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Cited by 426Endometrial and Cervical Cancer TreatmentsCancer Risks and FactorsGynecological conditions and treatments

Association of Endometrial Cancer Risk With Postmenopausal Bleeding in Women

Open access
Clarke, Megan A., Long, Beverly J., Del Mar Morillo, Arena, Arbyn, Marc, Bakkum-Gamez, Jamie N., Wentzensen, Nicolas·2018·JAMA Internal Medicine
DOI 10.1001/jamainternmed.2018.2820PMC PMC6142981
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Abstract

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.

Integrity signals

Registry

Crossref · 10.1001/jamainternmed.2018.2820

Cites

184 of 184 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

4 of 26 cited sources checked · 2 supported · 0 flagged · accuracy not yet measured

  • Findingown data
    § Association of Endometrial Cancer Risk With Postmenopausal Bleeding in Women ASystematic Review and Meta-analysis · p. 1

    The pooled risk of endometrial cancer in women with postmenopausal bleeding varied by geographic region, from 5% (95% CI, 3%-11%) in North America to 13% (95% CI, 9%-19%) in Western Europe, with P = .09 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).”
    Quote in the paperNot a substantial claim
  • Findingown data
    § Discussion · p. 6

    Postmenopausal bleeding is present in roughly 90% of women who are diagnosed with endometrial cancer.

    “Oursystematicreviewandmeta-analysisdemonstrates that PMB is very sensitive for endometrial cancer detection,occurringinapproximately90%ofcases.”
    • Also stated in: § Strengths and Limitations · p. 8 · hedged
      “Our results suggest that approximately10%ofwomendiagnosedwithendometrialcancer donotpresentwithPMB.”
    Quote in the paperSubstantial claim
  • Findingown data
    § Association of Endometrial Cancer Risk With Postmenopausal Bleeding in Women ASystematic Review and Meta-analysis · p. 1

    The meta-analytic pooled risk of endometrial cancer among women with postmenopausal bleeding was 9% (95% CI, 8%-11%).

    “The pooled risk of endometrial cancer among women with PMB was 9% (95% CI, 8%-11%), with estimates varying by use of hormone therapy”
    • Also stated in: § Risk of Endometrial Cancer in Women With PMB · p. 3 · plain
      “yielding an overall pooled estimate of 9% (95% CI, 8%-11%), with moderate variability observed between studies (τ 2 = 0.56).”
    Quote in the paperSubstantial claim
  • Findingown data
    § Strengths and Limitations · p. 8

    The results suggested a lower prevalence of endometrial cancer in retrospective and prospective cohort studies than in cross-sectional studies.

    “Finally, our results suggested a lower prevalence of endometrial cancer in retrospective and prospective cohort studiescomparedwithcross-sectionalstudies.”
    Quote in the paperNot a substantial claim
  • Findingown data
    § Discussion · p. 7

    Women with postmenopausal bleeding and endometrial polyps have a lower risk of endometrial cancer.

    “Ourmeta-analysisconfirmsa lower risk of endometrial cancer among women with PMB and polyps.”
    Quote in the paperSubstantial claim
  • Classified as probably not a substantial claim. 14
  • May combine two claims. 15
  • The quote only partly states this claim. 1

  • Classified as probably not a substantial claim.

    Premisecitation
    § Discussion · p. 6

    Current practice guidelines recommend workup to rule out endometrial cancer in all women with postmenopausal bleeding.

    “Currentpracticeguidelines recommend workup to rule out endometrial cancer among all womenwithPMB.”
    Quote in the paperSubstantial claim1 of 4 sources checked
    • cites [18] source
    • cites [19] source
    • cites [166] source
    • cites [167] source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation
    § Discussion · p. 7

    In the United States, guidelines recommend transvaginal ultrasonography or endometrial biopsy as the first step in evaluating postmenopausal bleeding.

