Reviewer’s report
Title: 
Serum Antioxidant Vitamin Concentrations and Oxidative Stress Markers
Associated with Symptoms and Severity of Premenstrual Syndrome: A
Prospective Cohort Study
Version: 
0 
Date: 
04 May 2020
Reviewer's report:
This manuscript reports the results of a prospective study of 259 women
followed for two menstrual cycles in which the associations of premenstrual
symptoms with serum levels of antioxidants and oxidative stress were assessed.
In general, the manuscript is well-written. 
However, a number of comments, as
indicated below, should be addressed.
Major comments:
Because individual symptoms were largely the focus of these analyses, it would
seem that "PMS", premenstrual syndrome, throughout the manuscript should be
revised to "PMSx", premenstrual symptoms, particularly in the Discussion and
Conclusion sections, which would also better reflect the title of the manuscript.
Abstract: The first sentence of the Background suggests that the imbalance
between oxidative stress and antioxidant vitamins in relation to premenstrual
symptoms will be examined, but the study examined each of these independent
variables separately in relation to symptoms; so, the authors should consider
revising the wording of this section.
The Methods section should indicate the frequency and timing of blood draws
for assessing antioxidant vitamins and oxidative stress.
Methods: The first paragraph should provide a summary description of the
reference population or source of sampling as well as the methods used to
identify, select, recruit and screen for eligibility and the eligibility and
participation (among those eligible) rates so that readers can assess the potential
for selection and/or participation biases.
In the last paragraph on page 6, consideration should be given to determining
whether the blood values measured at certain times in the menstrual cycle were
related to premenstrual symptoms (eg, the mid- and late luteal phase and perhaps
menstrual measurements might be most relevant to premenstrual symptoms) or
provide a rationale for not using such an approach. 
The first two and last paragraphs of the subsection on Antioxidant vitamin and
F2-isoprostane Concentrations Assessment should include the limits of detection
for each of these measures.
Definitions of premenstrual symptoms usually require that symptoms disappear
within 1-3 days after the start of the menstrual period, but it is unclear from the
subsection on PMS Symptoms Severity Assessment if this was included in the
definition, and it should be considered.
The second paragraph of the subsection on PMS Symptoms Severity Assessment
should describe the methods used to determine the groupings of symptoms (eg,
factor analyses or similar methods) as the rationale for some groupings (eg,
hydration and cravings or all types of pain) is unclear.
In the second sentence of the subsection on Covariate Assessment the standard
instruments that were used for question about smoking and reproductive history
should be cited. 
It would also be helpful to know if a question on symptom
sensitivity was included as a covariate.
The second paragraph of the Statistical Analysis subsection should specify the
criteria used for including covariates in the multivariate models because it is
unclear why smoking, for example, was not included.
Results: 
In the last paragraph on page 11, "increasing" should be replaced with
"higher mean" because that is what Table 2 is reporting.
Supplemental Figure 1 required clarification because the number eligible and
ineligible are the same and sum to more than the number screened, and the
number enrolled and not enrolled are the same and sum to more than the number
eligible. 
Further the numbers who completed and withdrew do not total the
number enrolled. 
Discussion: Given that many of the observed individual significant associations
were no longer significant when adjustment for multiple testing was made, the
first sentence (and perhaps the second sentence) should be modified to reflect the
results of such adjustment, as should the second sentence of the Conclusions
section.
The fourth paragraph reports on the results of other studies that have examined
antioxidant and oxidative stress levels across the menstrual cycle, which
provides interesting information, but this was not examined in this study and
could have been; it would be a useful addition to the results.
The last paragraph should have an introductory sentence, such as "Our study also
had some limitations."
References: More than half of the references cited are more than 10 years old so
that papers cited in the Introduction and Discussion section that are 10 or more
years old should be reviewed and replaced, if possible, with more recent relevant
citations.
Minor comments:
The past tense should be used consistently in the Abstract, Methods and Results
sections, because the study has been completed, and as appropriate in the
Introduction and Discussion sections.
Abstract: In the first sentence of Methods section (and on line 63 in the Methods
section of the text of the manuscript), insert "years" after "18-44".
The first sentence of the Results section gives the impression that no associations
were observed, but then the remainder of the section reports significant
associations. 
So, at the end of the first sentence of the Results, the authors should
consider adding "but associations with selected symptoms were observed".
The third sentence of the Results section implies that F2-isoprostane was
examined as a continuous variable and thus that with each unit (not specified) of
increase the odds ratio was increased for each of the three symptoms reported
there. 
Either the units should be clarified, or "increasing" should be changed to
"increased".
Methods: Delete "in order" in line 106
BMI is used for the first time on line 144 and should thus be spelled out and the
computation defined.
Results: In line 185, replace "commonly" with "frequently", and in line 187
replace "common" with "frequently reported".
In line 192, "alpha-tocopherol" 
should be "alpha- and gamma-tocopherol".
Lines 203 and 207 should indicate "positive" associations.
In the title of Table 4, replace "PMS" with "number of symptoms".
Discussion: in line 252, consider adding "and generalizability" to the end of the
sentence.
Are the methods appropriate and well described?
If not, please specify what is required in your comments to the authors.
Yes
Does the work include the necessary controls?
If not, please specify which controls are required in your comments to the
authors.
Yes
Are the conclusions drawn adequately supported by the data shown?
If not, please explain in your comments to the authors.
Yes
Are you able to assess any statistics in the manuscript or would you
recommend an additional statistical review?
If an additional statistical review is recommended, please specify what aspects
require further assessment in your comments to the editors.
I recommend additional statistical review
Quality of written English
Please indicate the quality of language in the manuscript:
Acceptable
Declaration of competing interests
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