Response to progestin-based therapy in endometrial intraepithelial neoplasia: An exploratory biomarker study

Objective With the incidence of endometrial intraepithelial neoplasia (EIN) rising among premenopausal women, fertility-sparing management with progestin-based therapy is increasingly utilized, yet a substantial proportion of patients fail to respond. This study explored associations between baseline tissue biomarker expression and response to progestin-based therapy in premenopausal women with EIN. Methods This was a single-institution retrospective cohort study of premenopausal women with EIN undergoing conservative management between March 2015 and December 2023. Immunohistochemical expression of progesterone receptor A (PR-A), progesterone receptor B (PR-B), and glucagon-like peptide-1 receptor (GLP-1R) was evaluated in pre-treatment and post-treatment endometrial biopsy specimens. Treatment response was dichotomized as complete response (CR) or progesterone resistance (PGR), defined as failure to achieve CR within 12 months of initiating progestin-based therapy. Associations between biomarker expression and treatment response were explored using descriptive and regression analyses. Results Endometrial biopsies were analyzed from 28 premenopausal patients prior to the initiation of progestin-based therapy. Baseline PR-A expression was significantly lower among non-responders in both glandular and stromal compartments. A pre-treatment PR-A:PR-B ratio ≤ 1 was associated with progesterone resistance in glandular tissue, whereas pre-treatment GLP-1R expression was not significantly associated with treatment response. Post-treatment glandular GLP-1R expression differed between groups, with a higher proportion of high expression observed among non-responders (54.6% vs. 6.7%, p = 0.021). Conclusion In this exploratory cohort, baseline progesterone receptor expression patterns were associated with response to progestin-based therapy. These findings warrant validation in larger, prospective studies.