A systematic review of sex differences in the placebo and the nocebo effect

Abstract

Objectives

The present review investigated whether there are systematic sex differences in the placebo and the nocebo effect.

Methods

A literature search was conducted in multiple electronic databases. Studies were included if the study compared a group or condition where a placebo was administered to a natural history group or similar cohort.

Results

Eighteen studies were identified – 12 on placebo effects and 6 on nocebo effects. Chi-square tests revealed that 1) males responded more strongly to placebo treatment, and females responded more strongly to nocebo treatment, and 2) males responded with larger placebo effects induced by verbal information, and females responded with larger nocebo effects induced by conditioning procedures.

Conclusion

This review indicates that there are sex differences in the placebo and nocebo effects, probably caused by sex differences in stress, anxiety, and the endogenous opioid system.

Keywords:

• placebo response
• nocebo response
• placebo analgesia
• nocebo hyperalgesia
• sex differences

Supplementary materials

Box S1

Reference list of the included studies

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Acknowledgments

The study was supported by a grant from the Bial Foundation (grant no. 186/10) and the UiT, University of Tromsø, Tromsø, Norway.

Disclosure

The authors report no conflicts of interest in this work.