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Chapter 4 - Hormonal Influences in Women with Epilepsy

Published online by Cambridge University Press:  19 December 2024

By
Suchitra Joshi  and
Jaideep Kapur
Edited by
Esther Bui  and
P. Emanuela Voinescu
Esther Bui
Affiliation:
Toronto Western Hospital
P. Emanuela Voinescu
Affiliation:
Brigham & Women's Hospital, Boston, MA
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Summary

Progesterone and estrogen influence neuronal activity and regulate seizures in women with epilepsy. The reproductive cycle-linked fluctuations in these hormones alter seizure frequency and manifest as cyclic seizure exacerbation. This seizure precipitation is classified as catamenial when seizures occur exclusively during one phase of the cycle or seizure frequency double during one phase of the cycle compared to other phases. Studies in experimental animals have focused on understanding molecular mechanisms underlying the perimenstrual increase in seizures, which relates to progesterone and mid-cycle increase related to estrogen. These studies have revealed that progesterone could exert an acute anticonvulsant effect. However, after repeated administration in chronic epilepsy models, progesterone appears to have no effect or even worsened seizure frequency. The anticonvulsant effects require its metabolite allopregnanolone, with rapid actions causing potentiation of the GABAA receptor-mediated inhibitory neurotransmission. On the other hand, the seizure-promoting effects rely on slower progesterone receptor-dependent enhancement of glutamatergic transmission. These complex and opposing effects help explain the unexpected lack of anticonvulsant efficacy of this hormone in a clinical trial and warrant the further characterization of the diversity of progesterone’s neuronal actions exerted through multiple cellular signaling molecules. In contrast to the dual effects of progesterone, estrogens, which peak in mid-cycle, primarily exert proconvulsant effects. Estrogens potentiate excitatory transmission. These seizure-promoting actions of estrogens are also evident in women with epilepsy, some of who may experience increased seizures during the follicular phase concomitant with the rising estrogen levels. Some of the neuromodulatory actions of estrogens are dependent on the activation of their cognate receptors, the estrogen receptors. The estrogen receptor block could exert neuroprotective and antiseizure effects.

Keywords

Progesteroneestrogencatamenial seizuresallopregnanoloneprogesterone receptorsestrogen receptorsglutamatergic neurotransmissionGABA-A receptors
Type
Chapter
Information
Women with Epilepsy
A Practical Management Handbook
 , pp. 64 - 83
Publisher: Cambridge University Press
Print publication year: 2025

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