title: 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 μ and mixed μ/κ 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 Fifty unique studies (including three unpublished studies) were included in the analyses.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 μ-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 μ-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 μ/κ 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 μ and mixed μ/κ-opioids are less convincing and require further study.
authors.affiliation: Department of Anesthesiology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands Department of Psychology and Center for Developmental Neurosciences, The College of Staten Island, City University New York, NY 10314, USA Doctoral Program in Neuropsychology, Queens College, City University New York, Flushing, NY 11367, USA Department of Anesthesia and Critical Care, University of Chicago, Chicago, IL, USA Department of Medical Statistics, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
authors.forename: Marieke
authors.initials: M
authors.lastname: Niesters
authors.forename: Albert
authors.initials: A
authors.lastname: Dahan
authors.forename: Benjamin
authors.initials: B
authors.lastname: Kest
authors.forename: James
authors.initials: J
authors.lastname: Zacny
authors.forename: Theo
authors.initials: T
authors.lastname: Stijnen
authors.forename: Leon
authors.initials: L
authors.lastname: Aarts
authors.forename: Elise
authors.initials: E
authors.lastname: Sarton
mesh_terms: D000701:Analgesics, Opioid / Q000627:therapeutic use*; D016208:Databases, Factual / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D008297:Male; D010146:Pain / Q000188:drug therapy*; D012727:Sex Characteristics
chemical_list: D000701:Analgesics, Opioid