Neuroendocrine considerations in the treatment of men and women with epilepsy

Abstract

Complex, multidirectional interactions between hormones, seizures, and the medications used to control them can present a challenge for clinicians treating patients with epilepsy. Many hormones act as neurosteroids, modulating brain excitability via direct binding sites. Thus, changes in endogenous or exogenous hormone levels can affect the occurrence of seizures directly as well as indirectly through pharmacokinetic effects that alter the concentrations of antiepileptic drugs. The underlying structural and physiological brain abnormalities of epilepsy and the metabolic activity of antiepileptic drugs can adversely affect hypothalamic and gonadal functioning. Knowledge of these complex interactions has increased and can now be incorporated in meaningful treatment approaches for men and women with epilepsy.

Conflict of interest statement

Conflicts of interest

PBP declares that she has no conflicts of interest.

Copyright © 2013 Elsevier Ltd. All rights reserved.

Figures

Figure 1. Hypothalamic-pituitary-gonadal axis in women and men

Hormones relevant to the scope of this Review are shown for women (A) and men (B). FSH=follicle-stimulating hormone. LH=luteinising hormone. GnRH=gonadotropin-releasing hormone.

Figure 2. Patterns of catamenial epilepsy

Day 1 is the first day of menstrual flow and day –14 is the day of ovulation. (A) Normal cycle with normal ovulation. C1 pattern is associated with exacerbation of seizures in the perimenstrual phase, and C2 pattern is associated with exacerbation of seizures in the periovulatory phase. (B) Inadequate luteal phase cycle with anovulation. The C3 pattern is associated with exacerbations beginning day 10 of one cycle through day 3 of the next cycle. C=catamenial seizure pattern. F=follicular phase. O=periovulatory. L=luteal phase. M=perimenstrual. Modified and reproduced from Herzog and colleagues, by permission of Blackwell Publishing.

Figure 3. Treatment algorithm for catamenial C1 pattern of seizures

Most treatments are for focal-onset seizures in women with regular menses. C1 level 3=three times more seizures on days 25–3 compared with other days of the month. AEDs=antiepileptic drugs. PHT=phenytoin. IM=intramuscularly. *If menses start before day 26, start dose tapering on that day according to the same pattern of decreases. †Widely undertaken but not supported by data from randomised, controlled trials. ‡Increased risk of osteoporosis and slow return to normal fertility.