Новые перспективы применения мелатонина при менопаузальном метаболическом синдроме

Введение. Метаболический синдром представляет собой комплекс нарушений, включающих абдоминальное ожирение, нарушение толерантности к глюкозе, дислипидемию и артериальную гипертензию. Антиоксидантные и противовоспалительные свойства гормона эпифиза мелатонина имеют большое значение для сохранения гомеостаза организма. Потенциально мелатонин может быть безопасным и эффективным средством в комплексном лечении женщин с менопаузальным метаболическим синдромом.

Цель работы – определить перспективы применения гормона эпифиза мелатонина в комплексном лечении менопаузального метаболического синдрома на основании анализа научных публикаций.

Материал и методы. В обзор включены данные исследований о влиянии мелатонина (МТ) на компоненты метаболического синдрома у женщин в перии постменопаузе. Поиск источников проведен за период 2016–2023 гг. в международных базах данных Medline, Scopus, Web of Science и российской научной электронной библиотеке eLibrary по поисковым словам и словосочетаниям: melatonin, menopause, perimenopause, metabolic syndrome, obesity, insulin resistance, dyslipidemia, arterial hypertension, мелатонин, менопауза, перименопауза, метаболический синдром, ожирение, инсулинорезистентность, дислипидемия, артериальная гипертензия.

Результаты и обсуждение. Проведенный анализ литературных данных показал ряд преимуществ влияния препаратов экзогенного МТ на отдельные компоненты метаболического синдрома, но некоторые результаты были противоречивыми. Обнаружены научные доказательства влияния МТ на антропометрические показатели, маркеры гомеостаза глюкозы, гемодинамические показатели и признаки воспалительного ответа организма, а также разнонаправленного влияния на липидный профиль.

Заключение. Учитывая многофункциональность и безопасность препаратов экзогенного МТ, следует рассмотреть возможность его применения в комплексной терапии менопаузального метаболического синдрома.

1. Monteleone P, Mascagni G, Giannini A et al. Symptoms of menopause – global prevalence, physiology and implications. Nat Rev Endocrinol. 2018;14(4):19–215. https://doi.org/10.1038/nrendo.2017.180.

2. Юренева С.В., Ермакова Е.И. Менопауза и климактерическое состояние у женщины. Акушерство и гинекология. 2018;7:32–38. https://doi.org/10.18565/aig.2018.7.32-38.

3. Saul SR, Kase N. Aging, the menopausal transition, and hormone replenishment therapy: retrieval of confidence and compliance. Ann N Y Acad Sci. 2019;1440(1):5–22. https://doi.org/10.1111/nyas.13952.

4. Wang Y, Mishra A, Brinton RD. Transitions in metabolic and immune systems from pre-menopause to post-menopause: implications for age-associated neurodegenerative diseases. F1000Res. 2020;9:F1000 Faculty Rev-68. https://doi.org/10.12688/f1000research.21599.1.

5. Lurati AR. Effects of menopause on appetite and the gastrointestinal system. Nurs Womens Health. 2018;22(6):499–505. https://doi.org/10.1016/j.nwh.2018.09.004.

6. Greendale GA, Witt-Enderby P, Karlamangla AS et al. Melatonin patterns and levels during the human menstrual cycle and after menopause. J Endocr Soc. 2020;4(11):bvaa115. https://doi.org/10.1210/jendso/bvaa115.

7. Toffol E, Kalleinen N, Haukka J et al. Melatonin in perimenopausal and postmenopausal women: associations with mood, sleep, climacteric symptoms, and quality of life. Menopause. 2014;21(5):493–500. https://doi.org/10.1097/GME.0b013e3182a6c8f3.

8. Usoltseva EN, Soloviev AG, Mamontova AG. Perimenopausal melatonin deficiency syndrome in a system of personalized management for the quality of life of women with climacteric syndrome. Adv Gerontol. 2020;10:50– 56. https://doi.org/10.1134/S2079057020010154.

9. Mamontova A, Usoltseva E, Soloviev A. Syndrome of perimenopausal melatonin deficiency is a new marker of women reproductive system aging. BIO Web Conf. 2020;22:01021. https://doi.org/10.1051/bioconf/20202201021.

10. Kravitz HM, Kazlauskaite R, Joffe H. Sleep, health, and metabolism in midlife women and menopause: food for thought. Obstet Gynecol Clin North Am. 2018;45(4):679–694. https://doi.org/10.1016/j.ogc.2018.07.008.

