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Epilepsy and Menopause: Potential Implications for Pharmacotherapy

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Abstract

Being a woman with epilepsy is not the same as being a man with the disease. There is a complex multidirectional interaction between sex hormones, seizures and antiepileptic drugs (AEDs) with gender-specific implications. Estrogen can be a potent proconvulsant, whereas progesterone is an anticonvulsant in experimental models. It is well established that women with epilepsy can have changes in seizure propensity related to their menstrual cycle (catamenial epilepsy). There is good evidence that the gonadotropin-releasing hormone cell population in the hypothalamus can be affected by seizures originating in the limbic system, possibly leading to anovulatory menses, possibly contributing to lower fertility, and earlier menopause among women with epilepsy. Data on the effects of menopause on epilepsy are scarce. In general, menopause appears to have limited effects on seizure control, with the possible exception of women with catamenial epilepsy who may experience an increase in seizure frequency during perimenopause and a decrease after menopause. Hormone replacement therapy has the potential to increase seizure frequency and thus cannot be recommended for women with epilepsy. Of particular relevance for menopause is the adverse effect on bone mineral density caused by enzyme inducers and other AEDs. In general, there is a remarkable shortage of studies on the impact of menopause on epilepsy and on its implications for epilepsy treatment.

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References

  1. World Health Organisation. Epilepsy. http://www.who.int/topics/epilepsy. Accessed 13 Dec 2013.

  2. Hauser WA, Annegers JF, Kurland LT. Incidence of epilepsy and unprovoked seizures in Rochester, Minnesota: 1935–1984. Epilepsia. 1993;34(3):453–68.

    Article  PubMed  CAS  Google Scholar 

  3. Taubøll E, Luef G. Gender issues in epilepsy—the science of why it is special. Seizure. 2008;17:99–100.

    Article  PubMed  Google Scholar 

  4. Harden CL, Pennell PB. Neuroendocrine considerations in the treatment of men and women with epilepsy. Lancet Neurol. 2013;12(1):72–83.

    Article  PubMed  CAS  Google Scholar 

  5. Friedman MN, Geula C, Holmes GL, Herzog AG. GnRH-immunoreactive fiber changes with unilateral amygdala-kindled seizures. Epilepsy Res. 2002;52:73–7.

    Article  PubMed  CAS  Google Scholar 

  6. Quigg M, Kiely JM, Johnson ML, et al. Interictal and postictal circadian and ultradian luteinizing hormone secretion in men with temporal lobe epilepsy. Epilepsia. 2006;47:1452–9.

    Article  PubMed  CAS  Google Scholar 

  7. Luef G. Female issues in epilepsy: a critical review. Epilepsy Behav. 2009;15:78–82.

    Article  PubMed  Google Scholar 

  8. Cramer JA, Gordon J, Schachter S, et al. Women with epilepsy: hormonal issues from menarche through menopause. Epilepsy Behav. 2007;11:160–78.

    Article  PubMed  Google Scholar 

  9. Frye CA. Hormonal influences on seizures: basic neurobiology. Int Rev Neurobiol. 2008;83:27–77.

    Article  PubMed  Google Scholar 

  10. Logothetis J, Harner R, Morrell F, et al. The role of estrogens in catamenial exacerbation of epilepsy. Neurology. 1959;9:352–60.

    Article  PubMed  CAS  Google Scholar 

  11. Herzog AG, Klein P, Ransil BJ. Three patterns of catamenial epilepsy. Epilepsia. 1997;38:1082–8.

    Article  PubMed  CAS  Google Scholar 

  12. Terasawa E, Timiras PS. Electrical activity during the estrous cycle of the rat: cyclic changes in limbic structures. Endocrinology. 1968;83:207–16.

    Article  PubMed  CAS  Google Scholar 

  13. Mattson RH, Cramer JA, Caldwell BV, et al. Treatment of seizures with medroxyprogesterone acetate: preliminary report. Neurology. 1984;34:1255–8.

    Article  PubMed  CAS  Google Scholar 

  14. Herzog AG. Progesterone therapy in women with epilepsy: a 3-year follow-up. Neurology. 1997;52:1917–8.

    Article  Google Scholar 

  15. Scharfman HE, MacLusky NJ. The influence of gonadal hormones on neuronal excitability, seizures, and epilepsy in the female. Epilepsia. 2006;47:1423–30.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  16. Herzog AG, Fowler KM, Smithson SD, et al. Progesterone vs placebo therapy for women with epilepsy: a randomized clinical trial. Neurology. 2012;78:1959–66.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  17. North American Menopause Society. Menopause Core Curriculum Study Guide. 2nd ed. Cleveland: North American Menopause Society; 2002.

    Google Scholar 

  18. Soules MR, Sherman S, Parrott E, et al. Executive summary: stages of reproductive aging workshop (STRAW). Fertil Steril. 2001;76:874–8.

