Influence of sex, menstrual cycle, and oral contraceptives on cerebrovascular resistance and cardiorespiratory function during Valsalva or standing

Abstract

Women experience orthostatic intolerance more than men, and they experience faintness more in the early follicular [i.e., low-hormone (LH)] than luteal [i.e., high-hormone (HH)] phase of the menstrual cycle. Men (n = 13, 25.8 ± 1.8 yr old) and women in the LH (days 2-5; placebo) and HH (days 18-24; high dose) phases of the menstrual cycle with (OC; n = 14, 22.0 ± 0.8 yr old) or without (NOC; n = 12, 21.8 ± 0.5 yr old) oral contraceptive (OC) use underwent the Valsalva maneuver and a supine-sit-stand protocol. Blood pressure, normalized stroke volume [stroke volume index (SVi)], cardiac output index, heart rate, end-tidal CO₂, and middle cerebral artery (MCA) blood flow velocity were measured. When subjected to the Valsalva maneuver, all women had a greater increase in diastolic and mean MCA blood flow velocity than men (P ≤ 0.065), with no significant effect of menstrual cycle phase or OC use. When subjected to the supine-sit-stand protocol, men had lower MCA blood flow velocity (P < 0.038) than all women, and SVi was higher in men than in the NOC group in all postures (P < 0.011) and in the OC group in the LH phase of the menstrual cycle during standing (P = 0.010). Only men experienced higher resistance index (P < 0.001) and pulsatility index (P < 0.001) with standing. The OC group had lower end-tidal CO₂ (P = 0.002) than the NOC group (P = 0.030) and men (P ≤ 0.067). SVi (P = 0.004) and cardiac output index (P = 0.008) were higher in the OC than NOC group. A tendency toward a lower mean MCA blood flow velocity (P = 0.058) and higher SVi (P = 0.059) and pulsatility index (P = 0.058) was noted in the HH than LH phase. Mean arterial pressure was higher in the OC than NOC group in the LH phase (P = 0.049) and lower in the HH than LH phase (P = 0.014). Our results indicate that cycling estrogens/progestins can influence ventilatory, cardiovascular, and/or cerebrovascular physiology.NEW & NOTEWORTHY We have found sex differences in the cerebrovascular response to the Valsalva maneuver and standing. Men have greater cerebral vasoconstriction (or women have greater cerebral vasodilation) during late phase II of the Valsalva maneuver, and the cerebrovascular resistance index increases in men, but not in women, during standing. Furthermore, our findings indicate that both the menstrual cycle phase and oral contraceptive use can influence cardiovascular function both at rest and during active standing.

Keywords: cardiovagal baroreceptor sensitivity; center of balance; end-tidal gases; heart rate variability; hemodynamics.