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DOI: 10.1055/s-2007-985335
Gender-Specific Challenges in the Management of Epilepsy in Women
Publication History
Publication Date:
15 August 2007 (online)
ABSTRACT
The management of epilepsy in women encompasses a complex interplay between seizures, sex steroid hormones, and antiepileptic drugs (AEDs). These interactions impact every aspect of the sexual and reproductive health of women with epilepsy throughout their lifetimes. Neurologists comfortable treating seizures may feel unprepared to handle questions related to reproductive health. Several cases are provided to illustrate commonly encountered queries from women with epilepsy about catamenial epilepsy, pregnancy, breast-feeding, contraception, menopause, and bone health. Available evidence is reviewed, and guidelines for management are provided.
KEYWORDS
Antiepileptic drugs - catamenial epilepsy - teratogenesis - pregnancy - contraception
REFERENCES
- 1 Quality Standards Subcommittee of the American Academy of Neurology . Practice parameter: management issues for women with epilepsy. Neurology. 1998; 51 944-948
- 2 Seale C G, Morrell M J, Nelson L, Druzin M L. Analysis of prenatal and gestational care given to women with epilepsy. Neurology. 1998; 51 1039-1045
- 3 Morrell M J, Sarto G E, Shafer P O, Borda E A, Herzog A, Callanan M. Health issues for women with epilepsy: a descriptive survey to assess knowledge and awareness among healthcare providers. J Womens Health Gend Based Med. 2000; 9 959-965
- 4 Long L, Mantouris G. Knowledge of women's issues and epilepsy (KOWIE-II), a survey of healthcare professionals. Epilepsy Behav. 2005; 6 90-93
- 5 Klein P, van Passel-Clark L M, Pezzullo J C. Onset of epilepsy at the time of menarche. Neurology. 2003; 60 495-497
- 6 Herzog A G, Klein P, Ransil B J. Three patterns of catamenial epilepsy. Epilepsia. 1997; 38 1082-1088
- 7 Herzog A G, Harden C L, Liporace J et al.. Frequency of catamenial seizure exacerbation in women with localization related epilepsy. Ann Neurol. 2004; 56 431-434
- 8 Scharfman H E, MacLusky N J. The influence of gonadal hormones on neuronal excitability, seizures, and epilepsy in the female. Epilepsia. 2006; 47 1423-1440
- 9 Morrell M J, Giudice L, Flynn K L et al.. Predictors of ovulatory failure in women with epilepsy. Ann Neurol. 2002; 52 704-711
- 10 Lim L L, Foldvary N, Mascha E, Lee J. Acetazolamide in women with catamenial epilepsy. Epilepsia. 2001; 42 746-749
- 11 Mattson R H, Cramer J A, Caldwell B V, Siconolfi B C. Treatment of seizures with medroxyprogesterone acetate: preliminary report. Neurology. 1984; 34 1255-1258
- 12 Herzog A G. Progesterone therapy in women with complex partial and secondary generalized seizures. Neurology. 1995; 45 1660-1662
- 13 Herzog A G. Progesterone therapy in women with epilepsy: a three year follow-up. Neurology. 1999; 52 1917-1918
- 14 Speidel B D, Meadow S R. Maternal epilepsy and abnormalities of the fetus and newborn. Lancet. 1972; 2 839-843
- 15 Yerby M S. Management issues for women with epilepsy: neural tube defects and folic acid supplementation. Neurology. 2003; 61(suppl 2) S23-S26
- 16 Kaneko S, Battino D, Andermann E et al.. Congenital malformations due to antiepileptic drugs. Epilepsy Res. 1999; 33 145-158
