Premature Ovarian Failure and Epilepsy

Hendra Permana, Afriyeni Sri Rahmi, Syamel Muhammad


Premature ovarian failure (POF) or premature menopause refers to development of amenorrhoea due to cessation of ovarian function before the age of 40 years. The diagnosis is based on elevated FSH levels in menopausal range (usually above 40 IU/l) detected on at least two occasions a few weeks apart. The term “epilepsy” defines a group of disorders characterized by an enduring predisposition of the brain to produce seizures. The hypothalamic-pituitary-ovarian axis regulation is affected by the abnormal neurophysiology of seizures, and the hypothalamic-pituitary-ovarian associated hormones are affected by medications used to treat seizures in women with epilepsy. Ictal and interictal discharges can disrupt the normal activity of brain structures, including the limbic system, amygdala, hypothalamus, and pituitary gland. Management of epilepsy in women requires not only knowledge of epilepsy, but also recognition of the various roles and priorities women have in their lives (education, career development, child rearing, the role as carer within the extended family), and attention to gender-specific issues and their impact on patients’ wellbeing throughout life.

Keywords: premature ovarian failure (POF), epilepsy

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Hesdorffer, D.C., Begley, C.E. Surveillance of epilepsy and prevention of epilepsy and its sequelae: lessons from the Institute of Medicine report. Curr Opin Neurol, 2013, 26: 168-173

Christensen, J., Kjeldsen, M.J., Anderson, H., Friis, M.L., Sidenius, P. Gender differences in epilepsy, 2005, 46: 956-960.

Perucca, P., Camfield, P., Camfield, C. Does gender influence susceptibility and consequences of acquired epilepsies? Neurobiol. Dis, 2014, 72: 125–130.

Artama M, Isojärvi JIT, Raitanen J, Auvinen A. Birth rate among patients with epilepsy: a nationwide population-based cohort study in Finland. Am J Epidemiol 2004, 159: 1057–63

Rachel R. Fabris, Teresa Griffin Cascino, Jay Mandrekar, W. Richard Marsh, Frederic B. Meyer, Gregory D. Cascino.Drug-resistant focal epilepsy in women of childbearing age: Reproduction and the effect of epilepsy surgery. Epilepsy & Behavior, 2016, 60:17–20

Ayyagari M, Chitela SR, Kolachana V. Obesity, polycystic ovarian syndrome and thyroid dysfunction in women with epilepsy. Ann Indian Acad Neurol, 2012, 15:101–5.

Reddy DS. Neuroendocrine aspects of catamenial epilepsy. Horm Behav, 2013, 63: 254–66.

Conway GS. Premature ovarian failure. Br Med Bull, 2000, 56:643–649.

Santoro N. Mechanisms of Premature Ovarian Failure. Ann Endocrinol, 2003, 64: 87-92.

Nelson LM. Primary ovarian insuffi ciency. N Engl J Med, 2009, 360: 606-614.

Pellegrini VA, Lucidi RS. Ovarian Insuffi ciency Clinical Presentation. Hum Reprod. 2016

Knauff EA, Eijkemans MJ, Lambalk CB, ten Kate-Booij MJ, Hoek A et al. Anti-Mullerian hormone, inhibin B, and antral follicle count in young women with ovarian failure. J Clin Endocrinol Metab, 2009, 94: 786-792.

Malkan A, Beran RG. An appraisal of the new operational definition of epilepsy – then and now. Epilepsy Behav, 2014, 41:217-220.

Berg AT, Berkovic SF, Brodie MJ, et al. Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005-2009. Epilepsia, 2010, 51:676-685.

Fisher RS, Acevedo C, Arzimanoglou A, et al. ILAE official report: a practical clinical definition of epilepsy. Epilepsia, 2014, 55:475-482.

Pavel Klein, Andriana Serje, John C Pezzulo. Premature Ovarian Failure in Women with Epilepsy. Epilepsia, 2001, 42(12): 1584-1589

Laml T, Schulz-Lobmeyr I, Obruca A, Huber JC and Hartmann BW. Premature ovarian failure: etiology and prospects. Gynecol Endocrinol, 2000, 14,292–302.

