Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Catamenial epilepsy

Sabiha Merchant, MD
Cynthia L Harden, MD
Section Editor
Timothy A Pedley, MD
Deputy Editor
April F Eichler, MD, MPH


Catamenial epilepsy refers to a pattern of seizure clustering that is related to the menstrual cycle [1]. It does not describe a seizure localization, seizure type, or epilepsy syndrome. Catamenial seizure clusters have been described with every seizure type and epilepsy syndrome.

The definition of catamenial epilepsy has varied among investigators. The most accepted criterion requires a doubling of a baseline seizure frequency during a specific phase of the menstrual cycle [1-4].

This topic will discuss specific aspects of seizures and epilepsy that relate to a catamenial pattern of seizure clustering. Other aspects of seizures and epilepsy are discussed separately. (See "Overview of the management of epilepsy in adults" and "Initial treatment of epilepsy in adults" and "Pathophysiology of seizures and epilepsy".)


The reported prevalence of catamenial clustering among women with epilepsy varies widely between 10 to 78 percent. This is mainly due to methodological differences among studies, which have used different patient populations, various criterion for diagnosis, and different recording mechanisms to link seizures with menstrual cycle phases [2,5]. In studies that used the above definition, and rigorous recording methods, approximately one-third of women with medically refractory epilepsy have a catamenial pattern of exacerbations [2,6,7].

While catamenial epilepsy necessarily affects women of child-bearing age, no other demographic features or other risk factors have been clearly defined for this phenomenon. One study found that a catamenial pattern was more common in the younger half (median age 40 years) of their population of 100 women of childbearing age with intractable focal epilepsy [8].


Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Sep 2016. | This topic last updated: Oct 31, 2014.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
  1. Herzog AG. Catamenial epilepsy: definition, prevalence pathophysiology and treatment. Seizure 2008; 17:151.
  2. Herzog AG, Klein P, Ransil BJ. Three patterns of catamenial epilepsy. Epilepsia 1997; 38:1082.
  3. Foldvary-Schaefer N, Falcone T. Catamenial epilepsy: pathophysiology, diagnosis, and management. Neurology 2003; 61:S2.
  4. Reddy DS. The role of neurosteroids in the pathophysiology and treatment of catamenial epilepsy. Epilepsy Res 2009; 85:1.
  5. Duncan S, Read CL, Brodie MJ. How common is catamenial epilepsy? Epilepsia 1993; 34:827.
  6. El-Khayat HA, Soliman NA, Tomoum HY, et al. Reproductive hormonal changes and catamenial pattern in adolescent females with epilepsy. Epilepsia 2008; 49:1619.
  7. Herzog AG, Harden CL, Liporace J, et al. Frequency of catamenial seizure exacerbation in women with localization-related epilepsy. Ann Neurol 2004; 56:431.
  8. Quigg M, Smithson SD, Fowler KM, et al. Laterality and location influence catamenial seizure expression in women with partial epilepsy. Neurology 2009; 73:223.
  9. 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.
  10. Herzog AG, Friedman MN. Menstrual cycle interval and ovulation in women with localization-related epilepsy. Neurology 2001; 57:2133.
  11. Jones GS. The luteal phase defect. Fertil Steril 1976; 27:351.
  12. Morrell MJ, Giudice L, Flynn KL, et al. Predictors of ovulatory failure in women with epilepsy. Ann Neurol 2002; 52:704.
  13. Cummings LN, Giudice L, Morrell MJ. Ovulatory function in epilepsy. Epilepsia 1995; 36:355.
  14. Herzog AG, Fowler KM, Sperling MR, et al. Variation of seizure frequency with ovulatory status of menstrual cycles. Epilepsia 2011; 52:1843.
  15. Abbasi F, Krumholz A, Kittner SJ, Langenberg P. Effects of menopause on seizures in women with epilepsy. Epilepsia 1999; 40:205.
  16. Backstrom, T, Landgren, S, Zetterlund, B , et al. Effects of ovarian steroid hormones on brain excitability and their relation to epilepsy seizure variation during the menstrual cycle. In: Advances in epileptology: XVth epilepsy international symposium, Porter, RJ (Ed). Raven press, New York 1984. p.269.
  17. Buterbaugh GG. Estradiol replacement facilitates the acquisition of seizures kindled from the anterior neocortex in female rats. Epilepsy Res 1989; 4:207.
  18. Morrell MJ. Epilepsy in women: the science of why it is special. Neurology 1999; 53:S42.
  19. Smith SS, Woolley CS. Cellular and molecular effects of steroid hormones on CNS excitability. Cleve Clin J Med 2004; 71 Suppl 2:S4.
  20. LOGOTHETIS J, HARNER R, MORRELL F, TORRES F. The role of estrogens in catamenial exacerbation of epilepsy. Neurology 1959; 9:352.
  21. Selye, H. The antagonism between anesthetic steroid hormones and pentamethylenetetrazol (Metrazol). J Lab Clin Med 1942; 27:1051.
  22. Reddy DS, Rogawski MA. Neurosteroid replacement therapy for catamenial epilepsy. Neurotherapeutics 2009; 6:392.
  23. Rościszewska D, Buntner B, Guz I, Zawisza L. Ovarian hormones, anticonvulsant drugs, and seizures during the menstrual cycle in women with epilepsy. J Neurol Neurosurg Psychiatry 1986; 49:47.
  24. Herzog AG, Frye CA. Seizure exacerbation associated with inhibition of progesterone metabolism. Ann Neurol 2003; 53:390.
  25. Reddy DS, Castaneda DC, O'Malley BW, Rogawski MA. Anticonvulsant activity of progesterone and neurosteroids in progesterone receptor knockout mice. J Pharmacol Exp Ther 2004; 310:230.
  26. Majewska MD, Harrison NL, Schwartz RD, et al. Steroid hormone metabolites are barbiturate-like modulators of the GABA receptor. Science 1986; 232:1004.
  27. Peters JA, Kirkness EF, Callachan H, et al. Modulation of the GABAA receptor by depressant barbiturates and pregnane steroids. Br J Pharmacol 1988; 94:1257.
  28. Smith SS, Gong QH, Hsu FC, et al. GABA(A) receptor alpha4 subunit suppression prevents withdrawal properties of an endogenous steroid. Nature 1998; 392:926.
  29. Reddy DS, Rogawski MA. Enhanced anticonvulsant activity of neuroactive steroids in a rat model of catamenial epilepsy. Epilepsia 2001; 42:337.
  30. Reddy DS, Kim HY, Rogawski MA. Neurosteroid withdrawal model of perimenstrual catamenial epilepsy. Epilepsia 2001; 42:328.
  31. Reddy DS. Role of neurosteroids in catamenial epilepsy. Epilepsy Res 2004; 62:99.
  32. Scharfman HE, MacLusky NJ. The influence of gonadal hormones on neuronal excitability, seizures, and epilepsy in the female. Epilepsia 2006; 47:1423.
  33. Tuveri A, Paoletti AM, Orrù M, et al. Reduced serum level of THDOC, an anticonvulsant steroid, in women with perimenstrual catamenial epilepsy. Epilepsia 2008; 49:1221.
  34. Reddy DS. Pharmacology of endogenous neuroactive steroids. Crit Rev Neurobiol 2003; 15:197.
