medalphabetМедицинский алфавитMedical alphabet2078-56312949-2807ООО «Альфмед»medalphabet-161Research ArticleСтатьиЭндокринология когнитивных расстройств: возможности менопаузальной гормональной терапииEndocrinology of cognitive disorders: possibilities of menopausal hormonal therapyТапильскаяН. И.TapilskayaN. I.noemail@neicon.ruГлушаковР. И.GlushakovR. I.noemail@neicon.ruФГБОУ ВО «Санкт-Петербургский государственный педиатрический медицинский университет» Минздрава РоссииРоссияSaint-Petersburg State Pediatric Medical UniversityRussian FederationФГБВОУ ВО «Военно-медицинская академия имени С. М. Кирова» Минобороны РоссииРоссияMilitary Medical Academy n.a. S. M. KirovRussian Federation201701042017210Современная гинекология3034Copyright © Тапильская Н.И., Глушаков Р.И., 20172017Тапильская Н.И., Глушаков Р.И.Tapilskaya N.I., Glushakov R.I.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-alphabet.com/jour/article/view/161

В обзоре рассмотрены молекулярные, клеточные, тканевые и системные механизмы нейропротективного действия половых стероидов (эстрогенов, прогестагенов, андрогенов), недостаток которых в период пери- и постменопаузы приводит к дефициту нейропластичности и нейрогенеза. Длительный дефицит половых стероидов приводит к необратимым нейродегенеративным изменениям. Применение эстрогена в качестве средства МГТ снижает риски развития болезни Альцгеймера, болезни Паркинсона, сосудистой деменции. Прогестагены и андрогены также обладают нейропротективными эффектами и способны усиливать действие эстрогенов. В период перименопаузы, когда вследствие дефицита андрогенов возникают снижение физической активности, астения, сексуальная дисфункция, усиление стрессовой реакции, ухудшение коммуникативности, применение андрогенов или прогестагенов с проандрогенной активностью значительно улучшает качество жизни и усиливает нейропротективные эффекты эстрогенов.

In this paper we review molecular, cellular, tissue specific and systemic mechanisms of neuroprotective properties of sex steroids (oestrogens, progestogens, androgens). According to the findings obtained from animal and clinical studies, deficit of these sex steroids in the peri- and postmenopause period may lead to reduction of neuroplasticity and neurogenesis. Continuous deficiency of sex steroids causes irreversible neurodegenerative changes. Administration of oestrogen as a menopausal hormone therapy reduces risks of developing such neurodegenerative conditions as Alzheimer’s disease, Parkinson’s disease and vascular dementia. Additionally, progestogens and androgens also possess stress and neuroprotective properties and can strengthen the effects of oestrogens. In the perimenopause period a decrease in physical activity, asthenia, sexual dysfunction, higher vulnerability to psychological stress are observed due to androgens deficiency. Therefore, androgens or progestagenes with androgen characteristics treatment significantly enhances neuroprotective effects of oestrogenes and increases quality of life of women in menopause period.

