Endometrial Thickness as a Prognostic Marker in Premenopausal Abnormal Uterine Bleeding: Diagnostic Accuracy and Kaplan–Meier Survival Insights

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n.callMethod.apply(n,arguments):n.queue.push(arguments)} ;if(!f._fbq)f._fbq=n; n.push=n;n.loaded=!0;n.version='2.0';n.queue=[];t=b.createElement(e);t.async=!0; t.src=v;s=b.getElementsByTagName(e)[0];s.parentNode.insertBefore(t,s)}(window, document,'script','https://connect.facebook.net/en_US/fbevents.js'); fbq('init', '1641728616063202'); fbq('track', "PixelInitialized", {}); (function(h,o,t,j,a,r){ h.hj=h.hj||function(){(h.hj.q=h.hj.q||[]).push(arguments)}; h._hjSettings={hjid:2318163,hjsv:6}; a=o.getElementsByTagName('head')[0]; r=o.createElement('script');r.async=1; r.src=t+h._hjSettings.hjid+j+h._hjSettings.hjsv; a.appendChild(r); })(window,document,'https://static.hotjar.com/c/hotjar-','.js?sv='); search file_upload Submit your research search menu close search Browse Gateways & Collections How to Publish Submit your Research My Submissions Article Guidelines Article Guidelines (New Versions) Open Data, Software and Code Guidelines Open Data and Accessible Source Materials Guidelines (HSS) Open Data, Software and Code Guidelines (PSE) Prepublication Checks Production Process Posters and Slides Guidelines Document Guidelines Article Processing Charges Peer Review Finding Article Reviewers About How it Works For Reviewers Our Advisors Policies Glossary FAQs For Developers Newsroom Contact My Research Submissions Content and Tracking Alerts My Details Sign In file_upload Submit your research { "@context": "https://schema.org", "@type": "ScholarlyArticle", "mainEntityOfPage": { "@type": "WebPage", "@id": "https://f1000research.com/articles/14-1167" }, "headline": "Endometrial Thickness as a Prognostic Marker in Premenopausal Abnormal Uterine Bleeding: Diagnostic Accuracy...", "datePublished": "2025-10-27T10:33:43", "dateModified": "2026-05-19T11:43:47", "author": [ { "@type": "Person", "name": "Narjes karmous" }, { "@type": "Person", "name": "Hanene Jemli" }, { "@type": "Person", "name": "Abdelwahab Masmoudi" }, { "@type": "Person", "name": "Badreddine Bouguerra" }, { "@type": "Person", "name": "Aymen Mabrouk" }, { "@type": "Person", "name": "Anis Ben Dhaou" }, { "@type": "Person", "name": "Abdennour Karmous" } ], "publisher": { "@type": "Organization", "name": "F1000Research", "logo": { "@type": "ImageObject", "url": "https://f1000research.com/img/AMP/F1000Research_image.png", "height": 480, "width": 60 } }, "image": { "@type": "ImageObject", "url": "https://f1000research.com/img/AMP/F1000Research_image.png", "height": 1200, "width": 150 }, "description": " Background Abnormal uterine bleeding (AUB) in premenopausal women is frequent, yet distinguishing benign from malignant causes remains clinically challenging. Endometrial thickness (ET) measured by transvaginal ultrasound (TVUS) is well established in postmenopausal bleeding but less validated in premenopausal women due to cyclical variations. This study aimed to assess the diagnostic accuracy and prognostic value of ET, supplemented by Kaplan–Meier survival analysis, in predicting endometrial malignancy among premenopausal women with AUB. Methods We conducted a retrospective analytical study including premenopausal women presenting with AUB at Charles Nicolle Hospital, Tunis, Tunisia (2016–2024). All underwent TVUS followed by endometrial sampling (hysteroscopy or curettage) and definitive histological confirmation on hysterectomy specimens. Sonographic features were described using International Endometrial Tumor Analysis (IETA) criteria. Diagnostic performance of ET was evaluated using receiver operating characteristic (ROC) curve analysis. Kaplan–Meier survival analysis assessed the association between ET and time-to-consultation and time-to-diagnosis. Results In total, 209 patients were included. Mean age was 45.7 ± 3.2 years. ROC analysis identified ET as the strongest predictor of endometrial malignancy (AUC = 0.842, p 9 mm achieved 69.2% sensitivity, 87.1% specificity, and a negative predictive value of 97.7%, effectively ruling out malignancy in patients with ET ≤9 mm. Although the positive predictive value was modest (26.5%), ET reliably stratified risk for further invasive evaluation. Kaplan–Meier analysis demonstrated that ET >9 mm was associated with earlier consultation (mean 27.7 vs. 70.3 months, p < 0.0001) and shorter time-to-diagnosis (median 12 months vs. not reached, p 9 mm is a robust, non-invasive prognostic marker in premenopausal AUB, identifying high-risk women requiring urgent evaluation while safely excluding malignancy in low-risk patients. Incorporating ET into diagnostic algorithms may optimize triage, reduce unnecessary invasive procedures, and enhance timely cancer detection. " } { "@context": "http://schema.org", "@type": "BreadcrumbList", "itemListElement": [ { "@type": "ListItem", "position": "1", "item": { "@id": "https://f1000research.com/", "name": "Home" } }, { "@type": "ListItem", "position": "2", "item": { "@id": "https://f1000research.com/browse/articles", "name": "Browse" } }, { "@type": "ListItem", "position": "3", "item": { "@id": "https://f1000research.com/articles/14-1167/v1", "name": "Endometrial Thickness as a Prognostic Marker in Premenopausal Abnormal..." } } ] } Home Browse Endometrial Thickness as a Prognostic Marker in Premenopausal Abnormal... ALL Metrics - Views Downloads Get PDF Get XML Cite How to cite this article karmous N, Jemli H, Masmoudi A et al. Endometrial Thickness as a Prognostic Marker in Premenopausal Abnormal Uterine Bleeding: Diagnostic Accuracy and Kaplan–Meier Survival Insights [version 1; peer review: 2 not approved] . F1000Research 2025, 14 :1167 ( https://doi.org/10.12688/f1000research.170554.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. Close Copy Citation Details Export Export Citation Sciwheel EndNote Ref. Manager Bibtex ProCite Sente EXPORT Select a format first Track Share ▬ ✚ Research Article Endometrial Thickness as a Prognostic Marker in Premenopausal Abnormal Uterine Bleeding: Diagnostic Accuracy and Kaplan–Meier Survival Insights [version 1; peer review: 2 not approved] Narjes karmous https://orcid.org/0009-0001-9101-7849 1,2 , Hanene Jemli 1 , Abdelwahab Masmoudi 1 , [...] Badreddine Bouguerra 1,2 , Aymen Mabrouk 2,3 , Anis Ben Dhaou https://orcid.org/0000-0003-3064-3544 2,3 , Abdennour Karmous 2,4 Narjes karmous https://orcid.org/0009-0001-9101-7849 1,2 , Hanene Jemli 1 , [...] Abdelwahab Masmoudi 1 , Badreddine Bouguerra 1,2 , Aymen Mabrouk 2,3 , Anis Ben Dhaou https://orcid.org/0000-0003-3064-3544 2,3 , Abdennour Karmous 2,4 PUBLISHED 27 Oct 2025 Author details Author details 1 Gynaecology and Obstetrics department B, Charles Nicolle Hospital, Tunis, Tunisia 2 Faculty of medicine of Tunis, University Tunis el Manar, Tunis, Tunisia 3 General surgery department B, Charles Nicolle Hospital, Tunis, Tunisia 4 Psychiatric department, Razi Hospital, Tunis, Tunisia Narjes karmous Roles: Conceptualization, Methodology, Writing – Original Draft Preparation Hanene Jemli Roles: Data Curation, Visualization Abdelwahab Masmoudi Roles: Writing – Review & Editing Badreddine Bouguerra Roles: Supervision, Validation Aymen Mabrouk Roles: Writing – Review & Editing Anis Ben Dhaou Roles: Writing – Review & Editing Abdennour Karmous Roles: Writing – Review & Editing OPEN PEER REVIEW DETAILS REVIEWER STATUS Abstract Background Abnormal uterine bleeding (AUB) in premenopausal women is frequent, yet distinguishing benign from malignant causes remains clinically challenging. Endometrial thickness (ET) measured by transvaginal ultrasound (TVUS) is well established in postmenopausal bleeding but less validated in premenopausal women due to cyclical variations. This study aimed to assess the diagnostic accuracy and prognostic value of ET, supplemented by Kaplan–Meier survival analysis, in predicting endometrial malignancy among premenopausal women with AUB. Methods We conducted a retrospective analytical study including premenopausal women presenting with AUB at Charles Nicolle Hospital, Tunis, Tunisia (2016–2024). All underwent TVUS followed by endometrial sampling (hysteroscopy or curettage) and definitive histological confirmation on hysterectomy specimens. Sonographic features were described using International Endometrial Tumor Analysis (IETA) criteria. Diagnostic performance of ET was evaluated using receiver operating characteristic (ROC) curve analysis. Kaplan–Meier survival analysis assessed the association between ET and time-to-consultation and time-to-diagnosis. Results In total, 209 patients were included. Mean age was 45.7 ± 3.2 years. ROC analysis identified ET as the strongest predictor of endometrial malignancy (AUC = 0.842, p 9 mm achieved 69.2% sensitivity, 87.1% specificity, and a negative predictive value of 97.7%, effectively ruling out malignancy in patients with ET ≤9 mm. Although the positive predictive value was modest (26.5%), ET reliably stratified risk for further invasive evaluation. Kaplan–Meier analysis demonstrated that ET >9 mm was associated with earlier consultation (mean 27.7 vs. 70.3 months, p < 0.0001) and shorter time-to-diagnosis (median 12 months vs. not reached, p 9 mm is a robust, non-invasive prognostic marker in premenopausal AUB, identifying high-risk women requiring urgent evaluation while safely excluding malignancy in low-risk patients. Incorporating ET into diagnostic algorithms may optimize triage, reduce unnecessary invasive procedures, and enhance timely cancer detection. READ ALL READ LESS Keywords Premenopausal women; abnormal uterine bleeding; transvaginal ultrasound; endometrial thickness, endometrial cancer; diagnostic accuracy Corresponding Author(s) Narjes karmous ( [email protected] ) Close Corresponding author: Narjes karmous Competing interests: No competing interests were disclosed. Grant information: The author(s) declared that no grants were involved in supporting this work. Copyright: © 2025 karmous N et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite: karmous N, Jemli H, Masmoudi A et al. Endometrial Thickness as a Prognostic Marker in Premenopausal Abnormal Uterine Bleeding: Diagnostic Accuracy and Kaplan–Meier Survival Insights [version 1; peer review: 2 not approved] . F1000Research 2025, 14 :1167 ( https://doi.org/10.12688/f1000research.170554.1 ) First published: 27 Oct 2025, 14 :1167 ( https://doi.org/10.12688/f1000research.170554.1 ) Latest published: 19 May 2026, 14 :1167 ( https://doi.org/10.12688/f1000research.170554.4 )  There is a newer version of this article available. Suppress this message for one day. 1. Introduction Abnormal uterine bleeding (AUB) is a prevalent gynecological concern in premenopausal women. 1 While the majority of cases stem from benign conditions, the potential for endometrial hyperplasia (EH) or malignancy necessitates a careful diagnostic approach. 2 , 3 In postmenopausal women, transvaginal ultrasound (TVUS) measurement of endometrial thickness (ET) is a well-validated tool, with an ET <4 mm effectively ruling out cancer in most cases. 4 – 6 However, this single metric is of limited value in premenopausal women due to normal cyclical hormonal variations that cause ET to fluctuate significantly. This has created a diagnostic gap, leading to reliance on clinical risk factors (e.g., obesity, anovulation) for deciding on invasive endometrial sampling. 7 , 8 The limitations of this approach underscore the critical need for more objective, imaging-based criteria. This study aimed to evaluate the diagnostic and prognostic value of ET in premenopausal women with abnormal uterine bleeding. We assessed the accuracy of ET for predicting malignancy, determined the optimal cutoff, and used Kaplan–Meier analysis to examine its impact on the timing of consultation and definitive diagnosis. 2. Methods 2.1 Study design and setting A retrospective, longitudinal and analytical study was carried out over an 8- year and 11-month, from January 2016 to November 2024, at Gynaecology and Obstetrics Department B, Charles Nicolle Hospital, Tunis, Tunisia. 2.2 Study population Premenopausal women presenting with AUB who underwent TVUS followed by endometrial biopsy (via hysteroscopy or curettage) and subsequent definitive surgical treatment (hysterectomy) were identified. AUB refers to bleeding from the uterine corpus that is abnormal in regularity, volume, frequency or duration. It encompasses heavy menstrual bleeding, irregular menstrual bleeding and intermenstrual bleeding. 9 The ultrasound features of different endometrial and other intracavitary pathologies were assessed using the International Endometrial Tumor Analysis (IETA) terminology. 10 The study population consisted of patients who fulfilled the following criteria: ▪ Inclusion Criteria : − Presence of AUB. − Available TVUS report with detailed description of endometrial features. − Final histological diagnosis on hysterectomy specimen. ▪ Exclusion Criteria : − Pregnant women. − Incomplete TVUS data or poor image quality. − No subsequent hysterectomy performed. A study flowchart detailing case selection and exclusions has been developed ( Figure 1 ) . Figure 1. Flowchart of the study population. 2.3 Variables Data were collected from patient records onto a pre-established form. 2.3.1 Patients’ characteristics Age, family and personal history, AUB (type, abundance, number of haemorrhage episodes, associated symptoms …), delay before consultation, time to diagnosis … 2.3.2 TVUS features The primary data extracted from the TVUS reports included 10 : ▪ Endometrial thickness: ET was measured in the sagittal plane as the double-layer distance between the two endometrial–myometrial interfaces, at the point of greatest thickness perpendicular to the midline, using appropriately magnified images. The result was reported in millimetres. ▪ Endometrial-myometrial junction: Classified as regular, irregular, interrupted or not defined. ▪ Intracavitary images: Note of any focal lesions, such as polyps or masses, intracavitary fluid. ▪ Uterine Size: Measurement of uterine dimensions. ▪ Endometrial vascularity: Color Doppler assessment of the endometrium: a color score of 1 was given to indicate no color (no flow); a score of 2 indicates minimal color (minimal flow) and a score of 3 indicates moderate color (moderate flow). ▪ Associated Features: Presence of fibroids, adenomyosis, or ovarian cysts. 2.3.3 Uterine cavity exploration Hysteroscopy or curettage, date of endometrial sampling, abundance of the sample, anatomopathological diagnosis from the biopsy. 2.3.4 Definitive anatomopathological diagnosis The definitive histological diagnosis on the hysterectomy specimen was considered the reference standard. 2.4 Statistical analysis All analyses were performed using IBM SPSS Statistics (Version 26.0; IBM Corp, Armonk, NY, USA) for data management, descriptive statistics, correlation analysis, and non-parametric tests. For comparative analysis, variables significantly associated with endometrial malignancy were assessed using the chi-square test or Fisher’s exact test for categorical variables and Student’s t test or Mann-Whitney U test for continuous variables. Multivariate logistic regression models were constructed to identify independent predictors of endometrial malignancy cases. Variables with a p value ≤ 0.20 in the univariate analysis were included in the model. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were reported. A p value ≤ 0.05 was considered statistically significant. 11 , 12 The diagnostic performance of each sonographic feature for predicting endometrial malignancy was assessed using sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). 13 A Kaplan-Meier survival analysis was conducted to assess the prognostic value of ET for predicting the timing of a malignant diagnosis. 14 2.5 Ethical considerations The study protocol received approval from the institutional ethics committee of Charles Nicolle Hospital, Tunis, Tunisia on 6 Mars 2025 by before conducting the study (approval number FWA 00032748- IORG0011243). Given the retrospective design and the use of anonymized data, the committee granted a waiver of informed consent. 3. Results The study included 209 patients. Final histopathological examination revealed endometrial malignancy in 13 premenopausal women (6.2%), while 196 women (93.8%) had benign endometrium. 3.1 Comparative study The median age was 46 years in benign cases and 48 years in malignant cases (p = 0.217). The median BMI was 25 for benign and 26 for malignant cases (p = 0.576). Most patients had no family cancer history (94% benign vs. 6% malignant, p = 0.123). Diabetes (93% benign vs. 7% malignant, p = 0.338) and hypertension (94% benign vs. 6% malignant, p = 0.954) were uncommon. Median age at menarche was 12 years in both groups (p = 0.603). Gravidity and parity differed, with median gravidity of 3 versus 2 (p = 0.018) and median parity of 3 versus 2 (p = 0.060). Breast neoplasia, tamoxifen use, and pelvic irradiation were not associated with malignancy. Bleeding characteristics—including abundance and type—showed limited association, except for the number of hemorrhage episodes (p = 0.027), where patients with 0–1 episode had higher malignancy rates (25–33%) than those with ≥2 episodes. The median delay before consultation was significantly shorter in malignant cases (6 months) compared to benign cases (12 months, p = 0.011). Regarding ultrasound features ( Table 1 ) , ET was markedly higher in malignant cases (median 12 mm) than in benign cases (median 5 mm, p < 0.001). Vascularization (p < 0.001), with Score 2 showed 71% malignancy, whereas normal vascularization or Score 1 had much lower rates. The uterine size, the endometrial–myometrial interface and intracavitary images did not show significant differences. Ovarian cysts did not show a significant association with malignancy (p = 0.808). Table 1. Ultrasound features among the study population. Variable Category Benign Malignant Total Chi-square p Endometrial thickness (mm) - 5 10 - 0.000 Uterine size n (%) Normal 45 (94) 3 (6) 48 (100) 0.992 Increased 151 (94) 10 (6) 161 (100) Vascularization n (%) No 97 (98) 2 (2) 99 (100) 0.000 Score 1 97 (94) 6 (6) 103 (100) Score 2 2 (29) 5 (71) 7 (100) Endometrial–myometrial interface n (%) Unseen 84 (93) 6 (7) 90 (100) 0.828 Seen 111 (94) 7 (6) 118 (100) Intracavitary image n (%) No 149 (93) 11 (7) 160 (100) 0.871 Polyp 15 (94) 1 (6) 16 (100) Fibroma 31 (97) 1 (3) 32 (100) Other 1 (100) 0 (0) 1 (100) Profuse 114 (90) 13 (10) 127 (100) Presence of fibroids was associated with a lower risk of malignancy (3.8% malignant in patients with fibroids vs. 14% in those without, p = 0.009). Hemostatic curettage, and hysteroscopy did not show significant differences. Quantity of curettage specimen was significant (p = 0.003), with abundant specimens associated with 10% malignancy compared to 0% for scanty specimens. 