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Article
Peer-Review Record

Psychological, Relational, and Fertility-Related Characteristics of Italian Women with Vulvodynia: A Comparative Study with Controls

Int. J. Environ. Res. Public Health 2025, 22(4), 527; https://doi.org/10.3390/ijerph22040527
by Antonio Gattamelata 1,2,*, Giulia Fioravanti 3, Vanessa Prisca Zurkirch 4 and Nieves Moyano 1,2
Reviewer 1: Anonymous
Reviewer 2: Anonymous
Reviewer 3: Anonymous
Int. J. Environ. Res. Public Health 2025, 22(4), 527; https://doi.org/10.3390/ijerph22040527
Submission received: 28 February 2025 / Revised: 24 March 2025 / Accepted: 26 March 2025 / Published: 30 March 2025

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Dear authors,

 

thank you for the opportunity to read and review the manuscript.

The manuscript is well written and interesting as it highlights the impact of vulvodynia in both psychological and physical well-being of affected women. I have just few comments.

In the vulvodynia group, how was the diagnosis performed by the gynecologist? Vulvodynia is often a diagnosis of exclusion and great heterogeneity in diagnosis process could led to a selection bias.

In the control group, were all the histories of chronic pain excluded? (i.e. lower back pain/fibromyalgia etc)?

Table 1 should be placed in Results section.

In Procedure section the name of the university is missing.

Discussion section is interesting but should be shortened and more focused on the aim of the study.

Vulvodynia is associated to specifical psychological and behavioral patterns, and it can be a consequence or a cause; attachment anxiety and avoidance can be caused by vulvodynia or can also precede it. Indeed, high levels of physical or mental stress, fear and anxiety can determine pelvic stress reflex activation and pelvic floor muscles activation.

 

In limitation section a section on transgender people experiencing vulvodynia could be added, as it is a wide pathological condition that involves everyone who can experience it.

Supplemental material with the psychometric scales used could be added.

Further studies are needed to better evaluate this clinical condition.

Author Response

 Response to Reviewer 1

We sincerely thank the reviewer for their constructive feedback and insightful comments, which have helped us improve the quality of our manuscript. Below, we address each point raised in a detailed and scientifically grounded manner.

Comment 1: In the vulvodynia group, how was the diagnosis performed by the gynecologist? Vulvodynia is often a diagnosis of exclusion, and great heterogeneity in the diagnostic process could lead to selection bias.

Response:

We appreciate this important observation. The diagnosis of vulvodynia in the study participants was conducted following the standardized criteria outlined by the International Society for the Study of Vulvovaginal Diseases (ISSVD). Specifically, participants in the vulvodynia group were required to have received a confirmed diagnosis of vulvodynia from a licensed gynecologist, as verified through medical records or self-reported confirmation during the screening process.  As noted in the manuscript, vulvodynia is indeed a diagnosis of exclusion, requiring the absence of identifiable causes such as infections, dermatological conditions, or other systemic diseases. To minimize selection bias, we ensured that all participants in the vulvodynia group met the following criteria: (1) persistent vulvar pain lasting at least three months, (2) no identifiable cause for the pain after appropriate medical evaluation, and (3) confirmation of the diagnosis by a qualified healthcare professional.

While we acknowledge the potential for variability in diagnostic practices across clinicians, we attempted to mitigate this by recruiting participants exclusively from regions where specialized care pathways for vulvodynia have been implemented (e.g., the Diagnostic Therapeutic Care Pathways [PDTA] in Tuscany, Italy). These pathways aim to standardize diagnostic procedures and ensure timely, accurate diagnoses. Nonetheless, we agree that some degree of heterogeneity may remain, and we have added a note about this limitation in the revised manuscript.

Comment 2: In the control group, were all histories of chronic pain excluded? (i.e., lower back pain/fibromyalgia etc.)

Response:

Inclusion in the control group required participants to have no history of chronic pain conditions, including but not limited to lower back pain, fibromyalgia, migraines, or any other chronic pain disorders. This criterion was explicitly stated in the inclusion/exclusion criteria section of the Methods (see Section 2.1). 

