Department of Biomedical Sciences, Section of Neuroscience and Clinical Pharmacology, University of Cagliari, S.S. 554, km. 4.500, I-09042, Monserrato, CA, Italy.
Laboratory of Sex-gender Medicine, National Institute of Biostructures and Biosystems, 07100, Sassari, Italy.
Pharmacol Res. 2019 Oct;148:104447. doi: 10.1016/j.phrs.2019.104447. Epub 2019 Sep 6.
There are conflicting results about sex differences in the response to opioids for pain control and the role of potential influencing factors of these differences has not been investigated. We meta-analyzed differences and similarities between men and women in opioid response for pain control and investigated the potential influence of baseline pain intensity, age, body weight, and other factors in these findings. PubMed, Scopus, and Cochrane CENTRAL were searched through January 15, 2019, for clinical studies in which opioids were administered for pain control. We included clinical studies in which (a) opioids were used to treat acute or chronic pain, (b) the response to opioids was broken down for men and women, and (c) the response to opioids was reported as (i) difference between baseline and final Visual Analog Scale of Pain Intensity (VASPI) score 30 min after opioid administration (Delta-VASPI at 30'), or daily dose of opioids (ii) self-administered by patients (patient-controlled analgesia PCA), or (iii) administered by physicians. Risk of bias was evaluated using ROBINS-I and the overall quality of evidence for primary outcomes was evaluated using the GRADE system. Globally, we included 40 comparisons (6794 patients). Regarding acute pain, we found moderate quality of evidence that women and men do not differ in their response to opioids 30 min after their administration [Delta-VASPI at 30': mean difference, MD = 0.42 (-0.07; 0.91)]. We also found moderate quality of evidence that women self-administer lower daily amounts of opioids [daily PCA: standardized mean difference, SMD = -0.30 (-0.41; -0.18)]. Regarding chronic pain, we found low quality of evidence that women receive lower daily doses for non-cancer pain [MD = -36.42 (-57.86; -14.99)]. By contrast, we found very low quality of evidence that women and men do not differ in the daily dose of opioids for cancer pain [MD = -16.09 (-40.13; 7.94)]. Age, comorbid mental disorders, type of administration, type of opioids, type of patients, and body weight significantly modified these results. In conclusion, the results of the present meta-analysis suggest that men and women may differ in the response to opioids for pain relief, but these differences as well as similarities are significantly influenced by factors like age and comorbid mental disorders. However, the role of these factors is not usually evaluated in the prescription of opioids for pain control. There is an urgent need to conduct clinical trials on the use of opioid medications for pain, in which information about all possible influencing factors are provided and broken down for men and women.
关于性别在阿片类药物控制疼痛反应中的差异存在相互矛盾的结果，且这些差异的潜在影响因素尚未得到研究。我们对男性和女性在阿片类药物控制疼痛反应中的差异进行了荟萃分析，并研究了基线疼痛强度、年龄、体重和其他因素对这些发现的潜在影响。我们通过 2019 年 1 月 15 日检索 PubMed、Scopus 和 Cochrane CENTRAL，以查找阿片类药物用于疼痛控制的临床研究。我们纳入了（a）阿片类药物用于治疗急性或慢性疼痛，（b）阿片类药物反应按男性和女性进行细分，以及（c）阿片类药物反应报告为（i）阿片类药物给药后 30 分钟基线和最终视觉模拟评分法疼痛强度（VASPI）之间的差异[阿片类药物给药后 30 分钟的 Delta-VASPI（Delta-VASPI at 30'）]或（ii）患者自行给予的每日阿片类药物剂量（患者自控镇痛 PCA），或（iii）医生给予的阿片类药物剂量。使用 ROBINS-I 评估偏倚风险，使用 GRADE 系统评估主要结局的总体证据质量。总体而言，我们纳入了 40 项比较（6794 名患者）。关于急性疼痛，我们发现女性和男性在阿片类药物给药后 30 分钟的反应没有差异的证据质量为中等[Delta-VASPI at 30'：平均差异，MD=0.42（-0.07；0.91）]。我们还发现女性自我给予的每日阿片类药物剂量较低的证据质量为中等[每日 PCA：标准化均数差，SMD=-0.30（-0.41；-0.18）]。关于慢性疼痛，我们发现女性接受非癌症疼痛的每日剂量较低的证据质量为低[MD=-36.42（-57.86；-14.99）]。相比之下，我们发现女性和男性在癌症疼痛的每日阿片类药物剂量方面没有差异的证据质量非常低[MD=-16.09（-40.13；7.94）]。年龄、合并精神疾病、给药类型、阿片类药物类型、患者类型和体重显著改变了这些结果。总之，本荟萃分析的结果表明，男性和女性在阿片类药物缓解疼痛方面可能存在差异，但这些差异以及相似之处受到年龄和合并精神疾病等因素的显著影响。然而，在开具阿片类药物控制疼痛时，通常不会评估这些因素的作用。迫切需要进行关于阿片类药物治疗疼痛的临床试验，其中提供有关所有可能影响因素的信息，并按男性和女性进行细分。
