Also see:
Epilepsy and Progesterone by Ray Peat, PhD
Estrogen, Glutamate, & Free Fatty Acids
Estrogen’s Role in Seizures
The Brain – Estrogen’s Harm and Progesterone’s Protection
Women, Estrogen, and Circulating DHA
PUFA, Fish Oil, and Alzheimers
Ray Peat, PhD on the Menstrual Cycle
Autoimmune Disease and Estrogen Connection
Estrogen, Progesterone, and Epilepsy: What’s the Relationship?
“Seizures can be caused by lack of glucose, lack of oxygen, vitamin B6 deficiency, and magnesium deficiency. They are more likely to occur during the night, during puberty, premenstrually, during pregnancy, during the first year of life, and can be triggered by hyperventilation, running, strong emotions, or unusual sensory stimulation. Water retention and low sodium increase susceptibility to seizures. When I was in high school, our dog found and ate a pint of bacon grease, and shortly afterward had a convulsive seizure. I knew of veterinarians who treated seizures in dogs with a vermifuge, so it seemed obvious that a metabolic disturbance, especially if combined with intestinal irritation, could cause fits.
It was undoubtedly such observations that led some physicians to advocate removal of the colon as treatment for epilepsy. Pregnancy and the menstrual cycle have been recognized as having something to do with seizures, but when seizures occurred only during pregnancy, they were classified as nonepileptic, and when they had a clear premenstrual occurrence, they were likely to be classified as “hysterical fits,” to be treated with punishment.” -Ray Peat, PhD
Epilepsy Res. 2009 Apr;84(2-3):257-62. doi: 10.1016/j.eplepsyres.2009.01.014. Epub 2009 Mar 3.
Occurrence of menstrual cycle related seizure patterns among epileptic women attending the tertiary neurology clinics of the National Hospital of Sri Lanka.
Kariyawasam SH, Mannapperuma U, Jayasuriya WJ, Weerathunga J, Munasinghe K.
Female sex hormones estrogen and progesterone have effects on seizure activity. Patterns of seizure exacerbations associated with the menstrual cycle have been described as catamenial epilepsy. This study was done to investigate the menstrual cycle related seizure occurrence among female epileptics using seizure-menstrual calendars and sex hormonal assays. Frequency and the patterns of seizure occurrence within the menstrual cycles were determined analyzing seizure-menstrual calendars. Luteal phase serum estradiol and progesterone were determined in those with menstrual cycle related seizure patterns to be compared with that of healthy women. Out of 349 epileptics, 6% showed occurrence of perimenstrual, periovulatory or perimenstrual+periovulatory seizure patterns on analysis of seizure-menstrual calendars. These women showed significantly higher luteal serum estradiol concentrations in comparison to age-matched healthy volunteers. There was no significant difference in the luteal serum progesterone concentrations. This study showed menstrual cycle related patterns of seizure occurrence in a minority of Sri Lankan epileptic women, similar to catamenial epilepsy patterns described by previous studies. These seizure patterns may be due to altered hypothalamo-pituitary-gonadal axis function playing a role in the pathophysiology of epilepsy. We suggest the importance of maintaining seizure-menstrual calendars and hormonal studies in all epileptic women to establish the role of hypothalamo-pituitary-gonadal axis in epilepsy and to achieve efficient control of epilepsy in women of childbearing age.
Epilepsy Res. 1993 May;15(1):47-52.
Patterns of seizure occurrence in catamenial epilepsy.
Herkes GK, Eadie MJ, Sharbrough F, Moyer T.
The pattern of seizure occurrence was analysed over 44 menstrual cycles in 12 epileptic women who considered they had menstrually related seizures. Two peaks in the daily seizure rate were apparent. A significant increase in seizures occurred during the days of menstrual flow and the two days preceding it, with a second peak in the four days at midcycle. The lowest seizure rate was in the late phase of the menstrual cycle. Daily salivary progesterone levels were assayed in 11 women, and 12 ovulatory and eight anovulatory cycles were identified on this basis. No increase in seizures occurred at midcycle if ovulation did not occur, but the perimenstrual increase took place irrespective of ovulatory status.
Epilepsy Res. 1989 Mar-Apr;3(2):100-6.
Unbalanced progesterone and estradiol secretion in catamenial epilepsy.
Bonuccelli U, Melis GB, Paoletti AM, Fioretti P, Murri L, Muratorio A.
