Monoamine neurotransmitter theories of menopausal hot flashes

doi:10.16098/j.issn.0529-1356.2019.06.029

Abstract

Abstract:

Hot flashes are the most common symptoms of menopausal women, and their symptoms are closely related to the occurrence of cardiovascular disease, which seriously affects the physical and mental health of menopausal women. Therefore, avoiding and alleviating the occurrence of hot flashes during menopause has become a topic of great concern today. It is generally believed that the hot flashes are caused by the dysfunction of hypothalamic thermoregulatory center, but its exact pathogenesis has not been elucidated. Recent studies have shown that menopausal hot flashes are the result of the interaction of estrogen with a variety of neurotransmitters, and monoamine neurotransmitters like norepinephrine, 5-hydroxytryptamine and dopamine play a central role, which are summarized as follows.

Key words: Hot flash, Estrogen, Norepinephrine, 5-hydroxytryptamine, Dopamine

SUN Yan-rong YANG Qi-yue LI Yao WANG Wen-juan WANG Ke QIN Li-hua. Monoamine neurotransmitter theories of menopausal hot flashes[J]. Acta Anatomica Sinica, 2019, 50(6): 857-860.

References

［1］ Bansal R, Aggarwal N. Menopausal hot flashes: a concise review ［J］. J Midlife Health, 2019,10(1):6-13.

［2］ Santoro N, Epperson CN, Mathews SB. Menopausal symptoms and their management ［J］. Endocrinol Metab Clin North Am, 2015,44(3):497-515.

［3］ Davis SR, Lambrinoudaki Ⅰ, Lumsden M, et al. Menopause ［J］. Rev Dis Primers, 2015,1:15004.

［4］ Zhang JP, Wang YQ, Yan MQ, et al. Menopausal symptoms and sleep quality during menopausal transition and postmenopause ［J］. Chin Med J, 2016,129(7):771-777.

［5］ Zambotti M, Colrain IM, Javitz HS, et al. Magnitude of the impact of hot flashes on sleep in perimenopausal women ［J］. Fertil Steril, 2014,102(6):1708-1715.

［6］ Chen YN, Shi HR. Estrogen，hormonal replacement therapy and cardiovascular disease ［J］. Journal of International Obstetrics and Gynecology, 2012,39(1):26-28.(in Chinese

陈永宁, 史惠蓉. 雌激素、激素替代疗法与心血管疾病［J］. 国际妇产科学杂志, 2012,39(1):26-28.

［7］ Freedman RR. Menopausal hot flashes: mechanisms, endocrinology, treatment ［J］. J Steroid Biochem Mol Biol, 2014,142:115-120.

［8］ Jiang H, Zhang J, Wang WJ, et al. Mechanism of peripheral regulation of temperature in hot flushes of low estrogen ［J］. Acta Annatomica Sinica, 2016,47(5):709-713. (in Chinese)

姜海, 张晶, 王文娟, 等. 低雌激素引发潮热的外周机制［J］. 解剖学报, 2016,47(5):709-713.

［9］ Sievert LL. Subjective and objective measures of hot flashes ［J］. Am J Hum Biol, 2013,25(5):573-580.

［10］ Freedman RR, Dinsay R. Clonidine raises the sweating threshold in symptomatic but not in asymptomatic postmenopausal women ［J］. Fertil Steril, 2000,74(1):20-23.

［11］ Sturdee DW. The menopausal hot flushanything new［J］? Maturitas, 2008,60(1):42-49.

［12］ Berendsen HG. The role of serotonin in hot flushes ［J］. Maturitas, 2000,36(3):155-164.

［13］ Freedman RR. Hot flash trends and mechanisms ［J］. Menopause, 2002,9(3):151-152.

［14］ Biglia N, Cagnacci A, Gambacciani M, et al. Vasomotor symptoms in menopause: a biomarker of cardiovascular disease risk and other chronic diseases ［J］? Climacteric, 2017,20(4):306-312.

［15］ MacGregor EA. Migraine, menopause and hormone replacement therapy ［J］. Post Reprod Health, 2018,24(1):11-18.

［16］ Guthrie JR, Dennerstein L, Hopper JL, et al. Hot flushes, menstrual status, and hormone levels in a population-based sample of midlife women ［J］. Obstet Gynecol, 1996,88(3):437-442.

