Women and Epilepsy FACES 2014 Annual Epilepsy Conference April 27, 2014 Patricia Dugan, MD Assistant Professor of Neurology NYU Langone Medical Center

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Women and Epilepsy FACES 2014 Annual Epilepsy Conference April 27, 2014 Patricia Dugan, MD Assistant Professor of Neurology NYU Langone Medical Center Comprehensive Epilepsy Center Slide 2 Beyond Seizure Control: Key Issues That Affect Women Taking AEDs Menstrual cycle abnormalities Cosmetic side effects Bone health Sexual dysfunction Family planning Pregnancy and Fetal Outcomes Breast-feeding Slide 3 Puberty: onset of reproductive life Age of onset 7-14 yrs Changes in epilepsy phenotype-genetic syndromes may remit or arise Changes in AED pharmacokinetics Compliance/seizure provoking behaviors Slide 4 Sex Steroid Hormones and Epilepsy Estrogen may be proconvulsant Reduces inhibition at GABA A receptor Alters mRNA for GAD and inhibits GABA synthesis Progesterone may be an anticonvulsant Increases inhibition at GABA A receptor Attenuates excitation of glutamate in hippocampus Alters mRNA for GAD and increases GABA synthesis GABA = -aminobutyric acid; mRNA = messenger ribonucleic acid; GAD = glutamic acid decarboxylase. Morrell MJ. Neurology. 1999;53(suppl 1):S42-S48. Woolley CS, Schwartzkroin PA. Epilepsia. 1998;39(suppl 8):S2-S8. Slide 5 Catamenial Seizures Katamenios = monthly The tendency for increased seizures related to the menstrual cycle Changes in seizure patterns may begin with hormonal fluctuations at menarche and continue during the menstrual cycle a,b 30%-50% have epileptic patterns that correspond to their menstrual cycle b,c Vulnerability to seizures is highest just before and during flow and at ovulation (relatively high estrogen and low progesterone levels) a Herzog AG, et al. Epilepsia. 1997;38:1082-1088. b Cramer JA, Jones EE. Epilepsia. 1991;32(suppl 6)S19-S26. c Morrell MJ. In: Wyllie E, ed. The Treatment of Epilepsy: Principles and Practice. 2nd ed. Baltimore, Md: Williams & Wilkins; 1997:179-187. Slide 6 Treatment of Catamenial Epilepsy Difficult to control with AEDs Increasing doses of AEDs premenstrually may be beneficial Important to monitor serum levels to avoid under- or overdosing Acetozolamide of limited benefit Natural progesterone for women with regular menses Slide 7 Cosmetic side effects Connective tissue effects & coarsening of features: PHT & PB Hirsuitism: PHT Hair loss: VPA Weight gain: VPA, PGB, GBP, CBZ Slide 8 Effects of AEDs on Body Weight Weight change important consideration Leads to health hazards Impairs body image and self-esteem Leads to noncompliance Most data anecdotal Actual incidence and magnitude unknown Mechanisms unclear Biton V. CNS Drugs. 2003;17(11):781-791. Slide 9 Effects of AEDs on Body Weight GainNeutralLoss ValproateLamotrigineTopiramate GabapentinLevetiracetamZonisamide CarbamazepinPhenytoinFelbamate PregabalineLacosamide Slide 10 Manifestations of Bone Disease Osteopenia/Osteoporosis AEDs reported as a secondary cause Increased rates at multiple sites including hip and lumbar spine Osteomalacia Increased osteoid or unmineralized bone Most studies in institutionalized persons Confounded by poor diet, inadequate sunlight, limited exercise Andress DL, et al. Arch Neurol. 2002;59(5):781-786. Farhat G,et al. Neurology. 2002;58(9):1348-1353. Pack AM, et al. Epilepsy Behav. 2003;4(2):169-174. Sato Y, et al. Neurology. 2001;57(3):445-459. Valimaki MJ, et al. J Bone Miner Res. 1994;9(5):631-637. Slide 11 Percentages of Osteopenia and Osteoporosis at Femoral Neck Men and Women < 50Men and Women 50 Pack et al. Epil and Behav. 2003;4:169-174 Ensrud et al. Neurology 2004;62(11):2051-7 Hip fractures increased by 29% in women > 65 y/o taking AEDs! Slide 12 Antiepileptic Drugs Associated with Bone Disease Phenobarbital, primidone, phenytoin Associated with bone loss and fractures (Gough et al., 1986; Valimaki et al., 1994; Pack et al, 2005) Carbamazepine Associated with bone loss and fracture (Hoikka et al., 1984; Verrotti et al., 2000) Valproate Associated with bone loss (Sheth et al., 1995; Sato et al., 2001) Lamotrigine Not associated with bone loss (Pack et al, 2005) Limited information on new drugs More severe with polytherapy and prolonged use and institutionalization (Bogliun et al., 1986; Gough et al., 1986; Chung et al., 1994) Slide 13 Sexual Dysfunction and Hormones in Women With Epilepsy Women ages 18 to 40, cycling, at least 4 years post- menarche and taking a single AED Sexual dysfunction more prevalent in women receiving enzyme-inducing AEDs than in controls (P