Abstract
In 2011, there are greater than 20 antiepileptic medications available. These medications work by modulating neuronal excitability. Reproductive hormones have been found to have a role in the pathogenesis and treatment of seizures by also altering neuronal excitability, especially in women with catamenial epilepsy. The female reproductive hormones have in general opposing effects on neuronal excitability; estrogens generally impart a proconvulsant neurophysiologic tone, whereas the progestogens have anticonvulsant effects. It follows then that fluctuations in the levels of serum progesterone and estrogen throughout a normal reproductive cycle bring about an increased or decreased risk of seizure occurrence based upon the serum estradiol/progesterone ratio. Therefore, using progesterone, its metabolite allopregnanolone, or other hormonal therapies have been explored in the treatment of patients with epilepsy.
Similar content being viewed by others
References
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
French JA. Treatment with antiepileptic drugs, new and old. Continuum Lifelong Learning Neurol. 2007;13:71–80.
Morrell MJ. Hormones and epilepsy through the lifetime. Epilepsia. 1992;33 Suppl 4:S49–61.
•• Herzog AG. Catamenial epilepsy: definition, prevalence, pathophysiology and treatment. Seizure 2008; 17:151–9. This article provides a detailed definition of catamenial epilepsy and is a current evaluation of the pathophysiology and treatment, both hormonal and nonhormonal, of this disorder.
Bäckström T, Zetterlund B, Blom S, et al. Effects of intravenous progesterone during the menstrual cycle. Acta Neurol Scand. 1976;54:321–47.
Herzog AG, Friedman MN. Menstrual cycle interval and ovulation in women with localization-related epilepsy. Neurology. 2001;57:2133–5.
Abbasi F, Krumholz A, Kittner SJ, et al. Effects of menopause on seizures in women with epilepsy. Epilepsia. 1999;40:205–10.
Herzog AG, Klein P, Ransil BJ. Three patterns of catamenial epilepsy. Epilepsia. 1997;38:1082–8.
Sherman BM, Korenman SG. Measurement of serum LH, FSH, estradiol and progesterone in disorders of the human menstrual cycle: the inadequate luteal phase. J Clin Endocrinol Metab. 1974;39:145–9.
Morrell MJ, Giudice L, Flynn KL, et al. Predictors of ovulatory failure in women with epilepsy. Ann Neurol. 2002;52:704–7.
Cummings LN, Giudice L, Morrell MJ. Ovulatory function in epilepsy. Epilepsia. 1995;36:355–9.
• Velíšek L, Velíšková J. New avenue of research: antiepileptic drug and estradiol neuroprotection in epilepsy. Recent Pat CNS Drug Discov 2008; 3:128–37. This article reviews both the proconvulsant and neuroprotective features of estrogens when taking into account the dosage paradigm, timing, sex of the subjects, and their gonadal hormone status. It also reviews several studies that have demonstrated that estradiol has potency to protect neurons from seizure-induced brain damage.
Wooley DE, Timiras PS. The gonad-brain relationship: effects of female sex hormones and electroshock convulsions in the rat. Endocrinology. 1962;70:196–209.
Woolley CS. Estradiol facilitates kainic acid-induced, but not flurothyl-induced behavioral seizure activity in adult female rats. Epilepsia. 2000;41:510–5.
Wallis CJ, Luttge WG. Influence of estrogen and progesterone on glutamic acid decarboxylase activity in discrete regions of rate brain. J Neurochem. 1980;34:609–13.
Weiland NG. Estradiol selectively regulates agonist binding sites on the N-mehtyl-D-aspartate receptor complex in the CA-1 region of the hippocampus. Endocrinology. 1992;131:662–8.
• Reddy DS. The role of neurosteroids in the pathophysiology and treatment of catamenial epilepsy. Epilepsy Res 2009; 85: 1–30. This is a detailed review on the pathophysiology of catamenial epilepsy and in-depth analysis of how neurosteroids could be used in the treatment of women with this disorder.
•• Herzog AG. Hormonal therapies: progesterone. Neurotherapeutics 2009; 6:383–91. This article reviews the pathophysiology and treatment of catamenial epilepsy and provides an up-to-date review of using progesterone therapy in women with catamenial epilepsy.