- 17 Kaaja E, Kaaja R, Hiilesmaa V. Major malformations in the offspring of women with epilepsy. Neurology. 2003; 60 575-579
- 18 Morrow J, Russell A, Guthrie E et al.. Malformation risk of antiepileptic drugs in pregnancy: a prospective study from the UK Epilepsy and Pregnancy Register. J Neurol Neurosurg Psychiatry. 2006; 77 193-198
- 19 Artama M, Ritvanen A, Gissler M, Isojarvi J, Auvinen A. Congenital structural anomalies in offspring of women with epilepsy: a population based cohort study in Finland. Int J Epidemiol. 2006; 35 280-287
- 20 Wide K, Winbladh B, Kallen B. Major malformations in infants exposed to antiepileptic drugs in utero, with emphasis on carbamazepine and valproic acid: a nation-wide, population based register study. Acta Paediatr. 2004; 93 174-176
- 21 Wyszynski D F, Nambisan M, Surve T et al.. Increased rate of major malformations in offspring exposed to valproate during pregnancy. Neurology. 2005; 64 961-965
- 22 Vajda F J, Eadie M J. Maternal valproate dosage and fetal malformations. Acta Neurol Scand. 2005; 112 137-143
- 23 Vajda F J, Hitchcock A, Graham J et al.. Fetal malformations and seizure control: 52 months of data of the Australian Pregnancy Registry. Eur J Neurol. 2006; 13 645-654
- 24 Adab N, Kini U, Vinten J et al.. The longer term outcome of children born to mothers with epilepsy. J Neurol Neurosurg Psychiatry. 2004; 75 1575-1583
- 25 Holmes L B, Wyszynski D R, Baldwin E J, Haebecker E, Glassman L H, Smith C R. Increased risk for non-syndromic cleft palate among infants exposed to lamotrigine during pregnancy [abstract]. Birth Defects Res Part A Clin Mol Teratol. 2006; 76 318
- 26 Samren E B, van Duijn C M, Kock S et al.. Maternal use of antiepileptic drugs and the risk of major congenital malformations: a joint European prospective study of human teratogenesis associated with maternal epilepsy. Epilepsia. 1997; 38 981-990
- 27 Yerby M S, Kaplan P, Tran T. Risks and management of pregnancy in women with epilepsy. Cleve Clin J Med. 2004; 71(suppl 2) S25-S37
- 28 EURAP Investigators . Seizure control and treatment in pregnancy: observations from the EURAP epilepsy pregnancy registry. Neurology. 2006; 66 354-360
-
29 Teramo K, Hiilesmaa V K.
Pregnancy and fetal complications in epileptic pregnancies: review of the literature . In: Janz D, Dam M, Richens A, Bossi L, Helge H, Schmidt D Epilepsy, Pregnancy and the Child. New York; Raven Press 1982: 53-59 - 30 Teramo K, Hiilesmaa V, Saarikoski A B. Fetal heart rate during a maternal grand mal epileptic seizure. J Perinat Med. 1979; 7 3-6
- 31 Nei M, Daly S, Liporace J. A maternal partial complex seizure in labor can affect fetal heart rate. Neurology. 1998; 51 904-906
- 32 Sahoo S, Klein P. Maternal complex partial seizure associated with fetal distress. Arch Neurol. 2005; 62 1304-1305
- 33 Centers for Disease Control . Recommendations for the use of folic acid to reduce the number of cases of spina bifida and other neural tube defects. MMWR Recomm Rep. 1992; 41 1-7
- 34 Section of Breastfeeding, American Academy of Pediatrics . Breastfeeding and the use of human milk. Pediatrics. 2005; 115 496-506
- 35 Henshaw S K. Unintended pregnancy in the United States. Fam Plann Perspect. 1998; 30 24-29
- 36 Fairgrieve S D, Jackson M, Jonas P et al.. Population based prospective study of the care of women with epilepsy in pregnancy. BMJ. 2000; 321 674-675