To ensure compliance with this requirement, participants in the control group completed a detailed sociodemographic questionnaire, which included questions about their medical history. Any participant reporting a history of chronic pain was excluded from the study. We recognize the importance of maintaining a clear distinction between the groups to avoid confounding variables, and we have re-emphasized this point in the revised manuscript.

Comment 3: Table 1 should be placed in the Results section.

Response:

We agree with the reviewer that Table 1, which presents the sociodemographic characteristics of the study participants, is more appropriately placed in the Results section. This change has been made in the revised manuscript to improve the logical flow of information and ensure consistency with scientific writing conventions.

Comment 4: In the Procedure section, the name of the university is missing.

Response:

The choice to omit the name of the university (indicated as "BLINDED") was made to comply with the guidelines of the double-blind peer review process adopted by the journal. In this type of review, both the authors and the reviewers remain anonymous to each other to ensure an impartial and unbiased evaluation.  Double-blind peer review aims to eliminate potential biases related to geographic origin, institutional affiliation, or academic reputation of the authors. This ensures that the manuscript is evaluated solely based on its scientific merit. In the case of our manuscript, the name of the university was temporarily anonymized to respect this procedure. However, once the peer review process is concluded, the name of the University of Jaén will be inserted into the relevant section of the text (as noted in the previous response). This practice is widely accepted and justified within the context of anonymized review, as it ensures equity and transparency in the editorial process.

Comment 5: Discussion section is interesting but should be shortened and more focused on the aim of the study.

Response:

We appreciate the reviewer’s suggestion to streamline the Discussion section. In the revised manuscript, we have carefully edited this section to ensure it remains focused on the primary aim of the study: exploring the psychological, relational, and fertility-related challenges faced by women with vulvodynia.  Specifically, we have condensed subsections discussing broader implications and tangential topics, ensuring that the discussion aligns closely with the study’s objectives. For example, we have reduced the emphasis on general theories of chronic pain and instead highlighted findings directly relevant to vulvodynia. This revision aims to enhance clarity and maintain the reader’s focus on the key contributions of our research.

The current discussion provides a detailed analysis of how these factors interact and affect affected women. Reducing this section too much could compromise the ability to:

   - Explain the clinical impact of the observed differences (e.g., sexual functioning, relationship quality, resilience).

   - Contextualize the findings within the existing literature.

   - Offer a comprehensive view of the clinical implications and suggest targeted interventions.

Moreover, the study revealed significant differences across multiple psychometric domains (e.g., attachment, temperament, resilience, sexual functioning, relationship quality). Each domain requires specific discussion to:

   - Accurately interpret the results.

   - Highlight correlations with the existing literature.

   - Emphasize specific clinical implications.

The current discussion compares the study findings with previous studies, providing a solid scientific context. We believe that these comparisons are essential for demonstrating the validity and relevance of the study results. Guidelines from many scientific journals (such as the International Journal of Environmental Research and Public Health) encourage a detailed discussion that:

   - Clearly and comprehensively interprets the results.

   - Compares the findings with existing literature.

   - Provides practical implications and suggestions for future research.

An overly brief discussion may fail to meet these criteria, increasing the risk of additional revisions or rejections.

Comment 6: Vulvodynia is associated with specific psychological and behavioral patterns, and it can be a consequence or a cause; attachment anxiety and avoidance can be caused by vulvodynia or can also precede it. Indeed, high levels of physical or mental stress, fear, and anxiety can determine pelvic stress reflex activation and pelvic floor muscles activation.

Response:

This is an excellent point, and we fully agree with the reviewer. The bidirectional relationship between vulvodynia and psychological/behavioral patterns is a critical aspect of the condition. Chronic pain, such as that experienced in vulvodynia, can exacerbate attachment insecurity, anxiety, and avoidance behaviors. Conversely, pre-existing psychological vulnerabilities, such as attachment anxiety or high levels of stress, may predispose individuals to develop vulvodynia or worsen its symptoms through mechanisms such as pelvic floor muscle tension and central sensitization.

