Department of Neurology, Inselspital, Bern University Hospital and University of Bern, Freiburgstrasse, Bern, Switzerland.
Department of Neurology, Inselspital, Bern University Hospital and University of Bern, Freiburgstrasse, Bern, Switzerland; Department of Biomedical Research and Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland.
Int Rev Neurobiol. 2022;164:129-178. doi: 10.1016/bs.irn.2022.06.011. Epub 2022 Aug 9.
Multiple sclerosis (MS), Neuromyelitis optica spectrum disorder (NMOSD) and Myelin-Oligodendrocyte-Glycoprotein antibody associated disorder (MOGAD) are demyelinating disorders of the central nervous system (CNS) of autoimmune origin. Here, we summarize general considerations on sex-specific differences in the immunopathogenesis and hormonal influences as well as key clinical and epidemiological elements. Gender-specific issues are widely neglected starting with the lacking separation of sex as a biological variable and gender comprising the sociocultural components. As for other autoimmune diseases, female preponderance is common in MS and NMOSD. However, sex distribution in MOGAD seems equal. As in MS, immunotherapy in NMOSD and MOGAD is crucial to prevent further disease activity. Therefore, we assessed data on sex differences of the currently licensed disease-modifying treatments for efficacy and safety. This topic seems widely neglected with only fragmented information resulting from post-hoc analyses of clinical trials or real-world post-marketing studies afflicted with lacking power and/or inherent sources of bias. In summary, biological hypotheses of sex differences including genetic factors, the constitution of the immune system and hormonal influences are based upon human and preclinical data, especially for the paradigmatic disease of MS whereas specific data for NMOSD and MOGAD are widely lacking. Epidemiological and clinical differences between men and women are well described for MS and to some extent for NMOSD, yet, with remaining contradictory findings. MOGAD needs further detailed investigation. Sex-specific analyses of safety and efficacy of long-term immunotherapies need to be addressed in future studies designed and powered to answer the pressing questions and to optimize and individualize treatment.
多发性硬化症（MS）、视神经脊髓炎谱系障碍（NMOSD）和髓鞘少突胶质细胞糖蛋白抗体相关疾病（MOGAD）是自身免疫性中枢神经系统（CNS）脱髓鞘疾病。在这里，我们总结了免疫发病机制和激素影响以及关键临床和流行病学因素中性别特异性差异的一般考虑因素。从缺乏将性别作为生物学变量的分离以及包含社会文化成分的性别来看，性别特异性问题从一开始就被广泛忽视。与其他自身免疫性疾病一样，女性在 MS 和 NMOSD 中更为常见。然而，MOGAD 的性别分布似乎是平等的。与 MS 一样，NMOSD 和 MOGAD 的免疫治疗对于预防进一步的疾病活动至关重要。因此，我们评估了目前批准的疾病修正治疗在疗效和安全性方面的性别差异数据。这个主题似乎被广泛忽视，只有临床试验或上市后真实世界研究的事后分析产生的零碎信息，这些研究受到缺乏力量和/或固有偏倚源的影响。总之，性别差异的生物学假设包括遗传因素、免疫系统构成和激素影响，这些都是基于人体和临床前数据，特别是对于 MS 这一典范疾病，而 NMOSD 和 MOGAD 的具体数据则广泛缺乏。MS 和在一定程度上 NMOSD 中描述了男性和女性之间的流行病学和临床差异，但仍存在相互矛盾的发现。MOGAD 需要进一步详细调查。未来的研究需要对长期免疫疗法的安全性和疗效进行性别特异性分析，以解决紧迫的问题，并优化和个体化治疗。