- 37 Krauss G L, Brandt J, Cambell M, Plate C, Summerfield M. Antiepileptic medication and oral contraceptive interactions: a national survey of neurologist and obstetricians. Neurology. 1996; 46 1534-1539
- 38 Bensyl D M, Iuliano D A, Carter M, Santelli J, Gilbert B C. Contraceptive use: United States and territories, behavioral risk factor surveillance system, 2002. MMWR Surveill Summ. 2005; 54 1-72
- 39 O'Brien M D, Guillebaud J. Contraception for women with epilepsy. Epilepsia. 2006; 47 1419-1422
- 40 Thorneycroft I, Klein P, Simon J. The impact of antiepileptic drug therapy on steroidal contraceptive efficacy. Epilepsy Behav. 2006; 9 31-39
- 41 Harden C L, Leppik I. Optimizing therapy of seizures in women who use oral contraceptives. Neurology. 2006; 67(suppl 4) S56-S58
- 42 De Souza A, Brechin S, Penney G. The member's enquiry service: frequently asked questions. J Fam Plann Reprod Health Care. 2004; 30 57-58
- 43 Bounds W, Guillebaud J. Observational series on women using contraceptive Mirena concurrently with anti-epileptic and other enzyme-inducing drugs. J Fam Plann Reprod Health Care. 2002; 28 78-80
- 44 Dirubbo N E. Counsel your patients about contraceptive options. Nurse Pract. 2006; 31 40-44
- 45 Sabers A, Ohman I, Christensens J, Tomson T. Oral contraceptives reduce lamotrigine plasma levels. Neurology. 2003; 61 570-571
- 46 Klein P, Serje A, Pezzullo J C. Premature ovarian failure in women with epilepsy. Epilepsia. 2001; 42 1584-1589
- 47 Harden C L, Koppel B S, Herzog A G et al.. Seizure frequency is associated with age at menopause in women with epilepsy. Neurology. 2003; 61 451-455
- 48 Harden C L, Pulver M C, Ravdin L, Jacobs A R. The effect of menopause and perimenopause on the course of epilepsy. Epilepsia. 1999; 40 1402-1407
- 49 Abbasi F, Krumholz A, Kittner S J, Langenberg P. Effects of menopause on seizures in women with epilepsy. Epilepsia. 1999; 40 205-210
- 50 Hulley S, Grady D, Bush T et al.. Randomised trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. JAMA. 1998; 280 605-613
- 51 Rossouw J E, Anderson G L, Prentice R L et al.. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial. JAMA. 2002; 288 321-333
- 52 Harden C L, Herzog A G, Nikolov B G et al.. Hormone replacement therapy in women with epilepsy: a randomized double-blind placebo-controlled study. Epilepsia. 2006; 47 1447-1451
- 53 U.S. Department of Health and Human Services .Bone Health and Osteoporosis: A Report of the Surgeon General. Rockville, MD; U.S. Department of Health and Human Services, Public Health Service, Office of Surgeon General 2004
- 54 Empana J P, Dargent-Molina P, Breart G. Effect of hip fracture on mortality in elderly women: the EPIDOS prospective study. J Am Geriatr Soc. 2004; 52 685-690
- 55 Valmadrid C, Voorhees C, Litte B, Schneyer C. Practice patterns of neurologists regarding bone and mineral effects of antiepileptic drug therapy. Arch Neurol. 2001; 58 1369-1374
- 56 Cummings S R, Nevitt M C, Browner W S et al.. Risk factors for hip fracture in white women. N Engl J Med. 1995; 332 767-773
- 57 Van Staa T P, Leufkens H G, Cooper C. Utility of medical and drug history in fracture risk prediction among men and women. Bone. 2002; 31 508-514
- 58 Vestergaard P, Tigaran S, Rejnmark L, Tigaran C, Dam M, Mosekilde L. Fracture risk is increased in epilepsy. Acta Neurol Scand. 1999; 99 269-275