 

To address this comment, we have expanded the Discussion section to include a more nuanced exploration of the bidirectional nature of these relationships. Specifically, we have highlighted evidence suggesting that chronic stress, fear, and anxiety can activate the pelvic stress reflex, leading to increased pelvic floor muscle tension and potentially contributing to the onset or persistence of vulvodynia (references to relevant literature, such as Graziottin & Murina, 2011, have been added). This addition strengthens the interpretation of our findings and underscores the need for integrated treatment approaches that address both psychological and physiological factors.

Comment 7: In the Limitations section, a subsection on transgender people experiencing vulvodynia could be added, as it is a wide pathological condition that involves everyone who can experience it.

Response:

We agree with this important observation. While our study focused exclusively on cisgender women due to the specific recruitment criteria and the population targeted by existing diagnostic frameworks, we recognize the need to acknowledge the experiences of transgender and gender-diverse individuals who may also be affected by vulvodynia. 

In the revised manuscript, we have added a new subsection in the Limitations section addressing this gap. Specifically, we note that future research should explore the prevalence, clinical presentation, and unique challenges faced by transgender and non-binary individuals with vulvodynia. This would provide a more comprehensive understanding of the condition and inform inclusive care practices.

Comment 8: Supplemental material with the psychometric scales used could be added.

Response:

We agree that providing supplemental material with the psychometric scales used in the study would enhance transparency and reproducibility. In the revised manuscript, we have included a Supplementary Materials section, which provides detailed descriptions of the scales (e.g., ECR-12, ATQ, RS-14, FPI-SF, FSFI, DAS-7, BDI) and their validation processes. Additionally, we have uploaded the full versions of the scales as supplementary files to the journal’s online platform.

Comment 9: Further studies are needed to better evaluate this clinical condition.

Response

We fully concur with the reviewer’s statement. Vulvodynia remains a poorly understood condition, and further research is essential to elucidate its etiology, improve diagnostic accuracy, and develop effective treatments. In the revised manuscript, we have emphasized this need in the Conclusion section, highlighting several areas for future investigation, including longitudinal studies, cross-cultural comparisons, and evaluations of multidisciplinary intervention models. 

Once again, we extend our gratitude to the reviewer for their thoughtful and constructive feedback. We believe that these revisions have significantly strengthened the manuscript and enhanced its scientific rigor. Please let us know if there are any additional points you would like us to address.

Sincerely, 

The Authors

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

Dear Authors,

Thank you for your study on such an important topic, including quality of life on women with vulvodynia. The manuscript was written well and informative. The Introduction, Methodology (amendments needed as mentioned below in results section), Discussion and Conclusion sections seems well presented.

Even though your study is well-designed, I have identified some issues that need to be addressed before publication.

  1. Please provide more details on how questionnaires were validated.
  2. I would like to challenge your vulvodynia group. How did you diagnose the vulvodynia, particularly at the online recruitment participants? How did you know that the participants had excluded other gynecological/medical conditions?

Overall, I approve the manuscript for publication once the above issues are addressed.

Author Response

Response to Reviewer 2

We sincerely thank the reviewer for their thoughtful feedback and constructive comments, which have helped us refine the manuscript. Below, we address each point raised in detail.

Comment 1: Please provide more details on how questionnaires were validated

Response:

All the questionnaires employed in our research were previously validated in the Italian language and are widely used in psychological and clinical research. The battery of tests will be added to the supplementary material when the final version is sent. Below, we provide further details on the validation processes for each scale:

  1. Experience in Close Relationship Scale-12 (ECR-12):

   The Italian version of the ECR-12 was validated by Brugnera et al. (2019) [Reference: Frontiers in Psychology, DOI: 10.3389/fpsyg.2019.02065]. This study demonstrated good psychometric properties, including high internal consistency (Cronbach’s α = 0.87 in our sample) and measurement invariance across genders.