3.2 Receiver operating characteristic (ROC) and logistic regression analyses ( Figure 2 , Table 2 ) Figure 2. Predictive performance of endometrial thickness versus clinical features (gravidity, number of hemorrhage episodes) for endometrial malignancy based on ROC analysis. Table 2. Predictive performance of endometrial thickness comparatively with clinical features (gravidity, number of hemorrhage episodes) for endometrial malignancy was evaluated using ROC analysis. Variable AUC p-value 95% CI Criterion Sensitivity (%) Specificity (%) PPV * (%) NPV ** (%) Gravidity 0.690 0.022 0.542–0.838 ≤1 23.08 96.43 30 95 Number of hemorrhage episodes 0.576 0.360 0.398–0.754 ≤2 61.54 68.88 11.6 96.4 Endometrial thickness 0.842 9 69.23 87.11 26.5 97.7 * PPV: Predictive positive value. ** NPV: Negative predictive value. ET measured via TVUS was unequivocally identified as the single most robust independent predictor of endometrial malignancy within our studied cohort. Its superior performance, quantified by an excellent Area Under the Curve (AUC) of 0.842 (p < 0.001), underscores its unparalleled utility in the initial triage of patients presenting with AUB. This diagnostic power significantly surpassed that of other clinical variables, such as gravidity (AUC = 0.690) and the number of hemorrhage episodes (AUC = 0.576, nonsignificant), establishing ET as the cornerstone of non-invasive risk assessment. The derivation of an optimal cut-off >9 mm provides a clear, evidence-based threshold for clinical decision-making. This criterion successfully balances sensitivity (69.2%) and specificity (87.1%), ensuring a high detection rate for malignancies while effectively minimizing false alarms. The specificity of 87.1% is particularly noteworthy; it signifies that most patients with benign conditions can be correctly identified by this simple measure, preventing anxiety and unnecessary procedures. However, the most profound clinical implication of our findings lies in the metric of the NPV, which reached 97.7%. This is arguably the most significant result of the analysis. It translates to a powerful clinical rule: an endometrial measurement of ≤9 mm effectively rules out malignancy with a certainty of over 97%. This provides immense reassurance to both the clinician and the patient, creating a safe pathway to conservatively manage a large portion of low-risk individuals. It can justify a strategy of watchful waiting or medical management for these patients, thereby reducing the number of invasive, costly, and potentially uncomfortable procedures like hysteroscopy or dilation and curettage. Conversely, the PPV of 26.5% for a thickness >9 mm contextualizes its use. It confirms that while a thick endometrium is a strong risk marker mandating histological sampling, it is not diagnostic of cancer on its own. Most positive tests (73.5%) will be due to benign conditions like hyperplasia or polyps. Therefore, the role of ET is not to definitively diagnose cancer but to act as an exceptionally efficient screening gatekeeper—identifying all high-risk patients who require definitive biopsy while safeguarding low-risk patients from undue intervention. 3.3 Kaplan-Meier survival curve analysis To assess the prognostic value of ET for predicting the timing of a malignant diagnosis, two Kaplan-Meier survival analyses were conducted: - The first analysis evaluated the time from symptom onset to initial consultation: time-to-consultation. - The second evaluated the time from initial consultation to definitive histological diagnosis: time-to-diagnosis . The cohort was stratified by an ET cutoff of >9 mm: - The group with an ET ≤9 mm (n = 175), 4 (2.3%) received a final histological diagnosis of malignancy. - Conversely, in the group with an ET >9 mm (n = 34), 9 patients (26.5%) were diagnosed with malignancy, underscoring a substantially higher disease prevalence in this group. 3.3.1 Time-to-consultation analysis The interval from symptom onset to first consultation differed significantly between groups (Log-rank test χ 2 = 25.662, p 9 mm (27.7 months, 95% CI: 22.5 – 32.9). - The median time-to-consultation was 36 months for the high-ET group and was not reached for the low-ET group. Figure 3. Kaplan–Meier survival analyses: time from symptom onset to initial consultation (time-to-consultation). This indicates that symptoms associated with a thicker endometrium (e.g., heavier bleeding) prompt patients to seek medical attention much sooner. 3.3.2 Time-to-diagnosis analysis Analysis of the interval from consultation to definitive histological diagnosis also revealed a significant difference (log-rank t χ 2 = 25.662, *p* < .0001): ( Figure 4 ). - The median time-to-diagnosis was 12 months for the high-ET group, but not reached in the low-ET group, as fewer than 50% of patients in this group were diagnosed with malignancy. - The mean time-to-diagnosis was shorter for the high-ET group (7.95 months, 95% CI: 4.74 – 11.16) compared to the low-ET group (11.73 months, 95% CI: 11.47 – 11.99). Figure 4. Kaplan–Meier survival analyses: time from initial consultation to definitive histological diagnosis (time-to-diagnosis). This finding highlights the rapid clinical progression in the high-ET group compared to the indolent course associated with a thinner endometrium. In summary, ET exceeding 9 mm is a critical marker that shortens both the patient-related delay in seeking care and the system-related delay in achieving a diagnosis. It effectively identifies a high-risk subgroup of premenopausal women with AUB who require urgent and efficient clinical evaluation. 4. Discussion The evaluation of AUB in premenopausal women continues to represent a diagnostic dilemma. While ET measured by TVUS has been validated as a reliable screening tool in postmenopausal women, with a cutoff <4 mm effectively excluding endometrial cancer, 4 – 6 its role in premenopausal women is far less clear. Cyclical hormonal changes, structural abnormalities, and comorbidities contribute to marked variability in ET, limiting the establishment of universal thresholds. In this context, guidelines 15 , 16 acknowledge the absence of consensus and recommend individualized evaluation based on risk factors and imaging findings. 4.1 Endometrial thickness cutoff in premenopausal AUB Several studies have attempted to define an optimal cutoff value of ET for predicting endometrial pathology in women with AUB, yet the results remain inconsistent. Our findings identify an ET >9 mm as the optimal threshold for predicting endometrial malignancy in premenopausal women. This result aligns with earlier observations but provides more robust statistical validation. Smith et al. 17 and Tongsong et al. 18 were among the first to suggest a correlation between thickened endometrium and pathology. Smith et al., 17 evaluating 51 premenopausal women with irregular bleeding, proposed an ET cutoff of 8 mm. In a larger study including 177 peri- and postmenopausal women undergoing vaginosonography, Tongsong et al. 18 found that an ET ≤7 mm reliably excluded endometrial pathology. Subsequent studies yielded heterogeneous thresholds. Getpook et al. 19 reported ≤8 mm as rarely malignant. Mayuri et al. 20 in a cross-sectional study of 62 perimenopausal women above 40 years of age, proposed an ET cutoff of ≥8 mm. Luca et al., 21 in a cohort of 240 premenopausal women with AUB, identified >11 mm as the best cutoff for predicting endometrial carcinoma. This diagnostic performance was very close to Giannella et al. 22 who found ≥11 mm predictive in the presence of obesity or diabetes. Ruan et al. 23 and Li et al. 24 incorporated ET ≥10 mm into multivariate prediction models, emphasizing its central role when combined with clinical variables. Collectively, our findings bridge the gap between the lower cutoff values suggested in earlier work (7–8 mm) and the higher threshold of 11 mm reported by Luca et al., supporting >9 mm as a pragmatic and evidence-based threshold in premenopausal women with AUB. 4.2 Diagnostic performance of ET and AUC analysis The diagnostic accuracy of ET in our cohort was high, with an AUC of 0.842. Sensitivity was 69.2% and specificity 87.1%, which is consistent with prior reports. 20 , 22 Particularly noteworthy was the very high NPV (97.7%), highlighting the reliability of ET in excluding malignancy. This finding is in line with those of Smith et al. 17 and Mayuri et al., 20 who likewise reported NPVs exceeding 94%. Consistent with our results, Kumari et al. 25 reported that a TVS-ET threshold of 10.5 mm achieved the highest diagnostic accuracy, with sensitivity and specificity of 89.5% and 86.3%, respectively, corresponding to an AUC of 0.920 (95% CI 0.846–0.994, p < 0.0001). Their cutoff also demonstrated a high NPV (95.7%), together with a PPV of 70.7% and favorable likelihood ratios, further supporting ET as a robust rule-out tool. 24 Conversely, the PPV was modest (26.5%), reflecting the frequent occurrence of benign causes of thickened endometrium such as polyps or hyperplasia. This aligns with the findings of Smith et al., 17 who reported an even lower PPV of 14%. Taken together with our results, this mirrors the broader literature, where ET is consistently shown to be an excellent rule-out tool but insufficient as a stand-alone diagnostic marker. 19 , 22 , 23 Nevertheless, by effectively excluding malignancy in low-risk patients, the cutoff has the potential to substantially reduce unnecessary endometrial biopsies and invasive interventions. 4.3 Integration with clinical risk factors Although ET is highly informative, its predictive value increases when integrated with clinical parameters. Advanced age, obesity, diabetes, and hypertension are well-established contributors to endometrial carcinogenesis. 23 , 24 For instance, Giannella et al. 22 demonstrated that the risk of cancer is significantly higher in obese women with ET ≥11 mm compared to their lean counterparts. In our cohort, diabetes and hypertension were uncommon and not significantly associated with malignancy, likely reflecting the relatively small number of cancer cases (n = 13). Nevertheless, the combination of ET measurement with metabolic risk profiling remains promising, particularly in refining personalized risk stratification models. In conclusion, the paramount importance of ET is its ability to stratify risk with high efficiency. It moves beyond mere association to provide actionable intelligence. By offering an objective, reproducible, and non-invasive metric, it forms the critical first step in a modern diagnostic algorithm for AUB, optimizing resource allocation, minimizing patient burden, and enhancing the overall precision of patient care. 4.4 Kaplan–Meier analysis: A novel prognostic perspective A major innovation of our study lies in applying Kaplan–Meier survival analysis to ET, an approach not previously reported. We demonstrated that women with ET >9 mm had significantly shorter time-to-consultation and time-to-diagnosis compared with those with ET ≤9 mm. This observation has two implications: - First, it highlights ET as not only a static anatomical parameter but also a dynamic marker of disease burden: women with thicker endometrium likely experience more severe or symptomatic bleeding, prompting earlier medical attention. - Second, it suggests a prognostic dimension, as ET may reflect both the biological aggressiveness of the lesion and its clinical expression. Introducing Kaplan–Meier methodology into ET research thus provides a fresh lens for understanding patient trajectories and may inform prioritization strategies in healthcare systems with limited resources. 4.5 Strengths and limitations Our study has several notable strengths: ▪ Relatively large cohort : The study included 209 premenopausal women, making it one of the more substantial single-centre investigations of ET in the context of AUB. ▪ Systematic evaluation of ET by TVUS, following standardized IETA criteria, ensured methodological consistency and strengthened the internal validity of our findings. ▪ Innovative introduction of survival analysis : Which allowed us to explore not only diagnostic accuracy but also clinical dynamics such as time to consultation and time to diagnosis. ▪ Use of definitive histopathology on hysterectomy specimens as the gold standard minimized the risk of misclassification and reinforced diagnostic reliability. However, some limitations must also be acknowledged: ▪ Retrospective design carries inherent risks of selection bias and incomplete data collection, with possible underreporting of confounders such as hormonal therapy use or lifestyle factors. ▪ Absence of menstrual cycle phase standardization at the time of ultrasound: Which is known to affect ET measurements and could have attenuated diagnostic performance. ▪ Single-centre study conducted in a Tunisian tertiary hospital: The findings may reflect specific referral patterns and population characteristics, thereby limiting generalizability. ▪ External validation needed: Although our proposed cutoff of >9 mm demonstrated excellent discriminative performance, it requires external validation in multicentric, prospective cohorts before it can be adopted in routine clinical practice. 4.6 Clinical implications 1. Adoption of a >9 mm cutoff : ET >9 mm can be used as a pragmatic and evidence-based threshold for risk stratification in premenopausal women with AUB. 2. Conservative management in low-risk patients : For women with ET ≤9 mm, the probability of malignancy is extremely low. This supports a conservative, non-invasive management strategy and reduces reliance on unnecessary procedures such as hysteroscopy or curettage. 3. Trigger for histological assessment : ET >9 mm with premenopausal AUB should prompt immediate histological sampling, even if other clinical risk factors (e.g., obesity, diabetes, family history) are absent. This ensures early detection and prevents diagnostic delay. 4. Guidance for referral and timing of intervention : Kaplan–Meier findings demonstrate that women with ET >9 mm tend to present earlier and reach diagnosis faster. ET can thus serve as a practical tool for prioritizing referrals and expediting intervention in high-risk cases. 5. Dual diagnostic and prognostic role : ET functions not only as a diagnostic marker but also as a prognostic indicator of disease trajectory. This dual role reinforces its central place in the clinical evaluation of premenopausal AUB. 4.7 Recommendations for further research 1. Prospective validation of the >9 mm cutoff : Our results support ET >9 mm as a reliable threshold for ruling out malignancy in premenopausal women with AUB. However, prospective, multicenter studies are needed to confirm its robustness across diverse clinical settings, patient populations, and ultrasound operators. Such validation would enhance external generalizability and facilitate adoption into clinical guidelines. 2. Cross-ethnic and cross-geographic evaluation : Endometrial pathology prevalence, risk factors, and clinical presentation may differ according to ethnicity, genetics, lifestyle, and healthcare access. Studies in varied regions and populations are essential to determine whether the >9 mm cutoff is universally applicable or whether ethnicity-specific thresholds are warranted. 3. Integration into multivariate risk models : ET alone, while powerful, has limited PPV. Future research should investigate the incorporation of ET into multifactorial models that also include age, BMI, metabolic status (diabetes, hypertension), hormonal profiles, and molecular biomarkers. Such models may outperform ET alone, enabling more precise and individualized risk stratification. 4. Expansion of Kaplan–Meier methodology : Our study is the first to apply Kaplan–Meier analysis to explore diagnostic timelines in AUB. Further research should extend this approach to assess long-term outcomes, such as recurrence, progression from hyperplasia to carcinoma, and survival rates. This would position ET not only as a diagnostic triage tool but also as a prognostic marker of disease trajectory. 5. Evaluation of cost-effectiveness and patient-centered outcomes : Beyond diagnostic accuracy, studies should assess the economic implications of using ET as a triage criterion, particularly in resource-limited settings. Research should also explore patient-reported outcomes, including anxiety reduction, satisfaction, and quality of life when invasive procedures are avoided based on reassuring ET results. 5. Conclusions This study reinforces the pivotal role of ET as a cornerstone parameter in the evaluation of premenopausal women with AUB. We identified an ET >9 mm as an independent predictor of malignancy, with excellent NPV, supporting its use as a triage threshold to reduce unnecessary invasive procedures. Beyond its diagnostic accuracy, our application of Kaplan–Meier survival analysis provides an innovative perspective, suggesting that ET may also reflect disease dynamics and influence the timing of clinical presentation. Our findings add to growing evidence that integrating ET with clinical risk factors can enhance predictive accuracy, and that simplified risk scores may outperform ET alone in guiding selective endometrial sampling. While external validation is needed, this study provides a clinically relevant framework that could improve patient stratification, optimize use of diagnostic resources, and ultimately contribute to earlier and more targeted detection of endometrial malignancy in women with AUB. Ethical considerations We confirm adherence to the Journal’s ethical publication standards. The study protocol was approved by the Institutional Ethics Committee of Charles Nicolle Hospital, Tunis, Tunisia, on March 6, 2025 (approval number: FWA 00032748–IORG0011243). Consent to participate As this was a retrospective study using anonymized data, the requirement for informed consent was waived. Reporting guidelines This work has been reported in line with the STROBE guidelines. 