Reviewer’s report
Title: 
Can TSH level and premenstrual spotting constitute a non-invasivemarker
for the diagnosis of endometriosis?
Version: 
1 
Date: 
06 Aug 2021
Reviewer's report:
Dear authors, I appreciate the effort, but I still identify elements that can
seriously compromise the methodological design and, consequently, the
interpretation of the results.
The authors added superficial information in the introduction regarding the
relationship between endometriosis and ovarian cancer, metabolomics, genetics
and microbiome. However, when I comment on the weakness of the hypothesis, I
recommend making clear the plausibility of using TSH as a marker for
endometriosis. This plausibility is important to avoid searching for spurious
association markers.
The authors intend "to evaluate whether a combination of common markers for
endometriosis can increase the accuracy of a non-surgical diagnosis." but
investigate which markers???
The characterization of the casuistry is still poor. There is a paucity of clinical
data with the greatest potential to predict endometriosis. The absence of this
information in the regression models compromises the result and its
interpretation. It is not possible to exclude the role of confounding variables.
I understand that the casuistry is one of convenience, but the power of the test
still seems very low to me. I'm not convinced we have enough confidence to rule
out the null hypothesis.
If the authors seek to assess whether the TSH level would be a marker of
endometriosis, it does not seem appropriate to include women ingesting
levothyroxine in the experimental group. These patients should be excluded from
the sample, but this would further reduce the power of the test.
In my opinion, the authors need to redo the analysis considering the continuous
values 
​​
of the TSH, not categorized.
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Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
No
Are the methods sufficiently described to allow the study to be repeated?
No
Is the use of statistics and treatment of uncertainties appropriate?
No
Is the presentation of the work clear?
No
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes