Elsevier

Gender Medicine

Volume 7, Issue 6, December 2010, Pages 557-570
Gender Medicine

Review article
Effects of gender in amyotrophic lateral sclerosis

https://doi.org/10.1016/j.genm.2010.11.010Get rights and content

Abstract

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.

References (122)

  • JH Veldink et al.

    Sexual differences in onset of disease and response to exercise in a transgenic model of ALS

    Neuromuscul Disord.

    (2003)
  • CI Choi et al.

    Effects of estrogen on lifespan and motor functions in female hSOD1 G93A transgenic mice

    J Neurol Sci.

    (2008)
  • JS Allen et al.

    Sexual dimorphism and asymmetries in the gray-white composition of the human cerebrum

    Neuroimage.

    (2003)
  • S Spring et al.

    Sexual dimorphism revealed in the structure of the mouse brain using three-dimensional magnetic resonance imaging

    Neuroimage.

    (2007)
  • K Takase et al.

    Sex-specific 24-h acetylcholine release profile in the medial prefrontal cortex: Simultaneous measurement of spontaneous locomotor activity in behaving rats

    Neuroscience.

    (2009)
  • K Abhinav et al.

    Amyotrophic lateral sclerosis in South-East England: A population-based study. The South-East England register for amyotrophic lateral sclerosis (SEALS Registry)

    Neuroepidemiology.

    (2007)
  • MC Vazquez et al.

    Incidence and prevalence of amyotrophic lateral sclerosis in Uruguay: A population-based study

    Neuroepi-demiology.

    (2008)
  • A Chiò et al.

    Epidemiology of ALS in Italy: A 10-year prospective population-based study

    Neurology.

    (2009)
  • V McGuire et al.

    Incidence of amyotrophic lateral sclerosis in three counties in western Washington state

    Neurology.

    (1996)
  • LC Wijesekera et al.

    Amyotrophic lateral sclerosis

    Orphanet J Rare Dis.

    (2009)
  • F Fang et al.

    Familial aggregation of amyotrophic lateral sclerosis

    Ann Neurol.

    (2009)
  • NA Sutedja et al.

    Exposure to chemicals and metals and risk of amyotrophic lateral sclerosis: A systematic review

    Amyotroph Lateral Scler.

    (2009)
  • NA Sutedja et al.

    What we truly know about occupation as a risk factor for ALS: A critical and systematic review

    Amyotroph Lateral Scler.

    (2009)
  • P Talman et al.

    Clinical phenotypes and natural progression for motor neuron disease: Analysis from an Australian database

    Amyotroph Lateral Scler.

    (2009)
  • J Ganesalingam et al.

    Latent cluster analysis of ALS phenotypes identifies prognostically differing groups

    PLoS One.

    (2009)
  • A Binazzi et al.

    An exploratory case-control study on spinal and bulbar forms of amyotrophic lateral sclerosis in the province of Rome

    Amyotroph Lateral Scler.

    (2009)
  • IP Blair et al.

    FUS mutations in amyotrophic lateral sclerosis: Clinical, pathological, neurophysiological and genetic analysis

    J Neurol Neurosurg Psychiatry.

    (2010)
  • E Kabashi et al.

    TARDBP mutations in individuals with sporadic and familial amyotrophic lateral sclerosis

    Nat Genet.

    (2008)
  • Lai SL, Abramzon Y, Schymick JC, et al, for the ITALSGEN Consortium. FUS mutations in sporadic amyotrophic lateral...
  • P Corcia et al.

    The importance of the SMN genes in the genetics of sporadic ALS

    Amyotroph Lateral Scler.

    (2009)
  • IR Mackenzie et al.

    Pathological TDP-43 distinguishes sporadic amyotrophic lateral sclerosis from amyotrophic lateral sclerosis with SOD1 mutations

    Ann Neurol.

    (2007)
  • Q Sha et al.

    Genome-wide association reveals three SNPs associated with sporadic amyotrophic lateral sclerosis through a two-locus analysis

    BMC Med Genet.

    (2009)
  • T Dunckley et al.

    Whole-genome analysis of sporadic amyotrophic lateral sclerosis

    N Engl J Med.

    (2007)
  • AM Wills et al.

    A large-scale international meta-analysis of paraoxonase gene polymorphisms in sporadic ALS

    Neurology.

    (2009)
  • C Armon

    Smoking may be considered an established risk factor for sporadic ALS

    Neurology.

    (2009)
  • A Chio et al.

    ALS in Italian professional soccer players: The risk is still present and could be soccer-specific

    Amyotroph Lateral Scler.

    (2009)
  • E Beghi et al.

    Amyotrophic lateral sclerosis, physical exercise, trauma and sports: Results of a population-based pilot casecontrol study

    Amyotroph Lateral Scler.

    (2010)
  • NA Sutedja et al.

    Lifetime occupation, education, smoking, and risk of ALS

    Neurology.

    (2007)
  • F Fang et al.

    Workplace exposures and the risk of amyotrophic lateral sclerosis

    Environ Health Perspect.

    (2009)
  • BR Brooks et al.

    El Escorial revisited: Revised criteria for the diagnosis of amyotrophic lateral sclerosis

    Amyotroph Lateral Scler Other Motor Neuron Disord.

    (2000)
  • BJ Traynor et al.

    Incidence and prevalence of ALS in Ireland, 1995-1997: A population-based study

    Neurology.

    (1999)
  • E Beghi et al.

    Incidence of ALS in Lombardy, Italy

    Neurology.

    (2007)
  • The Scottish Motor Neuron Disease Register: A prospective study of adult onset motor neuron disease in Scotland. Methodology, demography and clinical features of incident cases in 1989

    J Neurol Neurosurg Psychiatry.

    (1992)
  • M Murphy et al.

    Increasing incidence of ALS in Canterbury, New Zealand: A 22-year study

    Neurology.

    (2008)
  • M Sajjadi et al.

    Epidemiology of amyotrophic lateral sclerosis in Isfahan, Iran

    Eur J Neurol.

    (2010)
  • LC Werneck et al.

    A clinical epidemiological study of 251 cases of amyotrophic lateral sclerosis in the south of Brazil

    Arq Neuropsiquiatr.

    (2007)
  • ZR Manjaly et al.

    The sex ratio in amyotrophic lateral sclerosis: A population based study

    Amyotroph Lateral Scler.

    (2010)
  • LJ Haverkamp et al.

    Natural history of amyotrophic lateral sclerosis in a database population. Validation of a scoring system and a model for survival prediction

    Brain.

    (1995)
  • N Stambler et al.

    Prognostic indicators of survival in ALS

    Neurology.

    (1998)
  • B Marin et al.

    Incidence of amyotrophic lateral sclerosis in the Limousin region of France, 1997–2007

    Amyotroph Lateral Scler.

    (2009)
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