α2-Adrenergic mechanism in menopausal hot flushes

It has been hypothesized that hot flushes are triggered within the hypothalamus by alpha 2-adrenergic receptors on noradrenergic neurons. We administered intravenous clonidine (an alpha 2-adrenergic agonist) and yohimbine (an alpha 2-adrenergic antagonist) to nine menopausal women with hot flushes and to an asymptomatic comparison group. Hot flushes were defined objectively by skin conductance responses recorded from the sternum; finger temperature recordings and symptom reports were also evaluated. The subjects were prescreened using ambulatory skin conductance monitoring. A significantly greater number of hot flushes occurred during yohimbine sessions than in corresponding placebo sessions (six versus zero). Clonidine significantly increased the amount of peripheral heating needed to provoke a hot flush (40.6 versus 33.6 minutes) and reduced the number of hot flushes that did occur (two versus eight). No hot flushes occurred in the asymptomatic women. These findings support the role of a central alpha 2-adrenergic mechanism in the initiation of hot flushes.