The impact of menstrual phase on brachial artery flow‐mediated dilatation during handgrip exercise in healthy premenopausal women

Abstract

What is the central question of this study? The aim of this study was to determine the influence of menstrual phase on flow-mediated dilatation in response to sustained, exercise-induced increases in shear stress. What is the main finding and its importance? We showed, for the first time, that in healthy, premenopausal women the flow-mediated dilatation stimulated by exercise-induced increases in shear stress did not fluctuate across two phases of the menstrual cycle, despite significant fluctuations in oestrogen. This suggests that endothelial function is not consistently augmented in the high-oestrogen phase. Flow-mediated dilatation (FMD) in response to a sustained shear-stress stimulus (e.g. via handgrip exercise; HGEX) is emerging as a useful tool for assessing endothelial function; however, the impact of menstrual phase on HGEX-FMD is unknown. The purpose of this study was to determine whether HGEX-FMD fluctuates with cyclical changes in oestrogen concentrations over two discrete phases (low and high oestrogen) of the menstrual cycle. Brachial artery (BA) diameter and blood velocity were assessed with two-dimesional and Doppler ultrasound, respectively. Shear stress was estimated using shear rate (SR = BA blood velocity/BA diameter). Participants (12 healthy, regularly cycling women, 21 ± 2 years of age) completed two experimental visits: (i) low oestrogen (early follicular, EF); and (ii) high oestrogen (late follicular, LF). Reactive hyperaemia-stimulated FMD (RH-FMD) and HGEX-FMD (6 min of handgrip exercise) were assessed during each visit. Results are mean values ± SD. Oestrogen increased from the EF to LF phase (EF, 33 ± 9 pg ml ; LF, 161 ± 113 pg ml , P = 0.003). However, neither the SR stimuli (HGEX, P = 0.501; RH, P = 0.173) nor the FMD responses differed between phases (EF versus LF: HGEX-FMD, 4.8 ± 2.8 versus 4.6 ± 2.2%, P = 0.601; RH-FMD, 7.9 ± 4.3 versus 6.4 ± 3.1%, P = 0.071). These results extend existing RH-FMD findings indicating that not all women experience fluctuations in FMD with the menstrual cycle. Further research is needed to investigate the mechanisms that underlie variability in the impact of menstrual phase on FMD.

The influence of acute hyperglycaemia on brachial artery flow‐mediated dilatation in the early and late follicular phases of the menstrual cycle

“…This is inconsistent with the dominant understanding that FMD is elevated in the LF phase (Adkisson et al, 2010;Harris et al, 2012;Hashimoto et al, 1995;Kawano et al, 1996;Williams et al, 2001). In contrast to seminal investigations, and in agreement with the present findings, the majority of recent studies have not detected changes in FMD throughout the menstrual cycle in healthy young women (D'Urzo et al, 2018;Luca et al, 2016;Rakobowchuk, Parsloe, Gibbins, Harris, & Birch, 2013;Saxena, Seely, & Goldfine, 2012;Shenouda, Priest, Rizzuto, & MacDonald, 2018). Elevated FMD during the LF phase is typically attributed to a positive impact of elevated estradiol on NO bioavailability (Adkisson et al, 2010;Cicinelli et al, 1996).…”

“…Although the estradiol concentrations in the LF phase of the present study were relatively low [∼290 pmol l −1 (Table 1), despite proximity to ovulation (∼3 days prior)] overall, studies that have identified elevated FMD in the LF phase relative to the EF phase have reported similar LF estradiol levels to studies reporting no impact of phase on FMD [elevated LF FMD: ∼560 pmol l −1 (Adkisson et al, 2010;Harris et al, 2012;Hashimoto et al, 1995;Kawano et al, 1996;Williams et al, 2001) versus no phase change in FMD: ∼580 pmol l −1 (D'Urzo et al, 2018;Luca et al, 2016;Rakobowchuk et al, 2013;Saxena et al, 2012;Shenouda et al, 2018)]. Furthermore, studies…”

“…to date, including recent studies by our group and others(D'Urzo et al, 2018;Shenouda et al, 2018), have not identified a relationship between circulating estradiol concentrations and FMD. Taken together, this suggests that insufficient elevation in estradiol during the LF phase FMD assessment does not fully explain the absence of phase differences in FMD.…”

“…Shear rate was calculated using the time‐aligned 3 s average blood velocity and diameter time bins, using the following expression: mean blood velocity/artery diameter. The SR stimulus for FMD was evaluated as an area under the curve (SR‐AUC) in the 30 s after cuff release (D'Urzo, King, Williams, Silvester, & Pyke, ; Pyke & Tschakovsky, ). Baseline SR is reported as the average shear rate in the 1 min before cuff inflation.…”

“…mean blood velocity/artery diameter. The SR stimulus for FMD was evaluated as an area under the curve (SR-AUC) in the 30 s after cuff release (D'Urzo, King, Williams, Silvester, & Pyke, 2018;Pyke & Tschakovsky, 2007). Baseline SR is reported as the average shear rate in the 1 min before cuff inflation.…”