Вазомоторные симптомы в менопаузе: центральные триггеры, эффекторы и новые возможности патогенетической терапии

Авторы:
  • С. В. Юренева
    ФГБУ «Национальный медицинский исследовательский центр акушерства, гинекологии и перинатологии им. акад. В.И. Кулакова» Минздрава России, Москва, Россия
  • В. Г. Аверкова
    ГБУЗ Москвы «Городская клиническая больница им. С.И. Спасокукоцкого» Департамента здравоохранения Москвы, Москва, Россия
Журнал: Российский вестник акушера-гинеколога. 2018;18(5): 43-48
Просмотрено: 1101 Скачано: 95
Настоящая статья представляет собой обзор современной литературы, в котором отражены данные о новых взглядах на механизмы регуляции гипоталамо-гипофизарно-яичниковой оси и о генезе «приливов жара», в том числе центральном с участием вазомоторных триггеров и эффекторном с участием сосудистых факторов, а также о новых возможностях патогенетической терапии при них, которые могут стать альтернативой менопаузальной гормональной терапии. Описаны вероятные ассоциации приливов с полиморфизмом генов ферментов метаболизма эстрогенов, а также с заболеваниями, начало и развитие которых наблюдается в период менопаузального перехода и в постменопаузе. «Приливы жара» могут иметь единые звенья патогенеза и связь с различными соматическими заболеваниями и неблагоприятными событиями в постменопаузе. Поэтому поиск средств их контроля и терапии является важным, а исследования, посвященные этому, перспективными. С этой целью необходимо продолжить изучение патогенетических механизмов возникновения вазомоторных симптомов в менопаузе.
Ключевые слова:
  • вазомоторные симптомы
  • патогенез приливов
  • KNDy-нейроны
  • кисспептин
  • нейрокинин В
  • динорфин
  • вазомоторные триггеры
  • эффекторы

КАК ЦИТИРОВАТЬ:

Юренева С.В., Аверкова В.Г. Вазомоторные симптомы в менопаузе: центральные триггеры, эффекторы и новые возможности патогенетической терапии. Российский вестник акушера-гинеколога. 2018;18(5):43-48. https://doi.org/10.17116/rosakush20181805143

Список литературы:

  1. Miller VM, Kling JM, Files JA, Joyner MJ, Kapoor E, Moyer AM, Rocca WA, Faubion SS. What’s in a name: are menopausal «hot flashes» a symptom of menopause or a manifestation of neurovascular dysregulation? Menopause. 2018;25:6:700-703. https://doi.org/10.1097/GME.0000000000001065
  2. Freedman RR. Menopausal hot flashes: mechanisms, endocrinology, treatment. J Steroid Biochem Mol Biol. 2014;142:115-120. https://doi.org/10.1016/j.jsbmb.2013.08.010
  3. Wuttke W, Jarry H, Haunschild J, Stecher G, Schuh M, Seidlova-Wuttke D. The non-estrogenic alternative for the treatment of climacteric complaints: Black cohosh (Cimicifuga or Actaea racemosa). Journal of Steroid Biochemistry & Molecular Biology. 2014;139:302-310. https://doi.org/10.1016/j.jsbmb.2013.02.007
  4. Sturdee DW, Hunter MS, Maki PM, Gupta P, Sassarini J, Stevenson JC, Lumsden MA. The menopausal hot flush: a review. Climacteric. 2017;20:4:296-305. https://doi.org/10.1080/13697137.2017.1306507
  5. Livadas S, Chrousos GP. Control of the onset of puberty. Curr Opin Pediatr. 2016;28:4:551-558. https://doi.org/10.1097/MOP.0000000000000386
  6. Lehman MN, Coolen LM, Goodman RL. Minireview: kisspeptin/neurokinin B/dynorphin (KNDy) cells of the arcuate nucleus: a central node in the control of gonadotropin-releasing hormone secretion. Endocrinology. 2010;151:3479-3489. https://doi.org/10.1210/en.2010-0022
