Progesterone therapy in women with intractable catamenial epilepsy

Najafi, M. Hassan; Sadeghi, Maedeh Mirmohamad; Mehvari, Jafar; Zare, Mohammad; Akbari, Mojtaba

doi:10.4103/2277-9175.107974

Cited by 21 publications

(6 citation statements)

References 33 publications

(48 reference statements)

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“…Subsequently, a second double-blind, placebo-controlled clinical study was conducted by Najafi's at al. This trial, which involved only women with catamential seizures, also showed a statistically significant reduction in seizure frequency in the progesterone treated group [38]. In clinical studies, therefore, it appears that progesterone benefits women with catamenial seizures, but not necessarily women with other types of epilepsy.…”

Section: Clinical Studiesmentioning

confidence: 68%

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Progesterone, 5a-dihydropogesterone and allopregnanolone's effects on seizures: A review of animal and clinical studies

Burnham

2018

Seizure

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Keywords:Progesterone 5a-dihydroprogesterone 5a-pregnane-3,20-dione Allopregnanolone 3a, 5a-tetrahydroprogesterone Animal models of seizure A B S T R A C TThe anti-seizure effects of progesterone family compounds have long been known. Over the years, however, most studies have focused on progesterone and on its secondary metabolite allopregnanolone (ALLO), with less attention being paid to its primary metabolite 5a-dihydroprogesterone (DHP).Here we review animal and clinical studies related to the anti-seizure effects of progesterone and its 5a neuroactive metabolites, including DHP and ALLO.Progesterone and its reduced metabolites all have demonstrated seizure-suppression effects in animal models except in models of absence seizureswith the common side effects of sedation and ataxia. Progesterone and ALLO have also shown anti-seizure effects in clinical trials. A large Phase III trial has revealed that female patients with premenstrual exacerbations of seizures benefit most from progesterone therapy. A liquid suspension of ALLO has also been tested in patients with supra-refractory status epilepticus with some success in a small phase II trial. ALLO's C3 methyl analog ganaxolone is under development as an anti-seizure drug.Progesterone's anti-seizure effects are mostly independent of its genomic receptors and are, in large part, due to its active metabolites. ALLO is a potent allosteric modulator of GABA receptors. Other membrane receptors are thought to be involved in the DHP's anti-seizure actions, but their exact nature is not yet known.Potential drawbacks to the development of progesterone family compounds as anti-seizure drug are their endocrine effects. These compounds might form a basis for the future development of novel anti-seizure drugs, however, with hormonal side effects being mitigated through rational drug design. Progesterone and seizuresEpilepsy, characterized by spontaneous and recurrent seizures, currently affects 1% of the world population [1]. Despite many available therapeutic options, 1/3 of patients do not achieve seizure control [2]. Thus, searching for new and effective anti-epileptic drugs remains a central theme of epilepsy research. Among the many different candidates for drug development, the progesterone family emerges as a potential therapeutic option.Progesterone (pregn-4-ene-3,20-dione, P4) is a neurosteroid hormone synthesized in both males and females. In females, there is a clear link between progesterone, the female fertility cycle and seizures. Generally speaking, seizure thresholds are high when blood progesterone levels are high, and low when blood progesterone is low or falling [3]. This has suggested the development of progesterone-like compounds for epilepsy therapy.The present review will discuss progesterone and its 5a metabolites in animal and clinical trials related to seizure therapy. Synthesis and metabolismThe synthesis of progesterone synthesis occurs in the mitochondrial membranes of body cells and in the brain [4]. As the first step, cholesterol is converted ...