11. Chitimus DM, Popescu MR, Voiculescu SE et al. Melatonin's impact on antioxidative and anti-inflammatory reprogramming in homeostasis and disease. Biomolecules. 2020;10(9):1211. https://doi.org/10.3390/biom10091211.

12. Borjigin J, Zhang LS, Calinescu AA. Circadian regulation of pineal gland rhythmicity. Mol Cell Endocrinol. 2012;349(1):13–19. https://doi.org/10.1016/j.mce.2011.07.009.

13. Potter GD, Skene DJ, Arendt J et al. Circadian rhythm and sleep disruption: causes, metabolic consequences, and countermeasures. Endocr Rev. 2016;37(6):584–608. https://doi.org/10.1210/er.2016-1083.

14. Reiter RJ, Tan DX, Korkmaz A, Ma S. Obesity and metabolic syndrome: association with chronodisruption, sleep deprivation, and melatonin suppression. Ann Med. 2012;44(6):564–577. https://doi.org/10.3109/07853890.2011.586365.

15. Cipolla-Neto J, Amaral FG, Afeche SC et al. Melatonin, energy metabolism, and obesity: a review. J Pineal Res. 2014;56(4):371–381. https://doi.org/10.1111/jpi.12137.

16. Amstrup AK, Sikjaer T, Mosekilde L, Rejnmark L. The effect of melatonin treatment on postural stability, muscle strength, and quality of life and sleep in postmenopausal women: a randomized controlled trial. Nutr J. 2015;14:102. https://doi.org/10.1186/s12937-015-0093-1.

17. Chojnacki C, Kaczka A, Gasiorowska A et al. The effect of long-term melatonin supplementation on psychosomatic disorders in postmenopausal women. J Physiol Pharmacol.2018;69(2). https://doi.org/10.26402/jpp.2018.2.15.

18. ParandavarN, Abdali K, Keshtgar S et al. The effect of melatonin on climacteric symptoms in menopausal women; a double-blind, randomized controlled, clinical trial. Iran J Public Health. 2014;43(10):1405–1416.

19. Janssen I, Powell LH, Crawford S et al. Menopause and the metabolic syndrome: the study of women's health across the nation. Arch Intern Med. 2008;168(14):1568–1575. https://doi.org/10.1001/archinte.168.14.1568

20. Jeong HG, Park H. Metabolic disorders in menopause. Metabolites. 2022;12(10):954. https://doi.org/10.3390/metabo12100954.

21. Hallajzadeh J, Khoramdad M, Izadi N et al. Metabolic syndrome and its components in premenopausal and postmenopausal women: a comprehensive systematic review and meta-analysis on observational studies. Menopause. 2018;25(10):1155–1164. https://doi.org/10.1097/GME.0000000000001136.

22. Pu D, Tan R, Yu Q, Wu J. Metabolic syndrome in menopause and associated factors: a meta-analysis. Climacteric. 2017;20(6):583–591. https://doi.org/10.1080/13697137.2017.1386649.

23. Treister-Goltzman Y, Peleg R. Melatonin and the health of menopausal women: A systematic review. J Pineal Res. 2021;71(2):e12743. https://doi.org/10.1111/jpi.12743.

24. Kravitz HM, Kazlauskaite R, Joffe H. Sleep, health, and metabolism in midlife women and menopause: food for thought. Obstet Gynecol Clin North Am. 2018;45(4):679–694. https://doi.org/10.1016/j.ogc.2018.07.008.

25. Farahmand M, Bahri Khomamid M, Rahmati M et al. Aging and changes in adiposity indices: the impact of menopause. J Endocrinol Invest. 2022;45(1):69–77. https://doi.org/10.1007/s40618-021-01616-2.

26. Ambikairajah A, Walsh E, Tabatabaei-Jafari H, Cherbuin N. Fat mass changes during menopause: a metaanalysis. Am J Obstet Gynecol. 2019;221(5):393–409.e50. https://doi.org/10.1016/j.ajog.2019.04.023.

27. Mostafavi SA, Akhondzadeh S, Mohammadi MR et al. Role of melatonin in body weight: a systematic review and meta-analysis. Curr Pharm Des. 2017;23(23):3445–3452. https://doi.org/10.2174/1381612822666161129145618.

28. Amstrup AK, Sikjaer T, Pedersen SB et al. Reduced fat mass and increased lean mass in response to 1 year of melatonin treatment in postmenopausal women: A randomized placebo-controlled trial. Clin Endocrinol (Oxf). 2016;84(3):342–347. https://doi.org/10.1111/cen.12942.

