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

Savelieva GM, Breusenko VG, Kareva EN, Golukhov GN, Gutorova DS, Ovchinnikova AV, Ivanovskaya TN, Shcherbatyuk KV
About authors

Pirogov Russian National Research Medical University, Moscow, Russia

Correspondence should be addressed: Dina S. Gutorova
Lobachevskogo, 42, Moscow, 119415, Russia; ur.relbmar@d-avorotug

About paper

Funding: the study was carried out as a part of "Molecular pharmacological markers of recurrence for proliferative processes of the reproductive tract tissues in postmenopausal patients" 2018–2020 research project at the Pirogov Russian National Research Medical University of the Ministry of Healthcare of Russia (universal decimal classifier 577.21; R&D No. АААА-А18-118051590095-4; info reg. ID No. АААА-Б20-220100690049-5)

Author contribution: Savelieva GM — design and supervision; Breusenko VG — clinical supervision; Kareva EN — laboratory supervision, laboratory tests and analysis of the data; Golukhov GN — consulting, data interpretation, manuscript editing; Gutorova DS — concept, patient database construction, statistical processing, analysis and interpretation of the data, manuscript writing; Ovchinnikova AV — statistical processing of the data; Ivanovskaya TN — formal analysis; Shcherbatyuk KV — patient data management.

Compliance with ethical standards: the study was approved by Ethical Review Board at the Pirogov Russian National Research Medical University (Protocol № 210 of 30 August 2021). All patients provided voluntary informed consent for the study.

Received: 2022-05-18 Accepted: 2022-06-13 Published online: 2022-06-28

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.

Keywords: postmenopause, endometrial proliferative process, endometrial hyperplasia, hormonal therapy, ER⍺, ERβ, mER, PRA, PRB, mPR, PGRmC1