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

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.

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.

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).

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.