Adults

Head-up orthostatic tilt (HUT) induces passive gravitational effects, decreasing cerebral blood flow (CBF) and mean arterial pressure (MAP). Compensatory mechanisms prevent excessive decreases in CBF and MAP. Biological sex and age can influence these mechanisms, leading to altered cardiovascular responses. While females typically have higher CBF compared with males earlier in life, this difference is diminished later in life. There is limited research on sex differences in the cardiovascular and cerebrovascular responses to HUT in middle-aged adults. The objective of this study was to investigate sex differences in cerebrovascular and cardiovascular responses to HUT among middle-aged healthy adults. We hypothesized middle-aged adults would have similar middle cerebral artery velocity (MCAv) at baseline and during HUT. Twenty-five healthy adults between 50-65 years of age were recruited for this study (56±5 years; 12 Males/13 Females). Participants were instrumented while lying supine on a tilt table. Following a baseline period, participants were tilted upright at 30°, 45°, and 60° for 3 minutes. For each level, MCAv, MAP, heart rate (HR), and stroke volume (SV) were recorded continuously. At baseline, there were no differences between females and males respectively in MCAv (65±14 cm/s vs 51±11 cm/s; P=0.06), MAP (105±10 mmHg vs 102±11 mmHg; P=0.46), HR (59±7 bpm vs 55±8 bpm; P=0.14), and SV (92± 44 mL vs 88±18 mL; P=0.71). As expected, MCAv significantly decreased at 45° and 60° of HUT in both sexes (p<0.05). At 45° and 60° of HUT, females had a higher MCAv than males (45°: 61±13 cm/s vs 51±10 cm/s, and 60°: 60±13 cm/s vs 45±10 cm/s, respectively; p<0.05 for both). There were no sex differences in MCAv during 30°of HUT (Females: 61±15 cm/s vs Males: 52±11 cm/s; P=0.10). There were no differences between males and females for absolute changes in HR (13±7 bpm vs 12±6 bpm; P=0.88), SV (-10±11 mL vs -15±18 mL; P=0.41), or MAP (-9±8 mmHg vs -8±8 mmHg; P=0.76) during HUT. The percent decline in MCAv from baseline to 60° HUT was greater in males compared with females (-18±14% vs -7±9%, respectively; p<0.05), but no differences were observed between males and females in percent changes in HR (23±10% vs 21±12%; P=0.67), SV (-11±11% vs -15±16%; P=0.44), or MAP (-9±8% vs -7±8%; P=0.71) during HUT. Taken together, there were no sex differences in the decrease MAP in response to HUT, yet middle-aged females appear to better maintain MCAv during orthostatic stress compared with middle-aged males. Future studies can investigate the mechanisms underlying this sex difference. Funding: American Heart Association and National Institutes of Health This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.