29. Bahrami M, Cheraghpour M, Jafarirad S et al. The role of melatonin supplement in metabolic syndrome: A randomized double blind clinical trial. Nutrition & Food Science. 2019;49(5):965–977. https://doi.org/10.1108/NFS-01-2019-0018.

30. Wehrens SMT, Christou S, Isherwood C et al. Meal timing regulates the human circadian system. Curr Biol. 2017;27(12):1768–1775.e3. https://doi.org/10.1016/j.cub.2017.04.059.

31. Hunter CM, Figueiro MG. Measuring light at night and melatonin levels in shift workers: a review of the literature. Biol Res Nurs. 2017;19(4):365–374. https://doi.org/10.1177/1099800417714069.

32. Sooriyaarachchi P, Jayawardena R, Pavey T, King NA. Shift work and the risk for metabolic syndrome among healthcare workers: A systematic review and meta-analysis. Obes Rev. 2022;23(10):e13489. https://doi.org/10.1111/obr.13489.

33. Marqueze EC, Nogueira LFR, Vetter C et al. Exogenous melatonin decreases circadian misalignment and body weight among early types. J Pineal Res. 2021;71(2):e12750. https://doi.org/10.1111/jpi.12750.

34. Cardinali DP, Hardeland R. Inflammaging, metabolic syndrome and melatonin: a call for treatment studies. Neuroendocrinology. 2017;104(4):382–397. https://doi.org/10.1159/000446543.

35. Welty FK, Alfaddagh A, Elajami TK. Targeting inflammation in metabolic syndrome. Transl Res. 2016;167(1):257– 280. https://doi.org/10.1016/j.trsl.2015.06.017.

36. Akbari M, Ostadmohammadi V, Tabrizi R et al. The effects of melatonin supplementation on inflammatory markers among patients with metabolic syndrome or related disorders: a systematic review and metaanalysis of randomized controlled trials. Inflammopharmacology. 2018;26(4):899–907. https://doi.org/10.1007/s10787-018-0508-7.

37. Lauritzen ES, Kampmann U, Smedegaard SB, Støy J. Effects of daily administration of melatonin before bedtime on fasting insulin, glucose and insulin sensitivity in healthy adults and patients with metabolic diseases. A systematic review and meta-analysis. Clin Endocrinol (Oxf). 2021;95(5):691–701. https://doi.org/10.1111/cen.14576.

38. Li Y, Xu Z. Effects of melatonin supplementation on insulin levels and insulin resistance: a systematic review and meta-analysis of randomized controlled trials. Horm Metab Res. 2021;53(9):616–624. https://doi.org/10.1055/a-1544-8181.

39. Delpino FM, Figueiredo LM, Nunes BP. Effects of melatonin supplementation on diabetes: A systematic review and meta-analysis of randomized clinical trials. Clin Nutr. 2021;40(7):4595–4605. https://doi.org/10.1016/j.clnu.2021.06.007.

40. Abood SJ, Abdulsahib WK, Hussain SA, Ismail SH. Melatonin potentiates the therapeutic effects of metformin in women with metabolic syndrome. Scientia Pharmaceutica. 2020;88(2):28. https://doi.org/10.3390/scipharm88020028.

41. Ghorbaninejad P, Sheikhhossein F, Djafari F et al. Effects of melatonin supplementation on oxidative stress: a systematic review and meta-analysis of randomized controlled trials. Horm Mol Biol Clin Investig. 2020;41(4). https://doi.org/10.1515/hmbci-2020-0030.

42. Morvaridzadeh M, Sadeghi E, Agah S et al. Effect of melatonin supplementation on oxidative stress parameters: A systematic review and meta-analysis. Pharmacol Res. 2020;161:105210. https://doi.org/10.1016/j.phrs.2020.105210.

43. Koziróg M, Poliwczak AR, Duchnowicz P et al. Melatonin treatment improves blood pressure, lipid profile, and parameters of oxidative stress in patients with metabolic syndrome. J Pineal Res. 2011;50(3):261–266. https://doi.org/10.1111/j.1600-079X.2010.0083.

44. Семенова Н.В., Мадаева И.М., Колесникова Л.И. Роль мелатонина как компонента антиоксидантной защиты при инсомнии в перименопаузе. Журнал неврологии и психиатрии им. С.С. Корсакова. 2019;119(7):7–13. https://doi.org/10.17116/jnevro20191190717.