27 Harvard Dataverse: “Endometrial Thickness as a Prognostic Marker in Premenopausal Abnormal Uterine Bleeding: Diagnostic Accuracy and Kaplan–Meier Survival Insights,” https://doi.org/10.7910/DVN/W6QVWI . 26 This project contains the following: • STROBE Checklist Data are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication). Data availability statement All data sets can be assessed and all study findings reported in the article are shared via Harvard Dataverse: “Endometrial Thickness as a Prognostic Marker in Premenopausal Abnormal Uterine Bleeding: Diagnostic Accuracy and Kaplan–Meier Survival Insights,” https://doi.org/10.7910/DVN/W6QVWI . 26 This project contains the following: • Dataset Endometrial Thickness • Study findings (1) • Study findings (2) Extended data Harvard Dataverse: “Endometrial Thickness as a Prognostic Marker in Premenopausal Abnormal Uterine Bleeding: Diagnostic Accuracy and Kaplan–Meier Survival Insights,” https://doi.org/10.7910/DVN/W6QVWI . 26 This project contains the following: • Canvas (English) References 1. Vitale SG, Urman B, Angioni S, et al. : Abnormal uterine bleeding in perimenopausal women: the role of hysteroscopy and its impact on quality of life and sexuality. Diagnostics. 2022; 12 (5): 1176. PubMed Abstract | Publisher Full Text | Free Full Text 2. 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Publisher Full Text Comments on this article Comments (0) Version 4 VERSION 4 PUBLISHED 27 Oct 2025 ADD YOUR COMMENT Comment Author details Author details 1 Gynaecology and Obstetrics department B, Charles Nicolle Hospital, Tunis, Tunisia 2 Faculty of medicine of Tunis, University Tunis el Manar, Tunis, Tunisia 3 General surgery department B, Charles Nicolle Hospital, Tunis, Tunisia 4 Psychiatric department, Razi Hospital, Tunis, Tunisia Narjes karmous Roles: Conceptualization, Methodology, Writing – Original Draft Preparation Hanene Jemli Roles: Data Curation, Visualization Abdelwahab Masmoudi Roles: Writing – Review & Editing Badreddine Bouguerra Roles: Supervision, Validation Aymen Mabrouk Roles: Writing – Review & Editing Anis Ben Dhaou Roles: Writing – Review & Editing Abdennour Karmous Roles: Writing – Review & Editing Competing interests No competing interests were disclosed. Grant information The author(s) declared that no grants were involved in supporting this work. Article Versions (4) version 4 Revised Published: 19 May 2026, 14:1167 https://doi.org/10.12688/f1000research.170554.4 version 3 Revised Published: 09 Jan 2026, 14:1167 https://doi.org/10.12688/f1000research.170554.3 version 2 Revised Published: 31 Dec 2025, 14:1167 https://doi.org/10.12688/f1000research.170554.2 version 1 Published: 27 Oct 2025, 14:1167 https://doi.org/10.12688/f1000research.170554.1 Copyright © 2025 karmous N et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Download Export To Sciwheel Bibtex EndNote ProCite Ref. 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Key to Reviewer Statuses VIEW HIDE Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Version 1 VERSION 1 PUBLISHED 27 Oct 2025 Views 0 Cite How to cite this report: SARICOBAN CT. Reviewer Report For: Endometrial Thickness as a Prognostic Marker in Premenopausal Abnormal Uterine Bleeding: Diagnostic Accuracy and Kaplan–Meier Survival Insights [version 1; peer review: 2 not approved] . F1000Research 2025, 14 :1167 ( https://doi.org/10.5256/f1000research.188024.r428684 ) The direct URL for this report is: https://f1000research.com/articles/14-1167/v1#referee-response-428684 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 20 Nov 2025 CANSU TURKER SARICOBAN , Pathology, Istanbul University-Cerrahpasa, Cerrahpasa Faculty of Medicine, Istanbul, Turkey Not Approved VIEWS 0 https://doi.org/10.5256/f1000research.188024.r428684 The authors present a retrospective analytical study evaluating the diagnostic and purported prognostic utility of transvaginal ultrasound–based endometrial thickness (ET) in premenopausal women with abnormal uterine bleeding (AUB). The study aims to define an optimal ET cutoff (>9 mm) for ... Continue reading READ ALL The authors present a retrospective analytical study evaluating the diagnostic and purported prognostic utility of transvaginal ultrasound–based endometrial thickness (ET) in premenopausal women with abnormal uterine bleeding (AUB). The study aims to define an optimal ET cutoff (>9 mm) for predicting endometrial malignancy and further applies Kaplan–Meier time-to-event analyses (time-to-consultation and time-to-diagnosis) to explore clinical dynamics associated with different ET thresholds. Although the topic is clinically relevant and the dataset includes hysterectomy-confirmed outcomes, the study suffers from substantial methodological, analytical, and reporting limitations that significantly compromise the validity, reliability, and generalizability of its findings. A fundamental methodological limitation is the complete lack of menstrual cycle phase standardization at the time of ET measurement. Endometrial thickness varies markedly between the proliferative and secretory phases, making ET uninterpretable without cycle context. This single issue undermines the scientific foundation of the proposed cutoff value. Additionally, ET assessment via transvaginal ultrasound is known to have considerable interobserver variability; yet the manuscript does not state whether measurements were performed by a single operator or multiple clinicians, nor does it report any interobserver agreement or standardization procedures. These omissions severely restrict reproducibility and weaken the internal validity of the imaging data. The decision to use hysterectomy specimens as the “gold standard” for definitive diagnosis is also problematic. In a subset of endometrial carcinomas—particularly early or superficially located tumors—the entire neoplastic tissue may be removed by curettage or hysteroscopy, leading to an absent residual tumor in the hysterectomy specimen. The authors do not report any comparison between preoperative biopsy/hysteroscopy findings and post-hysterectomy pathology, nor do they address the risk of misclassification bias arising from these discrepancies. This omission raises concerns about reference standard accuracy. Furthermore, the presentation of baseline characteristics is confusing and potentially misleading. Percentages reported for variables such as diabetes, hypertension, and family history (“93% benign vs. 7% malignant”) are not clearly defined—whether they refer to patients with the risk factor, patients without it, or proportions within total groups is unclear. This ambiguity compromises interpretation of the risk factor analysis and represents a deviation from appropriate epidemiologic reporting standards. There are also inconsistencies within the dataset itself. For example, the manuscript states that the median ET in malignant cases is 12 mm, whereas Table 1 appears to present a different value (e.g., 10 mm or an incomplete notation). Such discrepancies reduce confidence in the accuracy and integrity of the reported data. Additionally, the application and interpretation of Kaplan–Meier analysis are conceptually flawed. “Time-to-consultation” reflects health-seeking behavior rather than biological disease progression and should not be presented as a prognostic marker. Given that symptom onset times were extracted retrospectively, this metric is particularly vulnerable to recall bias. The malignant event count (n=13) is also extremely low, limiting the statistical power of ROC analyses, logistic regression, and survival models, and rendering the resulting cutoff and effect estimates unstable. Lastly, the sampling frame introduces significant selection bias: only women who ultimately underwent hysterectomy were included. This subgroup represents a higher-risk and highly selected population that does not reflect the broader premenopausal AUB cohort seen in routine practice. Consequently, the >9 mm cutoff cannot be generalized beyond this specific surgical population. The manuscript contains several typographical and formatting errors (e.g., “8- year and 11-month,” “Mars 2025”), and the tone of certain phrases (“cornerstone parameter,” “robust prognostic marker”) is overstated given the study’s methodological limitations. Table formatting requires substantial correction, as percentages, p-values, and variable categories are inconsistently aligned or inadequately defined. Some terminology is unclear or unconventional (e.g., “intracavitary fibroma”), and adherence to STROBE reporting guidelines is incomplete. While the research topic is important, the methodological flaws, analytical limitations, inconsistent reporting, and conceptual misinterpretations present in the current version significantly compromise the validity of the findings. Extensive revisions, additional clarifications, and methodological restructuring would be required before this work could be considered for indexing. As it stands, the manuscript is not acceptable in its current form. Is the work clearly and accurately presented and does it cite the current literature? Partly Is the study design appropriate and is the work technically sound? Partly Are sufficient details of methods and analysis provided to allow replication by others? Partly If applicable, is the statistical analysis and its interpretation appropriate? Partly Are all the source data underlying the results available to ensure full reproducibility? Partly Are the conclusions drawn adequately supported by the results? No Competing Interests: No competing interests were disclosed. Reviewer Expertise: Gynaecopathology I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT SARICOBAN CT. Reviewer Report For: Endometrial Thickness as a Prognostic Marker in Premenopausal Abnormal Uterine Bleeding: Diagnostic Accuracy and Kaplan–Meier Survival Insights [version 1; peer review: 2 not approved] . F1000Research 2025, 14 :1167 ( https://doi.org/10.5256/f1000research.188024.r428684 ) The direct URL for this report is: https://f1000research.com/articles/14-1167/v1#referee-response-428684 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Author Response 12 Jan 2026 Narjes karmous , Gynaecology and Obstetrics department B, Charles Nicolle Hospital, Tunis, Tunisia 12 Jan 2026 Author Response Dear dr CANSU TURKER SARICOBAN, We sincerely thank you for your thorough and constructive feedback on our manuscript. We have carefully addressed all the points raised. Our responses and the ... Continue reading Dear dr CANSU TURKER SARICOBAN, We sincerely thank you for your thorough and constructive feedback on our manuscript. We have carefully addressed all the points raised. Our responses and the corresponding changes made in the manuscript are summarized below: 1. A fundamental methodological limitation is the complete lack of menstrual cycle phase standardization at the time of ET measurement. ET varies markedly between the proliferative and secretory phases, making ET uninterpretable without cycle context. This single issue undermines the scientific foundation of the proposed cutoff value. Response: Thank you for raising this important methodological concern. We fully agree that endometrial thickness (ET) varies according to the menstrual cycle phase and that phase-specific measurement represents the optimal physiological approach. However, the present study was designed to reflect routine clinical practice in premenopausal women presenting with abnormal uterine bleeding (AUB), a population in whom menstrual cycle regularity and accurate phase determination are frequently unavailable or unreliable at the time of clinical assessment. Consequently, ET measurements were performed at presentation, irrespective of cycle phase, in line with real-world diagnostic pathways. Our objective was therefore not to define a physiological, cycle-dependent reference value for ET, but rather to evaluate its diagnostic and prognostic utility as a pragmatic clinical marker for identifying women at increased risk of endometrial malignancy in a symptomatic AUB population. Importantly, several previously published retrospective studies addressing ET in premenopausal AUB populations similarly lacked systematic cycle phase standardization and nonetheless reported clinically useful cutoff values. We acknowledge that the absence of menstrual cycle phase standardization represents a major limitation of our study and have explicitly addressed this in the Methods and Limitations sections. To avoid overinterpretation, we have also clarified that the proposed ET cutoff should be interpreted as a risk stratification threshold within a clinical context, rather than as an absolute physiological value. We agree that future prospective studies incorporating precise cycle phase control are required to refine and validate phase-specific thresholds. 2. The manuscript does not state whether measurements were performed by a single operator or multiple clinicians, nor does it report any interobserver agreement or standardization procedures. These omissions severely restrict reproducibility and weaken the internal validity of the imaging data. Response: Thank you for highlighting this important aspect related to reproducibility and internal validity. We have revised the Methods section to clarify that all TVUS examinations were performed by three experienced operators, each holding an inter-university diploma in gynecologic US and with over 10 years of clinical experience in pelvic US practice. Given the retrospective nature of the study, formal assessment of interobserver agreement (e.g., intraclass correlation coefficients) and predefined standardization protocols could not be performed. However, all operators followed institutional US protocols for endometrial assessment, and ET was measure in the sagittal plane as the double-layer distance between the two endometrial–myometrial interfaces, at the point of greatest thickness perpendicular to the midline, using appropriately magnified images, in accordance with standard ultrasound assessment protocols used at our institution. We acknowledge that the absence of formal interobserver variability analysis represents a limitation and have explicitly addressed this in the Limitations section. Future prospective studies incorporating predefined measurement protocols and interobserver agreement assessment are warranted to further strengthen reproducibility. 3. The decision to use hysterectomy specimens as the “gold standard” for definitive diagnosis is also problematic. In a subset of endometrial carcinomas—particularly early or superficially located tumors—the entire neoplastic tissue may be removed by curettage or hysteroscopy, leading to an absent residual tumor in the hysterectomy specimen. The authors do not report any comparison between preoperative biopsy/hysteroscopy findings and post-hysterectomy pathology, nor do they address the risk of misclassification bias arising from these discrepancies. This omission raises concerns about reference standard accuracy. Response: Thank you for raising this important point regarding the use of hysterectomy specimens as the reference standard. We agree that in some series, early or superficially located endometrial tumors may be completely removed during curettage or hysteroscopy, potentially leading to absent residual tumor in the hysterectomy specimen and misclassification. In our study, we systematically compared preoperative endometrial biopsy or hysteroscopy findings with post-hysterectomy pathology. This comparison demonstrated excellent concordance , with no discrepancies observed. This result has now been added to the Results section to clarify that hysterectomy specimens provided a reliable reference standard in our cohort. 4. Percentages reported for variables such as diabetes, hypertension, and family history (“93% benign vs. 7% malignant”) are not clearly defined—whether they refer to patients with the risk factor, patients without it, or proportions within total groups is unclear. This ambiguity compromises interpretation of the risk factor analysis and represents a deviation from appropriate epidemiologic reporting standards. Response: We have revised the Results section to report the presence of comorbidities rather than their absence, in accordance with epidemiological reporting standards. Percentages now clearly represent the proportion of patients presenting each risk factor within the benign and malignant groups, eliminating any ambiguity. 5. The manuscript states that the median ET in malignant cases is 12 mm, whereas Table 1 appears to present a different value (e.g., 10 mm or an incomplete notation). Such discrepancies reduce confidence in the accuracy and integrity of the reported data. Response: Thank you for drawing our attention to this discrepancy. We confirm that the correct median ET in malignant cases is 12 mm . The value initially reported in Table 1 (10 mm) resulted from a data transcription error and has now been corrected . In addition, following the request of Reviewer 1, a new table was added to the Methods section, and the baseline characteristics table has therefore been renumbered as Table 2 . The corrected ET value is now consistently reported in both the Results text and Table 2 . All numerical values reported in the text and tables were cross-checked to ensure internal consistency. 6. The application and interpretation of Kaplan–Meier analysis are conceptually flawed. “Time-to-consultation” reflects health-seeking behavior rather than biological disease progression and should not be presented as a prognostic marker. Given that symptom onset times were extracted retrospectively, this metric is particularly vulnerable to recall bias. Response: We agree that “ time-to-consultation” primarily reflects health-seeking behavior rather than intrinsic biological disease progression and, as such, should not be interpreted as a biological prognostic marker. In the revised manuscript, we have therefore clarified the objective and interpretation of the Kaplan–Meier analysis. The analysis is now explicitly presented as an exploratory assessment of diagnostic delay , illustrating differences in healthcare-seeking patterns according to endometrial thickness, rather than as a predictor of tumor aggressiveness or prognosis. We also acknowledge that symptom onset was collected retrospectively and is therefore susceptible to recall bias . This limitation has now been clearly stated in the Discussion/Limitations section. Importantly, the Kaplan–Meier analysis is no longer framed as prognostic, and its results are interpreted with appropriate caution. 