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→ Thank you for your comment. We have ensured that the manuscript meets PLOS ONE's style requirements.

2. Please provide additional details regarding participant consent. In the ethics statement in the Methods and online submission information, please ensure that you have specified (1) whether consent was informed and (2) what type you obtained (for instance, written or verbal, and if verbal, how it was documented and witnessed). If your study included minors, state whether you obtained consent from parents or guardians. If the need for consent was waived by the ethics committee, please include this information.

→ We did not obtain informed consent from individuals because we did not collect data for the study (line 89).

If you are reporting a retrospective study of medical records or archived samples, please ensure that you have discussed whether all data were fully anonymized before you accessed them and/or whether the IRB or ethics committee waived the requirement for informed consent. If patients provided informed written consent to have data from their medical records used in research, please include this information.

→ The patient records were anonymous before being released by the KNHANES. This study was approved by the Institutional Review Board of Ewha Medical Center (lines 90-91).

3. Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

→ Thank you for your valuable suggestion. We have reviewed the Reference list and corrected the format of References 3, 11, and 15.

Additional Editor Comments:

1. Abstract : the results do not give actual figures , like mean age is not mentioned, and BMI is not mentioned and cholesterol. Statistical measures are not mentioned

→ Thank you for highlighting this point. We have added the mean values to the Abstract. As you suggested, we have included the following information in the Abstract:

“Differences between groups adjusted for age and BMI were assessed.”

2. Line 53, second paragraph starts with ‘however”. Please change that .

→ Thank you for your feedback. We have removed “however” from the first sentence of the second paragraph in the Introduction.

3. Please describe the study outcome clearly

→ Thanks for your advice. As you suggested, we have included the following information in the Discussion, lines 254-255:

“In conclusion, we observed an association between menopausal status and increased total cholesterol levels only in non-obese subjects among middle-aged Korean women.”

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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: Yes

Reviewer #3: Yes

________________________________________

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

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: I Don't Know

________________________________________

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

________________________________________

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

________________________________________

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: This is an interesting study. BMI based difference in cardiovascular risk factors is well knows factor evident from your background too. I wonder if this is due to the limitation of available data that other factors such as smoking status, Family history of premature CVD are not assessed? Post-menopausal women are older than menopausal women are a universal fact.

→ Thanks for your advice. We have included the following details in the Discussion, lines 245-248: “Although we adjusted for potential confounding factors (age and BMI), residual confounding factors (smoking, alcohol intake, physical activity, dietary habits, or family history of premature cardiovascular diseases) could have influenced the results of our study.”

One thing that need some re writing is the result part. It was difficult for me to make a sense of results and i think partly it is due to the fact that there is duplication of what is written in words as it is in table. Can you make your result part easier for the readers? so that they make a good sense.

→ Thanks for your feedback. We have revised the Results (lines 138-144) as follows:

“The association between menopausal status and total cholesterol according to BMI was similar in the subgroup analysis. Subgroup analysis for 138 postmenopausal and 138 age- and BMI-matched premenopausal women showed that postmenopausal women had higher total cholesterol levels than premenopausal women with marginal significance in total (201 ± 25 mg/dL vs. 196 ± 27 mg/dL, P = 0.091) and non-obese subjects (201 ± 25 mg/dL vs. 194 ± 25 mg/dL, P = 0.060); however, total cholesterol levels did not differ between postmenopausal and premenopausal women in obese subjects (206 ± 23 mg/dL 141 vs. 205 ± 36 mg/dL, P = 0.944).”

