Quantitative analysis of placebo response and factors associated with menopausal hot flashes

Objective: The aim of the study was to quantitatively analyze the placebo response and the factors associated with menopausal hot flashes. Methods: The PubMed and Cochrane Library databases were searched for placebo-controlled trials that reported the treatment of menopausal hot flashes, with a retrieval deadline of December 31, 2015. The clinical and demographic characteristics of participants and placebo responses, defined as the percentage of reduction in hot flashes at each observation time point compared with that of baseline values, were extracted from the studies. Model-based meta-analysis was used to describe the time course of placebo response and identify the related factors. Results: Eighty-five trials in 78 articles, involving 8,302 women, were included in the analysis. Of these, 47 trials were about hormonal drugs, 37 were about nonhormonal drugs, and 1 included both hormonal and nonhormonal drugs. Our results indicated that the placebo responses for hot flashes increased in a time-dependent manner and reached a plateau after week 12. Additionally, the placebo responses were significantly higher in the trials of hormonal drugs than in the trials of nonhormonal drugs at week 24 (-51.2% vs -40.4%; P < 0.05), and the difference between them was comparable with the effect of paroxetine. Conclusions: The placebo response for menopausal hot flashes was related to the active comparator; a higher response rate was observed in trials of hormonal drugs than in trials of nonhormonal drugs. These findings suggest that subjective expectations affect the treatment efficacy of menopausal hot flashes.