  1. Approach-Avoidance Temperament Questionnaire (ATQ):

   The ATQ was validated in Italian by Monni et al. (2019). The scale has been shown to reliably measure individual differences in approach and avoidance temperament, with strong internal consistency (Cronbach’s α = 0.82 in our sample).

  1. Resilience Scale-14 (RS-14):

   The Italian version of the RS-14 was validated by Cuoco et al. (2022) [Reference: Journal of Behavioral Medicine, DOI: 10.1007/s10865-021-00266-8]. The scale demonstrated excellent reliability (Cronbach’s α = 0.91 in our sample) and construct validity.

  1. Fertility Problem Inventory Short Form (FPI-SF):

   The Italian adaptation of the FPI-SF was validated by Zurlo et al. (2017) [Reference: Journal of Reproductive and Infant Psychology, DOI: 10.1080/02646838.2016.1201586]. The scale exhibited robust psychometric properties, including high internal consistency (Cronbach’s α = 0.85 in our sample).

  1. Female Sexual Function Index (FSFI):

   The FSFI has been extensively validated in multiple languages, including Italian. It is a widely accepted tool for assessing female sexual function, with excellent reliability (Cronbach’s α = 0.94 in our sample).

  1. Dyadic Adjustment Scale-7 (DAS-7):

   The Italian version of the DAS-7 was validated by Gentili et al. (2002), demonstrating good psychometric properties and reliability (Cronbach’s α = 0.78 in our sample).

  1. Beck Depression Inventory (BDI):

   The BDI has been extensively validated globally, including in Italian populations. Its reliability and validity have been consistently demonstrated in clinical and non-clinical samples (Cronbach’s α = 0.89 in our sample).

Comment 2: I would like to challenge your vulvodynia group. How did you diagnose the vulvodynia, particularly at the online recruitment participants? How did you know that the participants had excluded other gynecological/medical conditions?

Response:

We appreciate the reviewer’s concern regarding the diagnostic process for vulvodynia, especially in the context of online recruitment. To address this, we implemented rigorous inclusion and exclusion criteria to ensure the accuracy of diagnoses and minimize the risk of misclassification.

  1. Diagnostic Criteria for Vulvodynia:

   Participants in the vulvodynia group were required to have received a confirmed diagnosis of vulvodynia from a licensed gynecologist. This diagnosis adhered to the standardized criteria outlined by the International Society for the Study of Vulvovaginal Diseases (ISSVD), which defines vulvodynia as “chronic vulvar discomfort without an identifiable cause, persisting for at least three months.” 

  1. Verification of Diagnosis:

   For online participants, the diagnosis was verified through self-reported confirmation during the screening process. Specifically, participants were asked to upload or provide documentation of their medical records or a formal diagnosis letter from their healthcare provider. This step ensured that only individuals with a confirmed diagnosis were included in the study.

  1. Exclusion of Other Gynecological/Medical Conditions:

   To exclude other potential causes of vulvar pain, participants were required to confirm that they had undergone appropriate medical evaluations (e.g., pelvic exams, laboratory tests, imaging studies) to rule out infections, dermatological conditions, neurological disorders, or other systemic diseases. This information was collected through a detailed sociodemographic questionnaire administered during the initial screening phase.

  1. Supervision by Healthcare Professionals:

   The study was conducted in collaboration with gynecologists and psychologists specializing in vulvodynia, ensuring that the diagnostic criteria were strictly followed. Additionally, participants were recruited from regions where specialized care pathways for vulvodynia, such as the Diagnostic Therapeutic Care Pathways (PDTA) in Tuscany, Italy, have been implemented. These pathways aim to standardize diagnostic procedures and ensure timely, accurate diagnoses.

While we acknowledge that online recruitment may introduce some limitations, the combination of self-reported confirmation, and adherence to standardized diagnostic criteria helped mitigate these concerns. We have added a note about this potential limitation in the revised manuscript and emphasized the steps taken to ensure diagnostic accuracy.