Ten women with a documented history of catamenial epilepsy underwent a hormonal study to evaluate hypophyseal-gonadal function. Baseline values of luteinizing hormone, follicle-stimulating hormone and prolactin were similar in catamenial seizure patients and in control groups throughout a complete menstrual cycle. Stimulated secretions of the same hypophyseal hormones in catamenial seizure patients overlapped those of the controls. The luteal secretion ratio of progesterone to estradiol was significantly reduced in catamenial seizure patients versus normal controls. In a subgroup of catamenial seizure patients on antiepileptic therapy, luteal progesterone levels were remarkably decreased compared to normal and epileptic controls. These results indicate that catamenial epilepsy is characterized by an imbalance in ovarian steroid secretion and emphasize the need for an endocrinological assessment in these patients.
Funct Neurol. 1986 Oct-Dec;1(4):399-403.
Neuroendocrine evaluation in catamenial epilepsy.
Murri L, Bonuccelli U, Melis GB.
The hypothesis that catamenial epilepsy depends on abnormal rhythmic hormone activity in the hypothalamus-pituitary-gonadal axis has never been critically tested. No significant modifications in the secretory pattern of pituitary hormones, both basally and in response to stimulatory tests, were found in a group of catamenial epileptic women. On the contrary, our data showed a reduction of luteal phase progesterone secretion. These findings indicate that an imbalanced secretion of ovarian steroids plays a role in the catamenial exacerbation of epilepsy.
Ter Arkh. 1994;66(4):68-71.
[The role of the female sex hormones in the pathogenesis of catamenial epileptic seizures].
[Article in Russian]
Balabolkin MI, Karlov VA, Vlasov PN.
The paper presents the results of evaluation of gonadotropins and female steroids concentrations in 46 female epileptics on catamenia day 1, in the middle of follicular and lutein phases. The control consisted of 7 healthy females of the same age with favourable heredity and free of neuroendocrine diseases. Two groups of patients were distinguished: females with catamenial epileptic seizures and those with catamenia-independent seizures. It is shown that changes in the concentrations of female steroid sex hormones were unidirectional in both the groups with a tendency to deficient luteal phase and relative hyperestrogenemia in all the cycle phases. The involvement of insufficient activation produced by brain stem formation reticularis in pathogenesis of catamenial epilepsy in suggested. A pathogenetic approach to epilepsy treatment in females when hormonal status is considered and psychostimulators are used is proposed.
J Ayub Med Coll Abbottabad. 2006 Jul-Sep;18(3):17-20.
Influence of steroid hormones in women with mild catamenial epilepsy.
Hussain Z, Qureshi MA, Hasan KZ, Aziz H.
BACKGROUND:
In view of considerable differences of opinion regarding the reproductive steroid hormonal pathogenesis in catamenial epilepsy, hormonal analysis of estrogen and progesterone in catamenial epileptics for a precise correlation is of significant importance.
METHODS:
Clinical, neurological and physiological assessments, and radioimmunoassay of plasma estradiol-17beta and progesterone a day prior to the onset of menstruation were carried out in noncatamenial and mild catamenial epileptics having multiple frequency tonic-clonic (primary and secondary generalized) seizures.
RESULTS:
Highly significant rise (p > 0.0001) of estradiol-17beta was obtained for catamenial epileptics compared to normal subjects as well as noncatamenial epileptics (p > 0.02). However, nonsignificant fluctuations of progesterone were found for both catamenial and noncatamenial epileptics against normal subjects as well as catamenial versus noncatamenial epileptics.
CONCLUSIONS:
The present report suggests that estradiol have a precise role in the mild premenstrual exacerbation of seizures. However, no significant change in progesterone levels might have been due to mild exacerbation of seizures in these patients. Furthermore, we suggest the importance of how we collect and categorize the data and which pathophysiologic process/ clinicobiological mechanism is involved in patients with catamenial epilepsy. Contradictory results in literature may be related to differential levels of excitation/inhibition equilibrium during various cycle phases. More precise studies including the determination of the blood levels of antiepileptic drugs, however, are required.
Neurology. 2014 Jul 22;83(4):339-44. doi: 10.1212/WNL.0000000000000619. Epub 2014 Jun 18.
Seizure course during pregnancy in catamenial epilepsy.
Cagnetti C, Lattanzi S, Foschi N, Provinciali L, Silvestrini M.