7. The malignant event count (n=13) is also extremely low, limiting the statistical power of ROC analyses, logistic regression, and survival models, and rendering the resulting cutoff and effect estimates unstable. Response: We acknowledge that the low number of malignant events (n = 13) limits the statistical power of the ROC analyses, logistic regression, and Kaplan–Meier models, and may result in unstable cutoff values and imprecise effect estimates. This limitation has now been explicitly stated in the Discussion/Limitations section, and the results of these analyses are interpreted with appropriate caution. We emphasize that our findings should be considered exploratory and hypothesis-generating rather than definitive. 8. Several typographical and formatting errors (e.g., “8- year and 11-month,” “Mars 2025”), and the tone of certain phrases (“cornerstone parameter,” “robust prognostic marker”) is overstated given the study’s methodological limitations. Table formatting requires substantial correction, as percentages, p-values, and variable categories are inconsistently aligned or inadequately defined. Some terminology is unclear or unconventional (e.g., “intracavitary fibroma”), and adherence to STROBE reporting guidelines is incomplete. Response: We have carefully revised the manuscript to address all typographical, stylistic, and formatting issues identified. All typographical and linguistic errors have been corrected, including inconsistencies in date and duration formatting (e.g., “8-year and 11-month period,” “March 2025”). The tone of the manuscript has been moderated to better reflect the methodological limitations of the study, and overstated expressions such as “cornerstone parameter” and “robust prognostic marker” have been replaced with more cautious and precise terminology. All tables have been comprehensively reformatted to ensure consistent alignment of variables, percentages, and p-values, with clear definition of categories and denominators where applicable. Terminology has been standardized in accordance with internationally accepted nomenclature, and ambiguous terms such as “intracavitary fibroma” have been replaced with clearer expressions (e.g., “intracavitary fibroid”). Finally, we have reviewed the manuscript in accordance with the STROBE reporting guidelines for observational studies and have ensured that all relevant items are adequately addressed. The manuscript sections have been revised to improve transparency and reporting completeness. Dear dr CANSU TURKER SARICOBAN, We sincerely thank you for your thorough and constructive feedback on our manuscript. We have carefully addressed all the points raised. Our responses and the corresponding changes made in the manuscript are summarized below: 1. A fundamental methodological limitation is the complete lack of menstrual cycle phase standardization at the time of ET measurement. ET varies markedly between the proliferative and secretory phases, making ET uninterpretable without cycle context. This single issue undermines the scientific foundation of the proposed cutoff value. Response: Thank you for raising this important methodological concern. We fully agree that endometrial thickness (ET) varies according to the menstrual cycle phase and that phase-specific measurement represents the optimal physiological approach. However, the present study was designed to reflect routine clinical practice in premenopausal women presenting with abnormal uterine bleeding (AUB), a population in whom menstrual cycle regularity and accurate phase determination are frequently unavailable or unreliable at the time of clinical assessment. Consequently, ET measurements were performed at presentation, irrespective of cycle phase, in line with real-world diagnostic pathways. Our objective was therefore not to define a physiological, cycle-dependent reference value for ET, but rather to evaluate its diagnostic and prognostic utility as a pragmatic clinical marker for identifying women at increased risk of endometrial malignancy in a symptomatic AUB population. Importantly, several previously published retrospective studies addressing ET in premenopausal AUB populations similarly lacked systematic cycle phase standardization and nonetheless reported clinically useful cutoff values. We acknowledge that the absence of menstrual cycle phase standardization represents a major limitation of our study and have explicitly addressed this in the Methods and Limitations sections. To avoid overinterpretation, we have also clarified that the proposed ET cutoff should be interpreted as a risk stratification threshold within a clinical context, rather than as an absolute physiological value. We agree that future prospective studies incorporating precise cycle phase control are required to refine and validate phase-specific thresholds. 2. The manuscript does not state whether measurements were performed by a single operator or multiple clinicians, nor does it report any interobserver agreement or standardization procedures. These omissions severely restrict reproducibility and weaken the internal validity of the imaging data. Response: Thank you for highlighting this important aspect related to reproducibility and internal validity. We have revised the Methods section to clarify that all TVUS examinations were performed by three experienced operators, each holding an inter-university diploma in gynecologic US and with over 10 years of clinical experience in pelvic US practice. Given the retrospective nature of the study, formal assessment of interobserver agreement (e.g., intraclass correlation coefficients) and predefined standardization protocols could not be performed. However, all operators followed institutional US protocols for endometrial assessment, and ET was measure in the sagittal plane as the double-layer distance between the two endometrial–myometrial interfaces, at the point of greatest thickness perpendicular to the midline, using appropriately magnified images, in accordance with standard ultrasound assessment protocols used at our institution. We acknowledge that the absence of formal interobserver variability analysis represents a limitation and have explicitly addressed this in the Limitations section. Future prospective studies incorporating predefined measurement protocols and interobserver agreement assessment are warranted to further strengthen reproducibility. 3. The decision to use hysterectomy specimens as the “gold standard” for definitive diagnosis is also problematic. In a subset of endometrial carcinomas—particularly early or superficially located tumors—the entire neoplastic tissue may be removed by curettage or hysteroscopy, leading to an absent residual tumor in the hysterectomy specimen. The authors do not report any comparison between preoperative biopsy/hysteroscopy findings and post-hysterectomy pathology, nor do they address the risk of misclassification bias arising from these discrepancies. This omission raises concerns about reference standard accuracy. Response: Thank you for raising this important point regarding the use of hysterectomy specimens as the reference standard. We agree that in some series, early or superficially located endometrial tumors may be completely removed during curettage or hysteroscopy, potentially leading to absent residual tumor in the hysterectomy specimen and misclassification. In our study, we systematically compared preoperative endometrial biopsy or hysteroscopy findings with post-hysterectomy pathology. This comparison demonstrated excellent concordance , with no discrepancies observed. This result has now been added to the Results section to clarify that hysterectomy specimens provided a reliable reference standard in our cohort. 4. Percentages reported for variables such as diabetes, hypertension, and family history (“93% benign vs. 7% malignant”) are not clearly defined—whether they refer to patients with the risk factor, patients without it, or proportions within total groups is unclear. This ambiguity compromises interpretation of the risk factor analysis and represents a deviation from appropriate epidemiologic reporting standards. Response: We have revised the Results section to report the presence of comorbidities rather than their absence, in accordance with epidemiological reporting standards. Percentages now clearly represent the proportion of patients presenting each risk factor within the benign and malignant groups, eliminating any ambiguity. 5. The manuscript states that the median ET in malignant cases is 12 mm, whereas Table 1 appears to present a different value (e.g., 10 mm or an incomplete notation). Such discrepancies reduce confidence in the accuracy and integrity of the reported data. Response: Thank you for drawing our attention to this discrepancy. We confirm that the correct median ET in malignant cases is 12 mm . The value initially reported in Table 1 (10 mm) resulted from a data transcription error and has now been corrected . In addition, following the request of Reviewer 1, a new table was added to the Methods section, and the baseline characteristics table has therefore been renumbered as Table 2 . The corrected ET value is now consistently reported in both the Results text and Table 2 . All numerical values reported in the text and tables were cross-checked to ensure internal consistency. 6. The application and interpretation of Kaplan–Meier analysis are conceptually flawed. “Time-to-consultation” reflects health-seeking behavior rather than biological disease progression and should not be presented as a prognostic marker. Given that symptom onset times were extracted retrospectively, this metric is particularly vulnerable to recall bias. Response: We agree that “ time-to-consultation” primarily reflects health-seeking behavior rather than intrinsic biological disease progression and, as such, should not be interpreted as a biological prognostic marker. In the revised manuscript, we have therefore clarified the objective and interpretation of the Kaplan–Meier analysis. The analysis is now explicitly presented as an exploratory assessment of diagnostic delay , illustrating differences in healthcare-seeking patterns according to endometrial thickness, rather than as a predictor of tumor aggressiveness or prognosis. We also acknowledge that symptom onset was collected retrospectively and is therefore susceptible to recall bias . This limitation has now been clearly stated in the Discussion/Limitations section. Importantly, the Kaplan–Meier analysis is no longer framed as prognostic, and its results are interpreted with appropriate caution. 7. The malignant event count (n=13) is also extremely low, limiting the statistical power of ROC analyses, logistic regression, and survival models, and rendering the resulting cutoff and effect estimates unstable. Response: We acknowledge that the low number of malignant events (n = 13) limits the statistical power of the ROC analyses, logistic regression, and Kaplan–Meier models, and may result in unstable cutoff values and imprecise effect estimates. This limitation has now been explicitly stated in the Discussion/Limitations section, and the results of these analyses are interpreted with appropriate caution. We emphasize that our findings should be considered exploratory and hypothesis-generating rather than definitive. 8. Several typographical and formatting errors (e.g., “8- year and 11-month,” “Mars 2025”), and the tone of certain phrases (“cornerstone parameter,” “robust prognostic marker”) is overstated given the study’s methodological limitations. Table formatting requires substantial correction, as percentages, p-values, and variable categories are inconsistently aligned or inadequately defined. Some terminology is unclear or unconventional (e.g., “intracavitary fibroma”), and adherence to STROBE reporting guidelines is incomplete. Response: We have carefully revised the manuscript to address all typographical, stylistic, and formatting issues identified. All typographical and linguistic errors have been corrected, including inconsistencies in date and duration formatting (e.g., “8-year and 11-month period,” “March 2025”). The tone of the manuscript has been moderated to better reflect the methodological limitations of the study, and overstated expressions such as “cornerstone parameter” and “robust prognostic marker” have been replaced with more cautious and precise terminology. All tables have been comprehensively reformatted to ensure consistent alignment of variables, percentages, and p-values, with clear definition of categories and denominators where applicable. Terminology has been standardized in accordance with internationally accepted nomenclature, and ambiguous terms such as “intracavitary fibroma” have been replaced with clearer expressions (e.g., “intracavitary fibroid”). Finally, we have reviewed the manuscript in accordance with the STROBE reporting guidelines for observational studies and have ensured that all relevant items are adequately addressed. The manuscript sections have been revised to improve transparency and reporting completeness. Competing Interests: No competing interests were disclosed. Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 12 Jan 2026 Narjes karmous , Gynaecology and Obstetrics department B, Charles Nicolle Hospital, Tunis, Tunisia 12 Jan 2026 Author Response Dear dr CANSU TURKER SARICOBAN, We sincerely thank you for your thorough and constructive feedback on our manuscript. We have carefully addressed all the points raised. Our responses and the ... Continue reading Dear dr CANSU TURKER SARICOBAN, We sincerely thank you for your thorough and constructive feedback on our manuscript. We have carefully addressed all the points raised. Our responses and the corresponding changes made in the manuscript are summarized below: 1. A fundamental methodological limitation is the complete lack of menstrual cycle phase standardization at the time of ET measurement. ET varies markedly between the proliferative and secretory phases, making ET uninterpretable without cycle context. This single issue undermines the scientific foundation of the proposed cutoff value. Response: Thank you for raising this important methodological concern. We fully agree that endometrial thickness (ET) varies according to the menstrual cycle phase and that phase-specific measurement represents the optimal physiological approach. However, the present study was designed to reflect routine clinical practice in premenopausal women presenting with abnormal uterine bleeding (AUB), a population in whom menstrual cycle regularity and accurate phase determination are frequently unavailable or unreliable at the time of clinical assessment. Consequently, ET measurements were performed at presentation, irrespective of cycle phase, in line with real-world diagnostic pathways. Our objective was therefore not to define a physiological, cycle-dependent reference value for ET, but rather to evaluate its diagnostic and prognostic utility as a pragmatic clinical marker for identifying women at increased risk of endometrial malignancy in a symptomatic AUB population. Importantly, several previously published retrospective studies addressing ET in premenopausal AUB populations similarly lacked systematic cycle phase standardization and nonetheless reported clinically useful cutoff values. We acknowledge that the absence of menstrual cycle phase standardization represents a major limitation of our study and have explicitly addressed this in the Methods and Limitations sections. To avoid overinterpretation, we have also clarified that the proposed ET cutoff should be interpreted as a risk stratification threshold within a clinical context, rather than as an absolute physiological value. We agree that future prospective studies incorporating precise cycle phase control are required to refine and validate phase-specific thresholds. 2. The manuscript does not state whether measurements were performed by a single operator or multiple clinicians, nor does it report any interobserver agreement or standardization procedures. These omissions severely restrict reproducibility and weaken the internal validity of the imaging data. Response: Thank you for highlighting this important aspect related to reproducibility and internal validity. We have revised the Methods section to clarify that all TVUS examinations were performed by three experienced operators, each holding an inter-university diploma in gynecologic US and with over 10 years of clinical experience in pelvic US practice. Given the retrospective nature of the study, formal assessment of interobserver agreement (e.g., intraclass correlation coefficients) and predefined standardization protocols could not be performed. However, all operators followed institutional US protocols for endometrial assessment, and ET was measure in the sagittal plane as the double-layer distance between the two endometrial–myometrial interfaces, at the point of greatest thickness perpendicular to the midline, using appropriately magnified images, in accordance with standard ultrasound assessment protocols used at our institution. We acknowledge that the absence of formal interobserver variability analysis represents a limitation and have explicitly addressed this in the Limitations section. Future prospective studies incorporating predefined measurement protocols and interobserver agreement assessment are warranted to further strengthen reproducibility. 3. The decision to use hysterectomy specimens as the “gold standard” for definitive diagnosis is also problematic. In a subset of endometrial carcinomas—particularly early or superficially located tumors—the entire neoplastic tissue may be removed by curettage or hysteroscopy, leading to an absent residual tumor in the hysterectomy specimen. The authors do not report any comparison between preoperative biopsy/hysteroscopy findings and post-hysterectomy pathology, nor do they address the risk of misclassification bias arising from these discrepancies. This omission raises concerns about reference standard accuracy. Response: Thank you for raising this important point regarding the use of hysterectomy specimens as the reference standard. We agree that in some series, early or superficially located endometrial tumors may be completely removed during curettage or hysteroscopy, potentially leading to absent residual tumor in the hysterectomy specimen and misclassification. In our study, we systematically compared preoperative endometrial biopsy or hysteroscopy findings with post-hysterectomy pathology. This comparison demonstrated excellent concordance , with no discrepancies observed. This result has now been added to the Results section to clarify that hysterectomy specimens provided a reliable reference standard in our cohort. 