Gender-Specific Challenges in the Management of Epilepsy in Women

Katherine H. Noe

doi:10.1055/s-2007-985335

Seminars in Neurology, Table of Contents

Semin Neurol 2007; 27(4): 331-339
DOI: 10.1055/s-2007-985335

Gender-Specific Challenges in the Management of Epilepsy in Women

Katherine H. Noe¹

¹Department of Neurology, Mayo Clinic Hospital, Phoenix, Arizona

Abstract

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

Full Text

References

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