  35. Harden CL, Pulver MC, Ravdin L, Jacobs AR. The effect of menopause and perimenopause on the course of epilepsy. Epilepsia 1999; 40:1402.
  36. Harden CL. Issues for mature women with epilepsy. Int Rev Neurobiol 2008; 83:385.
  37. Røste LS, Taubøll E, Svalheim S, Gjerstad L. Does menopause affect the epilepsy? Seizure 2008; 17:172.
  38. Harden CL. Hormone replacement therapy: will it affect seizure control and AED levels? Seizure 2008; 17:176.
  39. Harden CL, Herzog AG, Nikolov BG, et al. Hormone replacement therapy in women with epilepsy: a randomized, double-blind, placebo-controlled study. Epilepsia 2006; 47:1447.
  40. Kumar N, Behari M, Ahuja GK, Jailkhani BL. Phenytoin levels in catamenial epilepsy. Epilepsia 1988; 29:155.
  41. Shavit G, Lerman P, Korczyn AD, et al. Phenytoin pharmacokinetics in catamenial epilepsy. Neurology 1984; 34:959.
  42. Herzog AG, Blum AS, Farina EL, et al. Valproate and lamotrigine level variation with menstrual cycle phase and oral contraceptive use. Neurology 2009; 72:911.
  43. Bäckström T, Jorpes P. Serum phenytoin, phenobarbital, carbamazepine, albumin; and plasma estradiol, progesterone concentrations during the menstrual cycle in women with epilepsy. Acta Neurol Scand 1979; 59:63.
  44. Bäckström T. Epileptic seizures in women related to plasma estrogen and progesterone during the menstrual cycle. Acta Neurol Scand 1976; 54:321.
  45. Morrell, MJ, Hamdy, SF, Seale, CG, Springer, EA. Self-reported reproductive history in women with epilepsy: puberty onset and effects of menarche and menstrual cycle on seizures. Neurology 1998; 50:448.
  46. Marques-Assis L. [Influence of menstruation on epilepsy]. Arq Neuropsiquiatr 1981; 39:390.
  47. Kalinin VV, Zheleznova EV. Chronology and evolution of temporal lobe epilepsy and endocrine reproductive dysfunction in women: relationships to side of focus and catameniality. Epilepsy Behav 2007; 11:185.
  48. Herzog AG, Fowler KM, NIH Progesterone Trial Study Group. Sensitivity and specificity of the association between catamenial seizure patterns and ovulation. Neurology 2008; 70:486.
  49. Bauer J, Burr W, Elger CE. Seizure occurrence during ovulatory and anovulatory cycles in patients with temporal lobe epilepsy: a prospective study. Eur J Neurol 1998; 5:83.
  50. Poser CH. Letter: Modification of therapy for exacerbation of seizures during menstruation. J Pediatr 1974; 84:779.
  51. Ansell, B, Clarke, E. Acetazolamide in treatment of epilepsy. BMJ 1956; 1:650.
  52. Lim LL, Foldvary N, Mascha E, Lee J. Acetazolamide in women with catamenial epilepsy. Epilepsia 2001; 42:746.
  53. LOMBROSO CT, FORXYTHE I. A long-term follow-up of acetazolamide (diamox) in the treatment of epilepsy. Epilepsia 1960; 1:493.
  54. Gilad R, Sadeh M, Rapoport A, et al. Lamotrigine and catamenial epilepsy. Seizure 2008; 17:531.
  55. Feely M, Calvert R, Gibson J. Clobazam in catamenial epilepsy. A model for evaluating anticonvulsants. Lancet 1982; 2:71.
  56. Feely M, Gibson J. Intermittent clobazam for catamenial epilepsy: tolerance avoided. J Neurol Neurosurg Psychiatry 1984; 47:1279.
  57. Zimmerman AW, Holden KR, Reiter EO, Dekaban AS. Medroxprogesterone acetate in the treatment of seizures associated with menstruation. J Pediatr 1973; 83:959.
  58. Mattson RH, Cramer JA, Caldwell BV, Siconolfi BC. Treatment of seizures with medroxyprogesterone acetate: preliminary report. Neurology 1984; 34:1255.
  59. Herzog AG. Intermittent progesterone therapy and frequency of complex partial seizures in women with menstrual disorders. Neurology 1986; 36:1607.
  60. Herzog AG. Progesterone therapy in women with complex partial and secondary generalized seizures. Neurology 1995; 45:1660.
  61. Herzog AG. Progesterone therapy in women with epilepsy: a 3-year follow-up. Neurology 1999; 52:1917.
  62. Herzog AG, Fowler KM, Smithson SD, et al. Progesterone vs placebo therapy for women with epilepsy: A randomized clinical trial. Neurology 2012; 78:1959.
  63. Pennell PB. Hormonal aspects of epilepsy. Neurol Clin 2009; 27:941.
  64. Hall SM. Treatment of menstrual epilepsy with a progesterone-only oral contraceptive. Epilepsia 1977; 18:235.
  65. Dana-Haeri J, Richens A. Effect of norethisterone on seizures associated with menstruation. Epilepsia 1983; 24:377.
  66. Herzog AG. Clomiphene therapy in epileptic women with menstrual disorders. Neurology 1988; 38:432.
  67. Bauer J, Wildt L, Flügel D, Stefan H. The effect of a synthetic GnRH analogue on catamenial epilepsy: a study in ten patients. J Neurol 1992; 239:284.
  68. Haider Y, Barnett DB. Catamenial epilepsy and goserelin. Lancet 1991; 338:1530.
  69. Nohria V, Giller E. Ganaxolone. Neurotherapeutics 2007; 4:102.
  70. Cagnetti C, Lattanzi S, Foschi N, et al. Seizure course during pregnancy in catamenial epilepsy. Neurology 2014; 83:339.