Archives of Gynecology and Obstetrics

, Volume 284, Issue 3, pp 749–755

Epilepsy and menopause

Reproductive Medicine



Epilepsy and menopause have complicated interactions. Treatment of epilepsy may cause exacerbation of osteoporosis and alter the effects of hormone replacement therapy (HRT) whereas HRT may influence the frequency of seizures.

Materials and methods

An extensive search was performed in the Cochrane Central Trials Registry, the Web of Science, and PubMed for publications using the keywords “(epilepsy OR Seizure) AND (menopause OR osteoporosis)”; “Anti-epileptic drugs AND (menopause OR osteoporosis); HRT AND epilepsy” between 1970 and 2010 and English language. All eligible trials were included.


The frequency of catamenial type of epileptic seizures may increase during perimenopause due to hyperestrogenism and subside after menopause. Sexual dysfunction can be severe depending upon the effect of lack of estrogen in menopause and epilepsy itself. Osteoporosis and fractures may increase due to hypoestrogenism in menopause and cytochrome P450 inducing anti-epileptic drugs. According to the current data, conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate may increase the frequency of epileptic seizures. Women with epilepsy may need to take HRT, at least for symptomatic relief and to allow adequate sleep when “hot flushes” are disruptive. A combination of a single estrogenic compound such as 17-β-estradiol along with natural progesterone could be considered in these patients.


