Glucagon-like Peptide-1 Receptor Agonists and Endometrial Cancer: Potential Future in Fertility-Sparing Treatment

Background: Endometrial cancer (EC) is one of the most prevalent cancers in women globally, which has recently gained attention as an increase has been noted among premenopausal women. Improving fertility-sparing treatments is crucial to assist women in completing their family planning. Methods: This study aims to explore the current evidence on the mechanisms of action and correlation between Glucagon-like Peptide-1 (GLP-1) and its agonists with EC, as well as the potential application in the conservative therapy for early-stage EC. A narrative review of the worldwide literature was conducted according to Scale for the Assessment of Narrative Review Articles (SANRA) principles, intending to analyze the correlation of GLP-1 receptor agonists (GLP-1RAs) with EC and their precise effect in the fertility-sparing treatment in women with atypical endometrial hyperplasia (AEH) or early-stage EC. Results: Preclinical studies indicate that GLP-1 receptor (GLP-1R) expression on healthy and malignant endometrial tissues of models regulates apoptosis via the AMPK-mTOR pathway. Observational and early clinical studies conclude that their role in the improvement of metabolic and hormonal imbalance increases the risk for the development of EC, as well as anti-tumour and anti-inflammatory effects. Conclusions: GLP-1RAs represent a potentially promising addition to the conservative management of AEH and early-stage EC in premenopausal women; however, further extensive clinical trials are required to ensure their safety and efficacy in future treatment algorithms and preconception exposure.