Dynamics of the functional state of the liver and endothelium in patients with metabolic syndrome on the background of menopausal hormone therapy

The aim. To evaluate the dynamics of metabolic status, functional state of the liver and endothelium in patients with metabolic syndrome on the background of menopausal hormone therapy (MGT). Materials and methods. 40 menopausal women were examined, of which 25 patients with metabolic syndrome with an average age of 51.2 ± 1.2 years and 15 practically healthy women of 50.2 ± 1.9 years. anamnesis was collected, the presence of vasomotor symptoms was assessed, anthropometric data was measured with the calculation of body mass index, laboratory examination, including determination of blood levels of sex hormones, functional liver tests, metabolic parameters and markers of endothelial dysfunction- endothelin-1, vascular endothelial growth factor, the number of desquamated endotheliocytes and the activity of Willebrand factor, instrumental examination, including ultrasound examination of the liver and assessment of the vascular response to local heating on the Microtest device (Russia), as well as calculation of the Hepatic steatosis index (HSI). Results. In patients with metabolic syndrome in menopause, vasomotor symptoms, complaints of dysuria, dyspeptic phenomena were observed, an increase in blood pressure was recorded in 60%, an increase in Kurlov’s ordinates in 24%, 36% were overweight, 64% were obese 1-2 degrees. According to ultrasound, liver steatosis was verified in 76% of patients, the HSI index >36.0 was in all women with MS. Against the background of estrogen deficiency, the course of menopause in women was accompanied by insulin resistance, dyslipidemia, increased alkaline phosphatase levels in 28% of individuals and endothelial dysfunction with impaired physiological response to local heating, increased vascular tone, increased thrombogenic potential of the vascular wall and activation of angiogenesis mechanisms. Conclusion: MGT with Femoston ® 1 in continuous mode in women with metabolic syndrome reduces the severity of menopausal syndrome, insulin resistance and liver steatosis, improves anthropometric parameters and functional characteristics of the liver and endothelium, which reduces the risk of cardiovascular events in this risk group.

metabolic syndrome, fatty liver disease, endothelial dysfunction, menopause, hormone replacement therapy

1. Balanova Yu.A., Imaeva A. E., Kutsenko V. A. et al. Metabolic syndrome and its associations with socio-demographic and behavioral risk factors in the Russian population aged 25-64 years. Cardiovascular Therapy and Prevention. 2020;19(4):2600. (In Russ.) doi: 10.15829/1728-8800-2020-2600.@@ Баланова Ю. А., Имаева А. Э., Куценко В. А., Капустина А. В., Муромцева Г. А., Евстифеева С. Е., Максимов С. А., Карамнова Н. С., Яровая Е. Б., Шальнова С. А., Драпкина О. М. Метаболический синдром и его ассоциации с социально-демографическими и поведенческими факторами риска в российской популяции 25-64 лет. Кардиоваскулярная терапия и профилактика. 2020;19(4):2600. doi: 10.15829/1728-8800-2020-2600.

2. Jeenduang N., Trongsakul R., Inhongsa P., Chaidach P. The prevalence of metabolic syndrome in premenopausal and postmenopausal women in Southern Thailand. Gynecol Endocrinol. 2014 Aug;30(8):573-6. doi: 10.3109/09513590.2014.907261.

3. Turola E., Petta S., Vanni E. Ovarian senescence increases liver fibrosis in humans and zebrafish with steatosis. Dis Model Mech. 2015 Sep;8(9):1037-46. doi: 10.1242/dmm.019950.

4. Li L., Liu D. W., Yan H. Y. et al. Obesity is an independent risk factor for non-alcoholic fatty liver disease: evidence from a meta-analysis of 21 cohort studies. Obes Rev. 2016 Jun;17(6):510-9. doi: 10.1111/obr.12407.

5. Charkoudian N., Hart E. C.J., Barnes J. N., Joyner M. J. Autonomic control of body temperature and blood pressure: influences of female sex hormones. Clin Auton Res. 2017 Jun;27(3):149-155. doi: 10.1007/s10286-017-0420-z.

6. Yeung E.H., Zhang C., Albert P. S. et al. Adiposity and sex hormones across the menstrual cycle: the BioCycle Study.Int J Obes (Lond). 2013 Feb;37(2):237-43. doi: 10.1038/ijo.2012.9.

7. Kuznetsova I. V. Endothelial dysfunction as a link between menopausal syndrome and cardiovascular diseases. Effective pharmacotherapy. 2019;15(32):32-40. (In Russ.) doi: 10.33978/2307-3586-2019-15-32-32-40.@@ Кузнецова И. В. Эндотелиальная дисфункция как связующее звено климактерического синдрома и сердечно-сосудистых заболеваний. Эффективная фармакотерапия. 2019;15(32):32-40. doi: 10.33978/2307-3586-2019-15-32-32-40.

8. Sullivan S.D., Sarrel P. M., Nelson L. M. Hormone replacement therapy in young women with primary ovarian insufficiency and early menopause. Fertil Steril. 2016 Dec;106(7):1588-1599. doi: 10.1016/j.fertnstert.2016.09.046.

9. Baber R.J., Panay N., Fenton A.; IMS Writing Group. 2016 IMS Recommendations on women’s midlife health and menopause hormone therapy. Climacteric. 2016 Apr;19(2):109-50. doi: 10.3109/13697137.2015.1129166.

10. Nudy M., Chinchilli V. M., Foy A. J. A systematic review and meta-regression analysis to examine the ‘timing hypothesis’ of hormone replacement therapy on mortality, coronary heart disease, and stroke.Int J Cardiol Heart Vasc. 2019 Jan 18;22:123-131. doi: 10.1016/j.ijcha.2019.01.001.

