Supplementary Material for: Association between Serum Prolactin Levels and Neurodegenerative Diseases: Systematic Review and Meta-Analysis

<b><i>Introduction:</i></b> Prolactin (PRL) exerts inflammatory and anti-inflammatory properties and is also thought to play an important role in the pathogenesis of neurodegenerative diseases (NDs). However, serum PRL levels in patients with NDs were inconsistent in the research literature. <b><i>Objective:</i></b> We aimed to assess the serum PRL levels in patients with NDs. <b><i>Methods:</i></b> Electronic databases, including MEDLINE, Embase, Cochrane Library database, clinicaltrials.gov, Web of Science, and Google Scholar, and reference lists of articles were searched up to December 31, 2020. Pooled standard mean difference (SMD) with 95% confidence interval (CI) was calculated by fixed-effect or random-effect model analysis. <b><i>Results:</i></b> A total of 36 comparisons out of 29 studies (3 RCTs and 26 case controls) focusing on NDs (including Parkinson’s disease, Alzheimer’s disease, Huntington’s disease [HD], multiple sclerosis [MS], and epilepsy) were reported. The meta-analysis showed that there was no statistically significant difference in serum PRL levels between patients with NDs and healthy controls (SMD = 0.40, 95% CI: −0.16 to 0.96, <i>p</i> = 0.16). Subgroup analysis showed that serum PRL levels in patients with HD and MS were higher than those of healthy controls. Furthermore, patients with NDs aged &lt;45 years had higher serum PRL levels (SMD = 0.97, 95% CI: 0.16–1.78, <i>p</i> = 0.018) than healthy controls. High serum PRL levels were found in subgroups such as the microenzymatic method, Asia, and the Americas. <b><i>Conclusions:</i></b> Our meta-analysis showed serum PRL levels in patients with HD and MS were significantly higher than those in healthy controls. Serum PRL levels were associated with age, region, and detection method. Other larger sample studies using more uniform detection methods are necessary to confirm our results.

<b><i>引言：</i></b> 催乳素（Prolactin, PRL）兼具促炎与抗炎特性，同时被认为在神经退行性疾病（Neurodegenerative diseases, NDs）的发病机制中发挥重要作用。然而，现有研究文献中关于神经退行性疾病患者血清催乳素水平的报道并不一致。<b><i>目的：</i></b> 本研究旨在评估神经退行性疾病患者的血清催乳素水平。<b><i>方法：</i></b> 检索截至2020年12月31日的MEDLINE、Embase、考克兰图书馆数据库（Cochrane Library database）、clinicaltrials.gov、Web of Science及Google Scholar等电子数据库，并纳入相关文献的参考文献列表。采用固定效应模型或随机效应模型分析，计算合并标准均数差（Pooled Standard Mean Difference, SMD）及其95%置信区间（Confidence Interval, CI）。<b><i>结果：</i></b> 最终纳入29项研究（含3项随机对照试验（Randomized Controlled Trial, RCT）与26项病例对照研究），共36组对照数据，涉及的神经退行性疾病包括帕金森病、阿尔茨海默病、亨廷顿病（Huntington’s disease, HD）、多发性硬化（Multiple Sclerosis, MS）及癫痫。荟萃分析（meta-analysis）结果显示，神经退行性疾病患者与健康对照者的血清催乳素水平无统计学显著性差异（SMD=0.40，95%CI：-0.16~0.96，p=0.16）。亚组分析表明，亨廷顿病与多发性硬化患者的血清催乳素水平高于健康对照者。此外，年龄小于45岁的神经退行性疾病患者血清催乳素水平（SMD=0.97，95%CI：0.16~1.78，p=0.018）高于健康对照者。在微酶法（microenzymatic method）检测、亚洲及美洲地区等亚组中，患者血清催乳素水平更高。<b><i>结论：</i></b> 本荟萃分析（meta-analysis）显示，亨廷顿病与多发性硬化患者的血清催乳素水平显著高于健康对照者。血清催乳素水平与患者年龄、研究地区及检测方法相关。未来需开展样本量更大、检测方法更统一的研究以验证本研究结果。