Effects of gender in amyotrophic lateral sclerosis.

BACKGROUND There is evidence that amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND), is more common in men than in women and that gender influences the clinical features of the disease. The causes of this are unknown. OBJECTIVE This review examines the gender differences that are found in ALS and postulates reasons for these differences. METHODS A literature review of PubMed (with no date limits) was performed to find information about gender differences in the incidence, prevalence, and clinical features of ALS, using the search terms ALS or MND and gender or sex, ALS prevalence, and SOD1 mice and gender. Articles were reviewed for information about gender differences, together with other articles that were already known to the authors. RESULTS The incidence and prevalence of ALS are greater in men than in women. This gender difference is seen in large studies that included all ALS patients (sporadic and familial), but is not seen when familial ALS is studied independently. Men predominate in the younger age groups of patients with ALS. Sporadic ALS has different clinical features in men and women, with men having a greater likelihood of onset in the spinal regions, and women tending to have onset in the bulbar region. Gender appears to have no clear effect on survival. In animals with superoxide dismutase 1 (sod1) mutations, sex does affect the clinical course of disease, with earlier onset in males. Possible reasons for the differences in ALS between men and women include different exposures to environmental toxins, different biological responses to exogenous toxins, and possibly underlying differences between the male and female nervous systems and different abilities to repair damage. CONCLUSIONS There is a complex interaction between gender and clinical phenotypes in ALS. Understanding the causes of the gender differences could give clues to processes that modify the disease.