Менопаузальная гормональная терапия в профилактике нарушений липидного обмена

Подзолкова Н.М., Подзолков В.И., Тарзиманова А.И. Менопаузальная гормональная терапия в профилактике нарушений липидного обмена. Consilium Medicum. 2019; 21 (6): 81–85. DOI: 10.26442/20751753.2019.6.190557

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Podzolkova N.M., Podzolkov V.I., Tarzimanova A.I. Menopausal hormone therapy in the prevention of lipid metabolism disorders. Consilium Medicum. 2019; 21 (6): 81–85. DOI: 10.26442/20751753.2019.6.190557

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Аннотация

Сердечно-сосудистые заболевания являются основной причиной смертности женщин старших возрастных групп. Прогрессирование данных заболеваний у женщин тесно связано с естественными процессами угасания репродуктивной функции. Дефицит эстрогенов, возникающий в постменопаузе, способствует развитию нарушений липидного обмена: снижению уровня антиатерогенной фракции холестерина и повышению концентрации проатерогенных фракций, особенно липопротеина (а). В настоящее время имеются доказательства, что менопаузальная гормональная терапия (МГТ) может иметь кардиопротективную эффективность при условии, что она начата в период, близкий ко времени наступления менопаузы. Проведенные рандомизированные клинические исследования доказывают высокую эффективность проводимой МГТ в профилактике появления атеросклероза у женщин в ранней постменопаузе. Большое значение имеет индивидуализация МГТ, т.е. выбор оптимального для конкретной женщины эстрогенного, прогестагенного компонентов, их дозы и пути введения. Наиболее значимый кардиопротективный эффект МГТ доказан для комбинации 17b-эстрадиола и дидрогестерона. Одним из современных препаратов комбинированной МГТ можно считать препарат Фемостон®, который позитивно влияет на показатели липидного спектра и уменьшает инсулинорезистентность.

Ключевые слова: нарушения липидного обмена, менопаузальная гормональная терапия, профилактика атеросклероза, 17b-эстрадиол и дидрогестерон.

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Cardiovascular disease is the leading cause of mortality in older women. The progression of these diseases in women is closely related to a natural processes of reproductive function decline. Estrogen deficiency which occurs in postmenopausal women contributes to lipid metabolism disorders: a decrease in antiatherogenic HDL levels and an increase in levels of proatherogenic LDL, especially lipoprotein (a). Currently, there is evidence that menopausal hormone therapy (MHT) can have cardioprotective efficacy, provided that it begins at a time close to the onset of menopause. Randomized clinical trials proved a high efficacy of MHT for the prevention of atherosclerosis in early postmenopausal women. Individualization of MHT, i.e., selection of estrogen and progestogen components, their dose and route of administration which are optimal for a particular woman, is of great importance. The most significant cardioprotective effect of MHT has been proven for the combination of 17b-estradiol and dydrogesterone. One of modern drugs for combined MHT is Femoston®, which exerts beneficial effect on lipid metabolism and reduces insulin resistance.

Key words: lipid metabolism disorders, menopausal hormone therapy, prevention of atherosclerosis, 17b-estradiol and dydrogesterone.

