The role of sex steroids in catamenial epilepsy and premenstrual dysphoric disorder: Implications for diagnosis and treatment

Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
Epilepsy & Behavior (Impact Factor: 2.26). 08/2008; 13(1):12-24. DOI: 10.1016/j.yebeh.2008.02.004
Source: PubMed


Despite our understanding of hormonal influences on central nervous system (CNS) function, there is still much to learn about the pathogenesis of menstrual cycle-linked disorders. A growing literature suggests that the influence of sex steroids on neurological and psychiatric disorders is in part mediated by an aberrant CNS response to neuroactive steroids. Although sex steroids such as estradiol, progesterone, and the progesterone derivative allopregnanolone (ALLO) influence numerous neurotransmitter systems, it is their potent effect on the brain's primary inhibitory and excitatory neurotransmitters gamma-aminobutyric acid (GABA) and glutamate that links the study of premenstrual dysphoric disorder (PMDD) and catamenial epilepsy (CE). After providing an overview of these menstrual cycle-linked disorders, this article focuses on the preclinical and clinical research investigating the role of estradiol and progesterone (via ALLO) in the etiology of PMDD and CE. Through exploration of the phenomenological and neurobiological overlap between CE and PMDD, we aim to highlight areas for future research and development of treatments for menstrual cycle-linked neuropsychiatric disorders.

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    • "Also, a mutual relation is reported between serum estradiol/P 4 ratio and seizure incidence in ovulatory cycles. So, the lowest seizure activity was detected with high levels of P 4 compared to the estradiol levels (Juline et al. 1975; Holmes and Weber 1984; Mattson and Cramer 1985; Frye and Bayon 1999; Kokate et al. 1999; Borowicz et al. 2003; Guille et al. 2008). In Sprague-Dawley rats, estrous cycle includes a 4-day cycle: proestrus begins with a rapid increase in the estradiol concentration followed by P 4 surge in the afternoon and evening, which summits during the ovulation in the late evening and then declines rapidly. "
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    ABSTRACT: Catamenial epilepsy is a special form of epi-lepsy in women whom seizure aggravation is arranged with menstrual cycle that may affect up to 70 % of epileptic women. Antiepileptic effect of Ghrelin hormone has been proved recently. Due to effects of Ghrelin on GABA and LH concentration and periodic variation in the level of estrogen (E 2) and progesterone (P 4) during menstrual cycle, it seems that antiepileptic effect of Ghrelin can be different during various phases of estrous cycle. So this study was conducted to survey antiepileptic effect of Ghrelin during various phases of estrous cycle in rats. 72 adult female Wistar rats in three groups (control, 40 and 80 lg/kg of Ghrelin), each with four subgroups (proestrus, estrus, metestrus and diestrus) were used (n = 6). Then, intra-cerebroventricular (ICV) injection of Ghrelin (40 and 80 lg/kg) followed by intraperitoneal injection of 80 lg/kg pentylenetetrazole in control and treatment groups were done. Initiation time of myoclonic seizures (ITMS), initi-ation time of tonic–clonic seizures (ITTS), seizures dura-tion and mortality rate were monitored and recorded for 30 min. Results showed that, ICV injection of Ghrelin significantly increased ITMS and ITTS during luteal phase than follicular phase compared to control group (P \ 0.05). Also, seizure duration significantly decreased after ICV injection of Ghrelin during luteal phase and follicular phase compared to control group (P \ 0.05). Furthermore, there was no mortality after ICV injection of Ghrelin (40 and 80 lg/kg) during luteal and follicular phases compared to control group (P \ 0.05). These results suggest that Ghrelin has antiepileptic effects which are more prominent during luteal phase than follicular phase.
    Full-text · Article · Jul 2014 · International Journal of Peptide Research and Therapeutics
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    • "Seizure activity is exacerbated by menstrual cycle phase in approximately 40% of women with epilepsy [69]. As progesterone, estradiol, and the sex steroid metabolites allopregnanolone and androstenedione modulate neuronal excitation, fluctuations between pro- and anti-convulsant neurosteroids during the menstrual cycle contribute to epileptogenesis [70]. Consistent with the involvement of the sex steroids in catamenial epilepsy (a form of epilepsy that is sex hormone-sensitive), there is an increased prevalence of PCOS and other reproductive disorders among women with epilepsy [71]. "
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    ABSTRACT: Prenatal exposure to increased androgens has been implicated in both polycystic ovary syndrome (PCOS) and autism spectrum conditions (ASC), suggesting that PCOS may be increased among women with ASC. One study suggested elevated steroidopathic symptoms ('steroidopathy') in women with ASC. As the symptoms are not independent, we conducted a latent class analysis (LCA). The objectives of the current study are: (1) to test if these findings replicate in a larger sample; and (2) to use LCA to uncover affected clusters of women with ASC. We tested two groups of women, screened using the Autism Spectrum Quotient - Group 1: n = 415 women with ASC (mean age 36.39 +/- 11.98 years); and Group 2: n = 415 controls (mean age 39.96 +/- 11.92 years). All participants completed the Testosterone-related Medical Questionnaire online. A multiple-group LCA was used to identify differences in latent class structure between women with ASC and controls. There were significant differences in frequency of steroid-related conditions and symptoms between women with ASC and controls. A two-class semi-constrained model best fit the data. Based on response patterns, we identified the classes as 'Typical' and 'Steroidopathic'. The prevalence of the 'Steroidopathic' class was significantly increased within the ASC group (DeltaG2 = 15, df =1, P = 0.0001). In particular, we confirmed higher frequencies of epilepsy, amenorrhea, dysmenorrhea, severe acne, gender dysphoria, and transsexualism, and differences in sexual preference in women with ASC. Women with ASC are at increased risk for symptoms and conditions linked to steroids. LCA revealed this steroidopathy despite the apparent underdiagnosis of PCOS.
    Full-text · Article · Apr 2014 · Molecular Autism
    • "In patients with catamenial epilepsy, serum level of progesterone in the mid-luteal phase is significantly lower than in the control group.[6] There has already been no particular treatment for catamenial epilepsy and common anti-epileptic drugs are mostly used in controlling the catamenial epilepsy in women; however, given that the seizures are most often resistant to these drugs, more than one type of anti-epileptic drugs is used in these women, dependent on the seizure type.[30] Since progesterone has anti-epileptic effects, it can be useful for adjuvant treatment. "
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    ABSTRACT: 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. 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 15(th) to 25(th) 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. 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). 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.
    No preview · Article · Mar 2013
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