Weight loss measures and their impact on the risk of developing endometrial cancer: A systematic review and meta-analysis

Abstract

Background: Endometrial cancer (EC) is the most common gynecological malignancy, primarily affecting postmenopausal women. Obesity is a well-established risk factor for EC, yet the extent to which weight loss reduces this risk remains unclear.

Objectives: This study systematically reviews and quantifies the impact of intentional weight loss, through lifestyle interventions and bariatric surgery, on EC risk in obese patients.

Search strategy: A comprehensive search was conducted across Embase, LILACS, Web of Science, Scielo, and PubMed using the patient, intervention, comparison, outcome (PICO) strategy, with no restrictions on language or publication date. The review was registered in PROSPERO (CRD42024555555) and followed established methodological guidelines.

Selection criteria: Included studies were clinical trials, cohort studies, and case-control studies assessing EC risk in obese women (body mass index ≥30), aged ≥18 years, without prior EC diagnosis, who underwent intentional weight loss interventions. Studies with unclear intervention definitions or non-relevant populations were excluded.

Data collection and analysis: Two independent reviewers performed data extraction. ROBINS-E was used to assess study quality, and a meta-analysis synthesized hazard ratios (HR) and odds ratios (ORs).

Main results: From 785 identified articles, 12 studies met inclusion criteria, with 307 020 participants in the weight loss group and 8 664 414 in the control group. Weight loss interventions included lifestyle modifications and bariatric surgery, both showing EC risk reduction. A meta-analysis of five studies showed a significant risk reduction (HR 0.56 [95% CI 0.46-0.68], P < 0.001). A second meta-analysis of 12 studies confirmed the protective effect of weight loss (OR 0.46 [95% CI 0.33-0.65], P < 0.001), with bariatric surgery demonstrating greater effectiveness. Although most studies did not specify subtypes, the findings likely reflect a greater impact on type 1 endometrial cancer, which is predominantly associated with obesity.

Conclusions: Intentional weight loss achieved through structured interventions is associated with a significantly lower risk of developing EC, with surgical interventions showing stronger protective effects. However, study heterogeneity and biases highlight the need for more rigorous research. These findings reinforce weight loss as a preventive strategy for EC and underscore the necessity of further studies, particularly exploring modern pharmacological interventions.

Keywords: bariatric surgery; dieting; endometrial cancer; exercise; obesity; primary prevention; weight loss.