4. Percentages reported for variables such as diabetes, hypertension, and family history (“93% benign vs. 7% malignant”) are not clearly defined—whether they refer to patients with the risk factor, patients without it, or proportions within total groups is unclear. This ambiguity compromises interpretation of the risk factor analysis and represents a deviation from appropriate epidemiologic reporting standards. Response: We have revised the Results section to report the presence of comorbidities rather than their absence, in accordance with epidemiological reporting standards. Percentages now clearly represent the proportion of patients presenting each risk factor within the benign and malignant groups, eliminating any ambiguity. 5. The manuscript states that the median ET in malignant cases is 12 mm, whereas Table 1 appears to present a different value (e.g., 10 mm or an incomplete notation). Such discrepancies reduce confidence in the accuracy and integrity of the reported data. Response: Thank you for drawing our attention to this discrepancy. We confirm that the correct median ET in malignant cases is 12 mm . The value initially reported in Table 1 (10 mm) resulted from a data transcription error and has now been corrected . In addition, following the request of Reviewer 1, a new table was added to the Methods section, and the baseline characteristics table has therefore been renumbered as Table 2 . The corrected ET value is now consistently reported in both the Results text and Table 2 . All numerical values reported in the text and tables were cross-checked to ensure internal consistency. 6. The application and interpretation of Kaplan–Meier analysis are conceptually flawed. “Time-to-consultation” reflects health-seeking behavior rather than biological disease progression and should not be presented as a prognostic marker. Given that symptom onset times were extracted retrospectively, this metric is particularly vulnerable to recall bias. Response: We agree that “ time-to-consultation” primarily reflects health-seeking behavior rather than intrinsic biological disease progression and, as such, should not be interpreted as a biological prognostic marker. In the revised manuscript, we have therefore clarified the objective and interpretation of the Kaplan–Meier analysis. The analysis is now explicitly presented as an exploratory assessment of diagnostic delay , illustrating differences in healthcare-seeking patterns according to endometrial thickness, rather than as a predictor of tumor aggressiveness or prognosis. We also acknowledge that symptom onset was collected retrospectively and is therefore susceptible to recall bias . This limitation has now been clearly stated in the Discussion/Limitations section. Importantly, the Kaplan–Meier analysis is no longer framed as prognostic, and its results are interpreted with appropriate caution. 7. The malignant event count (n=13) is also extremely low, limiting the statistical power of ROC analyses, logistic regression, and survival models, and rendering the resulting cutoff and effect estimates unstable. Response: We acknowledge that the low number of malignant events (n = 13) limits the statistical power of the ROC analyses, logistic regression, and Kaplan–Meier models, and may result in unstable cutoff values and imprecise effect estimates. This limitation has now been explicitly stated in the Discussion/Limitations section, and the results of these analyses are interpreted with appropriate caution. We emphasize that our findings should be considered exploratory and hypothesis-generating rather than definitive. 8. Several typographical and formatting errors (e.g., “8- year and 11-month,” “Mars 2025”), and the tone of certain phrases (“cornerstone parameter,” “robust prognostic marker”) is overstated given the study’s methodological limitations. Table formatting requires substantial correction, as percentages, p-values, and variable categories are inconsistently aligned or inadequately defined. Some terminology is unclear or unconventional (e.g., “intracavitary fibroma”), and adherence to STROBE reporting guidelines is incomplete. Response: We have carefully revised the manuscript to address all typographical, stylistic, and formatting issues identified. All typographical and linguistic errors have been corrected, including inconsistencies in date and duration formatting (e.g., “8-year and 11-month period,” “March 2025”). The tone of the manuscript has been moderated to better reflect the methodological limitations of the study, and overstated expressions such as “cornerstone parameter” and “robust prognostic marker” have been replaced with more cautious and precise terminology. All tables have been comprehensively reformatted to ensure consistent alignment of variables, percentages, and p-values, with clear definition of categories and denominators where applicable. Terminology has been standardized in accordance with internationally accepted nomenclature, and ambiguous terms such as “intracavitary fibroma” have been replaced with clearer expressions (e.g., “intracavitary fibroid”). Finally, we have reviewed the manuscript in accordance with the STROBE reporting guidelines for observational studies and have ensured that all relevant items are adequately addressed. The manuscript sections have been revised to improve transparency and reporting completeness. Dear dr CANSU TURKER SARICOBAN, We sincerely thank you for your thorough and constructive feedback on our manuscript. We have carefully addressed all the points raised. Our responses and the corresponding changes made in the manuscript are summarized below: 1. A fundamental methodological limitation is the complete lack of menstrual cycle phase standardization at the time of ET measurement. ET varies markedly between the proliferative and secretory phases, making ET uninterpretable without cycle context. This single issue undermines the scientific foundation of the proposed cutoff value. Response: Thank you for raising this important methodological concern. We fully agree that endometrial thickness (ET) varies according to the menstrual cycle phase and that phase-specific measurement represents the optimal physiological approach. However, the present study was designed to reflect routine clinical practice in premenopausal women presenting with abnormal uterine bleeding (AUB), a population in whom menstrual cycle regularity and accurate phase determination are frequently unavailable or unreliable at the time of clinical assessment. Consequently, ET measurements were performed at presentation, irrespective of cycle phase, in line with real-world diagnostic pathways. Our objective was therefore not to define a physiological, cycle-dependent reference value for ET, but rather to evaluate its diagnostic and prognostic utility as a pragmatic clinical marker for identifying women at increased risk of endometrial malignancy in a symptomatic AUB population. Importantly, several previously published retrospective studies addressing ET in premenopausal AUB populations similarly lacked systematic cycle phase standardization and nonetheless reported clinically useful cutoff values. We acknowledge that the absence of menstrual cycle phase standardization represents a major limitation of our study and have explicitly addressed this in the Methods and Limitations sections. To avoid overinterpretation, we have also clarified that the proposed ET cutoff should be interpreted as a risk stratification threshold within a clinical context, rather than as an absolute physiological value. We agree that future prospective studies incorporating precise cycle phase control are required to refine and validate phase-specific thresholds. 2. The manuscript does not state whether measurements were performed by a single operator or multiple clinicians, nor does it report any interobserver agreement or standardization procedures. These omissions severely restrict reproducibility and weaken the internal validity of the imaging data. Response: Thank you for highlighting this important aspect related to reproducibility and internal validity. We have revised the Methods section to clarify that all TVUS examinations were performed by three experienced operators, each holding an inter-university diploma in gynecologic US and with over 10 years of clinical experience in pelvic US practice. Given the retrospective nature of the study, formal assessment of interobserver agreement (e.g., intraclass correlation coefficients) and predefined standardization protocols could not be performed. However, all operators followed institutional US protocols for endometrial assessment, and ET was measure in the sagittal plane as the double-layer distance between the two endometrial–myometrial interfaces, at the point of greatest thickness perpendicular to the midline, using appropriately magnified images, in accordance with standard ultrasound assessment protocols used at our institution. We acknowledge that the absence of formal interobserver variability analysis represents a limitation and have explicitly addressed this in the Limitations section. Future prospective studies incorporating predefined measurement protocols and interobserver agreement assessment are warranted to further strengthen reproducibility. 3. The decision to use hysterectomy specimens as the “gold standard” for definitive diagnosis is also problematic. In a subset of endometrial carcinomas—particularly early or superficially located tumors—the entire neoplastic tissue may be removed by curettage or hysteroscopy, leading to an absent residual tumor in the hysterectomy specimen. The authors do not report any comparison between preoperative biopsy/hysteroscopy findings and post-hysterectomy pathology, nor do they address the risk of misclassification bias arising from these discrepancies. This omission raises concerns about reference standard accuracy. Response: Thank you for raising this important point regarding the use of hysterectomy specimens as the reference standard. We agree that in some series, early or superficially located endometrial tumors may be completely removed during curettage or hysteroscopy, potentially leading to absent residual tumor in the hysterectomy specimen and misclassification. In our study, we systematically compared preoperative endometrial biopsy or hysteroscopy findings with post-hysterectomy pathology. This comparison demonstrated excellent concordance , with no discrepancies observed. This result has now been added to the Results section to clarify that hysterectomy specimens provided a reliable reference standard in our cohort. 4. Percentages reported for variables such as diabetes, hypertension, and family history (“93% benign vs. 7% malignant”) are not clearly defined—whether they refer to patients with the risk factor, patients without it, or proportions within total groups is unclear. This ambiguity compromises interpretation of the risk factor analysis and represents a deviation from appropriate epidemiologic reporting standards. Response: We have revised the Results section to report the presence of comorbidities rather than their absence, in accordance with epidemiological reporting standards. Percentages now clearly represent the proportion of patients presenting each risk factor within the benign and malignant groups, eliminating any ambiguity. 5. The manuscript states that the median ET in malignant cases is 12 mm, whereas Table 1 appears to present a different value (e.g., 10 mm or an incomplete notation). Such discrepancies reduce confidence in the accuracy and integrity of the reported data. Response: Thank you for drawing our attention to this discrepancy. We confirm that the correct median ET in malignant cases is 12 mm . The value initially reported in Table 1 (10 mm) resulted from a data transcription error and has now been corrected . In addition, following the request of Reviewer 1, a new table was added to the Methods section, and the baseline characteristics table has therefore been renumbered as Table 2 . The corrected ET value is now consistently reported in both the Results text and Table 2 . All numerical values reported in the text and tables were cross-checked to ensure internal consistency. 6. The application and interpretation of Kaplan–Meier analysis are conceptually flawed. “Time-to-consultation” reflects health-seeking behavior rather than biological disease progression and should not be presented as a prognostic marker. Given that symptom onset times were extracted retrospectively, this metric is particularly vulnerable to recall bias. Response: We agree that “ time-to-consultation” primarily reflects health-seeking behavior rather than intrinsic biological disease progression and, as such, should not be interpreted as a biological prognostic marker. In the revised manuscript, we have therefore clarified the objective and interpretation of the Kaplan–Meier analysis. The analysis is now explicitly presented as an exploratory assessment of diagnostic delay , illustrating differences in healthcare-seeking patterns according to endometrial thickness, rather than as a predictor of tumor aggressiveness or prognosis. We also acknowledge that symptom onset was collected retrospectively and is therefore susceptible to recall bias . This limitation has now been clearly stated in the Discussion/Limitations section. Importantly, the Kaplan–Meier analysis is no longer framed as prognostic, and its results are interpreted with appropriate caution. 7. The malignant event count (n=13) is also extremely low, limiting the statistical power of ROC analyses, logistic regression, and survival models, and rendering the resulting cutoff and effect estimates unstable. Response: We acknowledge that the low number of malignant events (n = 13) limits the statistical power of the ROC analyses, logistic regression, and Kaplan–Meier models, and may result in unstable cutoff values and imprecise effect estimates. This limitation has now been explicitly stated in the Discussion/Limitations section, and the results of these analyses are interpreted with appropriate caution. We emphasize that our findings should be considered exploratory and hypothesis-generating rather than definitive. 8. Several typographical and formatting errors (e.g., “8- year and 11-month,” “Mars 2025”), and the tone of certain phrases (“cornerstone parameter,” “robust prognostic marker”) is overstated given the study’s methodological limitations. Table formatting requires substantial correction, as percentages, p-values, and variable categories are inconsistently aligned or inadequately defined. Some terminology is unclear or unconventional (e.g., “intracavitary fibroma”), and adherence to STROBE reporting guidelines is incomplete. Response: We have carefully revised the manuscript to address all typographical, stylistic, and formatting issues identified. All typographical and linguistic errors have been corrected, including inconsistencies in date and duration formatting (e.g., “8-year and 11-month period,” “March 2025”). The tone of the manuscript has been moderated to better reflect the methodological limitations of the study, and overstated expressions such as “cornerstone parameter” and “robust prognostic marker” have been replaced with more cautious and precise terminology. All tables have been comprehensively reformatted to ensure consistent alignment of variables, percentages, and p-values, with clear definition of categories and denominators where applicable. Terminology has been standardized in accordance with internationally accepted nomenclature, and ambiguous terms such as “intracavitary fibroma” have been replaced with clearer expressions (e.g., “intracavitary fibroid”). Finally, we have reviewed the manuscript in accordance with the STROBE reporting guidelines for observational studies and have ensured that all relevant items are adequately addressed. The manuscript sections have been revised to improve transparency and reporting completeness. Competing Interests: No competing interests were disclosed. Close Report a concern COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Palo S. Reviewer Report For: Endometrial Thickness as a Prognostic Marker in Premenopausal Abnormal Uterine Bleeding: Diagnostic Accuracy and Kaplan–Meier Survival Insights [version 1; peer review: 2 not approved] . F1000Research 2025, 14 :1167 ( https://doi.org/10.5256/f1000research.188024.r428689 ) The direct URL for this report is: https://f1000research.com/articles/14-1167/v1#referee-response-428689 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 06 Nov 2025 Seetu Palo , All India Institute of Medical Sciences, Hyderabad, India Not Approved VIEWS 0 https://doi.org/10.5256/f1000research.188024.r428689 This article presents a retrospective analytical study investigating the diagnostic and prognostic value of endometrial thickness (ET) in premenopausal women with abnormal uterine bleeding (AUB). The authors aim to define an optimal ET cutoff for predicting endometrial malignancy and ... Continue reading READ ALL This article presents a retrospective analytical study investigating the diagnostic and prognostic value of endometrial thickness (ET) in premenopausal women with abnormal uterine bleeding (AUB). The authors aim to define an optimal ET cutoff for predicting endometrial malignancy and to explore the prognostic implications of ET using Kaplan–Meier survival analysis. The manuscript is generally well-written and addresses a clinically relevant topic, but certain aspects require clarification, additional rigor, and scientific refinement. In the abstract, clearly clarify that Kaplan–Meier analysis was applied to time-to-consultation and time-to-diagnosis, not survival outcomes. Include the AUC value (0.842) and the >9 mm cutoff directly in the abstract. The concept of “time-to-consultation” as a survival endpoint is unorthodox. It