［17］ Horst GJ. Estrogen in the limbic system ［J］. Vitam Horm, 2010,82:319-338.

［18］ Casper RF, Yen SS. Neuroendocrinology of menopausal flushes: an hypothesis of flush mechanism ［J］. Clin Endocrinol, 1985,22(3):293-312.

［19］ Lopez-Lanza JR, Villa Puente M, Lopez Videras R, et al. Management of a first depressive episode in the primary care setting. Use of antidepressants and referrals ［J］. Semergen, 2016,42(2):88-93.

［20］ Albertazzi P. Noradrenergic and serotonergic modulation to treat vasomotor symptoms ［J］. J Br Menopause Soc, 2006,12(1):7-11.

［21］ Bruck K, Zeisberger E. Adaptive changes in thermoregulation and their neuropharmacological basis ［J］. Pharmacol Ther, 1987,35(1-2):163-215.

［22］ Freedman RR, Woodward S, Sabharwal SC. Alpha 2-adrenergic mechanism in menopausal hot flushes ［J］. Obstet Gynecoly, 1990,76(4):573-578.

［23］ Palacios S, Coronado PJ. New options for menopausal symptoms after 15 years of whi study ［J］. Minerva Ginecol, 2017,69(2):160-170.

［24］ Etgen AM, Ansonoff MA, Quesada A. Mechanisms of ovarian steroid regulation of norepinephrine receptor-mediated signal transduction in the hypothalamus: implications for female reproductive physiology ［J］. Horm Behav, 2001,40(2):169-177.

［25］ Liu Y, Zhang J, Liu S, et al. Effects of oestrogen and cimicifuga racemosa on the cardiac noradrenaline pathway of ovariectomized rats ［J］. Exp Physiol, 2017,102(8):974-984

［26］ Briski KP, Shrestha PK. Hindbrain estrogen receptor-beta antagonism normalizes reproductive and counter-regulatory hormone secretion in hypoglycemic steroid-primed ovariectomized female rats ［J］. Neuroscience, 2016,331:62-71.

［27］ Wang W, Wang Z, Bai W, et al. Effect of low estrogen on neurons in the preoptic area of hypothalamus of ovariectomized rats ［J］. Acta Histochem, 2014,116(8):1259-1269.

［28］ Fontana R, Della Torre S, Meda C, et al. Estrogen replacement therapy regulation of energy metabolism in female mouse hypothalamus ［J］. Endocrinology, 2014,155(6):2213-2221.

［29］ Cruz G, Fernandois D, Paredes AH. Ovarian function and reproductive senescence in the rat: role of ovarian sympathetic innervation ［J］. Reproduction, 2017,153(2):R59-R6

［30］ Zeleke BM, Davis SR, Fradkin P, et al. Vasomotor symptoms and urogenital atrophy in older women: a systematic review ［J］. Climacteric, 2015,18(2):112-120.

［31］ Archer DF, Sturdee DW, Baber R, et al. Menopausal hot flushes and night sweats: where are we now ［J］ ? Climacteric, 2011,14(5):515-528.

［32］ Sturdee DW, Hunter MS, Maki PM, et al. The menopausal hot flush: a review ［J］. Climacteric, 2017,20(4):296-305.

［33］ Luo XM, Xie ShZh, Chen YQ. The pathogenesis of perimenopausal hot flush ［J］. Journal of Reproductive Medicine, 2008, 17(6):495-498.(in Chinese)

罗晓梅, 谢守珍, 陈亚琼. 围绝经期潮热发病机制［J］. 生殖医学杂志, 2008,17(6):495-498.

［34］ Brummelte S, Mc Glanaghy E, Bonnin A, et al. Developmental changes in serotonin signaling: Implications for early brain function, behavior and adaptation ［J］. Neuroscience, 2017,342:212-231.

［35］ Li L, Fan TSh, Li ShD, Serotonin neurons in sulcus nucleus of rats-light microscopy and immunoelectron microscopy ［J］. Acta Annatomica Sinica, 1991,22(1):38-42. (in Chinese)

李戮, 范天生, 李世东. 大鼠中缝大核5-羟色胺神经元光镜和免疫电镜研究［J］. 解剖学报,1991,22(1):38-42.

［36］ Deneris E, Gaspar P. Serotonin neuron development: shaping molecular and structural identities ［J］. Wiley Interdiscip Rev Dev Biol, 2018,7(1).

