Cerebral blood flow regulation in women across menstrual phase: Differential contribution of cyclooxygenase to basal, hypoxic, and hypercapnic vascular tone

Abstract

In healthy young women, basal cerebral blood flow (CBF) and cerebrovascular reactivity may change across the menstrual cycle, but mechanisms remain untested. When compared with the early follicular phase of the menstrual cycle, we hypothesized women in late follicular phase would exhibit: 1) greater basal CBF, 2) greater hypercapnic increases in CBF, 3) greater hypoxic increases in CBF, and 4) increased cyclooxygenase (COX) signaling. We measured middle cerebral artery velocity (MCAv, transcranial Doppler ultrasound) in 11 healthy women (23 ± 1 yr) during rest, hypoxia, and hypercapnia. Subjects completed four visits: two during the early follicular (~day 3) and two during the late follicular (~day 14) phases of the menstrual cycle, with and without COX inhibition (oral indomethacin). Isocapnic hypoxia elicited an SPO2 = 90% and SPO2 = 80% for 5 min each. Separately, hypercapnia increased end-tidal CO2 10 mmHg above baseline. Cerebral vascular conductance index (CVCi = MCAv/MABP·100, where MABP is mean arterial blood pressure) was calculated and a positive change reflected vasodilation (ΔCVCi). Basal CVCi was greater in the late follicular phase (P < 0.001). Indomethacin decreased basal CVCi (~37%) and abolished the phase difference (P < 0.001). Hypoxic ΔCVCi was similar between phases and unaffected by indomethacin. Hypercapnic ΔCVCi was similar between phases, and indomethacin decreased hypercapnic ΔCVCi (~68%; P < 0.001) similarly between phases. In summary, while neither hypercapnic nor hypoxic vasodilation is altered by menstrual phase, increased basal CBF in the late follicular phase is fully explained by a greater contribution of COX. These data provide new mechanistic insight into anterior CBF regulation across menstrual phases and contribute to our understanding of CBF regulation in women.