The addition of glucagon-like peptide-1 receptor agonists to progestin therapy in women with benign uterine diseases or hyperplasia may be associated with reduced endometrial cancer risk, based on the results of a large retrospective cohort study published in JAMA Network Open by Ting-Tai Yen, MD, of Texas Tech University Health Sciences Center El Paso, and colleagues.
“As endometrial cancer incidence rises, particularly among [women] with obesity and metabolic disorders, effective strategies targeting hormonal and metabolic risks are needed,” they wrote.
Study Details
Using deidentified electronic health record data from TriNetX, the researchers identified adult women diagnosed with endometrial hyperplasia or benign uterine pathology who received progestins between May 1, 2005, and December 31, 2022. Four treatment comparisons were examined in the analysis: glucagon-like peptide-1 receptor agonists (GLP-1 RAs) plus progestins vs progestins alone; GLP-1 RAs plus progestins vs metformin plus progestins; triple therapy with GLP-1 RAs, metformin, and progestins vs metformin plus progestins; and triple therapy vs progestins alone. Subgroup analyses of GLP-1 RAs plus progestins vs progestins alone were stratified by progestin route, risk category, body mass index, and age.
A total of 18,414 women received GLP-1 RAs plus progestins and 426,406 received progestins alone. The mean age was 43 years in the combination group and 35 years in the progestin-only group.
The primary outcome was the incidence of endometrial cancer, and the secondary outcome was subsequent hysterectomy.
Key Findings
Adding GLP-1 RAs to progestin monotherapy was associated with a significantly lower risk of endometrial cancer compared with progestins alone; the protective association persisted across subgroups, the researchers noted. This combination also showed a lower risk of endometrial cancer than metformin plus progestins.
In addition, triple therapy was found to be associated with a greater reduction in endometrial cancer risk compared with metformin plus progestins and with progestin monotherapy.
The researchers reported a lower incidence of hysterectomy among women who received GLP-1 RAs plus progestins at both 2 and 5 years of follow-up.
The researchers concluded, “In this cohort study of women with benign uterine pathology or endometrial hyperplasia, adding GLP-1 RAs to progestin therapy was associated with lower endometrial cancer risk. Further prospective studies and clinical trials are warranted to validate these findings, to explore optimal dosing and duration strategies, and to better elucidate the biologic mechanisms of GLP-1 RAs.”
Disclosure: Dr. Yen reported no conflicts of interest. Dr. Toy reported receiving speaker fees from AstraZeneca outside the submitted work. For full disclosures of the other researchers, visit jamanetwork.com.
Source: JAMA Network Open
