PONE-D-23-42766Xenoestrogen concentration in women with endometriosis or leiomyomas: A case-control studyPLOS ONE

Dear Dr. Valdes-Devesa,

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Academic Editor

PLOS ONE

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Additional Editor Comments:

Dear Authors,

Thank you very much for submission to Plos One.

Our reviewers have commented on your manuscript.

Please revise the manuscript according to their comments.

I look forward to your revision soon.

Sincerely,

Kazunori Nagasaka

PLoS One

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Partly

Reviewer #3: No

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: No

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The aim of this study was to examine xenoestrogen concentration differences between women with leiomyomas or endometriosis and control women and to study the relationship between the clinical and sociodemographic characteristics of these patients and their xenoestrogen levels.

Authors reported no association between omental xenoestrogen levels and leiomyomas or endometriosis but their presence, in most participants and their association with highly polluted areas, emphasizes the importance of limiting environmental exposure to these substances. An association between hormonal contraceptive use and xenoestrogen concentration was also found.

I have the following comments for the Authors:

• Please revise your English and check for typos and tense mistakes.

• Methods: Authors should state clearly the outcomes of the study, and which were the related endpoints.

Reviewer #2: In the manuscript entitled “Xenoestrogen concentration in women with endometriosis or leiomyomas:

A case-control study” by Valdes-Devesa et al., the Authors analyzed the possible correlation between xenoestrogen concentration and the occurrence of leiomyomas or endometriosis in a case-control study. The study demonstrated that no statistically significances between TEXB- α and the uterine pathologies. The topic is interesting but some concerns should be addressed:

1. The Authors should modify the Abstract and add a background about Endocrine disrupting chemicals (EDCs) and Xenoestrogen

2. (line 89) “….with other non hormonal benign diseases”, specify them.

3. (line 110) “….17-β-estradiol was added to the culture”, of what?

4. (line 116) “The minimum concentration of TEXB-α required to elicit a significant proliferative effect”, of what?

5. It is not clear why in the Materials and Method the Authors reported “control group included women with other non hormonal benign diseases or pregnant women who needed a cesarean section”, instead in the Statistical analysis the said “In order to homogenize the groups, we performed a comparison of xenoestrogen concentrations including only pregnant women in the control group”. Are there different control groups? It is confusing.

Reviewer #3: Thank you for the opportunity to review this manuscript. I have several concerns.

1. Comparison Between Pregnant and Non-Pregnant Participants

a. Mean Xenoestrogen Levels: It is crucial to address potential differences in mean xenoestrogen levels between pregnant (control) and non-pregnant (case) participants. Factors such as gestational age in pregnant women and different basic characteristics like age and BMI between the two groups could significantly impact the results. Authors should consider including a validation to compare them. Additionally, the type of surgery (laparotomy vs. laparoscopic) could also affect the outcomes and should be addressed.

2. Study Protocol Clarity

a. Study Sample Enrollment Flow: A visual representation of the study sample enrollment flow, possibly in a figure, would greatly enhance clarity. This includes the explanation of the idea that they collected only pregnant women for the control group and only non-pregnant women for the case group.

b. Xenoestrogen Measurement: More details are needed regarding the materials and methods for measuring xenoestrogens in serum. In my opinion, it was uneasy to detect which material (omental fat or serum) was used for measurements in the Methods and Results section.

3. Clinical Implications

a. Clinical Implications: The manuscript should discuss more about the clinical implications of finding higher TEXB-alpha levels in women living or working in the Madrid Community within the case group, but not in the control group.

b. Effect of Time: Consider discussing whether the eight-year gap between finishing treatment and surgery could have affected xenoestrogen concentrations. Clarification is needed regarding the rapid metabolism of estrogens from contraceptives (lines 289-291).

Minor Comments:

1. Clarify the exact number of cesarean section cases instead of stating "approximately 90%".

2. Define "Madrid Community" and whether it refers to an urban area or a specific region.

3. Results mentioned in lines 206-211 and 227-230 should be presented as figures for better comprehension.

4. Clarify whether xenoestrogen levels were higher or lower in this study compared to the ENDO study (lines 268-270).

5. Consider presenting results for the control group similar to Figure 2.

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: No

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Attachments

Attachment

Submitted filename: Reviewers comments.docx

Xenoestrogen concentration in women with endometriosis or leiomyomas:

A case-control study

PONE-D-23-42766R1

Dear Dr. Valdes-Devesa,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Kazunori Nagasaka

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Dear Authors,

Congratulation!

I am pleased to tell you your manucript is acceptable for publication in PLos One.

The manuscript is very interesting and useful.

We look forward to your future manuscript and please submit to our journal.

Sincerely,

Kazunori Nagasaka

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: (No Response)

Reviewer #2: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: (No Response)

Reviewer #2: Yes

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: (No Response)

Reviewer #2: Yes

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4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: (No Response)

Reviewer #2: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: (No Response)

Reviewer #2: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: I kindly thank the authors for answering to all my comments. I believe the article was greatly improved with revisions and is now suitable for publication.

Reviewer #2: I have no additional comments. Authors have addressed and answered all the Reviewer' points. It is now suitable for publication.

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

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