Title: Early menopause is associated with higher disease activity independent of inflammation
in postmenopausal-onset rheumatoid arthritis
Version: 1 Date: 24 Dec 2024
Reviewer:  Claudiu C. Popescu
Reviewer's report:
1. “However, the exact interval between menopause and RA onset remains unclear.” – please
note that there is not any interval between menopause and RA onset. This is not the question.
Please rephrase to better capture your communication intention.
2. “The exclusion criteria were as follows” – did you take into consideration excluding patients
with polycystic ovary syndrome or specific medications (androgen inhibitors, anti-estrogens)?
If so and if relevant, please update the exclusion criteria.
3. “use of Mirena ring” – first, please note the it is not a “ring”, but a “intrauterine device” (IUD);
second, “Mirena” is a trade name, I would not use it unless I want to advertise it, therefore I
suggest a more neutral text, involving for example IUD and levonorgestrel. See also results.
4. “Clinical assessments and data collection” – it is not clear from the text if the authors did these
tests (clinical interview, clinical examination, X-ray interpretation) or if they were done by each
attending physician from the hospital. This should be clear as it impacts data errors/variability.
5. “menopause occusing before age of 40 years” – please spell “occurring”.
6. “erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), mTSS, JSN and JE was
normalized” – this piece of information from the Statistics section mentions 2 blood tests (ESR
and CRP), yet the Methods do not mention blood sampling for them. Please update the Methods
to report blood sampling, normal values of acute phase reactants and if it was done in the same
day for each patient with the clinical evaluation.
7. “a median disease duration of 79 months (IQR 27-132)” – first, you mentioned in the Statistics
section that you report non-normally distributed data as “median (IQR)” therefore there is no
need to write “IQR” again in the results; second, the IQR is defined as the difference between the
75th (3rd quartile) and 25th (1st quartile) percentiles of the data, therefore it is a single number,
not an interval like you wrote “27-132” (this is probably minimum-maximum, which is another
valid way to report non-normally distributed variables). So, the correct way to report the median
disease duration would be “79 (88) months” or whatever IQR you calculate.
8. “Among them, 383 patients (69.0%) had positive RF, 379 (68.2%) had positive ACPA” – this
piece of information from the Results section mentions 2 blood tests (RF and ACPA), yet the
Methods do not mention blood sampling for them. Please update the Methods to report them
and also report their normal values and if they were done in the same day for each patient with
the clinical evaluation. Please also see the Tables for this.
9. Figure 2 A – please get rid of the gridlines, nobody uses them anymore, they take attention
from the distribution lines.
10. “our results supported that the peak onset years of RA in women coincided with the
menopausal transition” – please note the use of the verb “to support” is unnatural for English in
this context. Please rephrase since the conclusions need to be extremely clear.
11. “This EM-related non-inflammatory disease activity imply treatment strategy rather than
more aggressive DMARD therapy.” – I am sorry to say, but I do not understand this phrase.
First, it is “implies” rather than “imply” since the subject is “activity”. Second, do you wish to
say that in early menopause RA patients we need to be more aggressive with the treatment? If
so, please be aware that this is not understood from your text, so rephrase.
12. “Further prospective studies are warranted.” – please note that concluding that “further
prospective studies are warranted” is not valid. The conclusion of your study should reflect the
results in the light of the literature and any explanation you may find to describe them. If you
conclude that other studies are necessary, you should not have done the study in the first place.
If further studies are necessary, you can indicate this in the Discussion section.