The Risk of Endometrial Malignancy and Other Endometrial Pathology in Women with Abnormal Uterine Bleeding: An Ultrasound-Based Model Development Study by the IETA Group

Laure Wynants*, Jan Yvan Jos Verbakel, Lil Valentin, Bavo De Cock, M Angela Pascual, Francesco P G Leone, Povilas Sladkevicius, Ruben Heremans, Juan Luis Alcazar, Angelo Votino, Robert Fruscio, Elisabeth Epstein, Tom Bourne, Ben Van Calster, Dirk Timmerman, Thierry Van den Bosch

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

3 Citations (Web of Science)


OBJECTIVES: The aim of this study was to develop a model that can discriminate between different etiologies of abnormal uterine bleeding.

DESIGN: The International Endometrial Tumor Analysis 1 study is a multicenter observational diagnostic study in 18 bleeding clinics in 9 countries. Consecutive women with abnormal vaginal bleeding presenting for ultrasound examination (n = 2,417) were recruited. The histology was obtained from endometrial sampling, D&C, hysteroscopic resection, hysterectomy, or ultrasound follow-up for >1 year.

METHODS: A model was developed using multinomial regression based on age, body mass index, and ultrasound predictors to distinguish between: (1) endometrial atrophy, (2) endometrial polyp or intracavitary myoma, (3) endometrial malignancy or atypical hyperplasia, (4) proliferative/secretory changes, endometritis, or hyperplasia without atypia and validated using leave-center-out cross-validation and bootstrapping. The main outcomes are the model's ability to discriminate between the four outcomes and the calibration of risk estimates.

RESULTS: The median age in 2,417 women was 50 (interquartile range 43-57). 414 (17%) women had endometrial atrophy; 996 (41%) had a polyp or myoma; 155 (6%) had an endometrial malignancy or atypical hyperplasia; and 852 (35%) had proliferative/secretory changes, endometritis, or hyperplasia without atypia. The model distinguished well between malignant and benign histology (c-statistic 0.88 95% CI: 0.85-0.91) and between all benign histologies. The probabilities for each of the four outcomes were over- or underestimated depending on the centers.

LIMITATIONS: Not all patients had a diagnosis based on histology. The model over- or underestimated the risk for certain outcomes in some centers, indicating local recalibration is advisable.

CONCLUSIONS: The proposed model reliably distinguishes between four histological outcomes. This is the first model to discriminate between several outcomes and is the only model applicable when menopausal status is uncertain. The model could be useful for patient management and counseling, and aid in the interpretation of ultrasound findings. Future research is needed to externally validate and locally recalibrate the model.

Original languageEnglish
Pages (from-to)54-61
Number of pages8
JournalGynecologic and Obstetric Investigation
Issue number1
Publication statusPublished - May 2022


  • Abnormal uterine bleeding
  • Atrophy/complications
  • Endometrial Hyperplasia/complications
  • Endometrial Neoplasms/pathology
  • Endometrial disease
  • Endometrial neoplasms
  • Endometritis/complications
  • Endometrium/diagnostic imaging
  • Female
  • Humans
  • Hyperplasia/complications
  • Male
  • Myoma/complications
  • Polyps/pathology
  • Precancerous Conditions/complications
  • Prediction model
  • Ultrasonography
  • Uterine Diseases/pathology
  • Uterine Hemorrhage/diagnostic imaging
  • Uterine Neoplasms/complications

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