Endoscopy Underuse for New-Onset Iron Deficiency Anemia in Younger Veterans

ABSTRACT

Objectives: Bidirectional endoscopy is recommended for new-onset iron deficiency anemia (IDA), given the risk of gastrointestinal (GI) cancer. The rate of endoscopic assessment in younger patients is unknown.

Study Design: Retrospective cohort study.

Methods: We assessed US veterans younger than 45 years with new-onset IDA and their outcomes of endoscopy within 1 year.

Results: There was a low rate of bidirectional endoscopy in this population (9.58% within 1 year). Predictors of undergoing any endoscopic evaluation included male sex (OR, 5.13; 95% CI, 4.55-5.78) and hemoglobin level (OR, 0.76 per 1-unit increase; 95% CI, 0.72-0.80).

Conclusions: Given low current rates of bidirectional endoscopic evaluation in this population, implementation of bidirectional endoscopy in all individuals with IDA would require significantly increased resources. Further study of this population is needed to determine the impact of the 2020 American Gastroenterological Association guidelines on endoscopic use and GI cancer diagnoses.

Am J Manag Care. 2026;32(5):e175-e178. https://doi.org/10.37765/ajmc.2026.89942

Takeaway Points

Bidirectional endoscopy (upper endoscopy and colonoscopy) is recommended for evaluation of new-onset iron deficiency anemia (IDA) to exclude potential gastrointestinal cancers.

• Low rates of bidirectional endoscopy were seen in younger veterans (9.6%) within 1 year.
• Women were less likely to receive endoscopic evaluation than men (concordant with guidelines, given a potential alternative benign cause from menstrual blood loss).
• Meeting American Gastroenterological Association recommendations for IDA evaluation would require more than 5-fold additional endoscopies.

New-onset iron deficiency anemia (IDA) is an important clinical sign, as it may be caused by an undiagnosed gastrointestinal (GI) tract cancer. American Gastroenterological Association (AGA) guidelines strongly recommend esophagogastroduodenoscopy (EGD) and colonoscopy (bidirectional endoscopy) in men and postmenopausal women with new-onset IDA.¹ However, endoscopic evaluation is only conditionally recommended in premenopausal women, as IDA is commonly caused by menorrhagia.^1,2 Prompt evaluation of IDA is increasingly important given the rising incidence of GI tract cancers in younger individuals.^3,4 However, prior work has shown that new-onset IDA is often underinvestigated.^5-7 In this study, we sought to evaluate contemporary clinical practice patterns in endoscopic evaluation of younger men and women with new-onset IDA in the Veterans Affairs (VA) health care system.

METHODS

We conducted a retrospective cohort study of individuals younger than 45 years receiving regular care within the VA health care system with new-onset anemia from 2005 to 2019. We identified patients with (1) at least 1 primary care visit every 2 years over a 5-year period; (2) at least 2 complete blood counts; (3) a normal baseline hemoglobin with subsequent development of anemia (World Health Organization [WHO] definition of hemoglobin < 12 g/dL for women or <13 g/dL for men⁸); (4) no GI endoscopic evaluation in the preceding 5 years; and (5) a ferritin level within 1 year following the incident anemia date consistent with IDA (< 45 ng/mL, per AGA guidelines, corresponding to a sensitivity of 85% and specificity of 92%).^1,2 To ensure ongoing VA primary care in the year following incident anemia diagnosis, we restricted the cohort to those with at least 1 primary care provider visit in the year following anemia diagnosis. We restricted the age on the incident anemia date to younger than 45 years to exclude those receiving routine colorectal cancer (CRC) screening.

Our primary outcome was the performance of endoscopy (EGD, colonoscopy, or bidirectional endoscopy) within 1 year of the new-onset IDA. We assessed baseline demographics at the time of the incident IDA. We also identified diagnoses of luminal GI tract cancers within the subsequent year and performance of video capsule endoscopy (VCE) testing within 1 year.