Epilepsy Menopause Anti-epileptic drugs Osteoporosis Seizure 


  1. 1.
    Brodie MJ, Elder AT, Kwan P (2009) Epilepsy in later life. Lancet Neurol 8:1019–1030PubMedCrossRefGoogle Scholar
  2. 2.
    Wallace H, Shorvon S, Tallis R (1998) Age-specific incidence and prevalence rates of treated epilepsy in an unselected population of 2,052,922 and age-specific fertility rates of women with epilepsy. Lancet 352:1970–1973PubMedCrossRefGoogle Scholar
  3. 3.
    Taubøll E, Luef G (2008) Gender issues in epilepsy—the science of why it is special. Seizure 17:99–100PubMedCrossRefGoogle Scholar
  4. 4.
    Herzog AG, Klein P, Ransil BJ (1997) Three patterns of catamenial epilepsy. Epilepsia 38:1082–1088PubMedCrossRefGoogle Scholar
  5. 5.
    Frye CA (2008) Hormonal influences on seizures: basic neurobiology. Int Rev Neurobiol 83:27–77PubMedCrossRefGoogle Scholar
  6. 6.
    Scharfman HE, MacLusky NJ (2006) The influence of gonadal hormones on neuronal excitability, seizures, and epilepsy in the female. Epilepsia 47:1423–1430PubMedCrossRefGoogle Scholar
  7. 7.
    Hom AC, Buterbaugh GG (1986) Estrogen alters the acquisition of seizures kindled by repeated amygdala stimulation or pentylenetetrazol administration in ovariectomized female rats. Epilepsia 27:103–108PubMedCrossRefGoogle Scholar
  8. 8.
    McEwen B (2002) Estrogen actions throughout the brain. Recent Prog Horm Res 57:357–384PubMedCrossRefGoogle Scholar
  9. 9.
    Scharfman HE, Goodman JH, Rigoulot M-A, Berger RE, Walling SG, Mercurio TC et al (2005) Seizure susceptibility in intact and ovariectomized female rats treated with the convulsant pilocarpine. Exp Neurol 196:73–86PubMedCrossRefGoogle Scholar
  10. 10.
    Nakumura NH, Rosell DR, Akama KT, McEwan BS (2004) Estrogen and ovariectomy regulate mRNA and protein of glutamic acid decarboxylases and cation-chloride cotransporters in the adult rat hippocampus. Neuroendocrinology 80(5):308–323CrossRefGoogle Scholar
  11. 11.
    Kokate TG, Svenssonn BE, Rogawski MA (1994) Anticonvulsant activity of neurosteroids: correlation with gamma-aminobutyric acid-evoked chloride current potentiation. J Pharmacol Exp Ther 270:1223–1229PubMedGoogle Scholar
  12. 12.
    Lavaque E, Sierra A, Azcoitia I, Garcia-Segura LM (2006) Steroidogenic acute regulatory protein in the brain. Neuroscience 138:741–747PubMedCrossRefGoogle Scholar
  13. 13.
    Veliskova J (2007) Estrogens and epilepsy: why are we so excited? Neuroscientist 13:77–88PubMedCrossRefGoogle Scholar
  14. 14.
    Herzog AG (1989) A hypothesis to integrate partial seizures of temporal lobe origin and reproductive disorders. Epilepsy Res 3:151–159PubMedCrossRefGoogle Scholar
  15. 15.
    Luef G (2009) Female issues in epilepsy: a critical review. Epilepsy Behav 15:78–82PubMedCrossRefGoogle Scholar
  16. 16.
    McAuley JW, Anderson GD (2002) Treatment of epilepsy in women of reproductive age: Pharmacokinetic considerations. Clin Pharmacokinet 41:559–579PubMedCrossRefGoogle Scholar
  17. 17.
    Dutton C, Foldvary-Schaefer N (2008) Contraception in women with epilepsy: pharmacokinetic interactions, contraceptive options, and management. Int Rev Neurobiol 83:113–134PubMedCrossRefGoogle Scholar
  18. 18.
    Crawford P (2005) Best practice guidelines for the management of women with epilepsy. Epilepsia 46(Suppl 9):117–124PubMedCrossRefGoogle Scholar
  19. 19.
    Harden CL, Pulver MC, Ravdin L, Jacobs AR (1999) The effect of menopause and perimenopause on the course of epilepsy. Epilepsia 40:1402–1407PubMedCrossRefGoogle Scholar
  20. 20.
    Roscizewska D (1978) Menopause in women and its effects on epilepsy. Neurol Neurochir Pol 12:315–319Google Scholar
  21. 21.
    Abbasi F, Krumholz A, Kittner SJ, Langenberg P (1999) Effects of menopause on seizures in women with epilepsy. Epilepsia 40:205–210PubMedCrossRefGoogle Scholar
  22. 22.
    McAuley JW, Sapna SJ, Moore JL, Peebles CT, Reeves AL (2000) Characterization and health risk assessment of postmenopausal women with epilepsy. Epilepsy Behav 1:353–355PubMedCrossRefGoogle Scholar
  23. 23.
    Berg AT, Berkovic SF, Brodie MJ, Buchhalter J, Cross JH, van Emde Boas W et al (2010) Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005–2009. Epilepsia 51(4):676–685PubMedCrossRefGoogle Scholar
  24. 24.
    Shorvon SD (2011) The etiologic classification of epilepsy. Epilepsia. doi:10.1111/j.1528-1167.2011.03041.x
  25. 25.
    Back DJ, Bates M, Bowden A, Breckenridge AM, Hall MJ, Jones H et al (1980) The interaction of phenobarbital and other anticonvulsants with oral contraceptive steroid therapy. Contraception 22:495–503PubMedCrossRefGoogle Scholar
  26. 26.
    Bartoli A, Gatti G, Cipolla G, Barzaghi N, Veliz G, Fattore C et al (1997) A double-blind, placebo-controlled study on the effect of vigabatrin on in vivo parameters of hepatic microsomal enzyme induction and on the kinetics of steroid oral contraceptives in healthy female volunteers. Epilepsia 38:702–707PubMedCrossRefGoogle Scholar
  27. 27.
    Crawford P, Lee P (1999) Gender difference in management of epilepsy—what women are hearing. Seizure 8:135–139PubMedCrossRefGoogle Scholar
  28. 28.
    Eldon MA, Underwood BA, Randinitis EJ, Sedman AJ (1998) Gabapentin does not interact with a contraceptive regimen of norethindrone acetate and ethinyl estradiol. Neurology 50:1146–1148PubMedGoogle Scholar
  29. 29.
    Griffith SG, Dai Y (2004) Effect of zonisamide on the pharmacokinetics and pharmacodynamics of a combination ethinyl estradiol–norethindrone oral contraceptive in healthy women. Clin Ther 26:2056–2065PubMedCrossRefGoogle Scholar
  30. 30.
    Mengel HB, Houston A, Back DJ (1994) An evaluation of the interaction between tiagabine and oral contraceptives in female volunteers. J Pharm Med 4:141–150Google Scholar
