Catamenial Epilepsy

  • P. Emanuela VoinescuEmail author


Catamenial epilepsy is a complex neuroendocrine disorder characterized by seizure clustering during different phases of the menstrual cycle (C1, perimenstrual; C2, periovulatory; C3, anovulatory cycles), with the majority of women experiencing seizure worsening perimenstrually. The working hypothesis for the ongoing basic and clinical research studies is that sex hormones influence neuronal excitability and their fluctuations during an ovarian-menstrual cycle drive the observed seizure clustering patterns (C1, progesterone decline; C2, estrogen surge; C3, low progesterone). At present, no personalized treatment is available for women with catamenial epilepsy whose seizures are frequently refractory to traditional antiepileptic medications. Common strategies involve increasing antiepileptic medication doses, addition of clobazam, or using contraceptive methods to suppress the hormonal cycling, but without solid clinical evidence. Progesterone lozenges used in the second part of the menstrual cycle is the only treatment with supporting evidence coming from the NIH Progesterone Treatment Trial, but only beneficial for a small subset of patients with C1 catamenial epilepsy.


Catamenial Perimenstrual Periovulatory Estrogen Progesterone Neurosteroid Epileptogenesis 


  1. 1.
    Herzog AG, Klein P, Ransil BJ. Three patterns of catamenial epilepsy. Epilepsia. 1997;38(10):1082–8.CrossRefGoogle Scholar
  2. 2.
    Herzog AG, Fowler KM, Sperling MR, Massaro JM. Distribution of seizures across the menstrual cycle in women with epilepsy. Epilepsia. 2015;56(5):e58–62.CrossRefGoogle Scholar
  3. 3.
    Reddy DS. The neuroendocrine basis of sex differences in epilepsy. Pharmacol Biochem Behav sciencedirect. 2017;152:97–104.CrossRefGoogle Scholar
  4. 4.
    Harden CL, Pennell PB. Neuroendocrine considerations in the treatment of men and women with epilepsy. Lancet Neurol. 2013;12(1):72–83.CrossRefGoogle Scholar
  5. 5.
    Herzog A. Catamenial epilepsy: update on prevalence, pathophysiology and treatment from the findings of the NIH Progesterone Treatment Trial. Seizure. sciencedirect. 2015;28:18–25.CrossRefGoogle Scholar
  6. 6.
    Duncan S, Read CL, Brodie M. How common is catamenial epilepsy? Epilepsia [Internet]. 1993. Available from:
  7. 7.
    Rosciszewska D. Analysis of seizure dispersion during menstrual cycle in women with epilepsy. Epilepsy [Internet]. 1980. Available from:
  8. 8.
    Taubøll E, Lundervold A, Gjerstad L. Temporal distribution of seizures in epilepsy. Epilepsy Res [Internet]. 1991;8:153–65. Available from: Scholar
  9. 9.
    Navis A, Harden C. A treatment approach to catamenial epilepsy. Curr Treat Options Neurol springer. 2016;18(7):30.CrossRefGoogle Scholar
  10. 10.
    Jones GS. The luteal phase defect. Fertil Steril [Internet]. 1976. Available from:
  11. 11.
    Haut S. Seizure clusters: characteristics and treatment. Curr Opin Neurol. 2015;28(2):143.CrossRefGoogle Scholar
  12. 12.
    Reddy D. Catamenial epilepsy: discovery of an extrasynaptic molecular mechanism for targeted therapy. Front Cell Neurosci. frontiers. 2016;10:101.Google Scholar
  13. 13.
    Velíšková J, DeSantis K. Sex and hormonal influences on seizures and epilepsy. Horm Behav. 2013;63(2):267–77.CrossRefGoogle Scholar
  14. 14.
    Velíšková J, Jesus G, Kaur R, Velíšek L. Females, their estrogens, and seizures. Epilepsia. 2010;51(s3):141–4.CrossRefGoogle Scholar
  15. 15.
    Weiland N. Estradiol selectively regulates agonist binding sites on the N-methyl-D-aspartate receptor complex in the CA1 region of the hippocampus. Endocrinology [Internet]. 1992;131:662–8. Available from: Scholar
  16. 16.
    Khayat H, Soliman N, Tomoum H, Omran M, Wakad A, Shatla R. Reproductive hormonal changes and catamenial pattern in adolescent females with epilepsy. Epilepsia. 2008;49(9):1619–26.CrossRefGoogle Scholar
  17. 17.
