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Diabetes, Obesity, and Endometrial Cancer: A Review
by
,
Olivia Hooks
1, 
Vama Jhumkhawala
1,
Kristen Sibson
1,
Abbigail Shrontz
1,
Syamala Soumya Krishnan
2 and
Sarfraz Ahmad
3,*
1
Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, FL 33431, USA
2
Department of Medicine, Division of Pulmonary and Critical Care, Downstate Health Sciences University, State University of New York, Brooklyn, NY 11203, USA
3
AdventHealth Cancer Institute, Gynecologic Oncology Program, Orlando, FL 32804, USA
*
Author to whom correspondence should be addressed.
Curr. Oncol. 2025, 32(12), 672; https://doi.org/10.3390/curroncol32120672 (registering DOI)
Submission received: 29 September 2025
/
Revised: 20 November 2025
/
Accepted: 27 November 2025
/
Published: 29 November 2025
(This article belongs to the Section Gynecologic Oncology)
Simple Summary
Endometrial cancer is the fourth most diagnosed cancer in women in the United States. Diabetes and obesity are very common, and both are known to increase the risk of developing endometrial cancer. Yet, their combined effect on the development and outcomes of endometrial cancer is less defined. The purpose of this review is to investigate these relationships. Studies consistently find that the risk of developing endometrial cancer is significantly higher in women with both diabetes and obesity than with each condition independently. Research also suggests that these conditions not only increase the risk of development but also worsen treatment outcomes and long-term survival in endometrial cancer. These findings emphasize the importance of continuing to research how these conditions impact the pathophysiological processes of endometrial cancer and the effectiveness of treatment options, especially with novel therapies.
Abstract
Endometrial cancer is the fourth most diagnosed cancer in U.S. women. Diabetes and obesity are established independent risk factors for EC, but their combined effect is less defined. This review investigates the literature on these comorbidities as risk factors and modifiers of EC. Multiple cohort and case–control investigations have shown an increased relative risk (RR) and odds ratio (OR) when diabetes and obesity coexist. In one prospective cohort, the RR of EC in diabetic women was 1.94 [95% CI, 1.23–3.08], but increased to 6.39 [95% CI, 3.28–12.06] with obesity; with low physical activity added, RR rose to 9.61 [95% CI, 4.66–19.83]. Case–control studies similarly show an OR of 1.4 [95% CI, 0.9–2.4] for diabetes alone, vs. 5.1 [95% CI, 3.0–8.7] with BMI > 30 and diabetes. Mechanistically, both conditions promote a pro-cancerous microenvironment through metabolic and inflammatory pathways. They also worsen treatment outcomes, with greater surgical complications, thromboembolic events (p < 0.01), prolonged hospitalizations 6.2 days versus 4.5 days (p < 0.03), and poorer survival with an elevated cancer-specific mortality (HR = 2.65, 95% CI 1.60–4.40). These findings underscore the urgent need for targeted interventions and translational research on how these comorbidities impact the pathophysiologic processes of EC.
Keywords:
diabetes; obesity; endometrial cancer; uterine cancer; comorbid risk factors; metabolism