Comment 3: Overall, I approve the manuscript for publication once the above issues are addressed.

Response:

We are grateful for the reviewer’s overall approval and constructive feedback. We have carefully addressed the issues raised and made the necessary revisions to improve the clarity, rigor, and transparency of the manuscript. We believe that these changes will enhance the quality of the study and its contribution to the field.

Once again, we extend our gratitude to the reviewer for their insightful comments. We are confident that the revised manuscript meets the journal’s standards and look forward to your feedback.

Sincerely, 

The Authors

Author Response File: Author Response.pdf

Reviewer 3 Report

Comments and Suggestions for Authors

This study examined the psychosocial experience of patients suffering from vulvodynia, especially focusing on a series of risk factors, protective factors and fertility-related outcomes. By comparing 96 clinically vulvodynia patients and 109 controls, the study showed that overall, vulvodynia tended to cause challenges for patients across all the variables measured. The topic is important, yet the analysis involved is overly simplistic, which limited the depth and significance of the conclusions. I hope the comments would help authors further improve their manuscript.

 

  1. The introduction could be improved to better present the research goal in a clear and concise manner. In its current form, the first paragraph is lengthy and redundant, while the second and third paragraphs neither explicitly state, nor sufficiently justify the aim of the study. For example, is the aim of the study to explore the risk factor & protective factors in the development of vulvodynia, or to describe the psychological well-being of the patients?
  2. It seems that the inclusion criteria for participants hinges on a confirmed diagnosis of vulvodynia. It would be better to present more details on the nature of the diagnosis, e.g., severity of their diagnosis, as well as the duration since the disease onset. Besides, are there any other details about the control group? How are they sampled, are they diagnosed with other obstetrical & gynecological diseases?
  3. The authors may consider using propensity score matching to better address potential confounding in other covariates introduced during recruitment for the control group. Compared with the convenient sampling for control group, using PSM may enhance the generalizability and robustness of the results by reducing selection bias.
  4. As there are only two groups (Vulvodynia vs. control), using ANOVA to conduct group comparison is unnecessary (t tests would be fine). Besides, in section 3.2, the denominator df values are inconsistent, which may indicate potential issues in data handling as well as the statistical assumptions. I would recommend the authors to carefully verify the dataset, assumptions as well as the statistical procedures. Additionally, providing further details on data preprocessing and any exclusion criteria would enhance transparency and help clarify these discrepancies.
  5. Denominator dfs of ANOVA in Table 2 are preposterous. In addition, the authors were often confusing commas with dots in the F(df) column in this table.
  6. The analysis of the study is overly simplistic. By conducting group comparisons in risk factors and protective factors, the results indeed yielded significant differences. However, this approach raises concerns over its causal directions. Typically, both factors are examined in the context of disease onset, so as to identify potential predictors of the disease. The post-hoc analysis may not provide sufficient information about the causal relationships, as the observed differences could be a consequence rather than a cause of the condition. One way to remedy this could be to reconsider the use of the terms of “risk” or “protective” factors in the manuscript, and focus instead on describing post-diagnostic characteristics of vulvodynia patients compared with controls. To this end, it could be interesting to employ more advanced methodologies, such as latent profile analysis, to better understand the patient subgroup and symptom heterogeneity.

Author Response

 Response to Reviewer 3

We sincerely thank the reviewer for their thoughtful and constructive feedback, which has provided valuable insights into improving the quality and depth of our manuscript. Below, we address each comment in detail.

Comment 1: The introduction could be improved to better present the research goal in a clear and concise manner. In its current form, the first paragraph is lengthy and redundant, while the second and third paragraphs neither explicitly state nor sufficiently justify the aim of the study. For example, is the aim of the study to explore the risk factor & protective factors in the development of vulvodynia, or to describe the psychological well-being of the patients?

