Endometrial immune profile in postmenopausal women receiving Menopausal Hormone Therapy: the role of lymphocyte subpopulations in the development of abnormal uterine bleeding
https://doi.org/10.33667/2078-5631-2025-17-56-62
Abstract
Relevance. Investigation of the endometrial immune profile in postmenopausal women receiving menopausal hormone therapy (MHT) is essential for understanding the mechanisms of abnormal uterine bleeding (AUB) and improving treatment safety. While the role of NK cells and T lymphocytes in reproductive regulation has been studied, endometrial lymphocyte subpopulations during MHT remain insufficiently explored.
Objective. To evaluate changes in lymphocyte subpopulations (CD3+, CD3+/CD16+/CD56+, CD3–/CD16+/CD56+) in the endometrium of postmenopausal women receiving MHT and their association with AUB development.
Materials and Methods. A randomized controlled trial included 106 postmenopausal women divided into three groups: control (n=34), MHT without AUB (n=35), and MHT with AUB (n=37). Endometrial pipelle biopsy was performed before and after 6 months of therapy. Flow cytometry was used for immunophenotyping.
Results. After 6 months of MHT, significant increases in CD3+ and CD3–/CD56+/CD16+ cells were observed compared to baseline. The most pronounced changes occurred in the AUB group. Intergroup differences were statistically significant for both absolute and relative lymphocyte counts.
Conclusion. Altered endometrial immune homeostasis may contribute to AUB development during MHT. These findings emphasize the relevance of immune profiling for individualized therapeutic strategies.
About the Authors
Yu. E. DobrokhotovaRussian Federation
Dobrokhotova Yulia E., DM Sci (habil.), professor, head of Dept of Obstetrics and Gynecology of the Institute of Surgery
Moscow
S. E. Safarli
Russian Federation
Safarli Sabina E., obstetrician and gynecologist, postgraduate student at Dept of Obstetrics and Gynecology of the Medical Faculty
Moscow
I. Yu. Ilyina
Russian Federation
Ilyina Irina Yu., DM Sci (habil.), pofessor at Dept of Obstetrics and Gynecology of the Institute of Surgery
Moscow
M. R. Narimanova
Russian Federation
Narimanova Metanat R., PhD Med, associate professor at Dept of Obstetrics and Gynecology of the Institute of Surgery
Moscow
M. D. Kazieva
Russian Federation
Kazieva Milana D., assistant at Dept of Obstetrics and Gynecology of the Institute of Surgery
Moscow
References
1. Gu Y., Han F., Xue M., Wang M., Huang Y. The benefits and risks of menopause hormone therapy for the cardiovascular system in postmenopausal women: a systematic review and meta-analysis. BMC Womens Health. 2024; 24 (1): 60. DOI: 10.1186/s12905-023-02788-0. PMID: 38263123; PMCID: PMC10804786.
2. Marjoribanks J., Farquhar C., Roberts H., Lethaby A., Lee J. Long-term hormone therapy for perimenopausal and postmenopausal women. Cochrane Database Syst Rev. 2017; 1 (1): CD004143. DOI: 10.1002/14651858.CD004143.pub5. PMID: 28093732; PMCID: PMC6465148.
3. Dobrokhotova Yu.E., Ilyina I. Yu., Safarli S.E. Abnormal uterine bleeding and postmenopausal bleeding in women taking menopausal hormone therapy: current data. RMJ. Mother and Child. 2024; 7 (3): 241–247. DOI: 10.32364/2618-8430-2024-7-3-9
4. Sriprasert I., Beydoun H., Barnabei V., Nassir R., LaCroix A.Z., Archer D.F. Incidence of endometrial spotting or bleeding during continuous-combined estrogen-progestin therapy in postmenopausal women with and without hypertension. Menopause. 2015; 22 (10): 1067–75. DOI: 10.1097/GME.0000000000000436. PMID: 25756697.
5. Carugno J. Clinical management of vaginal bleeding in postmenopausal women. Climacteric. 2020; 23 (4): 343–349. DOI: 10.1080/м13697137.2020.1739642. Epub 2020 Apr 1. PMID: 32233689.
6. Critchley HO.D., Maybin J.A., Armstrong G.M., Williams AR.W. Physiology of the Endometrium and Regulation of Menstruation. Physiol Rev. 2020; 100 (3): 1149–1179. DOI: 10.1152/physrev.00031.2019. Epub 2020 Feb 7. PMID: 32031903.
7. Middelkoop M.A., Don E.E., Hehenkamp WJ.K., Polman N. J., Griffioen A.W., Huirne JA.F. Angiogenesis in abnormal uterine bleeding: a narrative review. Hum Reprod Update. 2023; 29 (4): 457–485. DOI: 10.1093/humupd/dmad004. PMID: 36857162; PMCID: PMC10320491.
8. Hickey M., Crewe J., Goodridge J.P., Witt.CS., Fraser I.S., Doherty D., Christiansen FT, Salamonsen LA. Menopausal hormone therapy and irregular endometrial bleeding: a potential role for uterine natural killer cells? J Clin Endocrinol Metab. 2005; 90 (10): 5528–35. DOI: 10.1210/jc.2005–0688. Epub 2005 Jul 26. PMID: 16046584.
9. Wilkens J, Male V, Ghazal P, Forster T, Gibson DA, Williams AR, Brito-Mutunayagam SL, Craigon M, Lourenco P, Cameron IT, Chwalisz K, Moffett A, Critchley HO. Uterine NK cells regulate endometrial bleeding in women and are suppressed by the progesterone receptor modulator asoprisnil. J Immunol. 2013 Sep 1; 191 (5): 2226–35. DOI: 10.4049/jimmunol.1300958. Epub 2013 Aug 2. PMID: 23913972; PMCID: PMC3843142.
10. Shen Z, Patel MV, Rodriguez-Garcia M, Wira CR. Aging beyond menopause selectively decreases CD8+ T cell numbers but enhances cytotoxic activity in the human endometrium. Immun Ageing. 2022 Nov 12; 19 (1): 55. DOI: 10.1186/s12979-022-00312-w. PMID: 36371240; PMCID: PMC9652910.
11. Hickey M., Ameratunga D., Marino J. L. Unscheduled bleeding in continuous combined hormone therapy users. Maturitas. 2011; 70 (4): 400–3. DOI: 10.1016/j.maturitas.2011.09.010. Epub 2011 Oct 24. PMID: 22030385.
Review
For citations:
Dobrokhotova Yu.E., Safarli S.E., Ilyina I.Yu., Narimanova M.R., Kazieva M.D. Endometrial immune profile in postmenopausal women receiving Menopausal Hormone Therapy: the role of lymphocyte subpopulations in the development of abnormal uterine bleeding. Medical alphabet. 2025;(17):56-62. (In Russ.) https://doi.org/10.33667/2078-5631-2025-17-56-62