reflects healthcare-seeking behavior rather than biological survival. Consider reframe this as an auxiliary behavioural metric rather than a true prognostic parameter. Revise “prognostic marker” to “potential prognostic or triage marker.” In the methodology section, please specify whether TVUS was performed by a single operator or multiple radiologists. In section 2.4, consider including details of variables retained in the multivariate model and present odds ratios in a table. Similarly in the results, consider providing a regression summary table (with adjusted ORs and 95% CIs). Furthermore, Table 1 formatting can be improved (alignment of percentages and p-values). In the discussion section, clarify that “time-to-consultation” is an indicator of clinical presentation dynamics, not disease progression. A brief discussion on the implications for low-resource settings where hysteroscopy access is limited, can be added. Rather than claiming ET as a “robust prognostic marker,” the phrase “a potential surrogate marker reflecting disease burden” is suggested. Similarly, the phrase “cornerstone parameter” may be moderated to “key non-invasive parameter.” Formatting and minor errors also needs rectification, such as, correct “8- year and 11-month” to “8 years and 11 months” and “On 6 Mars 2025” to “on March 6, 2025.” Is the work clearly and accurately presented and does it cite the current literature? Partly Is the study design appropriate and is the work technically sound? Partly Are sufficient details of methods and analysis provided to allow replication by others? Partly If applicable, is the statistical analysis and its interpretation appropriate? Partly Are all the source data underlying the results available to ensure full reproducibility? Partly Are the conclusions drawn adequately supported by the results? No Competing Interests: No competing interests were disclosed. Reviewer Expertise: Oncopathology I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Palo S. Reviewer Report For: Endometrial Thickness as a Prognostic Marker in Premenopausal Abnormal Uterine Bleeding: Diagnostic Accuracy and Kaplan–Meier Survival Insights [version 1; peer review: 2 not approved] . F1000Research 2025, 14 :1167 ( https://doi.org/10.5256/f1000research.188024.r428689 ) The direct URL for this report is: https://f1000research.com/articles/14-1167/v1#referee-response-428689 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Author Response 31 Dec 2025 Narjes karmous , Gynaecology and Obstetrics department B, Charles Nicolle Hospital, Tunis, Tunisia 31 Dec 2025 Author Response Dear dr Seetu Palo, We sincerely thank you for your thorough and constructive feedback on our manuscript. We have carefully addressed all the points raised. Our responses and the corresponding ... Continue reading Dear dr Seetu Palo, We sincerely thank you for your thorough and constructive feedback on our manuscript. We have carefully addressed all the points raised. Our responses and the corresponding changes made in the manuscript are summarized below: 1. Abstract – Kaplan–Meier analysis, AUC, cutoff, and terminology Reviewer comment: Clearly clarify that Kaplan–Meier analysis was applied to time-to-consultation and time-to-diagnosis, not survival outcomes. Include the AUC value (0.842) and the >9 mm cutoff directly in the abstract. The concept of “time-to-consultation” as a survival endpoint is unorthodox. Consider reframe this as an auxiliary behavioural metric rather than a true prognostic parameter. Revise “prognostic marker” to “potential prognostic or triage marker.” Response: We have revised the abstract accordingly. Kaplan–Meier analysis is now clearly described as applied to time-to-consultation and time-to-diagnosis , reflecting healthcare-seeking behavior rather than survival. The AUC value (0.842) and the >9 mm cutoff are explicitly included. Terminology “robust prognostic marker” has been replaced with “potential prognostic or triage marker” . The concept of time-to-consultation is framed as an auxiliary behavioral metric , not a biological survival outcome. 2. Methodology – TVUS operators and multivariate model Reviewer comment: Please specify whether TVUS was performed by a single operator or multiple radiologists. In section 2.4, consider including details of variables retained in the multivariate model and present odds ratios in a table. Response: We have added in the Methods section (2.2 and 2.4) that three qualified operators with inter-university diplomas in ultrasound and at least 10 years of experience performed all TVUS examinations. In section 2.4, we have specified the variables included in the multivariate logistic regression model and added a table in Methods listing these variables (clinical, procedural, and sonographic), as requested. Adjusted ORs and 95% CI are now presented in Results in a regression summary table. 3. Results, Tables, and Discussion Reviewer comment: Table 1 formatting can be improved (alignment of percentages and p-values). In the discussion section, clarify that “time-to-consultation” is an indicator of clinical presentation dynamics, not disease progression. A brief discussion on the implications for low-resource settings where hysteroscopy access is limited, can be added. Rather than claiming ET as a “robust prognostic marker,” the phrase “a potential surrogate marker reflecting disease burden” is suggested. Similarly, the phrase “cornerstone parameter” may be moderated to “key non-invasive parameter.” Formatting and minor errors also needs rectification, such as, correct “8- year and 11-month” to “8 years and 11 months” and “On 6 Mars 2025” to “on March 6, 2025.” Response: Table 1 has been reformatted for proper alignment of percentages and p-values. In the Discussion , we clarified that time-to-consultation is an indicator of clinical presentation dynamics , not disease progression. A brief discussion has been added on implications for low-resource settings , highlighting that ET measurement by TVUS may guide triage and reduce reliance on hysteroscopy where access is limited. Terminology revised: “robust prognostic marker” → “potential surrogate marker reflecting disease burden” ; “cornerstone parameter” → “key non-invasive parameter” . Minor formatting and typographical errors have been corrected: “8- year and 11-month” → “8 years and 11 months” , “On 6 Mars 2025” → “on March 6, 2025” . We sincerely thank you for their valuable comments, which have helped us improve the clarity, rigor, and clinical relevance of our manuscript. Dear dr Seetu Palo, We sincerely thank you for your thorough and constructive feedback on our manuscript. We have carefully addressed all the points raised. Our responses and the corresponding changes made in the manuscript are summarized below: 1. Abstract – Kaplan–Meier analysis, AUC, cutoff, and terminology Reviewer comment: Clearly clarify that Kaplan–Meier analysis was applied to time-to-consultation and time-to-diagnosis, not survival outcomes. Include the AUC value (0.842) and the >9 mm cutoff directly in the abstract. The concept of “time-to-consultation” as a survival endpoint is unorthodox. Consider reframe this as an auxiliary behavioural metric rather than a true prognostic parameter. Revise “prognostic marker” to “potential prognostic or triage marker.” Response: We have revised the abstract accordingly. Kaplan–Meier analysis is now clearly described as applied to time-to-consultation and time-to-diagnosis , reflecting healthcare-seeking behavior rather than survival. The AUC value (0.842) and the >9 mm cutoff are explicitly included. Terminology “robust prognostic marker” has been replaced with “potential prognostic or triage marker” . The concept of time-to-consultation is framed as an auxiliary behavioral metric , not a biological survival outcome. 2. Methodology – TVUS operators and multivariate model Reviewer comment: Please specify whether TVUS was performed by a single operator or multiple radiologists. In section 2.4, consider including details of variables retained in the multivariate model and present odds ratios in a table. Response: We have added in the Methods section (2.2 and 2.4) that three qualified operators with inter-university diplomas in ultrasound and at least 10 years of experience performed all TVUS examinations. In section 2.4, we have specified the variables included in the multivariate logistic regression model and added a table in Methods listing these variables (clinical, procedural, and sonographic), as requested. Adjusted ORs and 95% CI are now presented in Results in a regression summary table. 3. Results, Tables, and Discussion Reviewer comment: Table 1 formatting can be improved (alignment of percentages and p-values). In the discussion section, clarify that “time-to-consultation” is an indicator of clinical presentation dynamics, not disease progression. A brief discussion on the implications for low-resource settings where hysteroscopy access is limited, can be added. Rather than claiming ET as a “robust prognostic marker,” the phrase “a potential surrogate marker reflecting disease burden” is suggested. Similarly, the phrase “cornerstone parameter” may be moderated to “key non-invasive parameter.” Formatting and minor errors also needs rectification, such as, correct “8- year and 11-month” to “8 years and 11 months” and “On 6 Mars 2025” to “on March 6, 2025.” Response: Table 1 has been reformatted for proper alignment of percentages and p-values. In the Discussion , we clarified that time-to-consultation is an indicator of clinical presentation dynamics , not disease progression. A brief discussion has been added on implications for low-resource settings , highlighting that ET measurement by TVUS may guide triage and reduce reliance on hysteroscopy where access is limited. Terminology revised: “robust prognostic marker” → “potential surrogate marker reflecting disease burden” ; “cornerstone parameter” → “key non-invasive parameter” . Minor formatting and typographical errors have been corrected: “8- year and 11-month” → “8 years and 11 months” , “On 6 Mars 2025” → “on March 6, 2025” . We sincerely thank you for their valuable comments, which have helped us improve the clarity, rigor, and clinical relevance of our manuscript. Competing Interests: No competing interests to disclose Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 31 Dec 2025 Narjes karmous , Gynaecology and Obstetrics department B, Charles Nicolle Hospital, Tunis, Tunisia 31 Dec 2025 Author Response Dear dr Seetu Palo, We sincerely thank you for your thorough and constructive feedback on our manuscript. We have carefully addressed all the points raised. Our responses and the corresponding ... Continue reading Dear dr Seetu Palo, We sincerely thank you for your thorough and constructive feedback on our manuscript. We have carefully addressed all the points raised. Our responses and the corresponding changes made in the manuscript are summarized below: 1. Abstract – Kaplan–Meier analysis, AUC, cutoff, and terminology Reviewer comment: Clearly clarify that Kaplan–Meier analysis was applied to time-to-consultation and time-to-diagnosis, not survival outcomes. Include the AUC value (0.842) and the >9 mm cutoff directly in the abstract. The concept of “time-to-consultation” as a survival endpoint is unorthodox. Consider reframe this as an auxiliary behavioural metric rather than a true prognostic parameter. Revise “prognostic marker” to “potential prognostic or triage marker.” Response: We have revised the abstract accordingly. Kaplan–Meier analysis is now clearly described as applied to time-to-consultation and time-to-diagnosis , reflecting healthcare-seeking behavior rather than survival. The AUC value (0.842) and the >9 mm cutoff are explicitly included. Terminology “robust prognostic marker” has been replaced with “potential prognostic or triage marker” . The concept of time-to-consultation is framed as an auxiliary behavioral metric , not a biological survival outcome. 2. Methodology – TVUS operators and multivariate model Reviewer comment: Please specify whether TVUS was performed by a single operator or multiple radiologists. In section 2.4, consider including details of variables retained in the multivariate model and present odds ratios in a table. Response: We have added in the Methods section (2.2 and 2.4) that three qualified operators with inter-university diplomas in ultrasound and at least 10 years of experience performed all TVUS examinations. In section 2.4, we have specified the variables included in the multivariate logistic regression model and added a table in Methods listing these variables (clinical, procedural, and sonographic), as requested. Adjusted ORs and 95% CI are now presented in Results in a regression summary table. 3. Results, Tables, and Discussion Reviewer comment: Table 1 formatting can be improved (alignment of percentages and p-values). In the discussion section, clarify that “time-to-consultation” is an indicator of clinical presentation dynamics, not disease progression. A brief discussion on the implications for low-resource settings where hysteroscopy access is limited, can be added. Rather than claiming ET as a “robust prognostic marker,” the phrase “a potential surrogate marker reflecting disease burden” is suggested. Similarly, the phrase “cornerstone parameter” may be moderated to “key non-invasive parameter.” Formatting and minor errors also needs rectification, such as, correct “8- year and 11-month” to “8 years and 11 months” and “On 6 Mars 2025” to “on March 6, 2025.” Response: Table 1 has been reformatted for proper alignment of percentages and p-values. In the Discussion , we clarified that time-to-consultation is an indicator of clinical presentation dynamics , not disease progression. A brief discussion has been added on implications for low-resource settings , highlighting that ET measurement by TVUS may guide triage and reduce reliance on hysteroscopy where access is limited. Terminology revised: “robust prognostic marker” → “potential surrogate marker reflecting disease burden” ; “cornerstone parameter” → “key non-invasive parameter” . Minor formatting and typographical errors have been corrected: “8- year and 11-month” → “8 years and 11 months” , “On 6 Mars 2025” → “on March 6, 2025” . We sincerely thank you for their valuable comments, which have helped us improve the clarity, rigor, and clinical relevance of our manuscript. Dear dr Seetu Palo, We sincerely thank you for your thorough and constructive feedback on our manuscript. We have carefully addressed all the points raised. Our responses and the corresponding changes made in the manuscript are summarized below: 1. Abstract – Kaplan–Meier analysis, AUC, cutoff, and terminology Reviewer comment: Clearly clarify that Kaplan–Meier analysis was applied to time-to-consultation and time-to-diagnosis, not survival outcomes. Include the AUC value (0.842) and the >9 mm cutoff directly in the abstract. The concept of “time-to-consultation” as a survival endpoint is unorthodox. Consider reframe this as an auxiliary behavioural metric rather than a true prognostic parameter. Revise “prognostic marker” to “potential prognostic or triage marker.” Response: We have revised the abstract accordingly. Kaplan–Meier analysis is now clearly described as applied to time-to-consultation and time-to-diagnosis , reflecting healthcare-seeking behavior rather than survival. The AUC value (0.842) and the >9 mm cutoff are explicitly included. Terminology “robust prognostic marker” has been replaced with “potential prognostic or triage marker” . The concept of time-to-consultation is framed as an auxiliary behavioral metric , not a biological survival outcome. 2. Methodology – TVUS operators and multivariate model Reviewer comment: Please specify whether TVUS was performed by a single operator or multiple radiologists. In section 2.4, consider including details of variables retained in the multivariate model and present odds ratios in a table. Response: We have added in the Methods section (2.2 and 2.4) that three qualified operators with inter-university diplomas in ultrasound and at least 10 years of experience performed all TVUS examinations. In section 2.4, we have specified the variables included in the multivariate logistic regression model and added a table in Methods listing these variables (clinical, procedural, and sonographic), as requested. Adjusted ORs and 95% CI are now presented in Results in a regression summary table. 3. Results, Tables, and Discussion Reviewer comment: Table 1 formatting can be improved (alignment of percentages and p-values). In the discussion section, clarify that “time-to-consultation” is an indicator of clinical presentation dynamics, not disease progression. A brief discussion on the implications for low-resource settings where hysteroscopy access is limited, can be added. Rather than claiming ET as a “robust prognostic marker,” the phrase “a potential surrogate marker reflecting disease burden” is suggested. Similarly, the phrase “cornerstone parameter” may be moderated to “key non-invasive parameter.” Formatting and minor errors also needs rectification, such as, correct “8- year and 11-month” to “8 years and 11 months” and “On 6 Mars 2025” to “on March 6, 2025.” Response: Table 1 has been reformatted for proper alignment of percentages and p-values. In the Discussion , we clarified that time-to-consultation is an indicator of clinical presentation dynamics , not disease progression. A brief discussion has been added on implications for low-resource settings , highlighting that ET measurement by TVUS may guide triage and reduce reliance on hysteroscopy where access is limited. Terminology revised: “robust prognostic marker” → “potential surrogate marker reflecting disease burden” ; “cornerstone parameter” → “key non-invasive parameter” . Minor formatting and typographical errors have been corrected: “8- year and 11-month” → “8 years and 11 months” , “On 6 Mars 2025” → “on March 6, 2025” . We sincerely thank you for their valuable comments, which have helped us improve the clarity, rigor, and clinical relevance of our manuscript. Competing Interests: No competing interests to disclose Close Report a concern COMMENT ON THIS REPORT Comments on this article Comments (0) Version 4 VERSION 4 PUBLISHED 27 Oct 2025 ADD YOUR COMMENT Comment keyboard_arrow_left keyboard_arrow_right Open Peer Review Reviewer Status info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Reviewer Reports Invited Reviewers 1 2 3 Version 4 (revision) 19 May 26 Version 3 (revision) 09 Jan 26 read read read Version 2 (revision) 31 Dec 25 Version 1 27 Oct 25 read read Seetu Palo , All India Institute of Medical Sciences, Hyderabad, India CANSU TURKER SARICOBAN , Istanbul University-Cerrahpasa, Cerrahpasa Faculty of Medicine, Istanbul, Turkey Deepthy Balakrishnan , All India Institute of Medical Sciences, Odisha, India Comments on this article All Comments (0) Add a comment Sign up for content alerts Sign Up You are now signed up to receive this alert Browse by related subjects keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2026 Balakrishnan D. