Articles

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

Niesters, Marieke^a; Dahan, Albert^a,*; Kest, Benjamin^b,c; Zacny, James^d; Stijnen, Theo^e; Aarts, Leon^a; Sarton, Elise^a

Author Information

^aDepartment of Anesthesiology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands

^bDepartment of Psychology and Center for Developmental Neurosciences, The College of Staten Island, City University New York, NY 10314, USA

^cDoctoral Program in Neuropsychology, Queens College, City University New York, Flushing, NY 11367, USA

^dDepartment of Anesthesia and Critical Care, University of Chicago, Chicago, IL, USA

^eDepartment of Medical Statistics, Leiden University Medical Center, 2300 RC Leiden, The Netherlands

^*Corresponding author. Address: Department of Anesthesiology, Leiden University Medical Center, P5-Q, P.O. Box 9600, 2300 RC Leiden, The Netherlands.

E-mail address:[email protected]

Submitted February 16, 2010; revised May 17, 2010; accepted June 11, 2010.

Pain 151(1):p 61-68, October 2010. | DOI: 10.1016/j.pain.2010.06.012

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 Fifty unique studies (including three unpublished studies) were included in the analyses.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