THE ROLE OF UNK-СELLS IN THE PATHOGENESIS OF ABNORMAL UTERINE BLEEDING IN WOMEN RECEIVING MENOPAUSAL HORMONE THERAPY



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Abstract

Abstract                   

Relevance. Abnormal uterine bleeding (AUB) is frequently observed during menopausal hormone therapy (MHT), significantly impairing the quality of life of postmenopausal women and reducing their adherence to treatment. In most cases, AUB associated with MHT is not linked to pathological changes in the endometrium. It is noteworthy that the role of uterine natural killer (uNK) cells in this process remains unexplored.

Objective. To evaluate the role of uNK cells in the pathogenesis of AUB in women receiving MHT.

Materials and methods. A randomized controlled trial was conducted at the City Clinical Hospital named after Pirogov N. I.  from November 2022 to October 2024, involving 75 postmenopausal women. Participants were divided into three groups: women receiving MHT with AUB (n=27); women receiving MHT without AUB (n=25); and postmenopausal women not receiving MHT (n=23). For the purpose of immunohistochemical analysis and flow cytometry endometrial samples obtained via pipelle biopsy were analyzed in the control group (not receiving MHT) and in the study group before MHT initiation, after 6 months of MHT, and during AUB episodes.

Results. Women with AUB during MHT exhibited a statistically significant increase in uNK cells in the endometrium compared to those without AUB (CD3-/CD16+/CD56+: 1.7 [1.46–1.85] vs. 0.66 [0.5–0.79], p<0.001). Immunohistochemical analysis revealed an increased density of CD56+ cells in the endometrial stroma of patients with AUB during MHT.

Conclusion. The study findings confirm the role of uNK cells in the pathogenesis of AUB in women receiving MHT. Further research may contribute to the development of new approaches for the prevention and treatment of AUB through modulation of uNK cell activity. 

About the authors

Yulia E. Dobrokhotova

Pirogov Russian National Research Medical University

Email: pr.dobrohotova@mail.ru
ORCID iD: 0000-0002-7830-2290

Dr. Sc. (Med.), Professor, Head of the Department of Obstetrics and Gynecology of the Institute of Surgery, Pirogov Russian National Research Medical University

Russian Federation, 1, Ostrovityanov str., Moscow, 117513, Russian Federation

Sabina E. Safarli

Pirogov Russian National Research Medical University

Email: sabina.safarli000@gmail.com
ORCID iD: 0009-0001-7966-7486
SPIN-code: 6041-2203
Scopus Author ID: 59394037300

obstetrician and gynecologist, postgraduate student of the Department of Obstetrics and Gynecology of the Medical Faculty, Pirogov Russian National Research Medical University

Russian Federation, 1, Ostrovityanov str., Moscow, 117513, Russian Federation

Irina Yu. Ilyina

Pirogov Russian National Research Medical University

Email: iliyina@mail.ru
ORCID iD: 0000-0001-8155-8775

Dr. Sc. (Med.), Professor of the Department of Obstetrics and Gynecology of the Institute of Surgery, Pirogov Russian National Research Medical University

Russian Federation, 1, Ostrovityanov str., Moscow, 117513, Russian Federation

Metanat R. Narimanova

Pirogov Russian National Research Medical University

Email: safarovametanat@yandex.ru
ORCID iD: 0000-0003-0677-2952

C. Sc. (Med.), associate professor of the Department of Obstetrics and Gynecology of the Institute of Surgery, Pirogov Russian National Research Medical University

Russian Federation, 1, Ostrovityanov str., Moscow, 117513, Russian Federation

Igor I. Grishin

Pirogov Russian National Research Medical University;
Pirogov City Clinical Hospital No. 1

Email: igrishin.md@gmail.com
ORCID iD: 0000-0001-5839-1858

Dr. Sc. (Med.), Professor of the Department of Obstetrics and Gynecology of the Institute of Surgery, Pirogov Russian National Research Medical University

Russian Federation, 1, Ostrovityanov str., Moscow, 117513, Russian Federation;

Alexander P. Raksha

Pirogov Russian National Research Medical University;
Pirogov City Clinical Hospital No. 1

Email: rakshadoc@yandex.ru
ORCID iD: 0009-0005-7897-5179

Dr. Sc. (Med.), Department of Pathological Anatomy and Clinical Pathological Anatomy, Pirogov Russian National Research Medical University; Head of the Pathological Anatomy Department, Pirogov City Clinical Hospital No. 1

Russian Federation, 1, Ostrovityanov str., Moscow, 117513, Russian Federation;

Ekaterina V. Scherbak

Pirogov City Clinical Hospital No. 1

Email: scherbakev2@zdrav.mos.ru
ORCID iD: 0009-0006-0346-4523

Pathologist, Pirogov City Clinical Hospital No. 1

Russian Federation, Leninsky Prospect, 8, Moscow, 117049, Russian Federation

Milana D. Kazieva

Pirogov Russian National Research Medical University

Email: mila1705@bk.ru
ORCID iD: 0009-0004-2567-6215

Assistant of the Department of Obstetrics and Gynecology of the Institute of Surgery, Pirogov Russian National Research Medical University

