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.
Pain. 2010 Oct;151(1):61-68. doi: 10.1016/j.pain.2010.06.012. Epub 2010 Aug 9.
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 Fifty unique studies (including three unpublished studies) were included in the analyses.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.
尽管性别对阿片类药物疗效的影响引起了广泛关注，但任何这种差异的确认和方向仍然难以捉摸。我们对现有的关于μ 和混合μ/κ 阿片类药物对急性和实验性疼痛的性别差异的文献进行了系统回顾。分析中包括 50 项独特的研究（包括 3 项未发表的研究）。在 25 项关于μ 阿片类药物的临床研究中，没有发现性别-镇痛作用的显著关联。将分析仅限于患者自控镇痛（PCA）研究（无论使用何种阿片类药物），结果显示女性的镇痛效果更好（n=15，效应大小 0.22，95%置信区间 0.02-0.42，P=0.028）。进一步将分析仅限于 PCA 吗啡研究，结果显示女性的效果更大（n=11，效应大小=0.36，95%置信区间 0.17-0.56，P=0.003）。元回归表明，PCA 的持续时间越长，两性之间的效应差异进一步增加。在关于μ 阿片类药物的实验性疼痛研究中，女性对阿片类药物的镇痛作用更大（n=11，效应大小=0.35；95%置信区间 0.01-0.69，P=0.047），这主要归因于 6 项吗啡研究。女性患者具有更大的μ/κ 阿片类药物镇痛作用（n=7，效应大小 0.84；95%置信区间 0.25-1.43，P=0.005），但在实验研究中（n=7）未发现性别-镇痛作用的关联。在实验性疼痛研究和临床 PCA 研究中，吗啡诱导的镇痛作用存在性别差异，女性的吗啡疗效更大。关于非吗啡μ 和混合μ/κ 阿片类药物的数据不太令人信服，需要进一步研究。
