Department of Oncology, Rigshospitalet - Copenhagen University Hospital, Copenhagen, Denmark.
Department of Lung Diseases, Hvidovre Hospital, Copenhagen, Denmark.
Eur J Pain. 2021 Oct;25(9):1859-1875. doi: 10.1002/ejp.1797. Epub 2021 Jun 22.
Long-term opioid treatment (L-TOT) of chronic non-cancer pain (CNCP) patients has been suspected to alter the endocrine system. This systematic review and meta-analysis aimed at investigating the published evidence of L-TOT effects on the endocrine system in adult CNCP patients.
A systematic search of the literature in MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and the CINAHL was performed. Studies examining measures of endocrine function of the hypothalamic-pituitary-gonadal, -adrenal, -thyroid, -somatotropic and -prolactin axis in adult CNCP patients in L-TOT (≥4 weeks of use) were included. Outcomes and the level of evidence were analyzed (The Cochrane Collaboration Tool, modified version of the Newcastle-Ottawa Scale and Rating of Recommendations Assessment, Development and Evaluation working group).
A total of 2,660 studies were identified; 1981 excluded and finally thirteen studies (one randomized controlled trial (RCT), three longitudinal- and nine cross-sectional studies) were analyzed. L-TOT was associated with low insulin, suppression of the hypothalamic-pituitary-gonadal axis and alterations of the hypothalamic-pituitary-adrenal axis in both men and women with CNCP compared to different control groups (CNCP or healthy pain-free). No other significant differences were reported. The studies had a high risk of bias and the overall quality of evidence was low.
There seems to be an impact of L-TOT in CNCP patients on several components of the endocrine system, but the level of evidence is weak. Given the high prevalence of L-TOT use systematic studies of larger patient populations are urgently needed.
This systematic review and meta-analysis suggested that long-term opioid treatment may suppress the hypothalamic-pituitary-gonadal axis, and result in lower insulin levels and alter the glucocorticoid adrenal axis in adult chronic non-cancer pain patients. This adds to the need of more research of both clinical and paraclinical outcomes and their association when initiating and maintaining long-term opioid treatment.
长期阿片类药物治疗（L-TOT）慢性非癌痛（CNCP）患者被怀疑会改变内分泌系统。本系统评价和荟萃分析旨在调查 L-TOT 对成年 CNCP 患者内分泌系统影响的已发表证据。
对 MEDLINE、EMBASE、Cochrane 对照试验中心注册库和 CINAHL 中的文献进行了系统搜索。纳入研究检查了 L-TOT（使用≥4 周）中成年 CNCP 患者下丘脑-垂体-性腺、肾上腺、甲状腺、生长激素和催乳素轴内分泌功能的测量。分析了结局和证据水平（Cochrane 协作工具、纽卡斯尔-渥太华量表和推荐评估、制定和评估工作组的改良版本）。
共确定了 2660 项研究；排除了 1981 项，最终分析了 13 项研究（1 项随机对照试验（RCT）、3 项纵向研究和 9 项横断面研究）。与不同对照组（CNCP 或健康无痛）相比，L-TOT 与 CNCP 男性和女性的胰岛素水平降低、下丘脑-垂体-性腺轴抑制以及下丘脑-垂体-肾上腺轴改变有关。没有报告其他显著差异。这些研究存在高偏倚风险，证据总体质量较低。
L-TOT 似乎对 CNCP 患者内分泌系统的几个组成部分有影响，但证据水平较低。鉴于 L-TOT 使用的高患病率，迫切需要对更大的患者人群进行系统研究。
本系统评价和荟萃分析表明，长期阿片类药物治疗可能会抑制下丘脑-垂体-性腺轴，导致成年慢性非癌痛患者的胰岛素水平降低，并改变糖皮质激素肾上腺轴。这增加了在开始和维持长期阿片类药物治疗时对临床和临床前结局及其相关性进行更多研究的必要性。