    Herzog AG, Fowler KM, Sperling MR, Liporace JD, Kalayjian LA, Heck CN, Krauss GL, Dworetzky BA, Pennell PB, Progesterone Trial Study Group. Variation of seizure frequency with ovulatory status of menstrual cycles. Epilepsia. 2011;52(10):1843–8.CrossRefGoogle Scholar
  18. 18.
    Quigg M, Fowler KM, Herzog AG, NIH Progesterone Trial Study Group. Circalunar and ultralunar periodicities in women with partial seizures. Epilepsia. 2008;49(6):1081–5.CrossRefGoogle Scholar
  19. 19.
    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(1):47–51.CrossRefGoogle Scholar
  20. 20.
    Herzog AG, Blum AS, Farina EL, Maestri XE, Newman J, Garcia E, Krishnamurthy KB, Hoch DB, Replansky S, Fowler KM, Smithson SD. Valproate and lamotrigine level variation with menstrual cycle phase and oral contraceptive use. Neurology. 2009;72(10):911–4.CrossRefGoogle Scholar
  21. 21.
    Wegner I, Edelbroek PM, Bulk S, Lindhout D. Lamotrigine kinetics within the menstrual cycle, after menopause, and with oral contraceptives. Neurology. 2009;73(17):1388–93.CrossRefGoogle Scholar
  22. 22.
    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. Wiley Online Library. 1979;59(2):63–71.CrossRefGoogle Scholar
  23. 23.
    Case AM, Reid R. Effects of the menstrual cycle on medical disorders. Arch Intern Med [Internet]. 1998;158:1405–12. Available from: Scholar
  24. 24.
    Cagnetti C, Lattanzi S, Foschi N, Provinciali L, Silvestrini M. Seizure course during pregnancy in catamenial epilepsy. Neurology. 2014;83(4):339–44.CrossRefGoogle Scholar
  25. 25.
    Herzog AG, Fowler KM, Smithson SD, Kalayjian LA, Heck CN, Sperling MR, et al. Progesterone vs placebo therapy for women with epilepsy: a randomized clinical trial. Neurology. 2012;78(24):1959–66.CrossRefGoogle Scholar
  26. 26.
    Herzog A. Intermittent progesterone therapy and frequency of complex partial seizures in women with menstrual disorders. Neurology [Internet]. 1986;36:1607–10. Available from: Scholar
  27. 27.
    Herzog AG, Frye C. Allopregnanolone levels and seizure frequency in progesterone-treated women with epilepsy. Neurol Int. 2014;83:345–8. Available from: Scholar
  28. 28.
    Herzog AG, Frye CA. Seizure exacerbation associated with inhibition of progesterone metabolism. Ann Neurol. 2003;53(3):390–1.CrossRefGoogle Scholar
  29. 29.
    Mattson RH, Cramer JA, Caldwell BV, Siconolfi BC. Treatment of seizures with medroxyprogesterone acetate: preliminary report. Neurology. 1984;34(9):1255–8.CrossRefGoogle Scholar
  30. 30.
    Bauer J, Wild L, Flügel D, Stefan H. The effect of a synthetic GnRH analogue on catamenial epilepsy: a study in ten patients. J Neurol [Internet]. 1992. Available from:
  31. 31.
    Harden CL, Herzog AG, Nikolov BG, Koppel BS, Christos PJ, Fowler K, et al. Hormone replacement therapy in women with epilepsy: a randomized, double-blind, placebo-controlled study. Epilepsia. 2006;47(9):1447–51.CrossRefGoogle Scholar
  32. 32.
    Harden CL, Pulver MC, Ravdin L, Jacobs AR. The effect of menopause and perimenopause on the course of epilepsy. Epilepsia. 1999;40(10):1402–7.CrossRefGoogle Scholar
  33. 33.
    Harden CL, Koppel BS, Herzog AG, Nikolov BG, Hauser WA. Seizure frequency is associated with age at menopause in women with epilepsy. Neurology. 2003;61(4):451–5.CrossRefGoogle Scholar
  34. 34.
    Sveinsson O, Tomson T. Epilepsy and menopause: potential implications for pharmacotherapy. Drugs Aging. springer. 2014;31(9):671–5.CrossRefGoogle Scholar
  35. 35.
    Ansell B, Clarke E. Acetazolamide in treatment of epilepsy. Br Med J [Internet]. 1956;1:650–4. Available from: Scholar
  36. 36.
    Lim LL, Foldvary N, Mascha E, Lee J. Acetazolamide in women with catamenial epilepsy. Epilepsia [Internet]. 2001. Available from:
  37. 37.
    Feely M, Calvert R, Gibson J. Clobazam in catamenial epilepsy. A model for evaluating anticonvulsants. Lancet. 1982;2(8289):71–3.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Brigham and Women’s Hospital, Harvard Medical SchoolBostonUSA

Personalised recommendations