Reduced orthostatic tolerance is common following periods of bed rest that are associated with illness or surgery, putting individuals at higher risk for syncope and falls following hospitalization. Following menopause, mechanisms of female cardiovascular regulation change, which may be associated with sex-specific responses to orthostatic stress following bed rest. The purpose of our experiment was to investigate sex differences between healthy postmenopausal women and similar-age men (age: 55-65 yr) for their orthostatic tolerance and cerebrovascular responses to standing following bed rest. Twenty-two late-middle-aged adults (11 women) completed 14 days of head-down bed rest, with half of the participants being randomized into an exercise group that performed high-intensity exercise during bed rest. Supine-to-stand tests were performed before and similar to 5 h after bed rest. Women had lower orthostatic tolerance than men after bed rest (bed rest x sex interaction: P = 0.004), without a protective effect of daily exercise. Both men and women were mildly hypocapnic while supine (main effect: P = 0.019) following bed rest and had lower middle cerebral artery blood velocity (MCAv) nadirs upon standing (main effect: P = 0.027). During the third minute of standing, both men and women had lower end-tidal Pco(2) (main effect: P < 0.001) and MCAv (main effect: P = 0.002) after bed rest, but only men had increased cerebrovascular resistance index (bed rest x sex interaction: P = 0.005) and only women were hypotensive (bed rest x sex interaction: P = 0.020) compared with pre-bed rest. Accordingly, lower MCAv of postmenopausal women and men while standing after bed rest was mediated by different factors. NEW & NOTEWORTHY Postmenopausal women had lower orthostatic tolerance than similar-age men while standing post-bed rest. Both sexes exhibited lower cerebral blood velocity nadirs upon standing; however, sex-specific interactions of the determinants of cerebral perfusion (i.e., Pco(2), cerebrovascular resistance index, and arterial pressure) were observed during prolonged standing after bed rest. These results indicate that postmenopausal women and men have different factors underlying reduced cerebral perfusion while standing after bed rest.