  7. Maione L, Christin-Maître S, Chanson P, Young J. Contrôle de l’axe gonadotrope: nouveaux aspects physiologiques et thérapeutiques: Control of the gonadotrope axis: new physiologic and therapeutic aspects. Ann Endocrinol (Paris). 2017;78:Suppl1:S31-S40. https://doi.org/10.1016/S0003-4266(17)30923-X
  8. Mittelman-Smith M, Williams H, Krajewski-Hall SJ, McMullen NT, Rance NE. Role for kisspeptin/neurokinin B/dynorphin (KNDy) neurons in cutaneous vasodilatation and the estrogen modulation of body temperature. Proc Natl Acad Sci USA. 2012; 109:48:19846-19851. https://doi.org/10.1073/pnas.1211517109
  9. Rometo AM, Krajewski SJ, Voytko ML, Rance NE. Hypertrophy and increased kisspeptin gene expression in the hypothalamic infundibular nucleus of postmenopausal women and ovariectomized monkeys. J Clin Endocrinol Metab. 2007;92:7:2744-2750. https://doi.org/10.1210/jc.2007-0553
  10. Jayasena CN, Comninos AN, Stefanopoulou E, Buckley A, Narayanaswamy S, Izzi-Engbeaya C, Abbara A, Ratnasabapathy R, Mogford J, Ng N, Sarang Z, Ghatei MA, Bloom SR, Hunter MS, Dhillo WS. Neurokinin B administration induces hot flushes in women. Sci Rep. 2015;5:8466. https://doi.org/10.1038/srep08466
  11. Prague JK, Roberts RE, Comninos AN, Clarke S, Jayasena CN, Nash Z, Doyle C, Papadopoulou DA, Bloom SR, Mohideen P, Panay N, Hunter MS, Veldhuis JD, Webber LC, Les Huson, Dhillo WS. Neurokinin 3 receptor antagonism as a novel treatment for menopausal hot flushes: a phase 2, randomised, double-blind, placebo-controlled trial. Lancet. 2017;389:10081:1809-1820. https://doi.org/10.1016/S0140-6736(17)30823-1
  12. Cully M. Deal watch: Neurokinin 3 receptor antagonist revival heats up with Astellas acquisition. Nat Rev Drug Discov. 2017;16:6:377. https://doi.org/10.1038/nrd.2017.102
  13. Prague JK, Roberts RE, Comninos AN, Clarke S, Jayasena CN, Mohideen P, Lin VH, Stern TP, Panay N, Hunter MS, Webber LC, Dhillo WS. Neurokinin 3 receptor antagonism rapidly improves vasomotor symptoms with sustained duration of action. Menopause. 2018;25:Mar 12. https://doi.org/10.1097/GME.0000000000001090
  14. Miragem AA, Homem de Bittencourt PI Jr. Nitric oxide-heat shock protein axis in menopausal hot flushes: neglected metabolic issues of chronic inflammatory diseases associated with deranged heat shock response. Hum Reprod Update. 2017;23:5:600-628. https://doi.org/10.1093/humupd/dmx020
  15. Ikegami K, Minabe S, Ieda N, Goto T, Sugimoto A, Nakamura S, Inoue N, Oishi S, Maturana AD, Sanbo M, Hirabayashi M, Maeda KI, Tsukamura H, Uenoyama Y. Evidence of involvement of neurone-glia/neurone-neurone communications via gap junctions in synchronised activity of KNDy neurons. Neuroendocrinol. 2017;29:6. https://doi.org/10.1111/jne.12480
  16. Pinet-Charvet C, Geller S, Desroziers E, Ottogalli M, Lomet D, Georgelin C, Tillet Y, Franceschini I, Vaudin P, Duittoz A. GnRH episodic secretion is altered by pharmacological blockade of gap junctions: Possible involvement of glial cells. Endocrinology. 2016; 157:1:304-322. https://doi.org/10.1210/en.2015-1437
  17. Topaloglu AK, Reimann F, Guclu M, Yalin AS, Kotan LD, Porter KM, Serin A, Mungan NO, Cook JR, Imamoglu S, Akalin NS, Yuksel B, O’Rahilly S, Semple RK. TAC3 and TACR3 mutations in familial hypogonadotropic hypogonadism reveal a key role for Neurokinin B in the central control of reproduction. Nat Genet. 2009;41:3:354-358. https://doi.org/10.1038/ng.306
