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Endogenous female reproductive hormones and the risk of amyotrophic lateral sclerosis

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Abstract

The pathogenesis of amyotrophic lateral sclerosis (ALS) is considered to be multifactorial. Several epidemiological studies showed a lower incidence of ALS in women than in men. This suggests a possible protective effect of female reproductive hormones. The aim of this study was to investigate the association between female reproductive hormones and ALS. We performed a population-based, case–control study in the Netherlands between 1st January 2006 and 1st December 2009. Only women with a natural menopause were included in the analysis. A total of 209 (85 %) of 246 female patients and 672 (93 %) of 719 controls returned a questionnaire on reproductive history to calculate the reproductive time-span and lifetime endogenous estrogen exposure (calculated by subtracting the duration of pregnancies and of oral contraceptive use, and the number of post-ovulatory weeks from the reproductive time-span). 131 (63 %) patients and 430 (64 %) age-matched, population-based controls had experienced a natural menopause. Multivariate analysis showed that increasing the reproductive time-span by a year decreases the risk of ALS with an OR of 0.95 (p = 0.005). Each year longer reproductive time-span [HR 0.90 (p = 0.01)] and lifetime endogenous estrogen exposure [HR 0.96 (p = 0.025)] were associated with a longer survival of ALS patients. The positive association of a longer reproductive time-span and susceptibility and survival of ALS might imply that longer exposure to female reproductive hormones has a neuroprotective effect on motor neurons.

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Acknowledgments

The study was funded by the Prinses Beatrix Fonds and The Netherlands ALS Foundation. The work leading to this investigation has received funding from the European Community’s Seventh Framework Program (FP7/2007-2013) under the Health Cooperation Program.

Conflicts of interest

The authors declare that they have no conflict of interest.

Ethical standard

All human studies have been approved by the appropriate ethics committee and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki.

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Authors and Affiliations

  1. Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands

    Sonja de Jong, Mark Huisman, Nadia Sutedja, Jan Veldink & Leonard van den Berg

  2. Department of Neurology, Academic Medical Center, Amsterdam, The Netherlands

    Anneke van der Kooi & Marianne de Visser

  3. Department of Neurology, Donders Institute for Brain, Cognition and Behavior, Centre for Neuroscience, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

    Jurgen Schelhaas

  4. Julius Center for Health Science and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands

    Yvonne van der Schouw

Authors
  1. Sonja de Jong
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  2. Mark Huisman
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  3. Nadia Sutedja
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  4. Anneke van der Kooi
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  5. Marianne de Visser
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  6. Jurgen Schelhaas
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  7. Yvonne van der Schouw
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  8. Jan Veldink
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  9. Leonard van den Berg
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Corresponding author

Correspondence to Sonja de Jong.

Additional information

J. Veldink and L. van den Berg shared last authors.

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de Jong, S., Huisman, M., Sutedja, N. et al. Endogenous female reproductive hormones and the risk of amyotrophic lateral sclerosis. J Neurol 260, 507–512 (2013). https://doi.org/10.1007/s00415-012-6665-5

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  • DOI: https://doi.org/10.1007/s00415-012-6665-5

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