Title: Associations of luteal phase changes in vagally mediated heart rate variability with
premenstrual emotional changes
Version: 1 Date: 21 Nov 2023
Reviewer's report:
This paper describes an interesting study of the relationship between among menstrual cycle
phase, heart rate variability (HRV) and negative affect, which presumably is related to
fluctuating hormone levels (estrogen (E2) and progesterone (P4). This is an important topic from
both basic and applied perspectives; it potentially adds to knowledge of autonomic (ANS) and
hormonal interactions as it pertains to affect, and could be of benefit in regard to a biomarker
for PMDD. The paper is generally well written and communicates clearly and succinctly. The
authors appear propose clear hypotheses and appear to have exercised methodological rigor in
verifying menstrual phase in the subjects. The results were in general unexpected and contrary
to the hypotheses, which renders them difficult to interpret. This does not necessarily mean they
aren’t worth publishing, but it is important to view them in proper context in order for them to
make a meaningful contribution to the literature. I detail these and other points below:
(1) The introduction is clear exposition of the distinct factors under study: hormonal fluctuations
associated with menstrual cycle phase, negative affect in the luteal phase, and HRV in relations
to these phases. The logic flows smoothly and coherently leads to the hypotheses. The
material is presented efficiently and succinctly, which I appreciated. I have a few questions
concerning the hypotheses. Is hypothesis 1 essentially confirming replication of individual
differences in emotional hormone sensitivity found in previous studies? Next, perhaps some
clarification of what operationally is meant by the speed of perimenstrual increases and
postmenstrual reductions. Does this mean a shorter latency of the onset of increases? Ditto
“slower postmenstrual reduction” (hypothesis 2)—does this mean a more sustained response
(i.e., slow return to baseline)?
(2) Subjects were “generally mentally healthy“–does this mean that subjects with PMDD were
excluded? This is an important point to clarify, because if yes, then the range of emotional
symptoms would be limited, as well as the generalizability of findings to a relevant group.
(3) It is good that the mood ratings were taken at a consistent time of day across subjects. I
wonder, though, about diurnal variations in mood. Might there be consistent circadian mood
variations across individuals, as well as individual differences in these patterns? (e.g., “morning
people” vs. “night owls”)? I tried to find studies on this phenomenon, but the literature seemed
limited to studies of depression. Perhaps the authors have some insights to share here. If not,
perhaps acknowledge this possibility in the discussion.
(4) Do you have demographic data on the ethnic/racial composition of the subject pool?
I’m a little confused as to how the ANOVA showing that including random effects of      cycle
day significantly improved model fit over a model without random effects maps onto Table 3;
please clarify.
(5) The biggest concern is how to interpret the unexpected findings that were contrary to
hypothesis 2, especially in view of the small number of subjects that composed the three post
hoc HRV groups. This is a crucial question that bears on the merits of publishing the results. On
one hand, the study was carefully conducted, and the results do seem to indicate the existence
of sub-types of HRV responders (relative to cycle phase). That there is variation the degree
of HRV reduction to the mid-luteal phase is not surprising, but that some people show the
*opposite* pattern (i.e., increases) is striking, and seems worthy of further investigation. As
to why the latter group is the one that showed great affective reactivity, counter to hypothesis
2, can only be explained by speculation. The authors invoke emotion regulation effort as a
possible explanation, which seems plausible, but not verifiable by these data. But as Gross and
colleagues have pointed out, different emotion regulation strategies have different physiological
consequences. For example, cognitive reappraisal seems to evoke less sympathetic activation
(and possibly more vagal activation as indexed by HRV) than emotion suppression—but this
also depends on context. Perhaps the authors could address this issue as a part of the discussion
of regulatory effort eliciting elevations in HRV.
(6) Regarding the cited U-shaped relationship between HRV and depression, I wonder how that
applies to the present findings that , neither the small decrease nor the large decrease group
showed the expected linear and quadratic effects of cycle day on their negative affect severity.
The specific procedure/conditions under which resting state was recorded needs to be described
in more detail.
In sum, this is an intriguing study that was carefully conducted and addressed an important topic
both scientifically and in relation to women’s health. The question is whether the small sample
size and unexpected finding compromise it’s publication value; this is a decision that the editor
must ultimately make. That said, I do think it would be of interest to readers of this journal, and
to the field of endocrinology and women’s health.