Russian Federation, 1, Ostrovityanov str., Moscow, 117513, Russian Federation

Amina Yu. Azimova

Pirogov Russian National Research Medical University

Author for correspondence.
Email: aminayous@mail.ru
ORCID iD: 0000-0001-8528-9648

obstetrician and gynecologist, senior research assistant of the Department of Obstetrics and Gynecology of the Institute of Surgery, Pirogov Russian National Research Medical University

Russian Federation, 1, Ostrovityanov str., Moscow, 117513, Russian Federation

References

  1. Доброхотова Ю.Э., Ильина И.Ю., Сафарли С.Э. Аномальные маточные кровотечения и кровотечения в по стменопаузе на фоне приема менопаузальной гормональной терапии: современные данные. РМЖ. Мать и дитя. 2024;7(3):241–247. doi: 10.32364/2618-8430-2024-7-3-9. Dobrokhotova Yu.E., Il'ina I.Yu., Safarli S.E. Abnormal uterine bleeding and postmenopausal bleeding with menopausal hormone therapy: current evidence. Russian Journal of Woman and Child Health. 2024;7(3):241–247 (in Russ.). doi: 10.32364/2618-8430-2024-7-3-9.
  2. Зайдиева Я.З., Казанцева В.Д. Сравнительный анализ распространенности аномальных маточных кровотечений у женщин в постменопаузе на фоне различной менопаузальной гормональной терапии (систематический обзор). Российский вестник акушера-гинеколога. 2021;21(6):51–58 https:// doi.org/10.17116/rosakush20212106151. Zaidieva Ya. Z., Kazantseva V. D. Comparative analysis of the prevalence of abnormal uterine bleeding in postmenopausal women against the background of various menopausal hormone therapy (systematic review). Russian Bulletin of Obstetrician-Gynecologist = Rossiiskii vestnik akushera-ginekologa. 2021;21(6):51–58. (In Russ.). https:// doi.org/10.17116/rosakush20212106151.
  3. Arbuckle R., Humphrey L., Abraham L., Dennerstein L., Simon J.A., Mirkin S., Bonner N., Walmsley S., Tatlock S., Symonds T. Qualitative cross-cultural exploration of vaginal bleeding/spotting symptoms and impacts associated with hormone therapy in post-menopausal women to inform the development of new patient-reported measurement tools. Maturitas. 2014;78(3):219-27. doi: 10.1016/j.maturitas.2014.04.019.
  4. Archer D.F. Endometrial bleeding during hormone therapy: the effect of progestogens //Maturitas. 2007. T. 57, №1. С. 71-76. doi: 10.1016/ j.maturitas.2007.02.022.
  5. Carugno J. Clinical management of vaginal bleeding in postmenopausal women. Climacteric. 2020;23(4):343-349. doi: 10.1080/м 13697137.2020.1739642.
  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.
  7. Dudley A.C., Griffioen A.W. Pathological angiogenesis: mechanisms and therapeutic strategies. Angiogenesis. 2023;26(3):313-347. doi: 10.1007/s10456-023-09876-7.
  8. Gasteiger G, Hemmers S, Firth MA, Le Floc'h A, Huse M, Sun JC, Rudensky AY. IL-2-dependent tuning of NK cell sensitivity for target cells is controlled by regulatory T cells. J Exp Med. 2013 Jun 3;210(6):1167-78. doi: 10.1084/jem.20122462.
  9. 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.
  10. Hapangama D.K., Bulmer .JN. Pathophysiology of heavy menstrual bleeding. Womens Health (Lond). 2016;12(1):3-13. doi: 10.2217/whe.15.81.
  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.
  12. 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.
  13. Kolatt T.S., Shufaro Y., Mashiach S., Czernobilsky B., Aviel-Ronen S., Apel-Sarid L., Dahan M., Or Y. Revealing the uterine blood vessel network via virtual pathology. Reprod Fertil. 2023;4(1):e220135. doi: 10.1530/RAF-22-0135.
  14. Li T, Li RHW, Ng EHY, Yeung WSB, Chiu PCN, Chan RWS. Interleukin 6 at menstruation promotes the proliferation and self-renewal of endometrial mesenchymal stromal/stem cells through the WNT/β-catenin signaling pathway. Front Immunol. 2024 May 3;15:1378863. doi: 10.3389/fimmu.2024.1378863.
  15. 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.
  16. 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.
  17. 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.

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Copyright (c) Dobrokhotova Y.E., Safarli S.E., Ilyina I.Y., Narimanova M.R., Grishin I.I., Raksha A.P., Scherbak E.V., Kazieva M.D., Azimova A.Y.

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