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Section: Clinical Studiesmentioning

confidence: 68%

“…In this fully controlled trial, there was no overall difference in responding between the treatment and control groups. A post-hoc analysis, however, revealed that patients those with catamenial epilepsy and severe perimenstrual exacerbations (C1) did benefit from progesterone therapy [38].…”

Section: Clinical Studiesmentioning

confidence: 95%

Progesterone, 5a-dihydropogesterone and allopregnanolone's effects on seizures: A review of animal and clinical studies

Burnham

2018

Seizure

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“…In recent times, no definitive cure for catamenial epilepsy is discovered. However, studies are suggestive of hormonal and non-hormonal therapies [17]. Acetazolamide, a carbonic-anhydrase inhibitor, as a non-hormonal treatment, displayed its efficacy against catamenial epilepsy, but its efficacy declined with time, and resistance against it developed.…”

Section: Discussionmentioning

confidence: 99%

The Frequency of Catamenial Epilepsy in Female Epileptic Patients of Reproductive Age Group Presented to the Tertiary Care Hospital

Kumar¹,

Iltaf

Umer

et al. 2020

Cureus

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Background and aim Catamenial epilepsy is the type of seizures during the reproductive phase of menstruation due to hormonal changes during the different phases of menstruation. This study aims to evaluate the frequency of epileptic seizures in women during the menstruation cycle and its management. Material and methods This study was conducted at the neurology department of Jinnah Postgraduate Medical Centre (JPMC), Karachi, Pakistan. The study's duration was six months, from the 22 nd of January 2020 to the 22 nd of July 2020. The sample size for catamenial epilepsy in female epileptic patients of reproductive age was 78%. After approval by the ethical committee of JPMC, data collection started. Data was collected and analyzed in the Statistical Package for the Social Sciences (SPSS, version 22; IBM Inc., Armonk, USA). Mean, and the standard deviation was calculated for age, duration of epilepsy, duration of antiepileptic, and antiepileptic drug. A Chi-square test was applied, and p≤0.05 was considered a statistically significant difference. Results A total of 184 female patients of reproductive age were selected for this study. The mean duration of epilepsy was 15.96 ± 8.85 months. The mean duration of antiepileptic drugs was 11.16 ± 7.53 months. In 73 patients (39.7%), EEG showed increased seizure activity during particular phases of the menstrual cycle. Catamenial epilepsy was seen in 73 patients (39.7%). The stratification according to age, duration of epilepsy, duration of antiepileptic drugs, the antiepileptic drug was done to observe the effect of these modifiers on catamenial epilepsy. Conclusion Catamenial epilepsy is relatively common epilepsy. The physician should evaluate patients when the seizures are refractory to the treatment. The females should manage a seizure diary, which will be beneficial in the management of epilepsy. In women with epilepsy, catamenial epilepsy should be considered in the diagnosis when the seizures are refractory to optimal treatment.

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“…On the contrary, progesterone and some of its metabolites reduce the incidence of epileptic attacks in women with epilepsy, which is associated with its anticonvulsant effects. Therefore, catamenial epilepsy may result from decrease in progesterone levels and/or a relative increase in estradiol/progesterone ratio (6).…”

Section: Endogenic Hormons and Catamential Epilepsymentioning

confidence: 99%

Catamenial Epilepsy - Update on Practical Management

Lukic¹

2018

AMM

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Catamenial epilepsy is a type of epilepsy that is characterized by aggravation and seizures clustering in a perimenstrual or periovulatory periods. Neuroactive properties of reproductive steroids and cyclic variations in their concentrations are important pathophysiological factors. Recent researches have demonstrated and confirmed the presence of at least three forms of catamenial aggravation of the attacks: perimenstrual and periovulatory in ovulation cycles and pattern throughout the whole luteal phase in anovulatory cycles. Rational models have identified that approximately one-third of women with epilepsy may have catamenial aggravation of the seizures. Open studies using cyclic natural progesterone as add-on therapy, medroxyprogesterone and gonadotropin-releasing hormone analogues have shown therapeutic benefits in certain forms of catamenial epilepsy. Therefore, it is important for the physician to consider catamenial epilepsy as a common type of epilepsy in women and recognize a particular pattern of this condition with the potential for good therapeutic response.

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Progesterone therapy in women with intractable catamenial epilepsy

Cited by 21 publications

References 33 publications

Progesterone, 5a-dihydropogesterone and allopregnanolone's effects on seizures: A review of animal and clinical studies

Progesterone, 5a-dihydropogesterone and allopregnanolone's effects on seizures: A review of animal and clinical studies

The Frequency of Catamenial Epilepsy in Female Epileptic Patients of Reproductive Age Group Presented to the Tertiary Care Hospital

Catamenial Epilepsy - Update on Practical Management

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