Reviewer #2: The study investigates an important question to evaluate the effect of menopause on cardiovascular risk factors, accounting for age and BMI. The subjects were analyzed in two groups: premenopausal and postmenopausal. All participants were free from traditional cardiovascular risk factors like diabetes mellitus, dyslipidemia and hypertension. They used a nationally representative sample. The menopausal status showed a significant relationship with increased glucose and cholesterol levels independent for age and BMI, particularly in non-obese women. This highlights the importance of monitoring and addressing the lipid levels to prevent cardiovascular disease during menopause tradition, particularly in the non-obese women ( traditionally may be considered low risk). Menopausal status was an independent predictor predictor of higher HbA1C levels. Statistical analysis was robust using multiple linear regression to determine independent association between menopausal status and total cholesterol after controlling for age , weight status, systolic blood pressure. They also looked at association of menopause and glycemic status (HbA1C) after controlling for age, BMI, systolic blood pressure and total cholesterol.

Reviewer #3: The topic is interesting. The authors have discussed the effect of menopause on cardiovascular risk factors which are important determinants of morbidity and mortality in menopausal women.

The statistical analysis needs to be verified by a statistician.

→ Thanks for your advice. We consulted a statistician and deleted the results of standardized coefficients in multiple linear regression analyses.

Overall language used is correct but there were a few grammatical errors that need to be corrected.

→ Thank you for your feedback. We have proofread the manuscript again for grammatical and typographical errors.

Discussion should be more crisp.

→ Thank you for raising this point. We have revised the Discussion as follows:

“Menopausal status was associated with increased total cholesterol levels only in non-obese women.” (lines 221-222)

“We excluded subjects with a history of diabetes, hypertension, or dyslipidemia because underlying diseases may affect cardiovascular risk factors.” (lines 239-241)

“In conclusion, we observed an association between menopausal status and increased total cholesterol levels only in non-obese subjects among middle-aged Korean women.” (lines 254-255)

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

After adjustment for age and BMI in non-obese subjects (not obese subjects), postmenopausal women exhibited higher HbA1c and total cholesterol levels than premenopausal women.

→ Thank you for your comment. We have revised the sentence as follows:

“After adjustment for age and BMI, postmenopausal women exhibited higher HbA1c and total cholesterol levels than premenopausal women only in non-obese subjects.” (Results, lines 133-134)

Subgroup analysis for 138 postmenopausal and 138 age- and BMI-matched premenopausal women 138 showed that postmenopausal women had higher total cholesterol levels than premenopausal women with marginal significance in total (201 ± 25 mg/dL vs. 196 ± 27 mg/dL, P = 0.091) and non-obese subjects (201 ± 25 mg/dL vs. 194 ± 25 mg/dL, P = 0.060) but not in obese subjects (206 ± 23 mg/dL 141 vs. 205 ± 36 mg/dL, P = 0.944).

→ Thank you for your comment. We have revised the Results as follows:

“Subgroup analysis for 138 postmenopausal and 138 age- and BMI-matched premenopausal women showed that postmenopausal women had higher total cholesterol levels than premenopausal women with marginal significance in total (201 ± 25 mg/dL vs. 196 ± 27 mg/dL, P = 0.091) and non-obese subjects (201 ± 25 mg/dL vs. 194 ± 25 mg/dL, P = 0.060); however, total cholesterol levels did not differ between postmenopausal and premenopausal women in obese subjects (206 ± 23 mg/dL 141 vs. 205 ± 36 mg/dL, P = 0.944).” (lines 138-144)

Menopausal status showed a significant relationship with increased total cholesterol levels even after adjusting for age and BMI in non-obese women, not obese women.

→ Thank you for your valuable suggestion. We have revised the Discussion as follows:

“Menopausal status showed a significant relationship with increased total cholesterol levels, even after adjusting for age and BMI in non-obese women. However, total cholesterol levels did not differ between postmenopausal and premenopausal subjects in obese women.” (lines 156-160)

The prevalence of metabolic syndrome increased during the menopausal transition in 949 women without diabetes, or the metabolic syndrome at baseline was independent of aging in the Study of Women’s Health Across the Nation.

→ Thank you for the suggestion. We have revised the Discussion as follows:

“The prevalence of metabolic syndrome increased during the menopausal transition in 949 women without diabetes or the metabolic syndrome at baseline was independent of aging in the Study of Women’s Health Across the Nation.” (lines 188-190)

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