Hormonal Influences on Epilepsy and Seizure Susceptibility

Hormones profoundly modulate neuronal excitability through dynamic fluctuations in sex steroids, corticosteroids and neurosteroids. Periodic changes in progesterone and oestrogen during the menstrual cycle give rise to catamenial epilepsy, in which perimenstrual progesterone withdrawal diminishes neuroprotective GABAergic inhibition and transiently lowers seizure thresholds. Conversely, oestrogens may enhance excitatory glutamatergic transmission. Stress-related hormones from the hypothalamic-pituitary-adrenal axis can prime limbic-cortical circuits to promote epileptogenesis following brain insult. Experimental models have elucidated the conversion of progesterone to allopregnanolone, a potent positive modulator of GABAA receptors, and the excitatory actions of oestrogen metabolites. Androgen derivatives also exert bidirectional effects, with some metabolites enhancing GABAergic tone and others potentiating excitability. Translational research underscores life-course considerations in women—from puberty through menopause—and highlights the need for personalised hormone-based strategies to mitigate seizure clusters. Emerging molecular targets support the development of neurosteroid replacement therapies and receptor-specific modulators, with significant implications for improving control in refractory and cyclical seizure disorders.

Research from Nature Portfolio

Studies in female Proechimys rodents reveal an innate resistance to status epilepticus induction linked to acute rises in progesterone and glucose that normalise shortly after seizure onset. Ovariectomy altered hippocampal GABAergic receptor density, indicating that ovarian hormones directly influence seizure thresholds. These findings uncover endogenous protective mechanisms and provide a comparative framework for the design of neurosteroid-based interventions aimed at enhancing seizure resilience.

Hormonal Influences on Epilepsy and Seizure Susceptibility publication trend

The graph below shows the total number of articles in hormonal influences on epilepsy and seizure susceptibility across all publications each year (not limited to Nature Index journals).

Technical terms

Catamenial epilepsy: A seizure pattern characterised by exacerbations linked to phases of the menstrual cycle due to fluctuations in sex steroid levels.

Neurosteroid: A steroid synthesised in the nervous system that modulates neuronal excitability independently of peripheral endocrine sources.

GABAA receptor: A ligand-gated chloride channel that mediates the majority of fast inhibitory neurotransmission and is sensitive to modulation by neurosteroids and progesterone.

Seizure susceptibility: The propensity of neuronal networks to initiate and propagate epileptic discharges in response to internal or external stimuli.

References

1. Catamenial Epilepsy: Discovery of an Extrasynaptic Molecular Mechanism for Targeted Therapy. Frontiers in Cellular Neuroscience (2016).
2. Role of hormones and neurosteroids in epileptogenesis. Frontiers in Cellular Neuroscience (2013).
3. Hormonal and biochemical changes in female Proechimys guyannensis, an animal model of resistance to pilocarpine-induced status epilepticus. Scientific Reports (2020).
4. Insights into neurosteroids and their role in women with epilepsy. Frontiers in Global Women's Health (2024).
5. THE IMPACT OF H YPOTHALAMIC-PITUITARY-ADRENAL SYSTEM HORMONES ON EPILEPTOGENESIS. Russian Journal of Child Neurology (2017).
6. Zyklusgebundene Anfälle der Frau. Clinical Epileptology (2024).
7. The menstrual-epilepsy nexus: exploring the relationship between menstrual cycle and epileptic seizures in women. Revista Română de Neurologie (2025).