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

What is the central question of this study? The purpose of this study was to determine intra-individual reproducibility of follicular phase changes in endothelial function (flow-mediated dilatation) over two menstrual cycles in healthy, premenopausal women. What is the main finding and its importance? Phase changes in endothelial function were not consistent at the individual level across two menstrual cycles, which challenges the utility of interpreting individual responses over one cycle.

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 (E₂ ; a primary female sex hormone). The purpose of this study was to examine changes in endothelial function from the early follicular (EF; low-E₂ ) phase to the late follicular (LF; high-E₂ ) 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)], E₂ 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.