［37］ Nakamura M, Shintani-Ishida K, Ikegaya H. 5-HT2a receptor agonist-induced hyperthermia is induced via vasoconstriction by peripheral 5-HT2a receptors and brown adipose tissue thermogenesis by peripheral serotonin loss at a high ambient temperature ［J］. J Pharmacol Exp Ther, 2018,367(2):356-362.

［38］ Luo XM, Chen YQ, Duan XL, et al. Localization of 5-HT1A and 5-HT2Areceptor subtypes in the normal female rat hypothalamus［J］. Chinese Journal of Neuroanatomy, 2004,20(6):557-562.(in Chinese)

罗晓梅, 陈亚琼, 段小莉, 等. 雌性大鼠下丘脑5-羟色胺1A和2A受体亚型的定位分布［J］. 神经解剖学杂志, 2004,20(6):557-562.

［39］ Stubbs C, Mattingly L, Crawford SA, et al. Do ssris and snris reduce the frequency and/or severity of hot flashes in menopausal women ［J］. J Okla State Med Assoc, 2017,110(5):272-274.

［40］ Luo XM, Chen YQ. Menopausal hot flashes with 5-HT ［J］. Foreign Medical Obstetrics and Gynecology, 2003,30(6):394-395. (in Chinese)

罗晓梅, 陈亚琼. 绝经期潮热与5羟色胺［J］. 国外医学妇产科学分册 2003,30(6):394-395

［41］ Shanafelt TD, Barton DL, Adjei AA, et al. Pathophysiology and treatment of hot flashes ［J］. Mayo Clin Proc, 2002,77(11):1207-1218.

［42］ Jovanovic H, Kocoska-Maras L, Radestad AF, et al. Effects of estrogen and testosterone treatment on serotonin transporter binding in the brain of surgically postmenopausal women-a pet study ［J］. NeuroImage, 2015,106:47-54.

［43］ Lu NZ, Bethea CL. Ovarian steroid regulation of 5-HT1a receptor binding and g protein activation in female monkeys［J］.Neuropsychopharmacology, 2002,27(1):12-24.

［44］ Halbreich U, Rojansky N, Palter S, et al. Estrogen augments serotonergic activity in postmenopausal women［J］.Biol Psychiatry, 1995,37(7):434-441.

［45］ Bethea CL, Reddy AP. Effect of ovarian steroids on gene expression related to synapse assembly in serotonin neurons of macaques ［J］. J Neurosci Res, 2012,90(7):1324-1334.

［46］ Chhibber A, Woody SK, Karim Rumi MA, et al. Estrogen receptor beta deficiency impairs bdnf-5-ht2a signaling in the hippocampus of female brain: a possible mechanism for menopausal depression ［J］. Psychoneuroendocrinology, 2017,82:107-116.

［47］ Long T, Yao JK, Li J, et al. Comparison of transitional vs surgical menopause on monoamine and amino acid levels in the rat brain ［J］. Mol Cell Endocrinol, 2018,476:139-147.

［48］ Vilar-Gonzalez S, Perez-Rozos A, Cabanillas-Farpon R. Mechanism of hot flashes ［J］. Clin Transl Oncol, 2011,13(3):143-147.

［49］ Carretti N, Florio P, Reis FM, et al. Reduction of serum serotonin precursors after veralipride treatment for postmenopausal hot flushes ［J］. Climacteric, 2010,13(2):141-146.