11. Kuznetsova I. V. Endothelial dysfunction in the context of women’s health disorders from menarche to menopause. The medical alphabet. 2019:33(4);39-47. (In Russ.) doi: 10.33667/2078-5631-2019-4-33(408)-6-14.@@ Кузнецова И. В. Эндотелиальная дисфункция в контексте нарушений здоровья женщин от менархе до менопаузы. Медицинский алфавит. 2019:33(4);39-47. doi: 10.33667/2078-5631-2019-4-33(408)-6-14.

12. Vasina L.V., Petrishchev N. N., Vlasov T. D. Endothelial dysfunction and its main markers. Regional blood circulation and microcirculation. 2017;16(1):4-15. (In Russ.) doi: 10.24884/1682-6655-2017-16-1-4-15.@@ Васина Л. В., Петрищев Н. Н., Власов Т. Д. Эндотелиальная дисфункция и ее основные маркеры. Регионарное кровообращение и микроциркуляция. 2017;16(1):4-15. doi: 10.24884/1682-6655-2017-16-1-4-15.

13. Lee J. H., Kim D., Kim H. J. et al. Hepatic steatosis index: a simple screening tool reflecting nonalcoholic fatty liver disease. Dig Liver Dis. 2010 Jul;42(7):503-8. doi: 10.1016/j.dld.2009.08.002.

14. Jeenduang N., Trongsakul R., Inhongsa P., Chaidach P. The prevalence of metabolic syndrome in premenopausal and postmenopausal women in Southern Thailand. Gynecol Endocrinol. 2014 Aug;30(8):573-6. doi: 10.3109/09513590.2014.907261.

15. Tolstov S. N., Salov I. A., Rebrov A. P. Assessment of cardiometabolic risk factors in women during menopausal transition and the possibility of a drospirenone-containing contraceptive in correcting the identified disorders. Obstetrics and gynecology. 2023;2:98-107. (In Russ.) doi: 10.18565/aig.2022.257.@@ Толстов С. Н., Салов И. А., Ребров А. П. Оценка кардиометаболических факторов риска у женщин периода менопаузального перехода и возможности дроспиренонсодержащего контрацептива в коррекции выявленных нарушений. Акушерство и гинекология. 2023;2:98-107. doi: 10.18565/aig.2022.257.

16. Bulatova I. A., Shevlyakova T. P., Sobol A. A., Gulyaeva I. L. Clinical and laboratory features of the course of non-alcoholic liver steatosis in women in the early postmenopausal period living in an industrial metropolis. Experimental and clinical gastroenterology. 2023;214(6):53-60. (In Russ.) doi: 10.31146/1682-8658-ecg-214-6-53-60.@@ Булатова И. А., Шевлюкова Т. П., Соболь А. А., Гуляева И. Л. Клинико- лабораторные особенности течения неалкогольного стеатоза печени у женщин в раннем периоде постменопаузы, проживающих на территории промышленного мегаполиса. Экспериментальная и клиническая гастроэнтерология. 2023;214(6):53-60. doi: 10.31146/1682-8658-ecg-214-6-53-60.

17. Klair J. S., Yang J. D., Abdelmalek M. F. et al.; Nonalcoholic Steatohepatitis Clinical Research Network. A longer duration of estrogen deficiency increases fibrosis risk among postmenopausal women with nonalcoholic fatty liver disease. Hepatology. 2016 Jul;64(1):85-91. doi: 10.1002/hep.28514.

18. Markova T. N., Mishchenko N. K., Petina D. V. Adipocytokines: a modern view on the definition, classification and role in the body. Problems of Endocrinology. 2022;68(1):73-80. (In Russ.) doi: 10.14341/probl12805.@@ Маркова Т. Н., Мищенко Н. К., Петина Д. В. Адипоцитокины: современный взгляд на дефиницию, классификацию и роль в организме. Проблемы Эндокринологии. 2022;68(1):73-80. doi: 10.14341/probl12805.

19. Engin A. Endothelial Dysfunction in Obesity. Adv Exp Med Biol. 2017;960:345-379. doi: 10.1007/978-3-319-48382-5_15.

20. Huang A. J., Sawaya G. F., Vittinghoff E. et al. Hot flushes, coronary heart disease, and hormone therapy in postmenopausal women. Menopause. 2018 Nov;25(11):1286-1290. doi: 10.1097/GME.0000000000001230.

21. Duckles S. P., Miller V. M. Hormonal modulation of endothelial NO production. Pflugers Arch. 2010 May;459(6):841-51. doi: 10.1007/s00424-010-0797-1.

22. Karim R., Stanczyk F. Z., Hodis H. N. et al. Associations between markers of inflammation and physiological and pharmacological levels of circulating sex hormones in postmenopausal women. Menopause. 2010 Jul;17(4):785-90. PMID: 20632462

23. Smirnova E. N., Lоran E. A., Shulkina S. G., Podtaev S. Yu. The relationship of endothelial dysfunction and metabolic manifestations of obesity. Regional blood circulation and microcirculation. 2020;19(1):53-59. (In Russ.) doi: 10.24884/1682-6655-2020-19-1-53-59.@@ Смирнова Е. Н., Лоран Е. А., Шулькина С. Г., Подтаев С. Ю. Взаимосвязь эндотелиальной дисфункции и метаболических проявлений ожирения. Регионарное кровообращение и микроциркуляция. 2020;19(1):53-59. doi: 10.24884/1682-6655-2020-19-1-53-59.