We performed a secondary analysis to evaluate other factors that might affect endoscopic decision-making, including abdominal pain, GI bleeding, and non-GI symptoms such as menorrhagia that could provide an alternative explanation for the IDA. We used International Classification of Diseases, Ninth Revision (ICD-9) and International Statistical Classification of Diseases, Tenth Revision (ICD-10) codes for identification of abdominal pain and GI bleeding (categorized as hematemesis or other intestinal bleeding). To maximize sensitivity of these codes, we assessed ICD codes within 12 months of the incident anemia (ie, 12 months preceding and following the incident anemic date). We identified those with menorrhagia using established ICD-9 and ICD-10 diagnostic codes for heavy menstrual bleeding.⁹ In addition, we used an expanded definition of abnormal menstrual disorders, which included menorrhagia (heavy menstrual bleeding) as well as ICD-9 and ICD-10 codes for other menstrual abnormalities, as described by Rosen et al.¹⁰

We used the VA national cancer registry to identify luminal GI tract cancer diagnoses within 1 year following the incident anemia date. We classified the tumors by GI tract region: upper GI (esophagus or stomach), small bowel, or lower GI (CRC). The study was not powered to detect differences in cancer incidence by sex or tumor site. Logistic regression was used to evaluate predictors of endoscopic evaluation within 1 year of incident anemia. A 2-sided P value less than .05 was considered statistically significant. Statistical analysis was performed using SAS 9.4 (SAS Institute Inc). The VA Ann Arbor Healthcare System Institutional Review Board (IRB#1747609) approved the study and waiver of informed consent.

RESULTS

A total of 8974 individuals met inclusion criteria, of whom 5945 (66.2%) were female (Table 1). The mean (SD) age at inclusion was 35.36 (6.58) years, with a younger female population (34.47 [6.59] years) than male (37.11 [6.19]). We categorized anemia severity using WHO criteria,⁸ with most having mild anemia (78.86%; n = 7077) and 20.06% having moderate anemia (n = 1800).

Primary Analysis

Within 1 year of new-onset IDA, 860 (9.58%) patients underwent bidirectional endoscopy, 451 (5.03%) underwent colonoscopy alone, and 431 (4.80%) underwent EGD alone (Table 1). Undergoing any endoscopic evaluation (EGD or colonoscopy) was more common in men (35.72%; n = 1082 of 3029) than women (11.10%; n = 660 of 5945). Overall, there were 1311 patients who underwent colonoscopies (14.61%) and 1291 patients who underwent EGDs (14.39%). We found low use of VCE testing, with 88 individuals (0.98%) undergoing VCE testing.

We performed multivariable logistic regression to evaluate the effects of hemoglobin, age, and sex as predictors of undergoing endoscopic evaluation within 1 year of incident anemia. In this model, the OR for undergoing any endoscopic evaluation within 1 year was 5.13 (95% CI, 4.55-5.78) for men compared with women, 0.76 (95% CI, 0.72-0.80) for each unit increase in hemoglobin level, and 1.02 for each year of age (95% CI, 1.02-1.03) (Table 2).

Secondary Analysis

We evaluated the prevalence of menorrhagia and the potential effect on a decision to undergo endoscopic evaluation for incident IDA (eAppendix Tables 1-2 [eAppendix available at ajmc.com]). Although there was a trend for a lower rate of endoscopic evaluation in those with ICD codes for menorrhagia (9.99% in 1 year; n = 138 of 1382) vs those without menorrhagia (11.44%; n = 522 of 4563), this was not a statistically significant difference (P = .13 by χ² test). Expanding the definition to any abnormal menstrual disorder, there remained no difference in endoscopic evaluation at 1 year (P = .85), at 10.99% (n = 217 of 1974) in those with abnormal menstrual diagnostic codes vs 11.16% (n = 443 of 3971) in those with normal menses.

We assessed the prevalence of abdominal pain and GI tract bleeding within 12 months of incident anemia and the impact on endoscopic assessment. Abdominal pain was present in 1895 (21.12%), intestinal bleeding in 1057 (11.78%), and hematemesis in 48 (0.53%) (Table 1). The presence of these symptoms was associated with an increased use of endoscopic assessment: 75.00% in the setting of hematemesis (n = 36 of 48), 54.59% with intestinal bleeding (n = 577 of 1057), and 29.82% (n = 565 of 1895) with abdominal pain (eAppendix Table 3). In a combined logistic regression model with hemoglobin, age, and sex (from the primary analysis) and diagnoses of abdominal pain, intestinal bleeding, and hematemesis, the primary variables remained statistically significant and the GI symptoms were also predictors of increased likelihood of endoscopic evaluation (eAppendix Table 4).

