Title: Associations of luteal phase changes in vagally mediated heart rate variability with
premenstrual emotional changes
Version: 1 Date: 28 Nov 2023
Reviewer:  Julia Sacher
Reviewer's report:
The authors present an interesting manuscript in which they explore HRV changes across the
menstrual cycle and whether midluteal HRV decreases predict more severe negative affect
premenstrually in healthy individuals who menstruate. Contrary to their hypothesis, the authors
found that only the subgroup who displayed luteal increases in vagally mediated HRV reported
negative affect markedly worsened premenstrually and improved postmenstrually.
We consider:
1. the longitudinal study design (3 assessment across the menstrual cycle)
2. the monitoring of ovulation by confirmation of LH surge, and
3. the counterbalancing of study visits according to menstrual cycle phase
as major methodological strengths of the manuscript.
Furthermore, the topic is highly relevant and adds a new perspective to the role of endogenous
ovarian steroids for cardiovascular and emotional regulation, an emerging frontier in women’s
health, thus the topic is timely. An additional commendable aspect is the establishment of a
clear and focused a-priori hypothesis, along with study-preregistration and transparent data
reporting, including outcomes that do not support the initial hypothesis. This adherence to
rigorous scientific practice strengthens the paper's credibility.
In summary, this manuscript is well written and demonstrates transparent methodology, and
clearly-defined research objectives and hypotheses. However, some areas need clarification.
Addressing these points would further refine the manuscript for potential publication in BMC
Women’s Health.
Methods:
- Include identifier/preregistration link info (OSF?)
- The authors outline three lab visits to measure cardiac vagal tone. However, while the proposed
HF-HRV change index focuses on ovulatory versus mid-luteal HF-HRV, it remains unclear
how the HRV recordings obtained during the perimenstrual lab visit factor into the investigation
of changes in negative affect. It would be beneficial to elucidate whether these recordings are
considered in the analysis. Theoretically, the extent of recovery of vagally mediated HRV,
or a return to ‘baseline’ values, may also contribute to improvements in negative affects
postmenstrually. This can be modelled in a similar way, and would prove a valuable control
analysis to demonstrate the specificity of the proposed ovulatory to mid-luteal HF-HRV change
index as a physiological marker for concurrent sensitivity to negative affect. To enhance the
manuscript's clarity, we recommend including an illustrative overview figure depicting the study
design, encompassing the assessed measures and analyses conducted throughout the study.
- The robustness of HF-HRV analysis typically relies on approx. 5 minutes of reliable data per
subject. It would be beneficial to clarify whether this was met for each participant and what
criteria were used for ECG data quality assessment (i.e., number of ectopic beats, percentages
of noisy data, etc.) throughout all assessments (as some of those contributors to signal noise
may also vary with menstrual cycle phase). This info could be incorporated in the study design
figure for improved illustration of the experiment. The manuscript might further benefit from
the authors providing a concise rationale for opting for frequency-domain measures (such as
HF-HRV) over time-based measures (e.g., RMSSD, which are thought to be more robust against
e.g. breathing-related confounds), considering the former's potential susceptibility to breathing-
related confounds.
- The manuscript's trichotomization of the continuous ovulation-to-midluteal HF-HRV change
index into three HRV Cyclicity presents a somewhat unconventional statistical approach. Given
that the categorizing of continuous variables can result in reduced statistical power, inappropriate
effect sizes, and information loss, the manuscript would benefit from clarifying the rationale
behind establishing three participant groups, as well as from the application of more nuanced
statistical methods, such a polynomial regression model allowing for multiple quadratic terms
or data-driven methods to determine thresholds based on optimizing specific test statistics.
Exploring such alternative methodologies that avoid the limitations associated with categorical
grouping would enhance the statistical robustness and depth of the analysis.
Discussion:
Given previous evidence of significant variations in heart rate and cardiac vagal tone across the
menstrual cycle, as evidenced in prior studies by the same research group, a notable gap in the
literature pertains to understanding sympathetic regulation at the cardiac level. Acknowledging
the difficulty in measuring cardiac sympathetic regulation through standard ECG could be
highlighted as a broader field limitation, potentially prompting future investigations to explore
this aspect further.
Minor:
1) Typo page 8 line 182: 'das' instead of 'days'
2) Maintain consistency in terminology: e.g. ‘vagally mediated HRV’, and not ‘HRV’
throughout the manuscript.