    “In the United States, guidelines recommend TVUSorendometrialbiopsyasthefirststepinevaluatingPMB. 19”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [19] source

      The Abstract says transvaginal sonography is used as a first step in evaluating postmenopausal bleeding. Section 2.2 describes guidelines advocating endometrial sampling after ultrasound shows increased endometrial thickness, not biopsy as an alternative first step. The paper does not identify these as United States guidelines. (LLM, conf=0.87)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation
    § Conclusions · p. 8

    Interest has grown in using biomarkers such as DNA methylation to improve early detection of endometrial cancer.

    “Interest has increased in the use of biomarkers, such as DNA methylation, to i mprove early detection of endometrial cancer. 31,32,170,171”
    Quote in the paperNot a substantial claim2 of 4 sources checked
    • cites [31] source
    • cites [32] source

      The Methylation Specific PCR section (page not provided) describes testing MLH1 methylation in tumor samples, and the Abstract discusses molecular markers for classifying high-risk endometrial cancers. The paper addresses prognosis and treatment decisions, not growing interest in DNA methylation biomarkers for early detection. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
    • cites [170] source
    • cites [171]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Findingown data
    § Discussion · p. 6

    Both the prevalence of postmenopausal bleeding in endometrial cancer and the risk of endometrial cancer in women with postmenopausal bleeding were higher before 2000 than after 2000.

    “TheprevalenceofPMBinendometrialcancerandtheriskof endometrialcancerinwomenwithPMBwerehigherbefore2000 comparedwithafter2000.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § Association of Endometrial Cancer Risk With Postmenopausal Bleeding in Women ASystematic Review and Meta-analysis · p. 1

    The meta-analysis analyzed 129 unique studies with 40,790 unique patients, including 34,432 women with postmenopausal bleeding and 6,358 women with endometrial cancer.

    “Atotal of 129 unique studies, including 34 432 unique patients with PMB and 6358 with endometrial cancer (40 790 women), were analyzed.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § Discussion · p. 7

    In the subset of studies that required a minimum endometrial thickness, the pooled risk of endometrial cancer among women with postmenopausal bleeding was 19%, more than twice the main analysis estimate.

    “Inthesubsetofstudiesincludedinour meta-analysis that included women with PMB and a minimum endometrialthickness,thepooledriskofendometrialcancerwas 19%,morethandoubletheriskobservedinourmainanalysis.”
    Quote in the paperNot a substantial claim

  • The quote only partly states this claim.

    Findingown data
    § Association of Endometrial Cancer Risk With Postmenopausal Bleeding in Women ASystematic Review and Meta-analysis · p. 1

    The pooled risk of endometrial cancer in women with postmenopausal bleeding was higher in studies that excluded hormone therapy users (12%; 95% CI, 9%-15%) than in studies that included them (7%; 95% CI, 6%-9%), with P < .001 for heterogeneity.

    “with estimates varying by use of hormone therapy (range, 7% [95% CI, 6%-9%] to 12% [95% CI, 9%-15%]; P < .001 for heterogeneity)”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § Risk of Endometrial Cancer in Women With PMB · p. 6

    The magnitude of increase in positive predictive value of both TVUS and the experimental methylation assay increased with increasing risk of endometrial cancer in women with postmenopausal bleeding, supporting evaluation of early-detection strategies in various populations.

    “magnitude of the increase in PPV of both tests with increasing risk of endometrial cancer in women with PMB, supporting the evaluation of early-detection strategies in various populations.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingnone given
    § Discussion · p. 7

    Endometrial cancer risk among women with postmenopausal bleeding varies geographically, with estimates of 13% in Western Europe, 5% in North America, and 7% in Northern Europe.

    “Wenotedstrikinggeographicdifferencesinendometrialcancer risk among women with PMB, ranging from 13% in Western Europe to 5% in North America and 7% in Northern Europe.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given
    § Conclusions · p. 8

    Referring all women with postmenopausal bleeding for transvaginal ultrasonography and/or endometrial biopsy imposes a considerable burden and cost.

    “The widespread practice of referring all women with PMB for TVUS and/or endometrial biopsy carries a considerable burden and cost.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductnone given
    § Search Strategy and Selection Criteria · p. 2

    Studies that included special populations, lacked detailed inclusion criteria, and/or included 25 or fewer women were excluded.

