The DOI matches its Crossref record; 184 of the 217 references it cites were found in a registry or an index; 4 of the 26 sources its claims cite were checked for support.
Association of Endometrial Cancer Risk With Postmenopausal Bleeding in Women
Open accessAbstract
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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Claims the paper makes
4 of 26 cited sources checked · 2 supported · 0 flagged · accuracy not yet measured
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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).”
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § Strengths and Limitations · p. 8 · hedged
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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).”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § Risk of Endometrial Cancer in Women With PMB · p. 3 · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Finally, our results suggested a lower prevalence of endometrial cancer in retrospective and prospective cohort studiescomparedwithcross-sectionalstudies.”
Strength:hedged· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Ourmeta-analysisconfirmsa lower risk of endometrial cancer among women with PMB and polyps.”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesThe paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“TheriskofendometrialcanceramongwomenwithPMBwas notablylowerinstudiesthatincludedHTuserscomparedwith those that excluded these women.”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The pooled prevalence of PMB among women with endometrial cancer was 91% (95% CI, 87%-93%), irrespective of tumor stage.”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“among women with PMB, only approximately9%willbediagnosedwithendometrialcancer”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesWhat the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Evidence of publication bias suggested that small studies may overestimate the risk of endometrial cancer in women with PMB (Egger regression intercept, 0.75; P = .001).”
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“Certaincombinedformulationsof estrogenplusprogestintherapyareestablishedtohaveaprotective effect on the endometrium. 163”
What the sources say
- Not checked — no full text of the sourcecites [163] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
- Probably not a substantial claim. 14
- It may state two separate claims as one. 15
- The quote only partly states this claim. 1
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Currentpracticeguidelines recommend workup to rule out endometrial cancer among all womenwithPMB.”
What the sources say
- Not checked — no full text of the sourcecites [18] source
- Supportedcites [19] source
The Introduction states that guidelines addressing postmenopausal bleeding aim to exclude endometrial carcinoma or precancerous lesions. The Abstract likewise says that diagnostic workup for patients with postmenopausal bleeding is aimed at excluding malignancy. (LLM, conf=0.90)
- Not checked — no full text of the sourcecites [166] source
- Not checked — no full text of the sourcecites [167] source
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In the United States, guidelines recommend TVUSorendometrialbiopsyasthefirststepinevaluatingPMB. 19”
What the sources say
- Partly supportedcites [19] sourceExperimental — accuracy not yet measured
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)
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Interest has increased in the use of biomarkers, such as DNA methylation, to i mprove early detection of endometrial cancer. 31,32,170,171”
What the sources say
- Supportedcites [31] source
The Introduction says a growing number of methylated genes have been identified in endometrial cancer and describes methylation assays as promising for detection. The Discussion explicitly describes work to develop a clinically useful early-detection assay and ongoing discovery of methylation biomarkers. The supplied passages do not provide page numbers. (LLM, conf=0.91)
- Partly supportedcites [32] sourceExperimental — accuracy not yet measured
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)
- Not checked — no full text of the sourcecites [170] source
- Not matchedcites [171]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“TheprevalenceofPMBinendometrialcancerandtheriskof endometrialcancerinwomenwithPMBwerehigherbefore2000 comparedwithafter2000.”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Atotal of 129 unique studies, including 34 432 unique patients with PMB and 6358 with endometrial cancer (40 790 women), were analyzed.”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Inthesubsetofstudiesincludedinour meta-analysis that included women with PMB and a minimum endometrialthickness,thepooledriskofendometrialcancerwas 19%,morethandoubletheriskobservedinourmainanalysis.”
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“with estimates varying by use of hormone therapy (range, 7% [95% CI, 6%-9%] to 12% [95% CI, 9%-15%]; P < .001 for heterogeneity)”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesThe quote only partly states this claim.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Wenotedstrikinggeographicdifferencesinendometrialcancer risk among women with PMB, ranging from 13% in Western Europe to 5% in North America and 7% in Northern Europe.”
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The widespread practice of referring all women with PMB for TVUS and/or endometrial biopsy carries a considerable burden and cost.”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✗ Based: failsProbably not a substantial claim. The paper may give no reason why it holds.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✗ Checkable: fails✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may be too vague to check against evidence. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“With respect to the analysis of the risk of endometrialcancerinwomenwithPMB,moststudieswerecrosssectional,andfewincludedprospectivefollow-up;thus,wewere unabletoevaluatelong-termriskofendometrialcancerinthese studies.”
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Ourfindingssupportthisrecommendationby providingreassurancethattargetingthishigh-riskgroupofwomenforearlydetectionandpreventionstrategieswillcapturemost endometrialcancers.”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“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”
What the sources say
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✗ Checkable: fails✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may be too vague to check against evidence. It may state two separate claims as one.
- 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.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Our findings can support risk-informed decision making in clinical management of women with PMB.”
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✗ Checkable: fails✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may be too vague to check against evidence.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“In general,dataonstudy-levelvariablessuchasyearssincemenopause andbodymassindexwereinconsistentlyreported,limitingour abilitytoevaluatethem.”
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“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”
What the sources say
- Not checked — no full text of the sourcecites [18] source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“InmanyEuropeancountries,guidelinesrecommendTVUS asthefirst-linetest,withhistologicassessmentindicatedforwomenwithathickenedendometriumbasedoncutoffsrangingfrom 3 to 5 mm. 18,166,167”
What the sources say
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Ourdataemphasizetheimportanceofconsideringawoman'sHTstatustoinformclinicaldecisionmaking, potentially supporting a less aggressive management approach in HT users.”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
In the paper
“TheunderlyingcausesofHT-induced bleedingisthoughttoinvolvechangesinthesizeofendometrial bloodvesselsandregulationofvasculargrowthandintegrity. 165”
What the sources say
- Not checked — no full text of the sourcecites [165] source
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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”
Tests✓ Asserted: passes? Checkable: unclear✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
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.”
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
MinorThe 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.
“comparedwiththe51studiesthatincludedwomen using HT 21,23,25-27,78-81,83-88,90,91,95-97,100,107-111,113,114,117,119, 122-126,128-131,134,135,139,142,148,151,153-157,159”
“and92 22-27,58,78-162 wereincludedforanalysisof theriskofendometrialcancerinwomenwithPMB(31220womenwithPMBand2611casesofendometrialcancer).”
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Metadata
- 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.
- Venue
- JAMA Internal Medicine
- Publisher
- American Medical Association (AMA)
- Published
- 2018-09-01
- Volume
- 178
- Issue
- 9
- Pages
- 1210
- ISSN
- 2168-6106 (ISSN-L)
- 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
- bronze
- doi.org
- 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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