Sharon L Dormire1. 1. University of Texas at Austin, School of Nursing, Austin, Texas 78701-1499, USA. Sdormire@mail.nur.utexas.edu
Abstract
PURPOSE: The purpose of this article is to detail a novel hypothesis regarding the role of changes in brain glucose delivery in menopausal hot flashes. ORGANIZING FRAMEWORK: The impaired glucose delivery hypothesis of menopausal hot flashes is presented as a potential model of hot flash physiology. As foundational to the hypothesis, brain glucose physiology, specifically neurobarrier coupling, is presented in detail. With brain activation, glucose needs immediate increase; additional glucose is supplied through increased production of glucose transporter 1 (GLUT1) at the blood-brain barrier (BBB) and through vasodilation. Estrogen is important to this system in stimulating production of GLUT1. As estrogen declines at menopause, upregulation of GLUT1 is less efficient. As a consequence, neurobarrier coupling overcompensates with an excess neurovascular response, or a hot flash. Research supporting this hypothesis is briefly reviewed and new questions raised are reviewed. CONCLUSIONS: The impaired glucose hypothesis of menopausal hot flashes proposes an inadequate neurobarrier response to neurometabolic stimulation as estrogen declines, resulting in additional neurometabolic stimulation with consequent neurovascular stimulation. In this model, the menopausal woman has diminished ability to respond to fluctuations in blood glucose over the course of the day, which results in hot flashes as a counter-regulatory response. This perspective accounts for observed physiological changes that have not been previously detailed. New research directions are identified.
PURPOSE: The purpose of this article is to detail a novel hypothesis regarding the role of changes in brain glucose delivery in menopausal hot flashes. ORGANIZING FRAMEWORK: The impaired glucose delivery hypothesis of menopausal hot flashes is presented as a potential model of hot flash physiology. As foundational to the hypothesis, brain glucose physiology, specifically neurobarrier coupling, is presented in detail. With brain activation, glucose needs immediate increase; additional glucose is supplied through increased production of glucose transporter 1 (GLUT1) at the blood-brain barrier (BBB) and through vasodilation. Estrogen is important to this system in stimulating production of GLUT1. As estrogen declines at menopause, upregulation of GLUT1 is less efficient. As a consequence, neurobarrier coupling overcompensates with an excess neurovascular response, or a hot flash. Research supporting this hypothesis is briefly reviewed and new questions raised are reviewed. CONCLUSIONS: The impaired glucose hypothesis of menopausal hot flashes proposes an inadequate neurobarrier response to neurometabolic stimulation as estrogen declines, resulting in additional neurometabolic stimulation with consequent neurovascular stimulation. In this model, the menopausal woman has diminished ability to respond to fluctuations in blood glucose over the course of the day, which results in hot flashes as a counter-regulatory response. This perspective accounts for observed physiological changes that have not been previously detailed. New research directions are identified.
Authors: Ruixin Hao; Maria Bondesson; Amar V Singh; Anne Riu; Catherine W McCollum; Thomas B Knudsen; Daniel A Gorelick; Jan-Åke Gustafsson Journal: PLoS One Date: 2013-11-06 Impact factor: 3.240