Combination GLP-1, hormone therapy may reduce risk for endometrial cancer
Key takeaways:
- Adding GLP-1s to progestin therapy appeared to reduce the risk for endometrial cancer among women with benign uterine or endometrial hyperplasia.
- Further research is needed to better understand their use.
The addition of glucagon-like peptide-1 receptor agonists to progestin therapy may help reduce endometrial cancer risk among certain women, according to study results.
Findings presented at Society of Gynecologic Oncology Annual Meeting on Women’s Cancer showed a protective benefit against endometrial cancer for women with certain non-malignant gynecologic conditions.
Ting-Tai Yen, MD, instructor in the department of obstetrics and gynecology at Texas Tech University Health Sciences Center El Paso, and colleagues conducted a real-world retrospective study to evaluate risk for endometrial cancer among women with benign uterine or endometrial hyperplasia treated with hormone therapy alone or in combination with GLP-1 receptor agonists.
The researchers used the TriNetX database to identify female patients aged 12 years or older with endometrial hyperplasia, endometrial polyps or abnormal uterine bleeding between May 2005 and August 2024.
The analysis included patients treated with a progestin-containing intrauterine device (IUD) or megestrol acetate.
Yen and colleagues created three cohorts to compare the risk for endometrial cancer: GLP-1s plus IUD vs. IUD alone, GLP-1s plus megestrol acetate vs. megestrol acetate alone, and GLP-1s plus IUD vs. metformin plus IUD.
Researchers propensity-score matched patients in each cohort by demographics and medical conditions.
Results showed the addition of GLP-1s to IUD reduced endometrial cancer incidence (HR = 0.44; 95% CI, 0.24-0.79).
Additionally, the addition of GLP-1s to megestrol acetate appeared associated with a significant reduction in incidence (HR = 0.56; 95% CI, 0.38-0.81), as did the addition of GLP-1s to IUD vs. metformin plus IUD (HR = 0.33; 95% CI, 0.11-0.99).
Researchers also observed a statistically significant reduction in endometrial cancer incidence among patients with abnormal uterine bleeding treated with IUD plus GLP-1s compared with those treated with IUD alone (0.19% vs. 0.45%; HR = 0.48; 95% CI, 0.27-0.86).
Results showed no such effect with the addition of GLP-1 receptor agonists to treatment with IUD among women with endometrial polyps or endometrial hyperplasia.
More research is needed to determine the potential of GLP-1s to reduce endometrial cancer risk, according to investigators. Further study also may provide insights into the mechanisms for the different effects observed with the addition of GLP-1 receptor agonists to progestins based on indications for progestin therapy, researchers added.
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Yen T-T, et al. Comparative effects of glucagon-like peptide-1 receptor agonists combined with hormone therapy on endometrial cancer risk among women with benign uterine or endometrial hyperplasia: A United States real-world retrospective study. Presented at: SGO Annual Meeting on Women’s Cancer; March 14-17, 2025; Seattle.