Sex biology in amyotrophic lateral sclerosis.

Although sex differences in amyotrophic lateral sclerosis (ALS) have not been studied systematically, numerous clinical and preclinical studies have shown sex to be influential in disease prognosis. Moreover, with the development of advanced imaging tools, the difference between male and female brain in structure and function and their response to neurodegeneration are more definitive. As discussed in this review, ALS patients exhibit a sex bias pertaining to the features of the disease, and their clinical, pathological, (and pathophysiological) phenotypes. Several epidemiological studies have indicated that this sex disparity stems from various aetiologies, including sex-specific brain structure and neural functioning, genetic predisposition, age, gonadal hormones, susceptibility to traumatic brain injury (TBI)/head trauma and lifestyle factors. • Sex along with factors such as genetics, site of onset and ethnicity contribute to ALS heterogeneity. • Sex differences is seen in major risk factors of ALS such as age, genetics, environment, physical activity. • ALS pathology such as neuroinflammation, neurodegeneration and muscle atrophy are also influenced by sex. • Due to the sex difference in response to treatment, it is important to include sex specific analysis in clinical trials. [ABSTRACT FROM AUTHOR]