  18. Karolina Skorupskaite, Jyothis T George, Richard A Anderson. The kisspeptin-GnRH pathway in human reproductive health and disease. Human Reproduction Update. 2014;20:4:485-500. https://doi.org/10.1093/humupd/dmu009
  19. Rometo AM, Rance NE. Changes in prodynorphin gene expression and neuronal morphology in the hypothalamus of postmenopausal women. J Neuroendocrinol. 2008;20:12:1376-1381. https://doi.org/10.1111/j.1365-2826.2008.01796.x
  20. Abreu AP, Dauber A, Macedo DB, Noel SD, Brito VN, Gill JC, Cukier P, Thompson IR, Navarro VM, Gagliardi PC, Rodrigues T, Kochi C, Longui CA, Beckers D, de Zegher F, Montenegro LR, Mendonca BB, Carroll RS, Hirschhorn JN, Latronico AC, Kaiser UB. Central precocious puberty caused by mutations in the imprinted gene MKRN3. N Engl J Med. 2013;368:26:2467-2475. https://doi.org/10.1056/NEJMoa1302160
  21. Hrabovszky E, Coofi P, Vida B, Horvath M, Keller E, Carary A, Bloom SR, Ghatei MA, Dhillo WS, Liposits Z, Kallo I. The kisspeptin system of the human hypothalamus: sexual dimorphism and relationship with gonadotropin-releasing hormone and neurokinin B neurons. European Journal of Neuroscience. 2010;31:1984-1998. https://doi.org/10.1111/j.1460-9568.2010.07239.x
  22. Lehman MN, Hileman SM, Goodman RL. Neuroanatomy of the kisspeptin signaling system in mammals: comparative and developmental aspects. Adv Exp Med Biol. 2013;784:27-62. https://doi.org/10.1007/978-1-4614-6199-9_3
  23. Lunenfeld B, Bühler K. The neuro control of the ovarain cycle — a hypothesis. Gynecol Endocrinol. 2018;34:4:278-282. https://doi.org/10.1080/09513590.2017.1405933
  24. Moore CA, Milano SK, Benovic JL. Regulation of receptor trafficking by GRKs and arrestins. Annu Rev Physiol. 2007;69:451-482. https://doi.org/10.1146/annurev.physiol.69.022405.154712
  25. Navarro VM, Bosch MA, León S, Simmavli S, True C, Pinilla L, Carroll RS, Seminara SB, Tena-Sempere M, Rønnekleiv OK, Kaiser UB. The integrated hypothalamic tachykinin-kisspeptin system as a central coordinator for reproduction. Endocrinology. 2015;156:627-637. https://doi.org/10.1210/en.2014-1651
  26. Wahab F, Shahab M, Behr R. The involvement of gonadotropin inhibitory hormone and kisspeptin in the metabolic regulation of reproduction. J Endocrinol. 2015;225:2:R49-R66. https://doi.org/10.1530/JOE-14-0688
  27. Takayoshi Ubuka, Morgan K, Pawson AJ, Osugi T, Chowdhury VS, Minakata H, Tsutsui K, Millar RP, Bently GE. Identification of human GnIH homologs, RFRP-1 and RFRP-3, and the cognate receptor, GPR147 in the human hypothalamic ptuitary axis. PLoS One. 2009;4:12:e8400. https://doi.org/10.1371/journal.pone.0008400
  28. Tsutsui K, Bentley GE, Ubuka T, Saigoh E, Yin H, Osugi T, Inoue K, Chowdhury VS, Ukena K, Ciccone N, Sharp PJ, Wingfield JC. The general and comparative biology of gonadotropin-inhibitory hormone (GnIH). Gen Comp Endocrinol. 2007;153:1-3:365-370. https://doi.org/10.1016/j.ygcen.2006.10.005
  29. Hay DL, Poyner DR. Calcitonin gene-related peptide, adrenomedullin and flushing. Maturitas. 2009;64:104-108. https://doi.org/10.1016/j.maturitas.2009.08.011
  30. Lima WG, Marques-Oliveira GH, da Silva TM, Chaves VE. Role of calcitonin gene-related peptide in energy metabolism. Endocrine. 2017;58:1:3-13. https://doi.org/10.1007/s12020-017-1404-4
  31. Iyengar S, Ossipov MH, Johnson KW. The role of calcitonin gene — related peptide in peripheral and central pain mechanisms including migraine. Pain. 2017;158:4:543-559. https://doi.org/10.1097/j.pain.0000000000000831