нейрогенезстероидогенезлевоноргестрелклимонормменопаузальная гормональная терапияneurogenesissteroidogenesislevonorgestrelclimonormmenopausal hormonal therapyReferencesКарева Е. Н., Олейникова О. М., Панов В. О., Шимановский Н.Л., Скворцова В. И. Эстрогены и головной мозг. Вестник Российской академии медицинских наук. 2012; 2: 48-59.Карева Е. Н., Олейникова О. М., Панов В. О., Шимановский Н.Л., Скворцова В. И. Эстрогены и головной мозг. Вестник Российской академии медицинских наук. 2012; 2: 48-59.Тапильская Н. И., Хамошина М. Б., Шестакова И. Г. Персонифицированный подход к гормональной терапии при преждевременной недостаточности яичников и в период менопаузального перехода. Доктор.Ру. 2016; 8 (125) - 9 (126): 47-51.Тапильская Н. И., Хамошина М. Б., Шестакова И. Г. Персонифицированный подход к гормональной терапии при преждевременной недостаточности яичников и в период менопаузального перехода. Доктор.Ру. 2016; 8 (125) - 9 (126): 47-51.Alexander A., Irving A.J., Harvey J. Emerging roles for the novel estrogen-sensing receptor GPER 1 in the CNS. Neuropharmacology. 2017; 113: 652-660.Alexander A., Irving A.J., Harvey J. Emerging roles for the novel estrogen-sensing receptor GPER 1 in the CNS. Neuropharmacology. 2017; 113: 652-660.Almey A, Milner TA, Brake WG. Estrogen receptors in the central nervous system and their implication for dopamine-dependent cognition in females. Horm. Behav. 2015; 74: 125-138.Almey A, Milner TA, Brake WG. Estrogen receptors in the central nervous system and their implication for dopamine-dependent cognition in females. Horm. Behav. 2015; 74: 125-138.Alyea R. A., Watson C. S. Nongenomic mechanisms of physiological estrogen-mediated dopamine efflux. BMC Neurosci. 2009; 10: 59.Alyea R. A., Watson C. S. Nongenomic mechanisms of physiological estrogen-mediated dopamine efflux. BMC Neurosci. 2009; 10: 59.Baber R. J. et al. IMS Recomendations on women's midlife health and menopause hormon therapy. Climacteric. 2016; 19: 109-150.Baber R. J. et al. IMS Recomendations on women's midlife health and menopause hormon therapy. Climacteric. 2016; 19: 109-150.Bourque M, Dluzen DE, Di Paolo T. Signaling pathways mediating the neuroprotective effects of sex steroids and SERMs in Parkinson’s disease. Front Neuroendocrinol. 2012; 33 (2): 169-178.Bourque M, Dluzen DE, Di Paolo T. Signaling pathways mediating the neuroprotective effects of sex steroids and SERMs in Parkinson’s disease. Front Neuroendocrinol. 2012; 33 (2): 169-178.Bove R., Secor E., Chibnik L. B. et al. Age at surgical menopause influences cognitive decline and Alzheimer pathology in older women. Neurology 2014; 82: 222-229.Bove R., Secor E., Chibnik L. B. et al. Age at surgical menopause influences cognitive decline and Alzheimer pathology in older women. Neurology 2014; 82: 222-229.Carroll J. C., Rosario E. R., Villamagna A., Pike C. J. Continuous and cyclic progesterone differentially interact with estradiol in the regulation of Alzheimer-like pathology in female 3x Transgenic-Alzheimer’s disease mice. Endocrinology. 2010; 151: 2713-2722.Carroll J. C., Rosario E. R., Villamagna A., Pike C. J. Continuous and cyclic progesterone differentially interact with estradiol in the regulation of Alzheimer-like pathology in female 3x Transgenic-Alzheimer’s disease mice. Endocrinology. 2010; 151: 2713-2722.de Villiers T. J., Pines A., Panay N. et al.; International Menopause Society. Updated 2013 International Menopause Society recommendations on menopausal hormone therapy and preventive strategies for midlife health. Climacteric. 