Programa de Pós-Graduação Em Ciências Fisiológicas, Instituto de Ciências Biológicas, Universidade Federal Do Rio Grande (FURG), Porto Alegre, Rio Grande do Sul, Brazil.
Departamento de Farmacologia, Instituto de Ciências Básicas da Saúde, Universidade Federal Do Rio Grande Do Sul (UFRGS), Rua Ramiro Barcelos 2600, Building UFRGS 21116, Room 430, Zip code, Porto Alegre - RS, 90035-003, Brazil.
Mol Neurobiol. 2022 Oct;59(10):6341-6362. doi: 10.1007/s12035-022-02970-9. Epub 2022 Aug 4.
Since the publication of two phase III clinical trials not supporting the use of progesterone in patients with traumatic brain injury (TBI), several possible explanations have been postulated, including limitations in the analysis of results from preclinical evidence. Therefore, to address this question, a systematic review and meta-analysis was performed to evaluate the effects of progesterone as a neuroprotective agent in preclinical animal models of TBI. A total of 48 studies were included for review: 29 evaluated brain edema, 21 evaluated lesion size, and 0 studies reported the survival rate. In the meta-analysis, it was found that progesterone reduced brain edema (effect size - 1.73 [- 2.02, - 1.44], p < 0.0001) and lesion volume (effect size - 0.40 [- 0.65, - 0.14], p = 0.002). Lack of details in the studies hindered the assessment of risk of bias (through the SYRCLE tool). A funnel plot asymmetry was detected, suggesting a possible publication bias. In conclusion, preclinical studies show that progesterone has an anti-edema effect in animal models of TBI, decreasing lesion volume or increasing remaining tissue. However, more studies are needed using assessing methods with lower risk of histological artifacts.
由于两项三期临床试验未能支持在创伤性脑损伤（TBI）患者中使用孕激素，因此提出了几种可能的解释，包括对临床前证据的结果分析存在局限性。因此，为了回答这个问题，进行了一项系统评价和荟萃分析，以评估孕激素作为 TBI 动物模型神经保护剂的作用。共有 48 项研究纳入综述：29 项评估脑水肿，21 项评估病灶大小，0 项研究报告存活率。荟萃分析发现，孕激素可减轻脑水肿（效应大小-1.73[-2.02，-1.44]，p<0.0001）和病灶体积（效应大小-0.40[-0.65，-0.14]，p=0.002）。研究中缺乏细节信息，阻碍了通过 SYRCLE 工具对偏倚风险的评估。漏斗图显示存在不对称性，提示可能存在发表偏倚。总之，临床前研究表明，孕激素在 TBI 动物模型中具有抗水肿作用，可减少病灶体积或增加剩余组织。然而，需要更多使用具有较低组织学伪影风险评估方法的研究。