    Article  PubMed  CAS  Google Scholar 

  19. Harden CL, Koppel BS, Herzog AG, et al. Seizure frequency is associated with age at menopause in women with epilepsy. Neurology. 2003;61:451–5.

    Article  PubMed  CAS  Google Scholar 

  20. McAuley JW, Koshy SJ, Moore JL, et al. Characterization and health risk assessment of postmenopausal women with epilepsy. Epilepsy Behav. 2000;1:353–5.

    Article  PubMed  CAS  Google Scholar 

  21. Klein P, Serje A, Pezzulo JC. Premature ovarian failure in women with epilepsy. Epilepsia. 2001;42:1584–9.

    Article  PubMed  CAS  Google Scholar 

  22. Burger HG, Dudley EC, Robertson DM, et al. Hormonal changes in the menopause transition. Recent Prog Horm Res. 2002;57:257–75.

    Article  PubMed  CAS  Google Scholar 

  23. Harden CL, Pulver MC, Ravdin L, et al. The effect of menopause and perimenopause on the course of epilepsy. Epilepsia. 1999;40:1402–7.

    Article  PubMed  CAS  Google Scholar 

  24. Abbasi F, Krumholz A, Kittner SJ, et al. Effects of menopause on seizures in women with epilepsy. Epilepsia. 1999;40:205–10.

    Article  PubMed  CAS  Google Scholar 

  25. McAuley JW, Sapna SJ, Moore JL, et al. Characterization and health risk assessment of postmenopausal women with epilepsy. Epilepsy Behav. 2000;1(353–355):23.

    Google Scholar 

  26. Tomson T, Lukic S, Ohman I. Are lamotrigine kinetics altered in menopause? Observations from a drug monitoring database. Epilepsy Behav. 2010;19:86–8.

    Article  PubMed  Google Scholar 

  27. Wegner I, Edelbroek PM, Bulk S, et al. Lamotrigine kinetics within the menstrual cycle, after menopause, and with oral contraceptives. Neurology. 2009;73:1388–93.

    Article  PubMed  CAS  Google Scholar 

  28. Wegner I, Wilhelm AJ, Sander JW, et al. The impact of age on lamotrigine and oxcarbazepine kinetics: a historical cohort study. Epilepsy Behav. 2013;29:217–21.

    Article  PubMed  Google Scholar 

  29. Harden CL, Herzog AG, Nikolov BG, et al. Hormone replacement therapy in women with epilepsy: a randomized, double-blind, placebo-controlled study. Epilepsia. 2006;47:1447–51.

    Article  PubMed  CAS  Google Scholar 

  30. Mattson RH, Gidal BE. Fractures, epilepsy, and antiepileptic drugs. Epilepsy Behav. 2004;5(Suppl. 2):S36–40.

    Article  PubMed  Google Scholar 

  31. Pack A. Bone health in people with epilepsy: is it impaired and what are the risk factors? Seizure. 2008;17(2):181–6.

    Article  PubMed  Google Scholar 

  32. Zare M, Ghazvini MR, Dashti M, et al. Bone turnover markers in epileptic patients under chronic valproate therapy. J Res Med Sci. 2013;18:338–40.

    PubMed  PubMed Central  Google Scholar 

  33. Jetté N, Lix LM, Metge CJ, et al. Association of antiepileptic drugs with nontraumatic fractures: a population-based analysis. Arch Neurol. 2011;68:107–12.

    Article  PubMed  Google Scholar 

  34. Pack AM, Morrell MJ, Randall A, et al. Bone health in young women with epilepsy after 1 year of antiepileptic drug monotherapy. Neurology. 2008;70(18):1586–93.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  35. Mikati MA, Dib L, Yamout B, et al. Two randomized vitamin D trials in ambulatory patients on anticonvulsants: impact on bone. Neurology. 2006;67(11):2005–14.

    Article  PubMed  CAS  Google Scholar 

  36. Cardozo L, Bachmann G, McClish D, et al. Meta-analysis of estrogen therapy in the management of urogenital atrophy in postmenopausal women: second report of the Hormones and Urogenital Therapy Committee. Obstet Gynecol. 1998;92:722–7.

    Article  PubMed  CAS  Google Scholar 

  37. Erel T, Guralp O. Epilepsy and menopause. Arch Gynecol Obstet. 2011;283(4):755–9.

    Article  Google Scholar 

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Acknowledgments

Torbjörn Tomson has received grants from Stockholm County Council, AFA Insurance, CURE, GSK, Eisai, UCB, Sanofi-Aventis, Novartis, Bial. He has received speaker’s or consultancy fees from Eisai, GSK, UCB, and Sun Pharma.

Olafur Sveinsson has no conflicts of interest to declare.

No funding was received for the preparation of this article.

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Correspondence to Torbjörn Tomson.

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Sveinsson, O., Tomson, T. Epilepsy and Menopause: Potential Implications for Pharmacotherapy. Drugs Aging 31, 671–675 (2014). https://doi.org/10.1007/s40266-014-0201-5

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