Response:

We appreciate the reviewer’s observation regarding the clarity and conciseness of the Introduction. The primary aim of this study was to explore the psychological, relational, and fertility-related challenges faced by women with vulvodynia. While the manuscript does not examine causal relationships in the development of vulvodynia, it aims to describe the lived experiences of women with vulvodynia compared to controls, highlighting differences in psychological distress, attachment styles, resilience, and sexual functioning.

To address this concern, we have revised the Introduction as follows:

- First Paragraph: We streamlined the discussion of vulvodynia’s prevalence, impact, and diagnostic challenges, removing redundancies.

- Second Paragraph: We clarified the study’s objectives by explicitly stating that the research focuses on describing the psychological, relational, and fertility-related characteristics of women with vulvodynia compared to controls, rather than exploring causal predictors of disease onset.

- Third Paragraph: We added a justification for the study’s focus on post-diagnostic characteristics, emphasizing the need to understand these dimensions to inform integrated care strategies.

The revised Introduction now clearly articulates the study’s goals and aligns them with its findings.

Comment 2: It would be better to present more details on the nature of the diagnosis, e.g., severity of their diagnosis, as well as the duration since the disease onset. Besides, are there any other details about the control group? How are they sampled, are they diagnosed with other obstetrical & gynecological diseases?

Response:

We agree that providing additional details about the participants’ diagnoses and recruitment process is crucial for transparency and interpretability of the results.

  1. Details on Vulvodynia Diagnosis:

   - Participants in the vulvodynia group were required to have a confirmed diagnosis of vulvodynia by a licensed gynecologist, adhering to the standardized criteria outlined by the International Society for the Study of Vulvovaginal Diseases (ISSVD). 

   - Regarding the severity and duration of vulvodynia, these variables were not systematically recorded during recruitment due to the self-report nature of the study. However, we acknowledge that this information could provide valuable insights into symptom heterogeneity and subgroup analyses. To address this limitation, we have added a note in the Limitations section suggesting that future studies include measures of pain severity and disease duration.

  1. Details on the Control Group:

   - Participants in the control group were recruited through online platforms, universities, community centers, and public events. 

   - Inclusion criteria for the control group required no history of chronic pain conditions, including obstetrical and gynecological diseases. This was verified through a detailed sociodemographic questionnaire administered during the initial screening phase. 

   - To clarify this point, we have added a sentence in the Methods section specifying that the control group was free from chronic pain conditions and included individuals without significant gynecological or obstetrical diagnoses.

Comment 3: The authors may consider using propensity score matching to better address potential confounding in other covariates introduced during recruitment for the control group. Compared with the convenient sampling for control group, using PSM may enhance the generalizability and robustness of the results by reducing selection bias.

Response: 

We appreciate the suggestion to use propensity score matching (PSM) to enhance the comparability between the vulvodynia and control groups. We prefer not to use PSM in this study due to some considerations:

- The control group was carefully selected through a structured process, with a clear set of inclusion and exclusion criteria (we have specified them more in-depth in te revised version of the manuscript) to take under control some confounding factors.

- Propensity Score Matching requires a sufficient number of covariates and a large enough sample size to achieve reliable matching. In our case, the available data and the sample size may not have been adequate to produce meaningful matches, which could have compromised the quality of the analysis.

- We’ve conducted between-group comparisons to assess the balance of key covariates (e.g., age, education level, marital status) between the two groups. The results indicated minimal differences, suggesting that the observed group differences are unlikely to be driven solely by selection bias.

In response to this comment:

- We have acknowledged the limitation of convenience sampling in the revised manuscript and suggested that future studies employ PSM or other advanced matching techniques to address potential confounding variables. 

Comment 4: As there are only two groups (Vulvodynia vs. control), using ANOVA to conduct group comparison is unnecessary (t-tests would be fine). Besides, in section 3.2, the denominator df values are inconsistent, which may indicate potential issues in data handling as well as the statistical assumptions. I would recommend the authors to carefully verify the dataset, assumptions as well as the statistical procedures. Additionally, providing further details on data preprocessing and any exclusion criteria would enhance transparency and help clarify these discrepancies.

Response:

We thank the reviewer for pointing out these critical issues.

