Hormone-Sensitive Seizures

Hormones, including gonadal, adrenal and thyroid hormones, can alter the excitability of neurons in the brain. The dynamic relationship between hormones and neuronal excitability is most clearly established for the ovarian sex steroid hormones: estrogen and progesterone. Testosterone has variable effects on neuronal excitability and the relationship is poorly understood.

Reproductive Hormones and Seizures

Many women with epilepsy experience changes in seizure patterns at times of hormonal change: at menarche, over the menstrual cycle and with menopause. Fluctuations in the pituitary hormones, including follicle stimulating hormone (FSH) and luteinizing hormone (LH), during the menstrual cycle trigger release of estrogen and progesterone from the developing ovarian follicle. Estrogen generally has an excitatory effect on neurons while progesterone has an inhibitory effect.

Catamenial epilepsy refers to seizure exacerbation related to the menstrual cycle. The most common pattern is an increased tendency for seizures just before, or at the onset of menstruation. Some women with epilepsy may have more frequent seizures mid-cycle, with ovulation. Causes of catamenial epilepsy include:

• progesterone withdrawal premenstrually;
• hormonal imbalances with high estrogen to progesterone ratios prior to ovulation; and
• changes in anti-epileptic drug (AED) levels, i.e., decreased AED levels premenstrually.

Seizure exacerbation may also occur during the entire second half of the cycle in anovulatory cycles where the estrogen level becomes high, before midcycle without the protective effect of progesterone, which is normally secreted by the corpus luteum.

Reproductive disorders such as polycystic ovarian syndrome or hypothalamic amenorrhea may occur more frequently in women with temporal lobe epilepsy than in women without seizures. Menopause may occur earlier as well.

Treatment of Hormone-Sensitive Seizures

The most effective treatment for any seizure disorder is a first-line AED appropriate for the patient’s seizure type. However, women with catamenial epilepsy may respond to hormone therapy or possibly a carbonic anhydrase inhibitor. Natural progesterone therapy used during the second half of each cycle with gradual tapering and discontinuation by the end of the cycle, may benefit some women with epilepsy. Gynecological and/or endocrine consultation is recommended if hormonal manipulation is contemplated.

Some women with epilepsy may experience decreased serum AED levels premenstrually, related to increased hepatic metabolism of AEDs. Adjusting doses accordingly or using adjunctive AED therapy during this time may be helpful.

Acetazolamide (Diamox) is a carbonic anhydrase inhibitor and possibly a useful adjunctive AED, although this is not a labeled indication. It is a mild diuretic and its anticonvulsant properties may be related to induction of a mild, transient metabolic acidosis. For most women with epilepsy who have predictable menstrual cycles, acetazolamide is given a few days premenstrually.

Other Therapeutic Interventions

Women with epilepsy should keep a careful record of seizures and menstrual cycles. Other factors that may affect seizures or menses (such as medication errors, sleep deprivation, fatigue, stress, intense physical training or intercurrent illness) should also be recorded and assessed.

Basal body temperature charts may be helpful in establishing when ovulation occurs, but a midluteal (usually around day 22) serum progesterone level is a more reliable indicator of ovulation.

Pelvic ultrasound may be indicated to rule out other causes of menstrual dysfunction, e.g., polycystic ovarian syndrome. If a hormonal component to seizures is suspected, a neuroendocrine or endocrine evaluation is suggested.

AED levels drawn during the midluteal phase and again at menstruation may provide information about alterations in AEDs related to the menstrual cycle.

CONTACT

For additional information, contact the Women and Epilepsy Initiative of the Epilepsy Foundation at (800) 332-4050.

REFERENCES

Herzog AG, Klein P, Ransil BJ. Three patterns of catamenial epilepsy. Epilepsia. 1997;38:1082-1088.

Herzog AG, Klein P. Endocrine aspects of partial seizures. In: Schachter SC, Schomer DL, eds. The Comprehensive Evaluation and Treatment of Epilepsy. Boston: Academic Press; 1997:207-232.

Herzog AG. Progesterone therapy in women with complex partial and secondary generalized seizures. Neurology. 1995;45:1660-1662.

Herzog AG. Progesterone therapy in women with epilepsy: a 3-year follow-up. Neurology. 1999;52:1917-1918.

Woolley CS, Schwartzkroin PA. Hormonal effects on the brain. Epilepsia. 1998;39(Suppl 8):2-8.