• Reddy DS, Rogawski MA. Neurosteroid replacement therapy for catamenial epilepsy. Neurotherapeutics 2009; 6:392–401. This article provides detail on the pathophysiology of catamenial epilepsy and evaluates how synthetic analogues of progesterone metabolites may work on GABAA channels to therapeutically reduce seizures.
El-Khayat HA, Soliman NA, Tomoum HY, et al. Reproductive hormonal changes and catamenial pattern in adolescent females with epilepsy. Epilepsia. 2008;49:1619–26.
Herzog AG, Frye CA. Seizure exacerbation associated with inhibition of progesterone metabolism. Ann Neurol. 2003;53:390–1.
Herzog AG. Intermittent progesterone therapy of partial complex seizures in women with menstrual disorders. Neurology. 1986;36:1607–10.
Herzog AG. Progesterone therapy in women with complex partial and secondary generalized seizures. Neurology. 1995;45:1660–2.
Herzog AG. Progesterone therapy in women with epilepsy: a 3-year follow-up. Neurology. 1999;52:1917–8.
Mattson RH, Cramer JA, Caldwell BV, et al. Treatment of seizures with medroxyprogesterone acetate: preliminary report. Neurology. 1984;34:1255–8.
Bauer J, Wildt L, Flugel D, et al. The effect of a synthetic GnRH analogue on catamenial epilepsy: a study in ten patients. J Neurol. 1992;239:284–6.
Haider Y, Barnett DB. Catamenial epilepsy and goserelin. Lancet. 1991;338:1530.
Herzog AG. Clomiphene therapy in epileptic women with menstrual disorders. Neurology. 1988;38:432–4.
Laxer K, Blum D, Abou-Khalil BW, et al. Assessment of ganaxolone’s anticonvulsant activity using a randomized, double-blind, presurgical trial design. Epilepsia. 2000;41:1187–94.
Kerrigan JF, Shields WD, Nelson TY, et al. Ganaxolone for treating intractable infantile spasms: a multicenter, open-label, add-on trial. Epilepsy Res. 2000;42:133–9.
Pieribone VA, Tsai J, Soufflet C, et al. Clinical evaluation of ganaxolone in pediatric and adolescent patients with refractory epilepsy. Epilepsia. 2007;48:1870–4.
Nohria V, Giller E. Ganaxolone. Neurotherapeutics. 2007;4:102–5.
Reddy DS. Testosterone modulation of seizure susceptibility is mediated by neurosteroids 3α-androstanediol and 17β-estradiol. Neuroscience. 2004;129:195–207.
Reddy DS. Anticonvulsant activity of the testosterone-derived neurosteroid 3α-androstanediol. Neuroreport. 2004;15:515–8.
Kaminski RM, Marini H, Kim W, et al. Anticonvulsant activity of androsterone and etiocholanolone. Epilepsia. 2005;46:819–27.
Herzog AG, Klein P, Jacobs AR. Testosterone versus testosterone and testolactone in treating reproductive and sexual dysfunction in men with epilepsy and hypogonadism. Neurology. 1998;50:782–4.
Herzog AG, Farina E, Drislane F, et al. A comparison of anastrozole and testosterone versus placebo and testosterone for treatment of sexual dysfunction in men with epilepsy and hypogonadism. Epilepsy Behav. 2010;17:264–71.
Harden CL, MackLusky NJ. Aromatase inhibitors as add-on treatment for men with epilepsy. Expert Rev Neurother. 2005;5:123–7.
Harden CL, Pulver MC, Jacobs AR. The effect of menopause and perimenopause on the course of epilepsy. Epilepsia. 1999;40:1402–7.
Harden CL, Herzog AG, Nikolov BG, et al. Hormone replacement therapy in women with epilepsy: a randomized, double-blind, placebo-controlled study. Epilepsy. 2006;47:1447–51.
• Chelbowski RT, Anderson GL, Gass M, et al. Estrogen plus progestin and breast cancer incidence and mortality in postmenopausal women. JAMA 2010; 304:1684–92. This article illustrates a greater breast cancer incidence and mortality in women taking estrogen plus progestin HRT.
Disclosure
No potential conflicts of interest relevant to this article were reported.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Stevens, S.J., Harden, C.L. Hormonal Therapy for Epilepsy. Curr Neurol Neurosci Rep 11, 435–442 (2011). https://doi.org/10.1007/s11910-011-0196-9
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11910-011-0196-9