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21. Hodis HN, Collins P, Mock WJ et al. The timing hypothesis for coronary heart disease prevention with hormone therapy: past, present and future in perspective. Climacteric 2012; 12: 217–28. DOI: 10.3109/13697137.2012.656401
22. Hanggi W, Lippuner K, Riesen W et al. Long term influence of different postmenopausal hormone replacement regimens on serum lipids and lipoprotein(a): a randomised study. Br J Obstet Gynaecol. 1997; 104: 708–17.
23. Pickar JH. Effects of lower doses of conjugated equine estrogens and medroxyprogesterone acetate on plasma lipids and lipoproteins, coagulation factors, and carbohydrate metabolism. Fertil Steril 2001; 76 (1): 13–24. DOI: 10.1016/S0015-0282(01)01829-5
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1. Mosca L, Hammond G, Mochari-Greenberger H et al. American Heart Association Cardiovascular Disease and Stroke in Women and Special Populations Committee of the Council on Clinical Cardiology, Council on Epidemiology and Prevention, Council on Cardiovascular Nursing, Council on High Blood. Fifteen-year trends in awareness of heart disease in women: results of a 2012 American Heart Association national survey. Circulation 2013; 127 (11): 1254–63, e1–29.
2. Podzolkov V.I., Bragina A.E., Podzolkova N.M. Menopauzal'naia gormonal'naia terapiia i serdechno-sosudistaia profilaktika: zhelaemoe ili deistvitel'noe? Kardiovask. terapiia i profilaktika. 2019; 18 (3): 94–106 (in Russian).
3. Mirovye demograficheskie prognozy. Obzor 2006 goda. Reziume. Organizatsiia Ob"edinennykh Natsii. http://www.un.org/esa/population/publications/wpp2006/Russian.pdf 26.02.2015. World population projected to reach 9.6 billion by 2050 with most growth in developing regions, especially Africa, says UN. http://esa.un.org/unpd/wpp/Documentation/pdf/WPP2012_Press_Release.pdf 26.02.2015 (in Russian).
4. Menopause: diagnosis and management. NICE guideline 2015. nice.org.uk/guidance/ng23
5. Baber RJ, Panay N, Fenton A; the IMS Writing Group. 2016 IMS Recommendations on women’s midlife health and menopause hormone therapy. Climacteric 2016; 19 (2): 109–50.
6. De Smedt D, De Bacquer D, De Sutter J et al. The gender gap in risk factor control: Effects of age and education on the control of cardiovascular risk factors in male and female coronary patients. The EUROASPIRE IV study by the European Society of Cardiology. Int J Cardiol 2016; 209: 284–90.
7. Kamstrup PR, Nordestgaard BG. Elevated Lipoprotein(a) Levels, LPA Risk Genotypes, and Increased Risk of Heart Failure in the General Population. JACC Heart Fail 2016; 4: 78–87. DOI: 10.1016/j.jchf.2015.08.006
8. Liu L, Boffa MB, Koschinsky ML. Apolipoprotein(а) inhibits in vitro tube formation in endothelial cells: identification of roles for Kringle V and the plasminogen activation system. PLoS One 2013; 8 (1): e52287. DOI: 10.1371/journal.pone.0052287
9. Van der Valk FM, Bekkering S, Kroon J et al. Oxidized Phospholipids on Lipoprotein(a) Elicit Arterial Wall Inflammation and an Inflammatory Monocyte Response in Humans. Circulation 2016; 134: 611–24. DOI: 10.1161/CIRCULATIONAHA.116.020838
10. Scipione CA, Sayegh SE, Romagnuolo R et al. Mechanistic insights into Lp(a)-induced IL-8 expression: a role for oxidized phospholipid modification of apo(а). J Lipid Res 2015; 56 (12): 2273–85. DOI: 10.1194/jlr.M060210
11. Bouchareb R, Mahmut A, Nsaibia MJ et al. Autotaxin Derived From Lipoprotein(a) and Valve Interstitial Cells Promotes Inflammation and Mineralization of the Aortic Valve. Circulation 2015; 132: 677–90. DOI: 10.1161/CIRCULATIONAHA.115.016757
12. Capoulade R, Chan KL, Yeang C et al. Oxidized Phospholipids, Lipoprotein(a), and Progression of Calcific Aortic Valve Stenosis. J Am Coll Cardiol 2015; 66: 1236–46. DOI: 10.1016/j.jacc.2015.07.020
13. Forbang NI, Criqui MH, Allison MA et al. Sex and ethnic differences in the associations between lipoprotein(a) and peripheral arterial disease in the Multi-Ethnic Study of Atherosclerosis. J Vasc Surg 2016; 63 (2): 453–8. DOI: 10.1016/j.jvs.2015.08.114
