School of Medicine, Trinity College Dublin, Dublin, Ireland.
Department of Psychiatry and Trinity Translational Medicine Institute (TTMI), Trinity College Dublin, Dublin, Ireland; Trinity College Institute of Neuroscience, Trinity College Dublin, Lloyd Building, Dublin 2, Dublin, Ireland; FutureNeuro, the SFI Research Centre for Chronic and Rare Neurological Diseases.
Neurobiol Dis. 2023 Aug;184:106214. doi: 10.1016/j.nbd.2023.106214. Epub 2023 Jun 28.
Many studies show the importance of biological sex for the onset, progression, and response to treatment in brain disorders. In line with these reports, health agencies have requested that all trials, both at the clinical and preclinical level, use a similar number of male and female subjects to correctly interpret the results. Despite these guidelines, many studies still tend to be unbalanced in the use of male and female subjects. In this review we consider three neurodegenerative disorders: Alzheimer's disease, Parkinson's disease, Amyotrophic lateral sclerosis, and three psychiatric disorders: Depression, Attention Deficit Hyperactivity Disorder, and Schizophrenia. These disorders were chosen because of their prevalence and their recognized sex-specific differences in onset, progression, and response to treatment. Alzheimer's disease and Depression demonstrate higher prevalence in females, whereas Parkinson's Disease, Amyotrophic lateral sclerosis, Attention Deficit Hyperactivity Disorder, and schizophrenia show higher prevalence in males. Results from preclinical and clinical studies examining each of these disorders revealed sex-specific differences in risk factors, diagnostic biomarkers, and treatment response and efficacy, suggesting a role for sex-specific therapies in neurodegenerative and neuropsychiatric disorders. However, the qualitative analysis of the percentage of males and females enrolled in clinical trials in the last two decades shows that for most of the disorders, there is still a sex bias in the patients' enrolment.
许多研究表明,生物学性别对脑疾病的发病、进展和治疗反应都很重要。与这些报告一致,卫生机构要求所有临床试验,包括临床前和临床阶段,都使用类似数量的男性和女性受试者,以正确解释结果。尽管有这些指导方针,但许多研究在使用男性和女性受试者方面仍然存在不平衡。在这篇综述中,我们考虑了三种神经退行性疾病:阿尔茨海默病、帕金森病、肌萎缩侧索硬化症,以及三种精神疾病:抑郁症、注意缺陷多动障碍和精神分裂症。选择这些疾病是因为它们的普遍性以及它们在发病、进展和治疗反应方面的公认性别差异。阿尔茨海默病和抑郁症在女性中的发病率更高,而帕金森病、肌萎缩侧索硬化症、注意缺陷多动障碍和精神分裂症在男性中的发病率更高。对这些疾病中的每一种进行的临床前和临床研究结果表明,在危险因素、诊断生物标志物和治疗反应及疗效方面存在性别差异,这表明性别特异性疗法在神经退行性和神经精神疾病中的作用。然而,对过去二十年中参加临床试验的男性和女性的百分比进行的定性分析表明,对于大多数疾病,在患者入组方面仍然存在性别偏见。