Inter-individual Variability In Passive Leg Movement-induced Hyperemia And Arterial Stiffness Across The Menstrual Cycle

Abstract

There is variability in the impact of menstrual phase on arterial stiffness with some, but not all, studies reporting a decrease in arterial stiffness from the early follicular (EF; low estradiol) to the late follicular (LF; high estradiol) phase at the group or individual level. However, the mechanisms driving inter-study and inter-individual phase differences in arterial stiffness remain unknown. Vasorelaxation reduces arterial resistance and arterial stiffness. Variable increases in the endothelial-derived vasodilator nitric oxide with elevated LF estrogen may result in variable smooth muscle relaxation and thus variability in the impact of phase on arterial stiffness. It is speculated that inter-individual phase changes in nitric oxide dependent endothelial function will be related to inter-individual phase changes in arterial stiffness. PURPOSE: to investigate whether changes in endothelial function are related to changes in arterial stiffness across the menstrual cycle. METHODS: 11 premenopausal women (22±4 years) completed two visits; 1 in EF and 1 in LF phase. Salivary estradiol and leg endothelial function and arterial stiffness were tested during each visit. Endothelial function was quantified by the hyperemic response to passive leg movement (PLM) characterized by area under the curve leg blood flow (AUC LBF) and leg vascular conductance (AUC LVC) assessed via duplex ultrasound. Leg femoral-foot pulse wave velocity (PWV) was assessed via applanation tonometry. RESULTS: Estradiol increased from the EF to LF phase (p=0.014; EF=1.43±0.38, LF=1.60±0.43 pg/ml). At the group level, PWV decreased from the EF to LF phase (p=0.022; EF=7.98±1.48, LF=7.21±1.85 m/s). There were no group-level phase changes in AUC LBF (p=0.308; EF=132.50, LF=149.07 ml/min) or AUC LVC (p=0.344; EF=1.76±1.13, LF=1.96±1.06 ml/min/mmHg). Phase changes in PWV were not associated with phase changes in AUC LBF (r=0.171, p =0.616) or AUC LVC (r=0.247, p=0.464). CONCLUSION: Peripheral arterial stiffness decreased with a rise in estrogen in the LF phase, however, individual phase changes in arterial stiffness were not related to individual changes in endothelial function. Future research is needed to understand the mechanisms resulting in individual responses to fluctuations in endogenous estradiol. Funded by NSERC