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 27 Apr 2026 | for Version 3 Deepthy Balakrishnan , All India Institute of Medical Sciences, Odisha, India 0 Views copyright © 2026 Balakrishnan D. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (1) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions 1. It is a retrospective observational study 2. Measurement of the details of ET is not specified for any particular phase of the menstrual cycle, but this has been mentioned in the limitations. Nevertheless, it creates a bias. 3. Please clarify the definition of "premenopausal women" 4. 4. Tamoxifen should come under the exclusion criteria because of the differences in ET caused by subepithelial stromal hypertrophy 5. It would have been better to have a combined score for risk stratification rather than an isolated ET because of various confounders The study aims to determine a cut-off value for endometrial thickness in premenopausal women with AUB. There is a difference in ET across various phases of the cycle, and it may also vary in women already on hormones to control bleeding. These can cause profound changes in the results. The article is beautifully written with good statistical analysis. The confounders may reduce the reproducibility of the data with difficulty in incorporating in to medical practice Is the work clearly and accurately presented and does it cite the current literature? Yes Is the study design appropriate and is the work technically sound? Yes Are sufficient details of methods and analysis provided to allow replication by others? Yes If applicable, is the statistical analysis and its interpretation appropriate? Yes Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Yes Competing Interests No competing interests were disclosed. Reviewer Expertise obstetrics, gynecology, maternal medicine, I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (1) Author Response 06 May 2026 Narjes karmous, Gynaecology and Obstetrics department B, Charles Nicolle Hospital, Tunis, Tunisia Dear Dr. Deepthy Balakrishnan, We sincerely thank you for your thoughtful and constructive feedback on our manuscript. We greatly appreciate your positive assessment of the clarity of the manuscript, the statistical analysis and the overall scientific presentation. We have carefully considered all the points raised and revised the manuscript accordingly. Our detailed responses and the corresponding modifications are presented below. 1. “It is a retrospective observational study.” Response: Thank you for this important observation. We agree that the study design should be described using standard epidemiological terminology. Accordingly, we revised the manuscript to describe the study as a retrospective observational study. The terminology was corrected in both the Abstract and the Methods section. 2. “Measurement of the details of ET is not specified for any particular phase of the menstrual cycle, but this has been mentioned in the limitations. Nevertheless, it creates a bias.” Response: We fully agree that the absence of menstrual cycle phase standardization represents an important source of bias in the interpretation of endometrial thickness (ET) in premenopausal women. Because of the retrospective design of the study and the high frequency of irregular, anovulatory, or unpredictable bleeding patterns among women presenting with abnormal uterine bleeding (AUB), menstrual cycle phase at the time of ultrasound examination was not consistently documented in medical records and therefore could not be standardized retrospectively. Our intention was not to establish a physiological cycle-specific ET reference value, but rather to evaluate ET as a pragmatic clinical marker in real-world symptomatic premenopausal women with AUB. To avoid overinterpretation, we further clarified in the manuscript that the proposed ET cutoff should be interpreted as a risk-stratification threshold within a clinical context rather than as a universal physiological cutoff. Additional clarifications were added to the Methods and Limitations sections regarding the absence of menstrual cycle phase standardization and its potential impact on ET interpretation. We emphasized that prospective studies incorporating cycle-phase standardization are necessary to improve reproducibility and biological interpretability. 3. “Please clarify the definition of premenopausal women.” Response: Thank you for highlighting the need for a clearer definition. We have now explicitly defined premenopausal women in the Methods section. The following definition was added: “Premenopausal women were defined as women with ongoing menstrual activity who had not experienced 12 consecutive months of amenorrhea unrelated to pregnancy, lactation or hormonal therapy.” 4. “Tamoxifen should come under the exclusion criteria because of the differences in ET caused by subepithelial stromal hypertrophy.” Response: Thank you for this important comment. We agree that tamoxifen exposure may alter endometrial morphology and thickness, potentially affecting the interpretation of ET. However, in our cohort, only one patient had a history of tamoxifen use. Given this extremely limited exposure, we believe that tamoxifen was unlikely to have had a significant impact on the overall results or on the proposed ET cutoff value. Therefore, no additional exclusion criterion was introduced retrospectively, as excluding this single patient would not have materially altered the study findings. We nevertheless acknowledge that tamoxifen exposure may represent a potential confounding factor in larger cohorts evaluating ET in premenopausal women with abnormal uterine bleeding. 5. “It would have been better to have a combined score for risk stratification rather than an isolated ET because of various confounders.” Response: Thank you for this valuable suggestion. We fully agree that ET alone cannot entirely capture the complexity of endometrial malignancy risk in premenopausal women with AUB, particularly given the influence of multiple clinical and hormonal confounding factors. The primary objective of the present study was to specifically evaluate the diagnostic performance of ET as a simple, non-invasive and widely accessible imaging marker in routine clinical practice. However, we agree that integrating ET into multifactorial risk prediction models combining clinical, metabolic, hormonal and imaging variables may improve predictive accuracy and clinical applicability. This perspective has been emphasized in the Recommendations for further research section. We sincerely thank you again for your insightful comments and constructive suggestions. Your observations significantly contributed to improving the methodological transparency, scientific rigor and clinical interpretation of our manuscript. Kind regards, Narjes Karmous On behalf of all authors View more View less Competing Interests No competing interests reply Respond Report a concern Balakrishnan D. Peer Review Report For: Endometrial Thickness as a Prognostic Marker in Premenopausal Abnormal Uterine Bleeding: Diagnostic Accuracy and Kaplan–Meier Survival Insights [version 1; peer review: 2 not approved] . F1000Research 2025, 14 :1167 ( https://doi.org/10.5256/f1000research.194905.r475875) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/14-1167/v3#referee-response-475875 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2026 SARICOBAN C. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 12 Jan 2026 | for Version 3 CANSU TURKER SARICOBAN , Pathology, Istanbul University-Cerrahpasa, Cerrahpasa Faculty of Medicine, Istanbul, Turkey 0 Views copyright © 2026 SARICOBAN C. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Not Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions I thank the authors for their revisions and for addressing several points raised by the other reviewer. However, after carefully reviewing Version 2 of the manuscript, I find that the major methodological concerns raised in my original review remain largely unaddressed. In particular, the absence of menstrual cycle phase standardization for endometrial thickness measurement continues to fundamentally limit the biological and diagnostic interpretability of the proposed cutoff. Reframing this issue as a “real-world” approach does not resolve the underlying methodological problem, but rather highlights it. Similarly, the restriction of the study population to patients who ultimately underwent hysterectomy introduces substantial selection bias, which cannot be adequately mitigated by post hoc clarification. The use of Kaplan–Meier analysis in this context, even when reinterpreted as reflecting healthcare-seeking behavior rather than prognosis, remains conceptually problematic and unsupported by the study design. Finally, the low number of malignant events continues to undermine the robustness of the ROC analysis and time-to-event modeling. While these limitations are now more explicitly acknowledged, acknowledgment alone does not sufficiently address their impact on the validity of the study’s conclusions. For these reasons, I maintain my original assessment that the manuscript does not meet acceptable methodological standards for approval. Competing Interests No competing interests were disclosed. Reviewer Expertise Gynaecopathology I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above. reply Respond to this report Responses (0) SARICOBAN CT. Peer Review Report For: Endometrial Thickness as a Prognostic Marker in Premenopausal Abnormal Uterine Bleeding: Diagnostic Accuracy and Kaplan–Meier Survival Insights [version 1; peer review: 2 not approved] . F1000Research 2025, 14 :1167 ( https://doi.org/10.5256/f1000research.194905.r448964) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/14-1167/v3#referee-response-448964 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2026 Palo S. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 10 Jan 2026 | for Version 3 Seetu Palo , All India Institute of Medical Sciences, Hyderabad, India 0 Views copyright © 2026 Palo S. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Revisions made are satisfactory. Competing Interests No competing interests were disclosed. Reviewer Expertise Oncopathology I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. reply Respond to this report Responses (0) Palo S. Peer Review Report For: Endometrial Thickness as a Prognostic Marker in Premenopausal Abnormal Uterine Bleeding: Diagnostic Accuracy and Kaplan–Meier Survival Insights [version 1; peer review: 2 not approved] . F1000Research 2025, 14 :1167 ( https://doi.org/10.5256/f1000research.194905.r448963) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/14-1167/v3#referee-response-448963 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 SARICOBAN C. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 20 Nov 2025 | for Version 1 CANSU TURKER SARICOBAN , Pathology, Istanbul University-Cerrahpasa, Cerrahpasa Faculty of Medicine, Istanbul, Turkey 0 Views copyright © 2025 SARICOBAN C. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (1) Not Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions The authors present a retrospective analytical study evaluating the diagnostic and purported prognostic utility of transvaginal ultrasound–based endometrial thickness (ET) in premenopausal women with abnormal uterine bleeding (AUB). The study aims to define an optimal ET cutoff (>9 mm) for predicting endometrial malignancy and further applies Kaplan–Meier time-to-event analyses (time-to-consultation and time-to-diagnosis) to explore clinical dynamics associated with different ET thresholds. Although the topic is clinically relevant and the dataset includes hysterectomy-confirmed outcomes, the study suffers from substantial methodological, analytical, and reporting limitations that significantly compromise the validity, reliability, and generalizability of its findings. A fundamental methodological limitation is the complete lack of menstrual cycle phase standardization at the time of ET measurement. Endometrial thickness varies markedly between the proliferative and secretory phases, making ET uninterpretable without cycle context. This single issue undermines the scientific foundation of the proposed cutoff value. Additionally, ET assessment via transvaginal ultrasound is known to have considerable interobserver variability; yet the manuscript does not state whether measurements were performed by a single operator or multiple clinicians, nor does it report any interobserver agreement or standardization procedures. These omissions severely restrict reproducibility and weaken the internal validity of the imaging data. The decision to use hysterectomy specimens as the “gold standard” for definitive diagnosis is also problematic. In a subset of endometrial carcinomas—particularly early or superficially located tumors—the entire neoplastic tissue may be removed by curettage or hysteroscopy, leading to an absent residual tumor in the hysterectomy specimen. The authors do not report any comparison between preoperative biopsy/hysteroscopy findings and post-hysterectomy pathology, nor do they address the risk of misclassification bias arising from these discrepancies. This omission raises concerns about reference standard accuracy. Furthermore, the presentation of baseline characteristics is confusing and potentially misleading. Percentages reported for variables such as diabetes, hypertension, and family history (“93% benign vs. 7% malignant”) are not clearly defined—whether they refer to patients with the risk factor, patients without it, or proportions within total groups is unclear. This ambiguity compromises interpretation of the risk factor analysis and represents a deviation from appropriate epidemiologic reporting standards. There are also inconsistencies within the dataset itself. For example, the manuscript states that the median ET in malignant cases is 12 mm, whereas Table 1 appears to present a different value (e.g., 10 mm or an incomplete notation). Such discrepancies reduce confidence in the accuracy and integrity of the reported data. Additionally, the application and interpretation of Kaplan–Meier analysis are conceptually flawed. “Time-to-consultation” reflects health-seeking behavior rather than biological disease progression and should not be presented as a prognostic marker. Given that symptom onset times were extracted retrospectively, this metric is particularly vulnerable to recall bias. The malignant event count (n=13) is also extremely low, limiting the statistical power of ROC analyses, logistic regression, and survival models, and rendering the resulting cutoff and effect estimates unstable. Lastly, the sampling frame introduces significant selection bias: only women who ultimately underwent hysterectomy were included. This subgroup represents a higher-risk and highly selected population that does not reflect the broader premenopausal AUB cohort seen in routine practice. Consequently, the >9 mm cutoff cannot be generalized beyond this specific surgical population. The manuscript contains several typographical and formatting errors (e.g., “8- year and 11-month,” “Mars 2025”), and the tone of certain phrases (“cornerstone parameter,” “robust prognostic marker”) is overstated given the study’s methodological limitations. Table formatting requires substantial correction, as percentages, p-values, and variable categories are inconsistently aligned or inadequately defined. Some terminology is unclear or unconventional (e.g., “intracavitary fibroma”), and adherence to STROBE reporting guidelines is incomplete. While the research topic is important, the methodological flaws, analytical limitations, inconsistent reporting, and conceptual misinterpretations present in the current version significantly compromise the validity of the findings. Extensive revisions, additional clarifications, and methodological restructuring would be required before this work could be considered for indexing. As it stands, the manuscript is not acceptable in its current form. Is the work clearly and accurately presented and does it cite the current literature? Partly Is the study design appropriate and is the work technically sound? Partly Are sufficient details of methods and analysis provided to allow replication by others? Partly If applicable, is the statistical analysis and its interpretation appropriate? Partly Are all the source data underlying the results available to ensure full reproducibility? Partly Are the conclusions drawn adequately supported by the results? No Competing Interests No competing interests were disclosed. Reviewer Expertise Gynaecopathology I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above. reply Respond to this report Responses (1) Author Response 12 Jan 2026 Narjes karmous, Gynaecology and Obstetrics department B, Charles Nicolle Hospital, Tunis, Tunisia Dear dr CANSU TURKER SARICOBAN, We sincerely thank you for your thorough and constructive feedback on our manuscript. We have carefully addressed all the points raised. Our responses and the corresponding changes made in the manuscript are summarized below: 1. A fundamental methodological limitation is the complete lack of menstrual cycle phase standardization at the time of ET measurement. ET varies markedly between the proliferative and secretory phases, making ET uninterpretable without cycle context. This single issue undermines the scientific foundation of the proposed cutoff value. Response: Thank you for raising this important methodological concern. We fully agree that endometrial thickness (ET) varies according to the menstrual cycle phase and that phase-specific measurement represents the optimal physiological approach. However, the present study was designed to reflect routine clinical practice in premenopausal women presenting with abnormal uterine bleeding (AUB), a population in whom menstrual cycle regularity and accurate phase determination are frequently unavailable or unreliable at the time of clinical assessment. Consequently, ET measurements were performed at presentation, irrespective of cycle phase, in line with real-world diagnostic pathways. Our objective was therefore not to define a physiological, cycle-dependent reference value for ET, but rather to evaluate its diagnostic and prognostic utility as a pragmatic clinical marker for identifying women at increased risk of endometrial malignancy in a symptomatic AUB population. Importantly, several previously published retrospective studies addressing ET in premenopausal AUB populations similarly lacked systematic cycle phase standardization and nonetheless reported clinically useful cutoff values. We acknowledge that the absence of menstrual cycle phase standardization represents a major limitation of our study and have explicitly addressed this in the Methods and Limitations sections. To avoid overinterpretation, we have also clarified that the proposed ET cutoff should be interpreted as a risk stratification threshold within a clinical context, rather than as an absolute physiological value. We agree that future prospective studies incorporating precise cycle phase control are required to refine and validate phase-specific thresholds. 