According to Andrew Herzog, M.D., MSc, Director of the Harvard Neuroendocrine Unit, Beth Israel Deaconess Medical Center, Boston, MA, the idea of a relationship between seizure frequency and a woman’s menstrual cycle, known as catamenial epilepsy, dates back more than a century to Sir William Richard Gowers, an eminent British neurologist who wrote a textbook considered at the time to be ‘The Bible of Neurology’. Herzog’s presentation at the 58th Annual Meeting of the American Academy of Neurology, San Diego, further characterizes the relationship between seizures and a woman’s menstrual cycle.

In preparation for a National Institutes of Health sponsored multicenter trial of progesterone therapy for catamenial epilepsy, Herzog and colleagues collected information for 3 months on the seizure frequency and menstrual periods of 100 women, ages 13-45 years. When women ovulate, there is an increase in progesterone in the latter part of the cycle. When they fail to ovulate (anovulatory cycle), progesterone doesn’t increase. To determine whether ovulation occurred, progesterone levels were measured. A level of >5 ng/ml indicated ovulation. Herzog proposed that the lack of progesterone increase during anovulatory cycles may be related to an increase in seizures.

The results of the study indicated that women who have menstrual cycles lasting 26-30 days were the most likely to have ovulatory cycles. However, women with short cycles (less than 26 days) or long cycles (longer than 30 days) were less likely to ovulate. For example, in cycles lasting longer than 35 days, ovulation occurred only a third of the time. During cycles when they didn’t ovulate, women had 28% more seizures than during cycles with ovulation.

“It has been recognized for quite a while that menstrual disorders are unusually common in women with epilepsy, occurring in about 36% of women with epilepsy versus 12% in the general population. Menstrual disorders are associated with failure of ovulation, which goes along with lower fertility” said Herzog.

Robert Greene, M.D., a reproductive endocrinologist and Assistant Clinical Professor, University of California, Davis, College of Family and Preventive Medicine, Davis, CA, commented, “One of the most important things is for women to track their menstrual cycles and seizures on the same calendar. If cycles are longer than 3 months or excessive bleeding occurs, these are indications to see an obstetrician gynecologist. If a woman doesn’t want to take a birth control pill to regulate her cycle, one of the easiest things to do is to use progesterone, because progesterone doesn’t cause birth defects, as it doesn’t cross the placenta. However, some of the synthetic forms of progesterone and estrogen can cause birth defects and shouldn’t be used if a woman is trying to conceive.”

Herzog concluded, “There is very much a reciprocal relationship between seizures and hormones. The temporo-limbic system, which is the site of origin for most adult epilepsy, has massive direct connections to the hypothalamus, which regulates the pituitary, which in turn regulates the ovaries. Anovulatory cycles feature estrogen without progesterone, and estrogen is epileptogenic. If hormones play a role in a woman’s seizures, they may be more likely to respond to progesterone treatment. We expect to learn more about the role of hormones and seizure frequency in our current trial of natural progesterone for women with epilepsy.”

References:

1. Herzog AG, Harden CL, Liporace JD, Pennell PB, Schomer DL, Sperling MR, Taylor G, Nikolov B, Newman ML, Fowler KM. Some relationships among ovulation rates, menstrual cycle intervals and seizure frequency: Preliminary data analysis in a prospective multicenter investigation. Neurology 2006;66(Suppl 2):A342.