    “we excluded studies that included special populations (eg, defined by comorbid conditions or specific histologic findings), lacked detailed inclusion criteria, and/or included 25 or fewer women.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S2 (checkable). May combine two claims.

    Interpretationreasoning
    § Conclusions · p. 8

    The results can help assess the potential clinical value of new markers and inform clinical and epidemiologic risk prediction models.

    “As new markers are discovered or new clinical management strategies are evaluated, our results can aid in the assessment of their potential clinical value and will help to inform clinical and epidemiologic risk prediction models to support clinical decision making.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductreasoning
    § Strengths and Limitations · p. 8

    Most included studies were cross-sectional and few had prospective follow-up, so long-term risk of endometrial cancer could not be evaluated.

    “With respect to the analysis of the risk of endometrialcancerinwomenwithPMB,moststudieswerecrosssectional,andfewincludedprospectivefollow-up;thus,wewere unabletoevaluatelong-termriskofendometrialcancerinthese studies.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Interpretationown data
    § Discussion · p. 6

    The findings support working up all women with postmenopausal bleeding by reassuring that targeting this high-risk group will capture most endometrial cancers.

    “Ourfindingssupportthisrecommendationby providingreassurancethattargetingthishigh-riskgroupofwomenforearlydetectionandpreventionstrategieswillcapturemost endometrialcancers.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation
    § Association of Endometrial Cancer Risk With Postmenopausal Bleeding in Women ASystematic Review and Meta-analysis · p. 2

    Postmenopausal bleeding is not specific for endometrial cancer and is often caused by benign conditions such as endometrial polyps or unscheduled bleeding in women using hormone therapy.

    “However, PMB is often associated with benign conditions such as endometrial polyps or may result from unscheduled bleeding in women using hormone therapy (HT). 18,21”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [18] source
    • cites [21] source

  • Probably not a substantial claim: may not pass S2 (checkable). May combine two claims.

    Interpretationreasoning
    § Association of Endometrial Cancer Risk With Postmenopausal Bleeding in Women ASystematic Review and Meta-analysis · p. 1

    These results can aid in assessing the potential clinical value of new early detection markers and clinical management strategies for endometrial cancer and can help inform clinical and epidemiologic risk prediction models to support decision making.

    “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.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: No recommendation for population-based screening for endometrial cancer currently exists.
    • Rests on an assumption: Studies evaluating early detection strategies for endometrial cancer are lacking.

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationown data
    § Strengths and Limitations · p. 7

    The findings can support risk-informed decision making in the clinical management of women with postmenopausal bleeding.

    “Our findings can support risk-informed decision making in clinical management of women with PMB.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given
    § Strengths and Limitations · p. 8

    Data on study-level variables such as years since menopause and body mass index were reported inconsistently, which limited the ability to evaluate them.

    “In general,dataonstudy-levelvariablessuchasyearssincemenopause andbodymassindexwereinconsistentlyreported,limitingour abilitytoevaluatethem.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation
    § Association of Endometrial Cancer Risk With Postmenopausal Bleeding in Women ASystematic Review and Meta-analysis · p. 2

    Postmenopausal bleeding is a common symptom of endometrial cancer and accounts for approximately two-thirds of all gynecologic visits among perimenopausal and postmenopausal women.

    “Postmenopausal bleeding (PMB) is a common symptom of endometrial cancer and accounts for approximately two-thirds of all gynecologic visits among perimenopausal and postmenopausal women. 18”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [18] source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation
    § Discussion · p. 7

    In many European countries, guidelines recommend transvaginal ultrasonography as the first-line test, with histologic assessment for women with thickened endometrium using cutoffs of 3 to 5 mm.

    “InmanyEuropeancountries,guidelinesrecommendTVUS asthefirst-linetest,withhistologicassessmentindicatedforwomenwithathickenedendometriumbasedoncutoffsrangingfrom 3 to 5 mm. 18,166,167”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [18] source
    • cites [166] source
    • cites [167] source

  • Classified as probably not a substantial claim. May combine two claims.

