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

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 Fifty unique studies (including three unpublished studies) were included in the analyses.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.