  31. 31.
    Molich T, Whiteman P, Orme M (1991) Effect of lamotrigine on the pharmacology of the combined oral contraceptive pill. Epilepsia 32:96CrossRefGoogle Scholar
  32. 32.
    Ragueneau-Majlessi I, Levy RH, Janik F (2002) Levetiracetam does not alter the pharmacokinetics of an oral contraceptive in healthy women. Epilepsia 43:697–702PubMedCrossRefGoogle Scholar
  33. 33.
    Crawford P, Chadwick D, Cleland P, Tjia J, Cowie A, Back DJ et al (1986) The lack of effect of sodium valproate on the pharmacokinetics of oral contraceptive steroids. Contraception 33:23–29PubMedCrossRefGoogle Scholar
  34. 34.
    Bergen D, Daugherty S, Eckenfels E (1992) Reduction of sexual activities in females taking antiepileptic drugs. Psychopathology 25:1–4PubMedCrossRefGoogle Scholar
  35. 35.
    Herzog AG, Seibel MM, Schomer DL, Vaitukaitis JL, Geschwind N (1986) Reproductive endocrine disorders in women with partial seizures of temporal lobe origin. Arch Neurol 43:341–346PubMedGoogle Scholar
  36. 36.
    Harden CL, Koppel BS, Herzog AG, Nikolov BG, Hauser WA (2003) Seizure frequency is associated with age at menopause in women with epilepsy. Neurology 61:451–455PubMedGoogle Scholar
  37. 37.
    Klein P, Serje A, Pezzulo JC (2001) Premature ovarian failure in women with epilepsy. Epilepsia 42:1584–1589PubMedCrossRefGoogle Scholar
  38. 38.
    Santoro M, Brown JR, Adel T, Skuurnick JH (1996) Characterization of reproductive hormonal dynamics in the perimenopause. J Clin Endocrinol Metab 81:1495–1501PubMedCrossRefGoogle Scholar
  39. 39.
    Harden CL, Herzog AG, Nikolov BG, Koppel BS, Christos PJ, Fowler K et al (2006) Hormone replacement therapy in women with epilepsy: a randomized, double-blind, placebo-controlled study. Epilepsia 47:1447–1451PubMedCrossRefGoogle Scholar
  40. 40.
    Herzog AG (1999) Progesterone therapy in women with epilepsy: a 3-year follow-up. Neurology 52:1917–1918PubMedGoogle Scholar
  41. 41.
    Peebles CT, McAuley JW, Moore JL, Malone HJ, Reeves AL (2000) Hormone replacement therapy in a postmenopausal woman with epilepsy. Ann Pharmacother 34(9):1028–1031PubMedCrossRefGoogle Scholar
  42. 42.
    Erel CT, Brincat M, Gambacciani M, Lambrinoudaki I, Moen MH, Schenck-Gustafsson K et al (2010) EMAS position statement: managing the menopause in women with epilepsy. Maturitas 66(3):327–328PubMedCrossRefGoogle Scholar
  43. 43.
    Shen W, Stearns V (2009) Treatment strategies for hot flushes. Expert Opin Pharmacother 10:1133–1144PubMedCrossRefGoogle Scholar
  44. 44.
    Pack AM, Gidal B, Vazquez B (2004) Bone disease associated with antiepileptic drugs. Cleve Clin J Med 71(Suppl 2):S42–S48PubMedCrossRefGoogle Scholar
  45. 45.
    Harden CL (2003) Menopause and bone density issues for women with epilepsy. Neurology. 61(6 Suppl 2):S16–S22PubMedGoogle Scholar
  46. 46.
    Vestergaard P (2005) Epilepsy, osteoporosis and fracture risk—a meta-analysis. Acta Neurol Scand 112:277–286PubMedCrossRefGoogle Scholar
  47. 47.
    Elliott JO, Jacobson MP, Haneef Z (2007) Homocysteine and bone loss in epilepsy. Seizure 16(1):22–34PubMedCrossRefGoogle Scholar
  48. 48.
    Petty SJ, Paton LM, O’Brien TJ, Makovey J, Erbas B, Sambrook P et al (2005) Effect of antiepileptic medication on bone mineral measures. Neurology 65:1358–1363PubMedCrossRefGoogle Scholar
  49. 49.
    Farhat G, Yamout B, Mikati A, Demirjian S, Sawaya R, Fuleihan GE (2002) Effect of antiepileptic drugs on bone density in ambulatory patients. Neurology 58:1348–1353PubMedGoogle Scholar
  50. 50.
    Cummings SR, Nevitt MC, Browner WS, Stone K, Fox KM, Ensrud KE et al (1995) Risk factors for hip fracture in white women, Study of Osteoporotic Fractures Research Group. N Engl J Med 332:767–773PubMedCrossRefGoogle Scholar
  51. 51.
    Souverein PC, Webb DJ, Petri H, Weil J, Van Staa TP, Egberts T (2005) Incidence of fractures among epilepsy patients: a population-based prospective cohort study in the General Practice Research Database. Epilepsia 46:304–310PubMedCrossRefGoogle Scholar
  52. 52.
    National Institutes of Health (2000) Osteoporosis prevention, diagnosis and therapy. NIH Consens Statement 17:1–52Google Scholar
  53. 53.
    Guo CY, Ronen GM, Atkinson SA (2001) Long-term valproate and lamotrigine treatment may be a marker for reduced growth and bone mass in children with epilepsy. Epilepsia 42:1141–1147PubMedCrossRefGoogle Scholar
  54. 54.
    Pack AM, Morrell MJ, Marcus R, Holloway L, Flaster E, Doñe S et al (2005) Bone mass and turnover in women with epilepsy on antiepileptic drug monotherapy. Ann Neurol 57:252–257PubMedCrossRefGoogle Scholar
  55. 55.
    Drezner MK (2004) Treatment of anticonvulsant drug-induced bone disease. Epilepsy Behav 5(Suppl 2):S41–S47PubMedCrossRefGoogle Scholar
  56. 56.
    Vestergaard P, Rejnmark L, Mosekilde L (2004) Fracture risk associated with use of antiepileptic drugs. Epilepsia 45:1130–1137CrossRefGoogle Scholar
  57. 57.
    Feldkamp J, Becker A, Witte OW, Scharff D, Scherbaum WA (2000) Long-term anticonvulsant therapy leads to low bone mineral density: evidence for direct drug effects of phenytoin and carbamazepine on human osteoblast-like cells. Exp Clin Endocrinol Diabetes 108:37–43PubMedGoogle Scholar
  58. 58.
    Cramer JA, Gordon J, Schachter S, Devinsky O (2007) Women with epilepsy: hormonal issues from menarche through menopause. Epilepsy Behav 11:160–178PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  1. 1.Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Cerrahpasa School of MedicineIstanbul UniversityIstanbulTurkey
  2. 2.Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Cerrahpasa School of MedicineIstanbul UniversityIstanbulTurkey

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