    Interpretationown data
    § Discussion · p. 7

    The data highlight the importance of considering a woman's hormone therapy status in clinical decisions, potentially supporting a less aggressive management approach for hormone therapy users.

    “Ourdataemphasizetheimportanceofconsideringawoman'sHTstatustoinformclinicaldecisionmaking, potentially supporting a less aggressive management approach in HT users.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation
    § Discussion · p. 7

    The causes of hormone therapy-induced bleeding are thought to involve changes in endometrial blood vessel size and in the regulation of vascular growth and integrity.

    “TheunderlyingcausesofHT-induced bleedingisthoughttoinvolvechangesinthesizeofendometrial bloodvesselsandregulationofvasculargrowthandintegrity. 165”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [165] source

  • May combine two claims.

    Interpretationown data
    § Conclusions · p. 8

    The study can serve as a reliable reference for the prevalence of postmenopausal bleeding in women with endometrial cancer and for the risk of endometrial cancer in women with postmenopausal bleeding.

    “Ourstudyrepresents an important and timely evaluation of the risk of endometrial cancer in women with PMB and can serve as a reliable reference for the prevalence of PMB in women with endometrial cancer and the risk of endometrial cancer in women with PMB”
    Quote in the paperNot a substantial claim
23 of 23

  • The paper relies on this without support.

    No recommendation for population-based screening for endometrial cancer currently exists.

    “However, studies evaluating early detection strategies for endometrial cancer are lacking, and at present no recommendation for population-based screening exists.”

  • The paper relies on this without support.

    Studies evaluating early detection strategies for endometrial cancer are lacking.

    “However, studies evaluating early detection strategies for endometrial cancer are lacking, and at present no recommendation for population-based screening exists.”
2 of 2

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • One hormone-therapy subgroup citation is outside the stated study set

    Minor

    The paper says the 92-study cancer-risk analysis comprises references 22-27, 58, and 78-162, but its subgroup of those studies includes reference 21.

1 of 1

Cites

Flagged first, then by citations

33 of the 217 references couldn’t be matched to a known paper.

Research works printed but not linked: 1

  1. Emanuel, 1995, An audit of true prevalence of intra-uterine pathology: the hysteroscopical findings controlled for patient selection in 1202 patients with abnormal uterine bleeding., Gynaecol Endosc, 4, 237

Cited by

Sorted by citations

Related

Authors
Clarke, M. A., Long, B. J., Del Mar Morillo, A., Arbyn, M., Bakkum-Gamez, J. N., & Wentzensen, N.
Affiliations
  • Division of Cancer Epidemiology and Genetics (US)
  • Mayo Clinic (US)
  • Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland
  • Sciensano (Belgium) (BE)
Corresponding author
Clarke, Megan A.
ORCID
Venue
JAMA Internal Medicine
Publisher
American Medical Association (AMA)
Published
2018-09-01
Volume
178
Issue
9
Pages
1210
ISSN
2168-6106 (ISSN-L)
DOI
10.1001/jamainternmed.2018.2820
PMC
PMC6142981
OpenAlex
W2885550086
Cited by
426
References
217
Citations by year
2026: 61 · 2025: 65 · 2024: 66 · 2023: 65 · 2022: 66 · 2021: 54 · 2020: 32 · 2019: 15 · 2018: 1
FWCI
4.13
Type
journal article
Language
en
Open access
Locations
  • JAMA Internal Medicine (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Obstetrics and Gynecology › Endometrial and Cervical Cancer Treatments
  • Health Sciences › Medicine › Oncology › Cancer Risks and Factors
  • Health Sciences › Medicine › Obstetrics and Gynecology › Gynecological conditions and treatments
Keywords
endometrial cancer, postmenopausal bleeding, cancer risk, prevalence, hormone therapy, early detection, cancer screening, tumor stage, regional variation, risk factors, women's health, cancer prevention, risk stratification, screening eligibility, risk communication, shared decision-making, quality of life, quality of life after cancer treatment
MeSH terms
Biopsy, Female, Humans, Risk Factors, Uterine Hemorrhage, Global Health, Prevalence, Endometrial Neoplasms, Postmenopause

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