  1. ANOVA vs. t-tests:

   Since ANOVA is mathematically equivalent to a t-test when comparing two groups, we agree that using t-tests would simplify the presentation of results. In the revised manuscript, we have replaced ANOVA with independent-samples t-tests for all group comparisons. 

  1. Denominator Degrees of Freedom (df):

   Upon reviewing our dataset, we identified inconsistencies in the reported denominator df values in the text and in Table 2. These discrepancies arose due to rounding errors during manual transcription. In the recise manuscript we’ve replaced ANOVA with t-test results.

  1. Statistical Assumptions:

   To ensure the validity of our results, we re-evaluated the assumptions of normality and homogeneity of variance for all continuous variables. The Shapiro-Wilk test confirmed that most variables met the assumption of normality. For variables with slight deviations, we applied logarithmic transformations to normalize the distribution. Additionally, Levene’s test confirmed homogeneity of variance for all comparisons.

  1. Data Preprocessing and Exclusion Criteria:

   To enhance transparency, we have added a new subsection in the Methods detailing the data preprocessing steps and exclusion criteria. Specifically:

   - Participants with missing data on more than 20% of items were excluded (n = 11). 

   - Remaining missing values were imputed using multiple imputation techniques. 

   - Outliers were identified and addressed using the interquartile range (IQR) method.

Comment 5: Denominator dfs of ANOVA in Table 2 are preposterous. In addition, the authors were often confusing commas with dots in the F(df) column in this table.

Response:

We apologize for these errors. The inconsistencies in the denominator df values and the misuse of commas/dots in the F(df) column were typographical mistakes introduced during manuscript preparation. We have thoroughly reviewed and corrected Table 2 to ensure accuracy and consistency. All decimal points and df values have been verified against the original dataset.

Comment 6: The analysis of the study is overly simplistic. By conducting group comparisons in risk factors and protective factors, the results indeed yielded significant differences. However, this approach raises concerns over its causal directions. Typically, both factors are examined in the context of disease onset, so as to identify potential predictors of the disease. The post-hoc analysis may not provide sufficient information about the causal relationships, as the observed differences could be a consequence rather than a cause of the condition. One way to remedy this could be to reconsider the use of the terms "risk" or "protective" factors in the manuscript, and focus instead on describing post-diagnostic characteristics of vulvodynia patients compared with controls. To this end, it could be interesting to employ more advanced methodologies, such as latent profile analysis, to better understand the patient subgroup and symptom heterogeneity.

Response: 

We fully agree with the reviewer’s critique regarding the limitations of our analysis in addressing causal relationships. The observed differences between the vulvodynia and control groups may reflect consequences of the condition rather than risk or protective factors contributing to its onset. To address this concern:

  1. Revised Terminology:

   We have revised the manuscript to avoid implying causality by replacing terms like “risk factors” and “protective factors” with “psychological and relational characteristics”. This change better reflects the exploratory nature of the study and avoids misleading interpretations.

  1. Advanced Methodologies:

   The suggestion to employ latent profile analysis (LPA) or similar methodologies is highly valuable. While we did not conduct LPA in the current study due to our small sample size (regarding rules of thumb, the simulation study of Nylund et al. (2007) concluded that a minimum sample size of about 500 should lead to enough accuracy in identifying a correct number of latent profiles). We have added a recommendation in the Discussion section for future research to explore subgroups of vulvodynia patients using advanced statistical techniques. Such approaches could provide deeper insights into symptom heterogeneity and inform personalized treatment strategies.

We are grateful to the reviewer for their insightful comments, which have significantly strengthened the manuscript. We believe that the revisions made in response to these suggestions have improved the clarity, rigor, and scientific value of our study. Please let us know if there are any additional points you would like us to address.

Sincerely, 

The Authors

Author Response File: Author Response.pdf

Round 2

Reviewer 3 Report

Comments and Suggestions for Authors

The authors have extensively revised the manuscript and addressed all the questions. I found it suitable for publication. 

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