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Women with epilepsy will often note an increase in their seizures around the time of their periods (Penovich, 2008). It is not unusual for the patient herself to bring this observation up to the doctor. The increase in seizure activity correlates with changes in hormones that occurs during the menstrual cycle. The worsening in seizure control can best be documented on a calendar: the patient’s periods can be charted along with the seizures. A clear clustering of seizures may be noted in close association with the periods. The medical term for an exacerbation of seizures around the menstrual cycle is catamenial epilepsy (Penovich 2008, Herzog 2008). I should stress-this is a common phenomenon! Approximately one-third of women with inadequately controlled seizures meet criteria for catamenial epilepsy (Herzog, 2008). The purpose of this article is to explore how hormones can change seizure activity in women with epilepsy.
32 year-old woman with history of seizures since 13 years of age. Her typical seizures are described as follows: She has an aura- it is a rising sensation in her stomach. It is a combination of mild nausea and fear. This will last for a few seconds. She then loses contact. She stares and is unresponsive. She will pick at her clothes and grab at people or items that are in front of her. Seizures last for 30 seconds. Frequency of seizures was 3 per month.
The patient pointed out to her doctor that her seizures seemed to occur around the time of her period. The patient ended up keeping a careful calendar for 5 months- charting the days of her period and the days of her seizures. Just like clock-work, her seizures occurred over a 2 day span, consistently two days before her period started. She was diagnosed with catamenial epilepsy.
The patient was started on progesterone therapy. Progesterone was given 10 days before her period started and was then tapered to off four days into her period. Thus, she was on progesterone for 14 days and off progesterone for 14 days. The progesterone was allowed to build-up in her system before the increase in her seizures was expected (seizures were expected to increase 2 days before her period started).
The patient had an excellent response. Her seizure frequency was reduced by 60%.
ESTROGEN AND PROGESTERONE
Estrogen and progesterone are two important hormones that change during the course of a menstrual cycle as well as during a woman’s lifetime. During the approximately 28 day cycle, the fluctuations in estrogen and progesterone can be quite dramatic. For example, around ovulation (mid-cycle), estrogen level may be quite high. During puberty, perimenopause and menopause, there are major changes in the relative levels of estrogen and progesterone. There is robust research in both human and animal models which support the following basic concepts:
It has been observed that when estrogen levels are high, seizure activity tends to cluster. In contrast, progesterone is being studied as a possible treatment for seizures (see below).
SEIZURES AND THE MENSTRUAL CYCLE
During the typical 28 day menstrual cycle, there are variations in the relative levels of estrogen and progesterone. At times, the levels of estrogen are much higher compared to the levels of progesterone. It is when estrogen is relatively high that seizure activity is most likely to occur. There are three times during the menstrual cycle that hormonally triggered seizures are most likely (Herzog, 2008):
It is during these three times that women with catamenial epilepsy will notice an increase in their seizures.
LIFETIME CHANGES IN SEIZURES: FROM PUBERTY TO MENOPAUSE
A very common question we receive in clinic is: What will happen to my seizures when I hit menopause? Another common question is: Did puberty trigger my daughter’s seizures? These are great questions. Research to answer these questions is ongoing. There is information currently available to guide patients on these important issues.
As everyone knows, puberty is a time of dramatic hormonal changes! The adolescent physical appearance, emotions and thinking are all undergoing remarkable changes. Mood changes can fluctuate in remarkable ways. Given all the hormonal activity, it is not surprising that some girls experience changes in their seizures during puberty. Certain types of epilepsy are more likely to start during puberty (for example, Juvenile Myoclonic Epilepsy).
Of course- pregnancy includes remarkable changes in hormones! These changes have many important effects. Pregnancy in women with epilepsy is such an important topic, I will plan on writing a separate article on this topic. Keep on the look-out for the article!
Perimenopause is the time in a woman’s life where her menstrual cycle is shifting- from regular cycles to toward permanent infertility. Perimenopause is characterized by erratic fluctuations in hormones. Estrogen levels can often be quite high during this perimenopause period. For some women with epilepsy, seizures can become much more frequent as they go through perimenopause. This is thought to be due to the high levels of estrogen.
When women enter menopause, hormone levels are characterized by low and stable estrogen levels. During menopause, women with epilepsy often have a reduction in the frequency of her seizures. Thus, women with epilepsy often will often have an increase in the frequency of seizures during perimenopause, and a reduction in seizures during menopause. This pattern is more frequently noted in those women who have a history of catamenial epilepsy (Harden, 1999).
TREATMENT OF CATEMENIAL EPILEPSY
There are several treatment options for catemanial epilepsy. Some of the options include:
Data on progesterone was presented at the most recent American Epilepsy Society Meeting (Herzog et al, December 2011). A randomized, double-blind, placebo controlled multicenter trial was described. Progesterone was noted to be an effective treatment for selected women with catamenial epilepsy. It appeared that the more frequent a patient’s seizures are around their periods, the better the response to progesterone.
A suggested treatment strategy is to give progesterone for 14 days of the menstrual cycle (Herzog 2008, Pennell 2009). Thus, the patient may be on progesterone for 14 days and then off for14 days. The progesterone is started several days before the period starts and before the seizures are expected to occur. This allows the progesterone to buildup in the body. The progesterone is then continued a few days into the period, and then tapered to off. It is hoped that the higher progesterone will stop the seizures!
Progesterone has side effects—sedation, mood changes, bloating, weight gain, breast tenderness and other side effects. These need to be considered—a thorough discussion between the patient and clinician is important. Also, natural progesterone appears to have better efficacy than synthetic progesterone. In order to obtain natural progesterone, ordering from a compounding pharmacy may be necessary.
Hormones can play an important role in seizures in women with epilepsy. Increasing levels of estrogen tends to increase seizures, while higher levels of progesterone tends to reduce seizures. Women who have an increase in their seizures related to their periods may be diagnosed with catamenial epilepsy. This is a surprisingly common condition, noted in one-third of woman with intractable epilepsy. In order to determine if a person has catamenial epilepsy, careful tracking of seizures and periods on a calendar is needed. Treatments that are relatively specific for hormone triggered seizures exist and appear to be effective. Clinicians can currently prescribe such treatments. Research is ongoing to develop better treatments for this important condition.
Harden CL, Pulver MC, Ravdin L, et al. The effect of menopause and perimenopause on the course of epilepsy. Epilepsia 1999;40:1402.
Herzog AG. Progesterone therapy in women with epilepsy: A 3-year follow-up . Neurology 1999;52:1917.
Herzog A. Catamenial epilepsy:Definition, prevalence, pathophysiology and treatment. Seizure 2008;17:151-159.
Herzog AG, Fowler JM, Massaro JM, et al. Progesterone therapy for women with epilepsy:results of the phase 3 NIH progesterone trial. Presented at the American Epilepsy Society Meeting, December 2012.
Pennell PB. Hormonal aspects of epilepsy. Neurol Clin 2009;27:1-25.
Penovich PE, Helmers S. Catamenial Epilepsy. International Review of Neurobiology 2008;83:79-90.
Dr. White has been practicing as a full-time epileptologist since 1999. His practice focuses on optimizing the diagnosis and treatment of patients with seizure disorders. Dr. White’s special interests include patient education, improving the side-effect profile of seizure medications, and epilepsy surgery.