Hot flashes are a common problem in many women. Although hormonal treatments, some newer antidepressants, gabapentin, and clonidine have been shown to decrease hot flashes,(1-4), improved treatment options are needed to provide substantial relief without unwanted risks or side effects. A better understanding of the physiology and measurement of hot flashes would expedite the development and testing of more effective treatment options.
Hot Flash Physiology
With regard to hot flash physiology, the article by Carpenter et al (5) in the current issue of Menopause looks at the question of whether tryptophan depletion, resulting in decreased serotonin, would cause increased hot flashes. The
authors’ innovative hypothesis was not supported by the results of this study.
Nonetheless, there was a study limitation that did not allow the authors to disprove their prestudy hypothesis. The study limitation was that, in the control arm of this trial, participants also experienced some tryptophan depletion.
Although the tryptophan depletion in the control arm was to a lesser degree than that seen in the study arm, it was quite marked, with 35% of participants having tryptophan levels less than 10 KM. The authors propose looking at this subject further by studying tryptophan supplementation versus depletion and by potentially adding in the use of a means to induce hot flashes in both groups (such as raising room temperature).
Although the authors proposed that a positive experiment would have supported a mechanism for why selective serotonin reuptake inhibitors or serotonin norepinephrine reuptake inhibitors decrease hot flashes, the negative results
from their trial neither prove nor disprove whether some of these antidepressants decrease hot flashes.
A recent metaanalysis does demonstrate that some of these drugs do moderately decrease hot flashes.3 Furthermore, the antidepressant agents demonstrated to be effective do modulate serotonin in some way, whereas antidepressants found to be
consistent with placebo effects in open-label pilot trials (ie, mirtazapine,6 bupropion,7 and desipramine8) do not impact serotonin.