Do sex differences exist in opioid analgesia? A systematic review and meta-analysis of human experimental and clinical studies

Abstract

Although a contribution of sex in opioid efficacy has garnered much attention, the confirmation and direction of any such difference remain elusive. We performed a systematic review of the available literature on sex differences in mu and mixed mu/kappa opioid effect on acute and experimental pain. Fifty unique studies (including three unpublished studies) were included in the analyses. Across the 25 clinical studies on mu-opioids there was no significant sex-analgesia association. Restricting the analysis to patient-controlled analgesia (PCA) studies (irrespective of the opioid) yielded greater analgesia in women (n = 15, effect size 0.22, 95% c.i. 0.02-0.42, P = 0.028). Further restricting the analysis to PCA morphine studies yielded an even greater effect in women (n = 11, effect size = 0.36, 95% c.i. 0.17-0.56, P = 0.003). Meta-regression indicated that the longer the duration of PCA, the difference in effect between the sexes further increased. Across experimental pain studies on mu-opioids women had greater antinociception from opioids (n = 11, effect size = 0.35; 95% c.i. 0.01-0.69, P = 0.047), which was predominantly due to 6 morphine studies. Female patients had greater mu/kappa opioid analgesia (n = 7, effect size 0.84; 95% c.i. 0.25-1.43, P = 0.005), but no sex-analgesia association was present in experimental studies (n = 7). Sex differences exist in morphine-induced analgesia in both experimental pain studies and clinical PCA studies, with greater morphine efficacy in women. The data on non-morphine mu and mixed mu/kappa-opioids are less convincing and require further study. (C) 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.Development and application of statistical models for medical scientific researc