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Implications of sex-related differences in central nervous system disorders for drug research and development
Research on sex differences in central nervous system disorders has developed substantially in recent years. Here, we discuss selected examples and the implications for drug development.
Sex-related differences have been reported in many medical conditions, including several central nervous system (CNS) disorders1. On the one hand, women are more likely than men to be affected by diseases such as Alzheimer disease (AD), major depressive disorder (MDD), meningioma, pain disorders, migraine, panic disorder or multiple sclerosis. On the other hand, women tend to be less affected than men by diseases such as Parkinson disease, attention deficit hyperactivity disorder (ADHD) or autism spectrum disorder1. Furthermore, the type and course of symptoms, as well as responses to medications, can also be affected by the sex of the individuals. The underlying mechanisms of these differences are thought to be multifactorial and include neurostructural and biological factors — particularly the influence of sex hormones — as well as psychological and socio-cultural factors such as social stressors1.
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Nature Reviews Drug Discovery20, 881-882 (2021)
doi: https://doi.org/10.1038/d41573-021-00115-6
Acknowledgements
We are grateful to the ECNP and to Barbara Franke for her contribution to the discussion.
Disclaimer
The views expressed in this article are the personal views of the author(s) and may not be understood or quoted as being made on behalf of or reflecting the position of the regulatory agency/agencies or organisations with which the author(s) is/are employed/affiliated.
References
Shansky, R. M. Sex Differences in the Central Nervous System 1st edn (Academic Press, 2015)
Ferretti, M. T. et al. Sex and gender differences in Alzheimer’s disease: current challenges and implications for clinical practice. Position paper of the Dementia and Cognitive Disorders Panel of the European Academy of Neurology. Eur. J. Neurol.27, 928–943 (2020).
Melchior, M., Poisbeau, P., Gaumond, I. & Marchand, S. Insight into the mechanisms and the emergence of sex differences in pain. Neuroscience338, 63–80 (2016).
Kokras, N., Hodes, G. E., Bangasser, D. A. & Dalla, C. Sex differences in the hypothalamic-pituitary-adrenal axis: An obstacle to antidepressant drug development? Br. J. Pharmacol.176, 4090–4106 (2019).
A.S.C. is currently an employee of Biogen and also the Vice-president of EU research. N.K. and C.D. have received honoraria and financial support from Janssen-Cilag, Lundbeck, Elpen and Medochemie. None of these is relevant to this work. M.T.F. is the co-founder and CSO of the Women’s Brain Project, a non-profit organization, and has received personal fees from Eli Lilly, not related to this work. The other authors declare no competing interests.
