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

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. Chisquare 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.