By: Vibha Chauhan
Editor’s Note: This week we feature a study by Najafi et al published in Advanced Biomedical Research titled, “Progesterone Therapy in Women with Intractable Catamenial Epilepsy.” [1] The term “catamenial” refers to the “menstrual cycle” or “menstruation,” as seizures in catamenial epilepsy tend to occur during or around the time of menses. Although the title implies the study evaluated the impact of progesterone on catamenial seizures, the drug studied—Megestrol—is a synthetic progestin, which may not cross the blood-brain barrier as easily as progesterone. Vibha Chauhan summarized the article during the FACTS elective, highlighting the need to foster innovation in research to support clinical care. Although more research is needed, this small study suggests adjunctive oral Megestrol alongside anti-epileptic medications in patients with intractable catamenial epilepsy may decrease seizure frequency. To learn more about a patient’s experiences with catamenial epilepsy, read this enlightening interview on the FACTS blog that explores the connection between hormones and seizures.
Introduction
Catamenial epilepsy is a form of epilepsy with exacerbations associated with hormonal fluctuations during the female cycle. [2] The study by Najafi et al summarized below investigated the effectiveness of adjunctive treatment with Megestrol, a synthetic progestin (acetate progesterone), in women with refractory seizures during the catamenial period. [1] Although progesterone is not confirmed as a proven treatment for catamenial epilepsy, it has been considered a valued treatment for exacerbated catamenial seizures.
“Catamenial epilepsy is a form of epilepsy with exacerbations associated with hormonal fluctuations during the female cycle.”
Methodology
This study was a double-blinded, randomized controlled trial conducted between June 2011 and March 2012. It enrolled women ages 18-45 with catamenial epilepsy, including complex partial seizure, secondary generalized seizure, or primary generalized seizure. Another important inclusion criterion was the use of full-dose anti-epileptic medications.
The study included women who had seizure exacerbations during the whole luteal phase or premenstrual period, which is between the 25th day of the previous cycle and the second day of the next cycle. Additionally, participants had to have cycles with inadequate luteal phase demonstrated by a mid-luteal progesterone level below 5mg/mL. Participants were not included if they had amenorrhea, abnormal uterine bleeding, or were pregnant and breastfeeding.
A total of 38 women who met the inclusion criteria were randomly divided into two 19-member groups. The case (treatment) group received two 40 mg progesterone tablets daily from cycle day 15 to 25. Progesterone was discontinued from the 25th day on to allow patients to have their natural menses. The control group was given placebo pills for the same duration and in the same manner. During the three months before treatment, the amount and duration of seizures and progesterone levels were studied in the case and control groups and compared three months after treatment.
Results
Out of the 19 participants in the case group, 2 patients were excluded due to side effects of severe headache, nausea, and vomiting while on progesterone. There were no statistically significant changes in variables such as epilepsy duration or progesterone level between the studied groups.
However, the number of seizures decreased in both the case and control groups compared from three months before to three months after treatment, with a statistically significant decrease in the case group. In the case group, the average number of seizures before treatment was 6.2 with a median of 5; this number dropped to a statistically significant mean of 1.2 with a median of 1 after treatment (P = 0.024). In the control group, the mean number of seizures decreased from 7.6 (median of 8) to 5.7 (median of 6).
“In the case group, the average number of seizures before treatment was 6.2 with a median of 5; this number dropped to a statistically significant mean of 1.2 with a median of 1 after treatment.”
Discussion
This trial sought to study the effects of progesterone as an adjuvant therapy for catamenial epilepsy. Catamenial seizures arise mostly during a 10-day period of the female cycle starting 4 days before menstruation. Studies have shown that in the mid-luteal phase, when progesterone levels are increased, the number of seizures decreased, and vice versa. A study by El-Khayat et al showed evidence that patients with catamenial epilepsy have lower serum progesterone levels compared to control groups. [3]
Side effects from progesterone, such as breast tenderness and vaginal bleeding, may limit its use as a treatment option. At higher dosages, progesterone may also cause depression and general feelings of weakness. Two participants in this study by Najafi et al [1] had side effects, and progesterone was discontinued. This raises a question regarding the optimal dosing for Megestrol (acetate progesterone) as adjunctive treatment in catamenial seizures to avoid or minimize side effects.
A few studies have assessed the use of progesterone to control catamenial seizures. One observation made was that this study [1] used Megestrol (a synthetic progestin) in its treatment group. Additional research utilizing other formulations of progesterone is another avenue to be explored. More research with an increased sample size and different dosages and types of progesterone would help define the most optimal adjunctive treatment for intractable catamenial seizures. Future research must also consider that patients with these types of seizures usually require more than one anti-epileptic medication to control their episodes.
A Restorative Approach
This study is an example of the intersection of neurology and women’s health. Although epilepsy is a predominantly neurologic condition, it can be approached from a restorative reproductive medicine (RRM) perspective that seeks to address underlying causes. Charting the female cycle is a way to understand the day-to-day hormonal shifts that may contribute to a woman’s symptoms, particularly in a condition such as catamenial epilepsy.* Charting can lead to more targeted treatment to meet patients’ needs. This trial points to the need to keep treatment options broad in catamenial epilepsy and engage in open dialogue with other medical professionals about reproductive health.
“Charting the female cycle is a way to understand the day-to-day hormonal shifts that may contribute to a woman’s symptoms, particularly in a condition such as catamenial epilepsy.”
* Editor’s Note: A review article published in 2020 by Frank and Tyson [2] mentions charting the female cycle as a tool to enhance the clinical approach to catamenial epilepsy. Learn more about charting the female cycle and restorative reproductive medicine by enrolling in our CME Courses. Parts D, E, and H of our CME courses illustrate the connection between the science of endocrinology and core concepts of FABMs, which may be used to diagnose and manage common women’s health conditions.
References
[1] Najafi, M., Sadeghi, M. M., Mehvari, J., Zare, M., & Akbari, M. (2013). Progesterone therapy in women with intractable catamenial epilepsy. Advanced biomedical research, 2, 8. https://doi.org/10.4103/2277-9175.107974
[2] Frank S, Tyson NA. A clinical approach to catamenial epilepsy: A review. Perm J 2020;24:19.145. DOI: https://doi.org/10.7812/TPP/19.145
[3] El-Khayat, H. A., Soliman, N. A., Tomoum, H. Y., Omran, M. A., El-Wakad, A. S., & Shatla, R. H. (2008). Reproductive hormonal changes and catamenial pattern in adolescent females with epilepsy. Epilepsia, 49(9), 1619–1626. https://doi.org/10.1111/j.1528-1167.2008.01622.x
ABOUT THE AUTHOR
Vibha Chauhan
Vibha Chauhan is a fourth-year medical student at Rowan-Virtua School of Osteopathic Medicine in Stratford, NJ. She completed her undergraduate education at the University of Pittsburgh in Pittsburgh, PA. She plans to pursue residency in neurology and is interested in education and narrative medicine. She enrolled in the FACTS elective to gain a better understanding of natural family planning methods and ways to share these methods with future patients so they have more treatment options and feel empowered to advocate for themselves.
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