Impact of menopausal hormone therapy on immune system parameters

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Abstract

The decline in sex hormone levels with age is known to affect the functioning of the immune system in both men and women. Immunological aging is a consequence of age-related changes in the function of immune cells and the composition of their subpopulations. Taking menopausal hormone therapy has been shown to neutralize these changes. The route of estrogen administration in postmenopausal women may play a crucial role in these processes.

Objective: To investigate the effect of combined menopausal hormone therapy (MHT), including transdermal estradiol gel combined with micronized intravaginal progesterone, on blood immune parameters.

Materials and methods: The subpopulation composition of leukocytes was assessed in 23 peri- and postmenopausal women aged 44–57 years who were referred to the Gynecological Endocrinology Department of the V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia. The treatment duration was 3 months. Clinical and laboratory examinations were performed before therapy and three months after MHT.

Results: After 3 months of MHT, the patients were found to have a significant reduction in the severity of vasomotor (by 4 times), physical (by 3 times), and psychoemotional and sexual symptoms (by 2 times) (p<0.05). The use of MHT significantly reduced the incidence of sleep disturbances by a factor of 1.6, from 82.6 to 52.2% (p=0.020), muscle and joint pain by a factor of 1.4, from 73.9 to 52.2% (p=0.026), hot flashes by a factor of 2.7, from 82.6 to 30.4% (p<0.001), and night sweats by a factor of 1.8, from 73.9 to 39.1% (p=0.012). The effect of MHT on immune system parameters was manifested by a significant increase in the percentage of T-helper cells (CD45+CD3+CD4+) and changes in the expression of CD163, CD206, and CX3CR1 markers in subpopulations of classical, intermediate, and non-classical blood monocytes.

Conclusion: Our findings suggest that combined MHT including transdermal estradiol in combination with intravaginal micronized progesterone influences patients' blood immune parameters. It affects both lymphocytes and monocytes, with changes in the monocyte phenotype in different subpopulations that are likely to contribute to the immunopotentiating properties of MHT.

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About the authors

Marina V. Averyanova

Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Author for correspondence.
Email: marisha199022@mail.ru
ORCID iD: 0000-0002-2995-5228

postgraduate student at the Department of Gynecological Endocrinology, obstetrician-gynecologist

Russian Federation, Moscow

Svetlana V. Yureneva

Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: syureneva@gmail.com
ORCID iD: 0000-0003-2864-066X

Dr. Med. Sci., Professor at the Department of Obstetrics and Gynecology of the Department of Vocational Education, Leading Researcher, Department of Gynecological Endocrinology

Russian Federation, Moscow

Victoria V. Kiseleva

Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia; Peoples' Friendship University of Russia named after Patrice Lumumba (RUDN)

Email: victoria.kurnosova.1991@gmail.com

Junior Researcher, Laboratory of Regenerative Medicine

Russian Federation, Moscow; Moscow

Oksana V. Yakushevskaya

Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: aluckyone777@gmail.com
ORCID iD: 0000-0002-7430-1207

PhD, obstetrician-gynecologist, oncologist, Researcher at the Department of Gynecological Endocrinology

Russian Federation, Moscow

Marina E. Iskusnykh

Peoples' Friendship University of Russia named after Patrice Lumumba (RUDN)

Email: iskusnyh.m@yandex.ru

Laboratory Assistant, Research Institute of Molecular and Cellular Medicine

Russian Federation, Moscow

Andrey V. Elchaninov

Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia; Federal State Budgetary Scientific Institution «Petrovsky National Research Centre of Surgery»

Email: elchandrey@yandex.ru

Dr. Med. Sci., Head of the Laboratory of Regenerative Medicine, Avtsyn Research Institute of Human Morphology

Russian Federation, Moscow; Moscow

Timur Kh. Fatkhudinov

Peoples' Friendship University of Russia named after Patrice Lumumba (RUDN); Federal State Budgetary Scientific Institution «Petrovsky National Research Centre of Surgery»

Email: tfat@yandex.ru

Dr. Med. Sci., Deputy Director, Avtsyn Research Institute of Human Morphology; Head of the Department of Histology, Cytology and Embryology, Director of the Research Institute of Molecular and Cellular Medicine

Russian Federation, Moscow; Moscow

Polina A. Vishnyakova

Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia; Peoples' Friendship University of Russia named after Patrice Lumumba (RUDN)

Email: p_vishnyakova@oparina4.ru
ORCID iD: 0000-0001-8650-8240

PhD, Senior Researcher, Laboratory of Regenerative Medicine

Russian Federation, Moscow; Moscow

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2. Fig.1. The number of T-helpers (CD3+CD4+) before and after 3 months of taking MHT. Data are presented as M(SD), where M is the mean and SD is the standard deviation of the mean. *p<0.05

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3. Fig.2. A statistically significant increase in CX3CR1+ cells among classical monocytes and a statistically significant increase in CD14+CD16++CD206+ cells among nonclassical monocytes after MHT use. Data are presented as Me (Q1; Q3), where Me is the median, Q1 and Q3 are the lower and upper quartiles. *p<0.05

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4. Fig.3. Stepwise gating of the total population of monocytes (A), CD14++CD16-CX3CR1+ (B) and CD14+CD16++CD206+ (C) populations. At the first stage, on the graph, direct versus side scatter in size and granularity, a population corresponding to monocytes is isolated. Next, for them on the graph of the expression of CD16 and CD14 determine the population of classical (CD14++CD16-) and non-classical (CD14+CD16++) monocytes (A). In the last step, populations carrying markers of interest, such as CX3CR1 (B) and CD206 (C), are isolated.

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