A new strategy in selection of hormone therapy for endometrial proliferative process in postmenopausal patients

Abstract

The limited efficacy of hormone therapy for endometrial proliferative process (EPP) in postmenopausal patients and its side effects on the immune system functionalities have not been studied in detail. Here we assess the feasibility of hormone therapy for EPP in postmenopausal patients through evaluation of estradiol and progesterone receptor gene expression in endometrial tissue and peripheral blood mononuclear cells (PBMC). The study enrolled 92 postmenopausal patients with EPP, including 37 pts with glandular-fibrous polyps, 7 pts with non-atypical endometrial hyperplasia (EH), 8 pts with atypical endometrial hyperplasia (AEH), 31 pts with moderately differentiated adenocarcinoma and 9 pts with highly differentiated adenocarcinoma. The PBMC isolates and endometrial samples were tested for ER⍺, ERβ, mER, PRA, PRB, mPR and PGRmC1 expression by reverse real time polymerase chain reaction (RT–PCR). Differential changes in PBMC receptor profiles upon in vitro exposure to progesterone or mifepristone were determined for patients with endometrial polyps and healthy women. The results indicate elevated expression of ERα, ERβ, PRA, PRB, mPR and PGRmC1 by endometrial tissues in EH and elevated expression of mER, ER⍺ and PRA by PBMC in AEH, apparently reflecting suppressed functionalities of monocytes, macrophages, Т-cells and natural killer cells. Unaltered expression of the studied genes by PBMC in endometrial adenocarcinoma may reflect the incrementing tumor autonomy. In vitro, mifepristone inhibited ER⍺, ERβ, mPR, PGRmC1, PRA and PRB expression in PBMC isolated from patients with endometrial polyps. We suppose that such effects can mitigate the negative influence of sex steroid hormones on immunocompetent cells.

Shared Pathogenic and Therapeutic Characteristics of Endometriosis, Adenomyosis, and Endometrial Cancer: A Comprehensive Literature Review

“…Additionally, it reduces uterine volume and exhibits antitumor effects on endometrial cancer. However, significant side effects include bleeding, pelvic pain, headaches, and nausea [ 2 , 5 , 10 , 33 , 36 , 40 , 62 ].…”

“…In a 2019 study by Xuan Che involving 20 patients with adenomyosis treated with mifepristone, it was found to induce G1/G0 and G2/M phase arrest in the cell cycle of endometrial epithelial cells [ 63 ]. According to Lukovic (2021), it induced a 3-fold increase in apoptosis in endometriotic cells compared to their control group [ 62 ]. Mifepristone also inhibits the migratory capacity of eutopic endometrial epithelial and stromal cells in adenomyosis, induces apoptosis in both eutopic and ectopic endometrial cells, and inhibits EMT [ 63 , 64 ].…”