Catamenial (from the Greek kata, by; men, month) epilepsy refers to seizure exacerbation in relation to the menstrual cycle. Traditionally, the term has been used to refer to seizure exacerbation at the time of menstruation.
In its purest form, a woman with catamenial epilepsy may have seizures only at the time of menstruation, but this form is not very common. More typically, the woman may tend to have more seizures at particular times during her menstrual cycle, usually just before or during the onset of menstruation or at the time of ovulation.1-3
Three patterns of catamenial seizure exacerbation may be observed:2
The three patterns of catamenial exacerbation of epilepsy in relation to serum estradiol (E2) and progesterone (P) levels. C1 = perimenstrual; C2 = preovulatory; C3 = luteal phase.
Seizure exacerbation around the time of menstruation or ovulation occurs in women with normal menstrual cycles.
Women with abnormal menstrual cycles may have exacerbation in the second half (luteal phase) of the cycle. This pattern is the most difficult one to distinguish because the time of seizure exacerbation is prolonged rather than focused. These women have anovulatory cycles and inadequate luteal phase syndrome.4 Because they do not ovulate, no corpus luteum (derived from the egg leaving the ovary) is formed during the second (luteal) half of the menstrual cycle and no progesterone is secreted.
Menstrually related hormonal fluctuations in estrogen and progesterone underlie the patterns of catamenial seizure exacerbation. Estrogens facilitate seizures, whereas progesterone protects against seizures. During the menstrual cycle, serum levels of estradiol and progesterone fluctuate.
Estrogens (in particular estradiol, the most important of the different estrogen forms) have potent proconvulsant properties. They exert an excitatory effect on neurons by stimulating the N-methyl-D-aspartate (NMDA)- type glutamate receptor.5 In women with epilepsy, intravenous administration of conjugated estrogens activates epileptiform discharges and may result in seizures.6
Progesterone hyperpolarizes neurons, acting via one of its natural endogenous metabolites, allopregnanolone, as an agonist at the γ- aminobutyric acid (GABA)-a receptor with a potency almost a thousandfold greater than that of pentobarbital and greater than the most potent benzodiazepine, nitroflurazepam.7,8 In women with partial seizures, intravenous infusion of progesterone, resulting in luteal phase plasma levels, suppresses interictal epileptiform discharges.9
In a normally menstruating woman, the surge of serum estrogen levels at the time of ovulation may be associated with increased seizure tendency; as may the fall in serum progesterone levels just before and during menstruation.
In a woman with an anovulatory cycle, estrogen levels rise at the end of the follicular phase and stay elevated throughout the luteal phase until premenstrually, as in normally menstruating women. Little or no progesterone is secreted, however, creating an estrogen:progesterone (E/P) imbalance with a relative excess of estrogen (or deficiency of progesterone) throughout the whole second (luteal) half of the menstrual cycle. Seizure exacerbation results.10
A number of studies have suggested that both progesterone deficiency and estrogen excess relative to progesterone contribute to the catamenial pattern of seizure exacerbation in both normal women and in women with menstrual irregularities.1,2,10 The E/P ratio appears to determine the overall reproductive hormonal effect upon seizure frequency.10
In addition, premenstrual exacerbation of seizures may also be related to a decline in anticonvulsant medication levels.11,12 In women with catamenial epilepsy, phenytoin levels decline premenstrually by up to one-third.11,12 This decline may be due to an increased rate of clearance at the beginning of menstruation, with an associated reduction in the half-life of phenytoin from 19 to 13 hours.11 Hepatic microsomal enzymes metabolize both gonadal steroids and anticonvulsants such as phenytoin, with competition between the two. The premenstrual decline in gonadal steroid secretion may therefore permit increased metabolism of AEDs, resulting in lower serum levels.11 It is not certain whether all AEDs are affected. Phenobarbital is not, and catamenial fluctuation in serum levels of other AEDs has not been studied.
Reviewed and revised February 2004 by Cynthia Harden, MD, Weill Cornell Medical College.
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