[1]	WANG Wen-juan DING Yu-tong SU Hao REN Jie SUN Yan-rong WANG Han-fei LU Jia-li ZHANG Lin-qian BAI Yu QIN Li-hua. Changes of Nogo-A expression in hippocampus and striatum of rats under low estrogen condition [J]. Acta Anatomica Sinica, 2023, 54(6): 620-627.
[2]	ZHANG Yi-zhou LI Sha MI Shi-xiong ZUO Hong-chun ZHANG Qian-qian LI Han-lin LEI Zi-han ZHANG Dong-ze CUI Hui-xian. Effect of estradiol regulating sortilin-related receptor A expression on hippocampal spine density and synaptic protein expression via estrogen receptor of mouse [J]. Acta Anatomica Sinica, 2023, 54(3): 261-268.
[3]	BIAN Wei LI Meng-yi ZHOU Peng LI Jun-wei ZHANG Ting WU An-ting QI Shuang-shuang CUI Huai-rui SUN Chen-you. Effects of activating mTORC2/Akt signaling pathway on dopaminergic neurons and behaviors in 6-hydroxydopamin model mice [J]. Acta Anatomica Sinica, 2023, 54(1): 13-22.
[4]	SUN Yan-rong Dai Li-xin WANG Wen-juan WANG Ke QING Li-hua. Mechanism of KNDy neurons in arcuate nucleus of hypothalamus involved in the occurrence of perimenopausal hot flashes [J]. Acta Anatomica Sinica, 2021, 52(6): 992-998.
[5]	ZHAO Xue-ying SI Li-na WEI Meng QIAO Yue-bing YANG Song-he CHENG Lu-yang. Proteomic analysis of uterine luminal fluid in ovariectomized estrogen primed rats with lateral cerebral ventricle injection of gonadotropin-inhibitory hormone/RF amide-related peptide-3 [J]. Acta Anatomica Sinica, 2021, 52(4): 499-505.
[6]	WANG Tong-tong YE Xin BIAN Wei CHEN Zhi-chi DU Juan-juan FU Wei-da CHEN Meng-jiao LI Jun-nan SUN Chen-you. Allopregnanolone protecting cell line SH-SY5Y against 6-hydroxydopamine induced lesion [J]. Acta Anatomica Sinica, 2021, 52(1): 5-13.
[7]	REN Ya-li GUO Lei PAN San-qiang. Amphetamine causing damage of dopamine cells via inhibiting of protein kinase B/glycogen synthase kinase-3β/collapsin response mediator protein-2 signal pathway [J]. Acta Anatomica Sinica, 2021, 52(1): 14-20.
[8]	HE Feng-qin YU Bing XIANG Quan-li ZHOU Deng-xiang QU Geng-chao. Changes in expression of estrogen receptor α and β associated with anxiety-like behavior of dams in dams-offspring separation of C57BL/6 J mice [J]. Acta Anatomica Sinica, 2021, 52(1): 30-35.
[9]	WANG Tong-tong CHEN Zhi-chi YE Xin BIAN wei DU Juan-juan FU Wei-da CHEN Meng-jiao LI Jun-nan SUN Chen-you. Allopregnanolone restores dopaminergic neurons and motor performance in Parkinson’s disease mice and its molecular mechanisms [J]. Acta Anatomica Sinica, 2020, 51(4): 473-482.
[10]	ZHOU Li ZHANG Da-wei WANG Zhi-yong. Expression of dopamine receptors in rat olfactory bulb and its role in hyposmia of Parkinson’s disease rat model [J]. Acta Anatomica Sinica, 2019, 50(4): 411-417.
[11]	XIE Ming-qi CHEN Zhi-chi QI Shuang-shuang WANG Tong-tong ZHANG Peng HUANG Hou-ju ZHOU Peng CUI Huai-rui SUN Chen-you. Effects of 6-hydroxydopamine on dopaminergic neurons in nigrostriatal system and on behavior of adult mice [J]. Acta Anatomica Sinica, 2017, 48(4): 361-374.
[12]	WANG Peng-xiang CHI Yi-li ZHANG Chan NIU Xue-yuan DING Yu-qiang LIAO Min. Blocking of canonical Notch signaling in dopaminergic neurons prevents its loss induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine [J]. Acta Anatomica Sinica, 2017, 48(4): 404-409.
[13]	JIANG Hai ZHANG Jing WANG Wen-juan WANG Ke QIN Li-hua* BAI Wen-pei*. Mechanism of peripheral regulation of temperature in hot flushes of low estrogen [J]. AAS, 2016, 47(5): 709-713.
[14]	JIANG Wen-xia ZHANG Xin-hua Lü Guang-ming GU Xiao-song*. Effects of traditional Chinese medicine nerve growth decoction on the model of Parkinson’s disease [J]. AAS, 2016, 47(4): 442-448.
[15]	WU Yuan-yuan JIANG Yong-liang SHAO Xiao-mei ZHAO Xiao-yun HE Xiao-fen FANG Jian-qiao*. Comparisons of 5-hydroxytryptamine expression at different levels of dorsal raphe nucleus in rats with pain-depression dyad [J]. AAS, 2015, 46(2): 170-174.