- 59 Vestergaard P, Rejnmark L, Mosekilde L. Fracture risk associated with use of antiepileptic drugs. Epilepsia. 2004; 45 1330-1337
- 60 Souverein P C, Webb D J, Petri H, Weil J, Van Staa T P, Egberts T. Incidence of fractures among epilepsy patients: a population-based prospective cohort study in the General Practice Research Database. Epilepsia. 2005; 46 304-310
- 61 Petty S J, Paton L M, O'Brien T J et al.. Effect of antiepileptic medication on bone mineral measures. Neurology. 2005; 65 1358-1363
- 62 Pack A M, Gidal B, Vazquez B. Bone disease associated with antiepileptic drugs. Cleve Clin J Med. 2004; 71(suppl 2) S42-S48
- 63 Valimaki M J, Tiihonen M, Laitinen K et al.. Bone mineral density measured by dual energy x-ray absorptiometry and novel markers of bone formation and resorption in patients on antiepileptic drugs. J Bone Miner Res. 1994; 9 631-637
- 64 Ensrud K E, Walzak T S, Blackwell T, Ensrued E R, Bowman P J, Stone K L. Antiepileptic drug use increases rates of bone loss in older women: a prospective study. Neurology. 2004; 62 2051-2057
- 65 Pack A M, Morrell M J, Marcus R et al.. Bone mass and turnover in women with epilepsy on antiepileptic drug monotherapy. Ann Neurol. 2005; 57 252-257
- 66 Verrotti A, Greco R, Latini G, Morgese G, Chiarelli F. Increased bone turnover in prepubertal, pubertal and postpubertal patients receiving carbamazepine. Epilepsia. 2002; 43 1488-1492
- 67 Sheth R D, Wesolowski C A, Jacob J C et al.. Effect of carbamazepine and valproate on bone mineral density. J Pediatr. 1995; 127 256-262
- 68 Mintzer S, Bopana P, Toguri J, DeSantis A. Vitamin D levels and bone turnover in epilepsy patients taking carbamazepine or oxcarbazepine. Epilepsia. 2006; 47 510-515
- 69 Sato Y, Kondo I, Ishida S et al.. Decreased bone mass and increased bone turnover with valproate therapy in adults with epilepsy. Neurology. 2001; 57 445-449
- 70 Boluk A, Guzelipek M, Savli H, Temel I, Ozisik H I, Kaygusuz A. The effect of valproate on bone mineral density in adult epileptic patients. Pharmacol Res. 2004; 50 93-97
- 71 Burke M S. Current roles and realities of noninvasive assessment of osteoporosis. Curr Opin Endocrinol Diabetes. 2004; 11 330-337
- 72 Pack A M, Olarte L S, Morrell M J, Flaster E, Resor S R, Shane E. Bone mineral density in an outpatient population receiving enzyme-inducing antiepileptic drugs. Epilepsy Behav. 2003; 4 169-174
- 73 Farhat G, Yamout B, Mikati A, Demirjian S, Sawaya R, Fuleihan G E. Effect of antiepileptic drugs on bone density in ambulatory patients. Neurology. 2002; 58 1348-1353
- 74 Binkley N, Bilezikian J P, Kendler D L et al.. Official positions of the International Society for Clinical Densitometry and Executive Summary of the 2005 Position Development Conference. J Clin Densitom. 2006; 9 4-14
- 75 Harden C L. Menopause and bone density issues for women with epilepsy. Neurology. 2003; 61(suppl 2) S16-S22
- 76 Mikati M A, Dib L, Yamout B, Sawaya R, Rahi A C, Fuleihan G E. Two randomized vitamin D trials in ambulatory patients on anticonvulsants. Neurology. 2006; 67 2005-2014
- 77 Drezner M K. Treatment of anticonvulsant drug-induced bone disease. Epilepsy Behav. 2004; 5 S41-S47
Katherine H NoeM.D Ph.D.
Department of Neurology
5 East, Mayo Clinic Hospital, 5777 East Mayo Boulevard, Phoenix, AZ 85054