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Original Investigation
September 2018

Association of Endometrial Cancer Risk With Postmenopausal Bleeding in Women: A Systematic Review and Meta-analysis

Author Affiliations
  • 1Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland
  • 2Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, Minnesota
  • 3Unit of Cancer Epidemiology, Belgian Cancer Centre, Sciensano, Brussels, Belgium
JAMA Intern Med. 2018;178(9):1210-1222. doi:10.1001/jamainternmed.2018.2820
Key Points

Question  What is the prevalence of postmenopausal bleeding in women with endometrial cancer and the risk of endometrial cancer in women with postmenopausal bleeding?

Findings  This systematic review and meta-analysis of 40 790 unique patients in 129 unique studies suggests that postmenopausal bleeding occurs in approximately 90% of women with endometrial cancer; however, only 9% of women with postmenopausal bleeding were diagnosed with endometrial cancer. These estimates varied by geographic region, hormone use, and calendar time.

Meaning  These findings provide a foundation for evaluating early detection strategies for endometrial cancer and can support risk-informed decision making in clinical management of postmenopausal bleeding.


Importance  As the worldwide burden of endometrial cancer continues to rise, interest is growing in the evaluation of early detection and prevention strategies among women at increased risk. Focusing efforts on women with postmenopausal bleeding (PMB), a common symptom of endometrial cancer, may be a useful strategy; however, PMB is not specific for endometrial cancer and is often caused by benign conditions.

Objective  To provide a reference of the prevalence of PMB in endometrial cancers and the risk of endometrial cancer in women with PMB.

Data Sources  For this systematic review and meta-analysis, PubMed and Embase were searched for English-language studies published January 1, 1977, through January 31, 2017.

Study Selection  Observational studies reporting the prevalence of PMB in women with endometrial cancer and the risk of endometrial cancer in women with PMB in unselected populations were selected.

Data Extraction and Synthesis  Two independent reviewers evaluated study quality and risk of bias using items from the Newcastle-Ottawa Quality Assessment Scale and the Quality Assessment of Diagnostic Accuracy Studies tool. Studies that included highly selected populations, lacked detailed inclusion criteria, and/or included 25 or fewer women were excluded.

Main Outcomes and Measures  The pooled prevalence of PMB in women with endometrial cancer and the risk of endometrial cancer in women with PMB.

Results  A total of 129 unique studies, including 34 432 unique patients with PMB and 6358 with endometrial cancer (40 790 women), were analyzed. The pooled prevalence of PMB among women with endometrial cancer was 91% (95% CI, 87%-93%), irrespective of tumor stage. The pooled risk of endometrial cancer among women with PMB was 9% (95% CI, 8%-11%), with estimates varying by use of hormone therapy (range, 7% [95% CI, 6%-9%] to 12% [95% CI, 9%-15%]; P < .001 for heterogeneity) and geographic region (range, 5% [95% CI, 3%-11%] in North America to 13% [95% CI, 9%-19%] in Western Europe; P = .09 for heterogeneity).

Conclusions and Relevance  Early detection strategies focused on women with PMB have the potential to capture as many as 90% of endometrial cancers; however, most women with PMB will not be diagnosed with endometrial cancer. These results can aid in the assessment of the potential clinical value of new early detection markers and clinical management strategies for endometrial cancer and will help to inform clinical and epidemiologic risk prediction models to support decision making.

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    1 Comment for this article
    Endometrial Cancer Risks
    Leslee Jaeger, MD | North Clinic

    Although only 10% of post-menopausal bleeding is associated with endometrial cancer, the remainder of the cases that are benign or hyperplasia allow for education around the future risks for endometrial cancer and can contribute to lifestyle change when  weight, centripetal obesity, hypertension and diabetes are addressed. When patients are concerned about "cancer" they tend to be more motivated.