Within the entire cohort, we identified 47 GI cancer diagnoses within 1 year (0.51% incidence), with 39 in men (1.24% incidence) and 8 in women (0.13% incidence). Most of the cancers were colorectal (78.72%; n = 37 of 47), 6 (12.77%) were small bowel cancers, and 4 (8.51%) were upper GI cancers (esophageal or gastric). By extending the interval to 2 years post incident anemia, we identified an additional 8 GI cancers in those who did not undergo any endoscopy in the first year (0.11%; n = 8 of 7521) and 2 GI cancers in those who did undergo endoscopy in the first year (0.11%; n = 2 of 1775).

DISCUSSION

In this analysis of new-onset IDA in younger patients in a large integrated health care system, we found low rates of bidirectional endoscopy overall (9.58%). Younger women were appropriately less likely to undergo endoscopic evaluation compared with men, as they may have a potentially benign alternative explanation for new-onset IDA (ie, menorrhagia). Although this study was not powered to detect differences between individual tumor types, we found a 1.25% incidence of cancer in men vs. 0.12% incidence in women, which likely reflects the potential benign non-GI etiology for IDA in women. This supports AGA guidelines with a strong recommendation for evaluation for IDA with bidirectional endoscopy in men, with only a conditional recommendation in premenopausal women.¹ We also found that patients with lower hemoglobin levels were more likely to undergo endoscopic assessment, suggesting that clinicians prioritize endoscopic evaluation by anemia severity rather than just as a binary state of anemia vs normal hemoglobin.

Limitations and Strengths

These findings are consistent with prior work demonstrating low rates of endoscopic utilization for new-onset IDA.^6,7 Surprisingly, however, given that prior work has suggested clinicians prioritize colonoscopy over EGD for IDA, we found similar rates of EGD (14.39%; n = 1291) and colonoscopy (14.61%; n = 1311) use in this population.¹¹ Potential limitations include that non-VA procedures were not assessed (non-VA fee basis and community care), potentially leading to underestimation of the true rate of endoscopic evaluation. In addition, because this was a veteran population receiving regular primary care, the results may not apply to other clinical settings. Strengths include the use of a national cancer registry and requiring regular clinical follow-up.

CONCLUSIONS

With increasing incidence of early-onset GI tract cancer, it is important to evaluate new-onset IDA, which may be the first diagnostic sign of malignancy. However, given low current rates of bidirectional endoscopic evaluation, implementation of AGA guideline–recommended bidirectional endoscopy for new-onset IDA would require significantly increased endoscopic resources (more than 5-fold additional endoscopies in this population). Our findings show that patients are more likely to undergo endoscopic assessment in the setting of more severe anemia or in the presence of other GI symptoms. In this context, additional individualized risk assessment tools could help further maximize endoscopic yield. Moreover, because this study period preceded the publication of the AGA guideline, next steps should evaluate the impact on endoscopic use and cancer outcomes after the guideline. In addition, further longitudinal prospective follow-up of younger individuals in other clinical practice settings could help further identify opportunities to improve cancer diagnoses.

Acknowledgments

The authors thank Jennifer Burns, MHSA, for analytic support.

Sameer D. Saini, MD, MS, and Akbar K. Waljee, MD, MS, contributed equally to this work and are listed as co–senior authors.

Author Affiliations: Department of Internal Medicine (AJR, SLK, SDS, AKW), Institute for Healthcare Policy and Innovation (AJR, SLK, SDS, AKW), Rogel Cancer Institute (AJR, SDS, AKW), and Department of Learning Health Sciences (AKW), University of Michigan, Ann Arbor, MI; Veterans Affairs Health Systems Research (VA HSR) Center for Clinical Management Research (SLK, KD, TV, SDS, AKW), Ann Arbor, MI.