2013; 16 (3): 316-37.de Villiers T. J., Pines A., Panay N. et al.; International Menopause Society. Updated 2013 International Menopause Society recommendations on menopausal hormone therapy and preventive strategies for midlife health. Climacteric. 2013; 16 (3): 316-37.Duarte-Guterman P., Yagi S., Chow C., Galea L.A. Hippocampal learning, memory, and neurogenesis: effects of sex and estrogens across the lifespan in adults. Horm. Behav. 2015; 74: 37-52.Duarte-Guterman P., Yagi S., Chow C., Galea L.A. Hippocampal learning, memory, and neurogenesis: effects of sex and estrogens across the lifespan in adults. Horm. Behav. 2015; 74: 37-52.Engler-Chiurazzi E.B., Brown C. M., Povroznik J. M., Simpkins J. W. Estrogens as neuroprotectants: estrogenic actions in the context of cognitive aging and brain injury. Prog Neurobiol. 2016.Engler-Chiurazzi E.B., Brown C. M., Povroznik J. M., Simpkins J. W. Estrogens as neuroprotectants: estrogenic actions in the context of cognitive aging and brain injury. Prog Neurobiol. 2016.Engler-Chiurazzia E. B., Singhc M., Simpkinsa J. W. From the 90-s to now: A brief historical perspective on more than two decades of estrogen neuroprotection // Brain Research. 2016; 1645: 79-82.Engler-Chiurazzia E. B., Singhc M., Simpkinsa J. W. From the 90-s to now: A brief historical perspective on more than two decades of estrogen neuroprotection // Brain Research. 2016; 1645: 79-82.Gibbs R. B. Effects of gonadal hormone replacement on measures of basal forebrain cholinergic function. Neuroscience 2000; 101: 931-938.Gibbs R. B. Effects of gonadal hormone replacement on measures of basal forebrain cholinergic function. Neuroscience 2000; 101: 931-938.Hara Y., Waters E.M., McEwen B.S., Morrison J. H. Estrogen Effects on cognitive and synaptic health over the lifecourse. Physiol. Rev. 2015; 95 (3): 785-807.Hara Y., Waters E.M., McEwen B.S., Morrison J. H. Estrogen Effects on cognitive and synaptic health over the lifecourse. Physiol. Rev. 2015; 95 (3): 785-807.Hodis H. N., Mack W. J., Shoupe D. et al. Methods and baseline cardiovascular data from the Early versus Late Intervention Trial with estradiol testing the menopausal hormone timing hypothesis. Menopause. 2015; 22:391-401.Hodis H. N., Mack W. J., Shoupe D. et al. Methods and baseline cardiovascular data from the Early versus Late Intervention Trial with estradiol testing the menopausal hormone timing hypothesis. Menopause. 2015; 22:391-401.Jayaraman A., Carroll J. C., Morgan T. E. et al. 17b-Estradiol and progesterone regulate expression of b-amyloid clearance factors in primary neuron cultures and female rat brain. Endocrinology. 2012; 153: 5467-5479.Jayaraman A., Carroll J. C., Morgan T. E. et al. 17b-Estradiol and progesterone regulate expression of b-amyloid clearance factors in primary neuron cultures and female rat brain. Endocrinology. 2012; 153: 5467-5479.Jayaraman A., Pike C. J. Differential effects of synthetic progestagens on neuron survival and estrogen neuroprotection in cultured neurons. Mol. Cell Endocrinol. 2014; 84 (1-2): 52-60.Jayaraman A., Pike C. J. Differential effects of synthetic progestagens on neuron survival and estrogen neuroprotection in cultured neurons. Mol. Cell Endocrinol. 2014; 84 (1-2): 52-60.Johnson M. L., Redmer, D.A., Reynolds, L.P., Grazul-Bilska A. T. Gap junctional connexin messenger RNA expression in the ovine uterus and placenta: effects of estradiol-17ßtreatment, early pregnancy stages, and embryo origin. Domestic Animal Endocrinology. 