14. Sanchez Muñoz-Torrero JF, Rico-Martín S, Álvarez LR et al. Lipoprotein(a) levels and outcomes in stable outpatients with symptomatic artery disease. Atherosclerosis 2018; 276: 10–4. DOI: 10.1016/j.atherosclerosis.2018.07.001
15. Dentali F, Gessi V, Marcucci R et al. Lipoprotein(a) as a Risk Factor for Venous Thromboembolism: A Systematic Review and Meta-analysis of the Literature. Semin Thromb Hemost 2017; 43 (6): 614–0. DOI: 10.1055/s-0036-1598002
16. Giperlipoproteidemiia(a) kak opasnoe geneticheski obuslovlennoe narushenie lipidnogo obmena i faktor riska aterotromboza i serdechno-sosudistykh zabolevaniĭ. Ros. kardiologicheskiĭ zhurn. 2019; 24 (5): 101–8. http://dx.doi.org/10.15829/1560-4071-2019-5-101-108 (in Russian).
17. Shively CA, Register TC, Appt SE, Clarkson TB. Effects of long-term sertraline treatment and depression on coronary artery atherosclerosis in premenopausal female primates. Psychosom Med 2015; 77 (3): 267–78. DOI: 10.1097/PSY.0000000000000163
18. Hodis HN, Mack WJ, Henderson VW. Effects of early versus late postmenopausal treatment with estradiol. N Engl J Med 2016; 374: 1221–31. DOI: 10.1056/NEJMoa1505241
19. Rossouw JE, Anderson GL, Prentice RL et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative randomized controlled trial. JAMA 2002; 288: 321–33.
20. Hulley S, Grady D, Bush T et al. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/progestin Replacement Study (HERS) Research Group. JAMA 1998; 280: 605–13.
21. Hodis HN, Collins P, Mock WJ et al. The timing hypothesis for coronary heart disease prevention with hormone therapy: past, present and future in perspective. Climacteric 2012; 12: 217–28. DOI: 10.3109/13697137.2012.656401
22. Hanggi W, Lippuner K, Riesen W et al. Long term influence of different postmenopausal hormone replacement regimens on serum lipids and lipoprotein(a): a randomised study. Br J Obstet Gynaecol. 1997; 104: 708–17.
23. Pickar JH. Effects of lower doses of conjugated equine estrogens and medroxyprogesterone acetate on plasma lipids and lipoproteins, coagulation factors, and carbohydrate metabolism. Fertil Steril 2001; 76 (1): 13–24. DOI: 10.1016/S0015-0282(01)01829-5
24. Hodis HN, Mack WJ, Henderson VW. Effects of early versus late postmenopausal treatment with estradiol. N Engl J Med. 2016; 374: 1221–31. DOI: 10.1056/NEJMoa1505241
25. Santen RJ. Use of cardiovascular age for assessing risks and benefits of menopausal hormone therapy. Menopause 2017; 24: 589–95. DOI: 10.1097/GME.0000000000000847
26. Dinger J, Bardenheuer K, Heinemann К. Drospirenone plus estradiol and the risk of setious cardiovascular events in postmenopausal women. Climacteric 2016; 19 (4): 349–56. DOI: 10.1080/13697137.2016.1183624
27. Willy Hanggi et al. Long term influence of different postmenopausal hormone replacement regimens on serum lipids and lipoprotein(a): a randomised study. Br J Obs Gynaecol 1997; 104: 708–17.
28. Godsland IF, Manassiev NA, Felton CV et al. Effects of low and high dose oestradiol and dydrogesterone therapy on insulin and lipoprotein metabolism in healthy postmenopausal women. Clin Endocrinol 2004; 60 (5): 541–9.
29. Canonico M et al. Postmenopausal hormone therapy and risk of idiopathic venous thromboembolism: results from the E3N cohort study. Arterioscler Thromb Vasc Biol 2010; 30 (2): 340–5.
30. The NAMS 2017 Hormone Therapy Position Statement Advisory Panel. The 2017 hormone therapy position statement of The North American Menopause Society. Menopause 2017; 24 (7): 728–53. DOI: 10.1097/GME.0000000000000921

Авторы

Н.М. Подзолкова*1, В.И. Подзолков2, А.И. Тарзиманова2

1 ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава России, Москва, Россия;
2 ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России (Сеченовский Университет), Москва, Россия
*podzolkovа@gmail.com

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Nataliya M. Podzolkova*1, Valerii I. Podzolkov2, Aida I. Tarzimanova2

1 Russian Medical Academy of Continuous Professional Education, Moscow, Russia;
2 Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
*podzolkovа@gmail.com

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