OBJECTIVE:
Our aim was to evaluate seizure course in catamenial epilepsy (CE) and noncatamenial epilepsy (NCE) during pregnancy.
METHODS:
We prospectively followed women referred to our Epilepsy Center for pregnancy planning to the end of the pregnancy. According to their seizure frequency variations across the menstrual cycle, all patients were divided into either the CE or the NCE group. Data on seizure frequency during pregnancy were collected for each patient and compared with seizure frequency during the pregestational 9 months.
RESULTS:
Fifty-nine women with CE and 215 with NCE were included. Forty-seven subjects (79.7%) with CE and 48 subjects (22.3%) with NCE remained seizure-free throughout pregnancy (odds ratio [OR] = 2.612, 95% confidence interval [CI] 1.901-3.323, p < 0.001), whereas 30 (50.8%) in the CE group and 18 (8.4%) in the NCE group had reduced seizure frequency during pregnancy (OR = 2.427, 95% CI 1.724-3.129, p < 0.001). Decreases in seizures ≥ 50% occurred in 26 women (44.1%) with CE and 14 women (6.5%) with NCE (OR = 2.426, 95% CI 1.679-3.173, p < 0.001). Multiple logistic regression models confirmed the significant role of catamenial pattern as predictor for better outcomes.
CONCLUSIONS:
Better seizure control during pregnancy in the catamenial group may be attributable to the absence of cyclical hormone variations and the increase in circulating progesterone levels. These data may have practical implications for therapeutic management of patients with CE during pregnancy.
Acta Neurol Scand. 1976 Oct;54(4):321-47.
Epileptic seizures in women related to plasma estrogen and progesterone during the menstrual cycle.
Bäckström T.
Nine periods in seven women with partial epilepsy have been invetigated with respect to frequency of fits, and estrogen-progesterone levels in blood plasma. Six cycles with ovulation showed a positive correlation between the number of secondary generalized seizures and the mean estrogen/progesterone (E/P) ratios and a negative correlation to plasma progesterone levels. Three periods without ovulation showed an increase in the number of fits during days of high estrogen. The number of fits seemed not to be correlated to changes in body weight.
Neurology September 1995 vol. 45 no. 9 1660-1662
Progesterone therapy in women with complex partial and secondary generalized seizures
Andrew G. Herzog, MD MSc
This open trial assessed the effects of adjunctive progesterone therapy on seizure frequency in 25 women with catamenial exacerbation of complex partial (CPS) and secondary generalized motor (SGMS) seizures. Progesterone was well tolerated by 23 of the 25 women and had readily reversible dose-related side effects of asthenia and emotional depression in two. Eighteen women (72%) experienced a decline in seizure frequency during a 3-month treatment period compared with the 3 months prior to therapy (p less than 0.01). Average daily CPS frequency declined by 54% (p less than 0.01), SGMS by 58% (p less than 0.02).
Adv Biomed Res. 2013; 2: 8.
Progesterone therapy in women with intractable catamenial epilepsy
Mohammadreza Najafi, Maedeh Mirmohamad Sadeghi, Jafar Mehvari, Mohammad Zare, and Mojtaba Akbari1
Background:
Catamenial epilepsy is a kind of epilepsy, known in this name, when the periodicity of the exacerbation of the seizure is in association with menstural cycle. The present study examined the progesterone effectiveness as a complementary treatment in women with intractable catamenial epilepsy.
Materials and Methods:
The present study was conducted as a double-blind randomized controlled trial on 38 women with intractable catamenial epilepsy. Patients were assessed in two groups: The case group received in addition to AEDs, two (Mejestrol) 40 mg progesterone tablets in the second half of the cycle from 15th to 25th day. And the control group received in addition to AEDs, two placebo tablets daily. Age, BMI, epilepsy duration, types of the drugs used, progesterone level, and the number of the seizures in 3 months before and after the study were compared.
Results:
Based on the results of which there was no statistically significant difference in regard to age, BMI, epilepsy duration, types of the drugs used, progesterone level between the case and the control groups (P-value > 0.05). The number of the seizures after treatment has significantly decreased compared to before-treatment state. The degree of decreasing in the case group receiving the progesterone was higher than in the control group receiving the placebo. The difference, thus, is significant, based on statistical tests (P-value = 0.024).
Conclusion:
Based on the findings of this study using progesterone in women with intractable catamenial epilepsy has a significant effect on the degree of decreasing in the number of the seizures.