2017; 58: 104-112.Johnson M. L., Redmer, D.A., Reynolds, L.P., Grazul-Bilska A. T. Gap junctional connexin messenger RNA expression in the ovine uterus and placenta: effects of estradiol-17ßtreatment, early pregnancy stages, and embryo origin. Domestic Animal Endocrinology. 2017; 58: 104-112.Irwin R. W., Yao J., Hamilton R. T. et al. Progesterone and Estrogen Regulate Oxidative Metabolism in Brain Mitochondria. Endocrinology. 2008; 149 (6): 3167-3175.Irwin R. W., Yao J., Hamilton R. T. et al. Progesterone and Estrogen Regulate Oxidative Metabolism in Brain Mitochondria. Endocrinology. 2008; 149 (6): 3167-3175.Kawas C., Resnick S., Morrison A. et al. A prospective study of estrogen replacement therapy and the risk of developing Alzheimer’s disease: the Baltimore Longitudinal Study of Aging. Neurology. 1997; 48: 1517-1521.Kawas C., Resnick S., Morrison A. et al. A prospective study of estrogen replacement therapy and the risk of developing Alzheimer’s disease: the Baltimore Longitudinal Study of Aging. Neurology. 1997; 48: 1517-1521.Lello S., Cavani A. Ethynilestradiol 20 mcg plus Levonorgestrel 100 mcg: Clinical Pharmacology. Int. J. Endocrinol. 2014; 2014: 102184.Lello S., Cavani A. Ethynilestradiol 20 mcg plus Levonorgestrel 100 mcg: Clinical Pharmacology. Int. J. Endocrinol. 2014; 2014: 102184.Lowenstein L., Shechter A., Porst H. et al. Physicians’ attitudes towards androgen replacement therapy for male and female sexual dysfunction. Int. J. Impot. Res. 2016; 28 (2): 57-60.Lowenstein L., Shechter A., Porst H. et al. Physicians’ attitudes towards androgen replacement therapy for male and female sexual dysfunction. Int. J. Impot. Res. 2016; 28 (2): 57-60.McCullough LD, Blizzard K, Simpson ER, Oz OK, Hurn PD. Aromatase cytochrome P450 and extragonadal estrogen play a role in ischemic neuroprotection. J. Neurosci. 2003; 23 (25): 8701-8705.McCullough LD, Blizzard K, Simpson ER, Oz OK, Hurn PD. Aromatase cytochrome P450 and extragonadal estrogen play a role in ischemic neuroprotection. J. Neurosci. 2003; 23 (25): 8701-8705.MacLusky N.J., Hajszan T., Prange-Kiel J., Leranth C. Androgen modulation of hippocampal synaptic plasticity. Neuroscience 2006; 138: 957-965.MacLusky N.J., Hajszan T., Prange-Kiel J., Leranth C. Androgen modulation of hippocampal synaptic plasticity. Neuroscience 2006; 138: 957-965.Marrocco J., McEwen B.S., Sex in the brain: hormones and sex differences. Dialogues Clin. Neurosci. 2016; 18: 373-383.Marrocco J., McEwen B.S., Sex in the brain: hormones and sex differences. Dialogues Clin. Neurosci. 2016; 18: 373-383.Newhouse P., Albert K. Estrogen, Stress, and Depression: A Neurocognitive Model. JAMA Psychiatry. 2015; 72 (7): 727-9.Newhouse P., Albert K. Estrogen, Stress, and Depression: A Neurocognitive Model. JAMA Psychiatry. 2015; 72 (7): 727-9.Paganini-Hill A., Henderson V. W. Estrogen deficiency and risk of Alzheimer’s disease in women. Am.J. Epidemiol. 1994; 140:256-261.Paganini-Hill A., Henderson V. W. Estrogen deficiency and risk of Alzheimer’s disease in women. Am.J. Epidemiol. 1994; 140:256-261.Paganini-Hill A, Henderson VW. Estrogen replacement therapy and risk of Alzheimer disease. Arch. Intern. Med. 1996; 156:2213-2217.Paganini-Hill A, Henderson VW. Estrogen replacement therapy and risk of Alzheimer disease. Arch. Intern. Med. 1996; 156:2213-2217.Phung T. K., Waltoft B. L., Laursen T. M. Hysterectomy, oophorectomy, and risk of dementia: a nationwide historical cohort study. Dement. Geriatr. Cogn. Disord. 