Pal L and Santoro N. Premature ovarian failure (POF): discordance between somatic and reproductive aging. Ageing Res Rev 1, 2002, 413–423.

Rugg-Gunn FJ, Sander JW. Management of chronic epilepsy. BMJ, 2012, 345:e4576

Fiest KM, Sauro KM, Wiebe S, et al. Prevalence and incidence of epilepsy. A systematic review and meta-analysis of international studies. Neurology, 2017; 88: 296–303.

Ngugi AK, Kariuki SM, Bottomley C, et al. Incidence of epilepsy: a systematic review and meta-analysis. Neurology, 2011;77(10):1005–1012.

Savic I. Sex differences in human epilepsy. Exp Neurol, 2014, 259:38-43.

Herzog AG, Coleman AE, Jacobs AR, et al. Interictal EEG discharges, reproductive hormones, and menstrual disorders in epilepsy. Ann Neurol, 2003

Herzog AG. Catamenial epilepsy: definition, prevalence pathophysiology and treatment. Seizure, 2008;17(2):151–159

Adhikari D, Zheng W, Shen Y, et al. Tsc/mTORC1 signaling in oocytes governs the quiescence and activation of primordial follicles. Hum Mol Genet, 2010, 19: 397–410

Johnson J, Canning J, Kaneko T, et al. Germline stem cells and follicular renewal in the postnatal mammalian ovary. Nature, 2004, 428: 145–150

Bachelot A, Rouxel A, Massin N, et al. Phenotyping and genetic studies of 357 consecutive patients presenting with premature ovarian failure. Eur J Endocrinol, 2009, 161: 179–187

Davis C J, Davison R M, Payne N N, et al. Female sex preponderance for idiopathic familial premature ovarian failure suggests an X chromosome defect: opinion. Hum Reprod, 2000, 15: 2418–2422

Hunter J E, Epstein M P, Tinker SW, et al. Fragile X-associated primary ovarian insufficiency: evidence for additional genetic contributions to severity. Genet Epidemiol, 2008, 32: 553–559

Harden CL, Pennell PB. Neuroendocrine considerations in the treatment of men and women with epilepsy. Lancet Neurol, 2013, 12:72-83.

Herzog AG, Fowler KM, Sperling MR, et al. Variation of seizure frequency with ovulatory status of menstrual cycles. Epilepsia, 2011, 52:1843-1848.

Isojärvi JI, Taubøll E, Herzog AG. Effect of antiepileptic drugs on reproductive endocrine function in individuals with epilepsy. CNS Drugs, 2005, 19(3):207–223.

Mona Sazgar. Treatment of Women With Epilepsy.CONTINUUM (MINNEAP MINN) 2019;25(2, EPILEPSY):408–430.

Reimers A, Brodtkorb E, Sabers A. Interactions between hormonal contraception and antiepileptic drugs: clinical and mechanistic considerations. Seizure, 2015;28:66–70.

Taubøll E, Gregoraszczuk EL, Tworzydø A, et al. Comparison of reproductive effects of levetiracetam and valproate studied in prepubertal porcine ovarian follicular cells. Epilepsia, 2006;47(9):1580–1583.

Svalheim S, Taubøll E, Leuf G, et al. Differential effects of levetiracetam, carbamazepine, and lamotrigine on reproductive endocrine function in adults. Epilepsy Behav, 2009, 16(2):281–287.

Deepti Goswami and Gerard S.Conway.Premature ovarian failure. Human Reproduction Update, Vol.11, 2005,4: 391–410

JIN Min, YU YiQi & HUANG HeFeng. An update on primary ovarian insufficiency.Sci China Life Sci Vol.55, 2012, 8: 677–686

L. Webber1, M. Davies1, R. Anderson, J. Bartlett, D. Braat, B. Cartwright, R. Cifkova, S. de Muinck Keizer-Schrama, E. Hogervorst, F. Janse, L. Liao1, V. Vlaisavljevic, C. Zillikens, N. Vermeulen. ESHRE Guideline: management of women with premature ovarian insufficiency. Human Reproduction, 2016, p: 1 –12



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