2. The manuscript does not state whether measurements were performed by a single operator or multiple clinicians, nor does it report any interobserver agreement or standardization procedures. These omissions severely restrict reproducibility and weaken the internal validity of the imaging data. Response: Thank you for highlighting this important aspect related to reproducibility and internal validity. We have revised the Methods section to clarify that all TVUS examinations were performed by three experienced operators, each holding an inter-university diploma in gynecologic US and with over 10 years of clinical experience in pelvic US practice. Given the retrospective nature of the study, formal assessment of interobserver agreement (e.g., intraclass correlation coefficients) and predefined standardization protocols could not be performed. However, all operators followed institutional US protocols for endometrial assessment, and ET was measure in the sagittal plane as the double-layer distance between the two endometrial–myometrial interfaces, at the point of greatest thickness perpendicular to the midline, using appropriately magnified images, in accordance with standard ultrasound assessment protocols used at our institution. We acknowledge that the absence of formal interobserver variability analysis represents a limitation and have explicitly addressed this in the Limitations section. Future prospective studies incorporating predefined measurement protocols and interobserver agreement assessment are warranted to further strengthen reproducibility. 3. The decision to use hysterectomy specimens as the “gold standard” for definitive diagnosis is also problematic. In a subset of endometrial carcinomas—particularly early or superficially located tumors—the entire neoplastic tissue may be removed by curettage or hysteroscopy, leading to an absent residual tumor in the hysterectomy specimen. The authors do not report any comparison between preoperative biopsy/hysteroscopy findings and post-hysterectomy pathology, nor do they address the risk of misclassification bias arising from these discrepancies. This omission raises concerns about reference standard accuracy. Response: Thank you for raising this important point regarding the use of hysterectomy specimens as the reference standard. We agree that in some series, early or superficially located endometrial tumors may be completely removed during curettage or hysteroscopy, potentially leading to absent residual tumor in the hysterectomy specimen and misclassification. In our study, we systematically compared preoperative endometrial biopsy or hysteroscopy findings with post-hysterectomy pathology. This comparison demonstrated excellent concordance , with no discrepancies observed. This result has now been added to the Results section to clarify that hysterectomy specimens provided a reliable reference standard in our cohort. 4. Percentages reported for variables such as diabetes, hypertension, and family history (“93% benign vs. 7% malignant”) are not clearly defined—whether they refer to patients with the risk factor, patients without it, or proportions within total groups is unclear. This ambiguity compromises interpretation of the risk factor analysis and represents a deviation from appropriate epidemiologic reporting standards. Response: We have revised the Results section to report the presence of comorbidities rather than their absence, in accordance with epidemiological reporting standards. Percentages now clearly represent the proportion of patients presenting each risk factor within the benign and malignant groups, eliminating any ambiguity. 5. The manuscript states that the median ET in malignant cases is 12 mm, whereas Table 1 appears to present a different value (e.g., 10 mm or an incomplete notation). Such discrepancies reduce confidence in the accuracy and integrity of the reported data. Response: Thank you for drawing our attention to this discrepancy. We confirm that the correct median ET in malignant cases is 12 mm . The value initially reported in Table 1 (10 mm) resulted from a data transcription error and has now been corrected . In addition, following the request of Reviewer 1, a new table was added to the Methods section, and the baseline characteristics table has therefore been renumbered as Table 2 . The corrected ET value is now consistently reported in both the Results text and Table 2 . All numerical values reported in the text and tables were cross-checked to ensure internal consistency. 6. The application and interpretation of Kaplan–Meier analysis are conceptually flawed. “Time-to-consultation” reflects health-seeking behavior rather than biological disease progression and should not be presented as a prognostic marker. Given that symptom onset times were extracted retrospectively, this metric is particularly vulnerable to recall bias. Response: We agree that “ time-to-consultation” primarily reflects health-seeking behavior rather than intrinsic biological disease progression and, as such, should not be interpreted as a biological prognostic marker. In the revised manuscript, we have therefore clarified the objective and interpretation of the Kaplan–Meier analysis. The analysis is now explicitly presented as an exploratory assessment of diagnostic delay , illustrating differences in healthcare-seeking patterns according to endometrial thickness, rather than as a predictor of tumor aggressiveness or prognosis. We also acknowledge that symptom onset was collected retrospectively and is therefore susceptible to recall bias . This limitation has now been clearly stated in the Discussion/Limitations section. Importantly, the Kaplan–Meier analysis is no longer framed as prognostic, and its results are interpreted with appropriate caution. 7. The malignant event count (n=13) is also extremely low, limiting the statistical power of ROC analyses, logistic regression, and survival models, and rendering the resulting cutoff and effect estimates unstable. Response: We acknowledge that the low number of malignant events (n = 13) limits the statistical power of the ROC analyses, logistic regression, and Kaplan–Meier models, and may result in unstable cutoff values and imprecise effect estimates. This limitation has now been explicitly stated in the Discussion/Limitations section, and the results of these analyses are interpreted with appropriate caution. We emphasize that our findings should be considered exploratory and hypothesis-generating rather than definitive. 8. Several typographical and formatting errors (e.g., “8- year and 11-month,” “Mars 2025”), and the tone of certain phrases (“cornerstone parameter,” “robust prognostic marker”) is overstated given the study’s methodological limitations. Table formatting requires substantial correction, as percentages, p-values, and variable categories are inconsistently aligned or inadequately defined. Some terminology is unclear or unconventional (e.g., “intracavitary fibroma”), and adherence to STROBE reporting guidelines is incomplete. Response: We have carefully revised the manuscript to address all typographical, stylistic, and formatting issues identified. All typographical and linguistic errors have been corrected, including inconsistencies in date and duration formatting (e.g., “8-year and 11-month period,” “March 2025”). The tone of the manuscript has been moderated to better reflect the methodological limitations of the study, and overstated expressions such as “cornerstone parameter” and “robust prognostic marker” have been replaced with more cautious and precise terminology. All tables have been comprehensively reformatted to ensure consistent alignment of variables, percentages, and p-values, with clear definition of categories and denominators where applicable. Terminology has been standardized in accordance with internationally accepted nomenclature, and ambiguous terms such as “intracavitary fibroma” have been replaced with clearer expressions (e.g., “intracavitary fibroid”). Finally, we have reviewed the manuscript in accordance with the STROBE reporting guidelines for observational studies and have ensured that all relevant items are adequately addressed. The manuscript sections have been revised to improve transparency and reporting completeness. View more View less Competing Interests No competing interests were disclosed. reply Respond Report a concern SARICOBAN CT. Peer Review Report For: Endometrial Thickness as a Prognostic Marker in Premenopausal Abnormal Uterine Bleeding: Diagnostic Accuracy and Kaplan–Meier Survival Insights [version 1; peer review: 2 not approved] . F1000Research 2025, 14 :1167 ( https://doi.org/10.5256/f1000research.188024.r428684) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/14-1167/v1#referee-response-428684 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Palo S. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 06 Nov 2025 | for Version 1 Seetu Palo , All India Institute of Medical Sciences, Hyderabad, India 0 Views copyright © 2025 Palo S. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (1) Not Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions This article presents a retrospective analytical study investigating the diagnostic and prognostic value of endometrial thickness (ET) in premenopausal women with abnormal uterine bleeding (AUB). The authors aim to define an optimal ET cutoff for predicting endometrial malignancy and to explore the prognostic implications of ET using Kaplan–Meier survival analysis. The manuscript is generally well-written and addresses a clinically relevant topic, but certain aspects require clarification, additional rigor, and scientific refinement. In the abstract, clearly clarify that Kaplan–Meier analysis was applied to time-to-consultation and time-to-diagnosis, not survival outcomes. Include the AUC value (0.842) and the >9 mm cutoff directly in the abstract. The concept of “time-to-consultation” as a survival endpoint is unorthodox. It reflects healthcare-seeking behavior rather than biological survival. Consider reframe this as an auxiliary behavioural metric rather than a true prognostic parameter. Revise “prognostic marker” to “potential prognostic or triage marker.” In the methodology section, please specify whether TVUS was performed by a single operator or multiple radiologists. In section 2.4, consider including details of variables retained in the multivariate model and present odds ratios in a table. Similarly in the results, consider providing a regression summary table (with adjusted ORs and 95% CIs). Furthermore, Table 1 formatting can be improved (alignment of percentages and p-values). In the discussion section, clarify that “time-to-consultation” is an indicator of clinical presentation dynamics, not disease progression. A brief discussion on the implications for low-resource settings where hysteroscopy access is limited, can be added. Rather than claiming ET as a “robust prognostic marker,” the phrase “a potential surrogate marker reflecting disease burden” is suggested. Similarly, the phrase “cornerstone parameter” may be moderated to “key non-invasive parameter.” Formatting and minor errors also needs rectification, such as, correct “8- year and 11-month” to “8 years and 11 months” and “On 6 Mars 2025” to “on March 6, 2025.” Is the work clearly and accurately presented and does it cite the current literature? Partly Is the study design appropriate and is the work technically sound? Partly Are sufficient details of methods and analysis provided to allow replication by others? Partly If applicable, is the statistical analysis and its interpretation appropriate? Partly Are all the source data underlying the results available to ensure full reproducibility? Partly Are the conclusions drawn adequately supported by the results? No Competing Interests No competing interests were disclosed. Reviewer Expertise Oncopathology I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above. reply Respond to this report Responses (1) Author Response 31 Dec 2025 Narjes karmous, Gynaecology and Obstetrics department B, Charles Nicolle Hospital, Tunis, Tunisia Dear dr Seetu Palo, We sincerely thank you for your thorough and constructive feedback on our manuscript. We have carefully addressed all the points raised. Our responses and the corresponding changes made in the manuscript are summarized below: 1. Abstract – Kaplan–Meier analysis, AUC, cutoff, and terminology Reviewer comment: Clearly clarify that Kaplan–Meier analysis was applied to time-to-consultation and time-to-diagnosis, not survival outcomes. Include the AUC value (0.842) and the >9 mm cutoff directly in the abstract. The concept of “time-to-consultation” as a survival endpoint is unorthodox. Consider reframe this as an auxiliary behavioural metric rather than a true prognostic parameter. Revise “prognostic marker” to “potential prognostic or triage marker.” Response: We have revised the abstract accordingly. Kaplan–Meier analysis is now clearly described as applied to time-to-consultation and time-to-diagnosis , reflecting healthcare-seeking behavior rather than survival. The AUC value (0.842) and the >9 mm cutoff are explicitly included. Terminology “robust prognostic marker” has been replaced with “potential prognostic or triage marker” . The concept of time-to-consultation is framed as an auxiliary behavioral metric , not a biological survival outcome. 2. Methodology – TVUS operators and multivariate model Reviewer comment: Please specify whether TVUS was performed by a single operator or multiple radiologists. In section 2.4, consider including details of variables retained in the multivariate model and present odds ratios in a table. Response: We have added in the Methods section (2.2 and 2.4) that three qualified operators with inter-university diplomas in ultrasound and at least 10 years of experience performed all TVUS examinations. In section 2.4, we have specified the variables included in the multivariate logistic regression model and added a table in Methods listing these variables (clinical, procedural, and sonographic), as requested. Adjusted ORs and 95% CI are now presented in Results in a regression summary table. 3. Results, Tables, and Discussion Reviewer comment: Table 1 formatting can be improved (alignment of percentages and p-values). In the discussion section, clarify that “time-to-consultation” is an indicator of clinical presentation dynamics, not disease progression. A brief discussion on the implications for low-resource settings where hysteroscopy access is limited, can be added. Rather than claiming ET as a “robust prognostic marker,” the phrase “a potential surrogate marker reflecting disease burden” is suggested. Similarly, the phrase “cornerstone parameter” may be moderated to “key non-invasive parameter.” Formatting and minor errors also needs rectification, such as, correct “8- year and 11-month” to “8 years and 11 months” and “On 6 Mars 2025” to “on March 6, 2025.” Response: Table 1 has been reformatted for proper alignment of percentages and p-values. In the Discussion , we clarified that time-to-consultation is an indicator of clinical presentation dynamics , not disease progression. A brief discussion has been added on implications for low-resource settings , highlighting that ET measurement by TVUS may guide triage and reduce reliance on hysteroscopy where access is limited. Terminology revised: “robust prognostic marker” → “potential surrogate marker reflecting disease burden” ; “cornerstone parameter” → “key non-invasive parameter” . Minor formatting and typographical errors have been corrected: “8- year and 11-month” → “8 years and 11 months” , “On 6 Mars 2025” → “on March 6, 2025” . We sincerely thank you for their valuable comments, which have helped us improve the clarity, rigor, and clinical relevance of our manuscript. View more View less Competing Interests No competing interests to disclose reply Respond Report a concern Palo S. Peer Review Report For: Endometrial Thickness as a Prognostic Marker in Premenopausal Abnormal Uterine Bleeding: Diagnostic Accuracy and Kaplan–Meier Survival Insights [version 1; peer review: 2 not approved] . F1000Research 2025, 14 :1167 ( https://doi.org/10.5256/f1000research.188024.r428689) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/14-1167/v1#referee-response-428689 Alongside their report, reviewers assign a status to the article: Approved - the paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved - fundamental flaws in the paper seriously undermine the findings and conclusions Adjust parameters to alter display View on desktop for interactive features Includes Interactive Elements View on desktop for interactive features Competing Interests Policy Provide sufficient details of any financial or non-financial competing interests to enable users to assess whether your comments might lead a reasonable person to question your impartiality. 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