Individual variation of follicular phase changes in endothelial function across two menstrual cycles

Abstract

Evidence regarding the impact of menstrual phase on endothelial function is conflicting, and studies to date have examined responses only over a single cycle.It is unknown whether the observed inter-individual variability of phase changes in endothelial function reflects stable, inter-individual differences in responses to oestrogen (E 2 ; a primary female sex hormone). The purpose of this study was to examine changes in endothelial function from the early follicular (EF; low-E 2 ) phase to the late follicular (LF; high-E 2 ) phase over two consecutive cycles. Fourteen healthy, regularly menstruating women [22 ± 3 years of age (mean ± SD)] participated in four visits (EF Visit 1 , LF Visit 2 , EF Visit 3 and LF Visit 4 ) over two cycles. Ovulation testing was used to determine the time between the LF visit and ovulation. During each visit, endothelial function [brachial artery flow-mediated dilatation (FMD)], E 2 and progesterone were assessed. At the group level, there was no impact of phase or cycle on FMD (P = 0.48 and P = 0.65, respectively). The phase change in FMD in cycle 1 did not predict the phase change in cycle 2 (r = 0.03, P = 0.92). Using threshold-based classification (2 × typical error threshold), four of 14 participants (29%) exhibited directionally consistent phase changes in FMD across cycles. Oestrogen was not correlated between cycles, and this might have contributed to variability in the FMD response. The intra-individual variability in follicular fluctuation in FMD between menstrual cycles challenges the utility of interpreting individual responses to phase over a single menstrual cycle.

Variation in physiological function within and between menstrual cycles: uncovering the contributing factors

“…However, the present paper byLiu et al (2021) used this three-step method and still discovered substantial variability within and between menstrual cycles, demonstrating that the conflicting findings reported in the research to date might not be fully explained solely by methodological differences. Additionally, whilst the threestep method is suitable for identifying and verifying menstrual cycle phase, it might not be sufficient for eliminating heterogeneity within menstrual cycle research Liu et al (2021). examined the group-level and intra-individual reproducibility of early follicular to late follicular changes in FMD across two consecutive menstrual cycles in healthy, eumenorrhoeic women.…”

“…In a recent systematic review and meta-analysis investigating the effects of menstrual cycle phase on exercise performance, we highlighted that few of the included studies used the trio of recommended methods to identify and verify menstrual cycle phases, which might partly explain the large between-study variance reported in the results(McNulty et al, 2020). However, the present paper byLiu et al (2021) used this three-step method and still discovered substantial variability within and between menstrual cycles, demonstrating that the conflicting findings reported in the research to date might not be fully explained solely by methodological differences. Additionally, whilst the threestep method is suitable for identifying and verifying menstrual cycle phase, it might not be sufficient for eliminating heterogeneity within menstrual cycle research Liu et al (2021).…”

“…Finally, the bi-directional relationship between female sex hormones and lifestyle factors (e.g., stress, sleep, nutrition and exercise) is known to alter physiology, and could conceivably contribute to the intra-individual variability in physiological function between menstrual cycles. Collectively, the results of Liu et al (2021) demonstrate that physiological changes might not be the same across consecutive menstrual cycles. Therefore is it any wonder there is heterogeneity in the literature?…”

“…One example of this is the assessment of vascular function via flow mediated dilatation (FMD), with a recent systematic review and meta-analysis by Williams et al (2020) highlighting considerable heterogeneity between studies investigating the change in FMD across the menstrual cycle. In a recent issue of Experimental Physiology, Liu et al (2021) aimed to explore the heterogeneity in FMD changes across the menstrual cycle, in an attempt to elucidate the contributing mechanisms.…”

“…The intention of this experimental design is to reduce wileyonlinelibrary.com/journal/eph did not predict the phase change in FMD in cycle 2. As such, the findings from Liu et al (2021) suggest that in addition to experimental design, there are other mechanisms contributing to this heterogeneity.…”