Multicenter cohort study of endometrial cancer risk with progestins with or without GLP-1RAs in nonmalignant uterine diseases

As endometrial cancer (EC) incidence rises, particularly among individuals with obesity and metabolic disorders, effective strategies targeting hormonal and metabolic risks are needed. A cohort study using TriNetX data evaluated impact of addition of glucagon-like peptide-1 receptor agonists (GLP-1RAs) to progestins on EC risk among patients with nonmalignant uterine conditions. The study included 444,820 participants with endometrial hyperplasia or benigng uterine pathology who received GLP-1RA plus progestins (n=18,414) or progestins alone (n=426,406) between May 2005 and December 2021. GLP-1RA with progestins was associated with a significantly lower risk of EC compared with progestins alone (HR 0.34; 95% CI 0.27-0.44). This protective association remained consistent across subgroups stratified by body mass index, age, baseline risk level, and progestin route. The authors conclude that adding GLP-1RAs to progestin therapy in women with benign uterine diseases or hyperplasia may be associated with reduced EC risk.