2010; 30:43-50.Phung T. K., Waltoft B. L., Laursen T. M. Hysterectomy, oophorectomy, and risk of dementia: a nationwide historical cohort study. Dement. Geriatr. Cogn. Disord. 2010; 30:43-50.Pike C.J. Sex and the development of Alzheimer’s disease. Journal of Neuroscience Research. 2017; 95: 671-680.Pike C.J. Sex and the development of Alzheimer’s disease. Journal of Neuroscience Research. 2017; 95: 671-680.Rubinow D. R., Johnson S. L., Schmidt P. J. et al. Efficacy of estradiol in perinenopausal depression: so much promise and so few answers. Depress. Anxiety. 2015; 32 (8): 539-49.Rubinow D. R., Johnson S. L., Schmidt P. J. et al. Efficacy of estradiol in perinenopausal depression: so much promise and so few answers. Depress. Anxiety. 2015; 32 (8): 539-49.Sobrino A., Vallejo S., Novella S. et al. Mas receptor is involved in the estrogen-receptor induced nitric oxide-dependent vasorelaxation. Biochemical Pharmacology (2017).Sobrino A., Vallejo S., Novella S. et al. Mas receptor is involved in the estrogen-receptor induced nitric oxide-dependent vasorelaxation. Biochemical Pharmacology (2017).Tang M.X., Jacobs D., Stern Y. et al. Effect of oestrogen during menopause on risk and age at onset of Alzheimer’s disease. Lancet. 1996; 348: 429-32.Tang M.X., Jacobs D., Stern Y. et al. Effect of oestrogen during menopause on risk and age at onset of Alzheimer’s disease. Lancet. 1996; 348: 429-32.Terauchi M., Honjo H., Mizunuma H,. Aso T. Effects of oral estradiol and levonorgestrel on cardiovascular risk markers in postmenopausal women // Arch. Gynecol. Obstet. 2012; 285 (6): 1647-1656.Terauchi M., Honjo H., Mizunuma H,. Aso T. Effects of oral estradiol and levonorgestrel on cardiovascular risk markers in postmenopausal women // Arch. Gynecol. Obstet. 2012; 285 (6): 1647-1656.Tskitishvili E., Pequeux C., Munaut C. et al. Estrogen receptors and estetrol-dependent neuroprotective actions: a pilot study. Journal of Endocrinology. 2017; 232 (1): 85-95.Tskitishvili E., Pequeux C., Munaut C. et al. Estrogen receptors and estetrol-dependent neuroprotective actions: a pilot study. Journal of Endocrinology. 2017; 232 (1): 85-95.Usselman, Charlotte W., Nina S. Stachenfeld, and Jeffrey R. Bender. The molecular actions of oestrogen in the regulation of vascular health. Experimental physiology. 2016; 101 (3): 356-361.Usselman, Charlotte W., Nina S. Stachenfeld, and Jeffrey R. Bender. The molecular actions of oestrogen in the regulation of vascular health. Experimental physiology. 2016; 101 (3): 356-361.Vinogradova Y., Coupland C., Hippisley-Cox J. Use of combined oral contraceptives and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases. BMJ. 2015; 350: h2135.Vinogradova Y., Coupland C., Hippisley-Cox J. Use of combined oral contraceptives and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases. BMJ. 2015; 350: h2135.Walker D. M., Gore A. C. Epigenetic impacts of endocrine disruptors in the brain. Frontiers in Neuroendocrinology. 2017; 44: 1-26.Walker D. M., Gore A. C. Epigenetic impacts of endocrine disruptors in the brain. Frontiers in Neuroendocrinology. 2017; 44: 1-26.Zandi P. P., Carlson M. C., Plassman B. L. et al. Hormone replacement therapy and incidence of Alzheimer disease in older women: the Cache County study. JAMA. 2002; 288: 2123-2129.Zandi P. P., Carlson M. C., Plassman B. L. et al. Hormone replacement therapy and incidence of Alzheimer disease in older women: the Cache County study. JAMA. 2002; 288: 2123-2129.

The authors declare that there are no conflicts of interest present.