Why a Negative Endometrial Biopsy May Not End the Abnormal Bleeding Workup

A benign endometrial biopsy should not automatically end the evaluation of persistent abnormal or postmenopausal bleeding, Linda Bradley, MD, professor of obstetrics and gynecology and reproductive biology and director of hysteroscopic services at Cleveland Clinic, explained during The Menopause Society’s 2026 Annual Meeting in San Diego.¹

Bradley’s central concern was that office endometrial biopsy is a blind sampling procedure. It can identify diffuse endometrial disease but may miss focal pathology, including polyps, submucosal fibroids, hyperplasia, or a malignancy involving a limited portion of the uterine cavity. She encouraged clinicians to ask what a “negative” biopsy actually excluded when bleeding continued or the clinical picture remained concerning.

Evidence supports that distinction. A systematic review of 12 studies involving 1029 women with postmenopausal bleeding found that, when hysteroscopy was the reference standard, endometrial sampling had a weighted sensitivity of 90% for endometrial cancer, 82% for atypical hyperplasia, and 39% for broader endometrial disease, including benign polyps. Sampling failed in 11% of patients, and 31% had insufficient specimens.²

Bradley contrasted blind sampling with hysteroscopy, which permits direct examination of the uterine cavity and targeted biopsy of a visible lesion. A 2026 joint society guideline concluded that hysteroscopy with visually directed sampling provided greater diagnostic accuracy than blind biopsy for endometrial cancer, endometrial intraepithelial neoplasia, hyperplasia, polyps, and submucosal myomas.³

For primary care physicians, the practical message was not that every patient requires immediate hysteroscopy. Rather, persistent or recurrent bleeding, an insufficient specimen, suspected focal disease, or symptoms that do not improve should prompt additional evaluation or gynecologic referral. Saline infusion sonohysterography may offer a more detailed assessment of intracavitary lesions, while hysteroscopy can combine visualization with targeted tissue collection. A negative blind biopsy should be interpreted alongside the bleeding pattern, imaging quality, risk factors, and whether the entire uterine cavity has been adequately assessed.

References:

1. Bradley L. Hysteroscopy and evaluation of abnormal bleeding. Presented at: The Menopause Society 2026 Annual Meeting; October 20-24, 2026; San Diego, CA.
2. van Hanegem N, Prins MMC, Bongers MY, et al. The accuracy of endometrial sampling in women with postmenopausal bleeding: a systematic review and meta-analysis. Eur J Obstet Gynecol Reprod Biol. 2016;197:147-155. doi:10.1016/j.ejogrb.2015.12.008
3. AAGL, European Society for Gynaecological Endoscopy, Global Community on Hysteroscopy. Visually directed hysteroscopic biopsy in the evaluation of abnormal uterine bleeding and postmenopausal bleeding: a joint society practice guideline. J Minim Invasive Gynecol. 2026;33(8):1027-1040. doi:10.1016/j.jmig.2026.06.018