Prior Presentation: A preliminary abstract version of this work was presented at Digestive Disease Week in May 2025.

Source of Funding: Dr Read is supported by National Institutes of Health (NIH) grant K08CA279659; the content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Dr Krein is supported by VA HSR Research Career Scientist award RCS 11-222.

Author Disclosures: The authors report no relationship or financial interest with any entity that would pose a conflict of interest with the subject matter of this article.

Authorship Information: Concept and design (AJR, SLK, SDS, AKW); acquisition of data (AJR, KD, TV); analysis and interpretation of data (AJR, KD, TV); drafting of the manuscript (AJR, KD, SDS, AKW); critical revision of the manuscript for important intellectual content (SLK, SDS, AKW); statistical analysis (AJR, TV); obtaining funding (AJR); administrative, technical, or logistic support (AJR); and supervision (SLK, SDS, AKW).

Address Correspondence to: Andrew J. Read, MD, MS, University of Michigan, 3912 Taubman Center, 1500 E Medical Center Dr, SPC 5362, Ann Arbor, MI 48109-5362. Email: reada@med.umich.edu.

REFERENCES

1. Ko CW, Siddique SM, Patel A, et al. AGA clinical practice guidelines on the gastrointestinal evaluation of iron deficiency anemia. Gastroenterology. 2020;159(3):1085-1094. doi:10.1053/j.gastro.2020.06.046

2. Rockey DC, Altayar O, Falck-Ytter Y, Kalmaz D. AGA technical review on gastrointestinal evaluation of iron deficiency anemia. Gastroenterology. 2020;159(3):1097-1119. doi:10.1053/j.gastro.2020.06.045

3. Ben-Aharon I, van Laarhoven HWM, Fontana E, Obermannova R, Nilsson M, Lordick F. Early-onset cancer in the gastrointestinal tract is on the rise-evidence and implications. Cancer Discov. 2023;13(3):538-551. doi:10.1158/2159-8290.CD-22-1038

4. Siegel RL, Kratzer TB, Giaquinto AN, Sung H, Jemal A. Cancer statistics, 2025. CA Cancer J Clin. 2025;75(1):10-45. doi:10.3322/caac.21871

5. Singh H, Daci K, Petersen LA, et al. Missed opportunities to initiate endoscopic evaluation for colorectal cancer diagnosis. Am J Gastroenterol. 2009;104(10):2543-2554. doi:10.1038/ajg.2009.324

6. Read AJ, Waljee AK, Chen CS, Holleman R, Kumbier KE, Saini SD. Prevalence of appropriate testing for incident anemia in the US Department of Veterans Affairs. JAMA Netw Open. 2021;4(1):e2034406. doi:10.1001/jamanetworkopen.2020.34406

7. Demb J, Liu L, Murphy CC, Doubeni CA, Martinez ME, Gupta S. Time to endoscopy or colonoscopy among adults younger than 50 years with iron-deficiency anemia and/or hematochezia in the VHA. JAMA Netw Open. 2023;6(11):e2341516. doi:10.1001/jamanetworkopen.2023.41516

8. Guideline on Haemoglobin Cutoffs to Define Anaemia in Individuals and Populations. World Health Organization; March 5, 2024. Accessed March 7, 2025. https://www.who.int/publications/i/item/9789240088542

9. Wang A, Wang S, Owens CD, Vora JB, Diamond MP. Health care costs and treatment patterns associated with uterine fibroids and heavy menstrual bleeding: a claims analysis. J Womens Health (Larchmt). 2022;31(6):856-863. doi:10.1089/jwh.2020.8983

10. Rosen MW, Weyand AC, Pennesi CM, et al. Adolescents presenting to the emergency department with heavy menstrual bleeding. J Pediatr Adolesc Gynecol. 2020;33(2):139-143. doi:10.1016/j.jpag.2019.11.010

11. Read AJ, Waljee AK, Sussman JB, et al. Testing practices, interpretation, and diagnostic evaluation of iron deficiency anemia by US primary care physicians. JAMA Netw Open. 2021;4(10):e2127827. doi:10.1001/jamanetworkopen.2021.27827