  32. Muka T, Oliver-Williams C, Colpani V, Kunutsor S, Chowdhury S, Chowdhury R, Kavousi M, Franco OH. Association of vasomotor and other menopausal symptoms with risk of cardiovascular disease: a systematic review and meta-analysis. PLoS One. 2016;11: e0157417. https://doi.org/10.1371/journal.pone.0157417
  33. Thurston RC, Johnson BD, Shufelt CL, Braunstein GD, Berga SL, Stanczyk FZ, Pepine CJ, Bittner V, Reis SE, Thompson DV, Kelsey SF, Sopko G, Bairey Merz CN. Menopausal symptoms and cardiovascular disease mortality in the Women’s Ischemia Syndrome Evaluation (WISE). Menopause. 2017;24:126-132. https://doi.org/10.1097/GME.0000000000000731
  34. Gordon JL, Rubinow DR, Thurston RC, Paulson J, Schmidt PJ, Girdler SS. Jennifer L. Cardiovascular, hemodynamic, neuroendocrine, and inflammatory markers in women with and without vasomotor symptoms. Menopause. 2016;23:11:1189-1198. https://doi.org/10.1097/GME.0000000000000689
  35. Van Dijk GM, Maneva M, Colpani V, Dhana K, Muka T, Jaspers L, Kavousi M, Franco OH. The association between vasomotor symptoms and metabolic health in peri- and postmenopausal women: a systematic review. Maturitas. 2015;80:2:140-147. https://doi.org/10.1016/j.maturitas.2014.11.016
  36. Thurston RC, El Khoudary SR, Sutton-Tyrrell K, Crandall CJ, Sternfeld B, Joffe H, Gold EB, Selzer F, Matthews KA. Vasomotor symptoms and insulin resistance in the study of women’s health across the nation. J Clin Endocrinol Metab. 2012;97:3487-3494. https://doi.org/10.1210/jc.2012-1410
  37. Franco OH, Muka T, Colpani V, Kunutsor S, Chowdhury S, Chowdhury R, Kavousi M. Vasomotor symptoms in women and cardiovascular risk markers: systematic review and meta-analysis. Maturitas. 2015;81:353-361. https://doi.org/10.1016/j.maturitas.2015.04.016
  38. Thurston RC, Chang Y, Barinas-Mitchell E, Jennings JR, von Känel R, Landsittel DP, Matthews KA. Physiologically assessed hot flashes and endothelial function among midlife women. Menopause. 2017;24:8:886-893. https://doi.org/10.1097/GME.0000000000000857
  39. Herber-Gast GCM, Brown WJ, Mishra GD. Hot flushes and night sweats are associated with coronary heart disease risk in midlife: a longitudinal study. Menopause. 2014;19:11:1208-1214. https://doi.org/10.1111/1471-0528.13163
  40. Moyer AM, de Andrade M, Weinshilboum RM, Miller VM. Influence of SULT1A1 genetic variation on age at menopause, estrogen levels, and response to hormone therapy in recently postmenopausal white women. Menopause. 2016;23:863-869. https://doi.org/10.1097/GME.0000000000000648
  41. Moyer AM, Miller VM, Faubion SS. Could personalized management of menopause based on genomics become a reality? Pharmacogenomics. 2016;17:7:659-662. https://doi.org/10.2217/pgs.16.17
  42. Archer DF, Sturdee DW, Baber R, de Villiers TJ, Pines A, Freedman RR, Gompel A, Hickey M, Hunter MS, Lobo RA, Lumsden MA, MacLennan AH, Maki P, Palacios S, Shah D, Villaseca P, Warren M. Menopausal hot flushes and night sweats: where are we now? Climacteric. 2011;14:515-528. https://doi.org/10.3109/13697137.2011.608596
  43. Kronenberg F. Menopausal hot flashes: a review of physiology and biosociocultural perspectives on methods of assessment. J Nutr. 2010;140:1380S-1385S. https://doi.org/10.3945/jn.109.12084
  44. Юренева С.В., Эбзиева З.Х. Роль гипоталамических (триггеров) нейропептидов в генезе приливов жара. Перспективы новых терапевтических подходов к лечению вазомоторных климактерических симптомов. Акушерство и гинекология. 2017;8:115-120. https://doi.org/10.18565/aig.2017.8