45. Imenshahidi M, Karimi G, Hosseinzadeh H. Effects of melatonin on cardiovascular risk factors and metabolic syndrome: a comprehensive review. Naunyn Schmiedebergs Arch Pharmacol. 2020;393(4):521-536. https://doi.org/10.1007/s00210-020-01822-4.

46. Corbalán-Tutau D, Madrid JA, Nicolás F, Garaulet M. Daily profile in two circadian markers “melatonin and cortisol” and associations with metabolic syndrome components. Physiol Behav. 2014;123:231–235. https://doi.org/10.1016/j.physbeh.2012.06.005.

47. Deng WG, Tang ST, Tseng HP, Wu KK. Melatonin suppresses macrophage cyclooxygenase-2 and inducible nitric oxide synthase expression by inhibiting p52 acetylation and binding. Blood. 2006;108(2):518–524. https://doi.org/10.1182/blood-2005-09-3691.

48. Fan W, He Y, Guan X et al. Involvement of the nitric oxide in melatonin-mediated protection against injury. Life Sci. 2018;200:142–147. https://doi.org/10.1016/j.lfs.2018.03.035.

49. Klimentova J, Cebova M, Barta A et al. Effect of melatonin on blood pressure and nitric oxide generation in rats with metabolic syndrome. Physiol Res. 2016;65(Suppl 3):S373–S380. https://doi.org/10.33549/physiolres.933436.

50. Akbari M, Ostadmohammadi V, Mirhosseini N et al. The effects of melatonin supplementation on blood pressure in patients with metabolic disorders: a systematic review and meta-analysis of randomized controlled trials. J Hum Hypertens. 2019;33(3):202–209. https://doi.org/10.1038/s41371-019-0166-2.

51. Hadi A, Ghaedi E, Moradi S et al. Effects of melatonin supplementation on blood pressure: a systematic review and meta-analysis of randomized controlled trials. Horm Metab Res. 2019;51(3):157–164. https://doi.org/10.1055/a-0841-6638.

52. Grossman E, Laudon M, Zisapel N. Effect of melatonin on nocturnal blood pressure: meta-analysis of randomized controlled trials. Vasc Health Risk Manag. 2011;7:577–584. https://doi.org/10.2147/VHRM.S24603.

53. Miola A, Fornaro M, Sambataro F, Solmi M. Melatonin and melatonin-agonists for metabolic syndrome components in patients treated with antipsychotics: A systematic review and meta-analysis. Hum Psychopharmacol. 2022;37(2):e2821. https://doi.org/10.1002/hup.2821.

54. Mohammadi-Sartang M, Ghorbani M, Mazloom Z. Effects of melatonin supplementation on blood lipid concentrations: A systematic review and meta-analysis of randomized controlled trials. Clin Nutr. 2018;37(6 Pt A):1943–1954. https://doi.org/10.1016/j.clnu.2017.11.003.

55. Loloei S, Sepidarkish M, Heydarian A et al. The effect of melatonin supplementation on lipid profile and anthropometric indices: A systematic review and meta-analysis of clinical trials. Diabetes Metab Syndr. 2019;13(3):1901–1910. https://doi.org/10.1016/j.dsx.2019.04.043.

56. Parandavar N, Hojat M, Abdali K et al. The effect of melatonin on the lipid levels in menopausal women: A double-blind, controlled, clinical trial. J Educ Health Promot. 2018;7:144. https://doi.org/10.4103/jehp.jehp_187_17.

57. Bazyar H, Zare Javid A, Bavi Behbahani H et al. Consumption of melatonin supplement improves cardiovascular disease risk factors and anthropometric indices in type 2 diabetes mellitus patients: a double-blind, randomized, placebo-controlled trial. Trials. 2021;22(1):231. https://doi.org/10.1186/s13063-021-05174-z.

58. Rezvanfar M, Heshmati G, Chehrei A et al. Effect of bedtime melatonin consumption on diabetes control and lipid profile. Int J Diabetes Dev Countries. 2017;37:74–77. https://doi.org/10.1007/s13410-016-0497-2.

59. Bahrami M, Cheraghpour M, Jafarirad S et al. The effect of melatonin on treatment of patients with non-alcoholic fatty liver disease: a randomized double blind clinical trial. Complement Ther Med. 2020;52:102452. https://doi.org/10.1016/j.ctim.2020.102452.