1. Women’s Issues and Epilepsy Deana M. Gazzola, M.D. Instructor, NYU School of Medicine NYU Comprehensive Epilepsy Center NYU Women’s Epilepsy Center, Co-Director Lara V. Marcuse, M.D. Instructor, NYU School of Medicine NYU Comprehensive Epilepsy Center

2. Topics Dr. Gazzola: General Overview – Hormones General Overview – Hormones –Catamenial Epilepsy and treatment Bone Health Bone Health Dr. Marcuse: AED Pregnancy Registries AED Pregnancy Registries Breastfeeding Breastfeeding Birth Control Birth Control

3. What makes Women with Epilepsy Unique? Why do we give this talk? Hormones affect seizures. Hormones affect seizures. Pregnancy can affect seizures and antiepileptic drugs. Pregnancy can affect seizures and antiepileptic drugs. Antiepileptic drugs can affect baby. Antiepileptic drugs can affect baby. Antiepileptic drugs can affect bone health, and women are at increased risk of osteoporosis. Antiepileptic drugs can affect bone health, and women are at increased risk of osteoporosis.

4. Hormones and the Menstrual Cycle

5. The Hormonal Effect Estrogen = Pro-convulsant Estrogen = Pro-convulsant Progesterone = Anti-convulsant Progesterone = Anti-convulsant Estrogen levels gradually increase approximately 2-4 years prior to the first menses. Estrogen levels gradually increase approximately 2-4 years prior to the first menses. Progesterone production increases after the first ovulation (about 1-2 years after menarche). Progesterone production increases after the first ovulation (about 1-2 years after menarche).

6. The Hormonal Effect There is a relative “pro-convulsant” state for several years, during which estrogen effects outweigh progesterone effects. There is a relative “pro-convulsant” state for several years, during which estrogen effects outweigh progesterone effects. During this period, young women may experience an increase in seizure frequency. During this period, young women may experience an increase in seizure frequency. Several studies have shown worsened seizures during puberty or menarche in approximately one-third of young women. Several studies have shown worsened seizures during puberty or menarche in approximately one-third of young women.

7. The Hormonal Effect: Catamenial Epilepsy Catamenial derived from “katamenios” (monthly). Catamenial derived from “katamenios” (monthly). Seizures increase or occur exclusively during a certain phase of the menstrual cycle. Seizures increase or occur exclusively during a certain phase of the menstrual cycle.

8. Catamenial Epilepsy: History Galen: “(the moon’s) effects were weak at half moon, but strong at full moon.” Galen: “(the moon’s) effects were weak at half moon, but strong at full moon.” Middle Ages: Vapor arising from the uterus thought to induce attacks. Middle Ages: Vapor arising from the uterus thought to induce attacks. Sir Charles Locock first described the relationship between seizures and the menstrual cycle in 1857. Sir Charles Locock first described the relationship between seizures and the menstrual cycle in 1857.

9. Gowers described the first series of menses- related seizures affecting 46 of 82 women in 1881. Catamenial Epilepsy: History

10. Catamenial epilepsy: Categories Periovulatory (about 2 weeks before ovulation) *high estrogen:progesterone ratio) Periovulatory (about 2 weeks before ovulation) *high estrogen:progesterone ratio) Perimenstrual (within the week before and during menses) *high estrogen:progesterone ratio) Perimenstrual (within the week before and during menses) *high estrogen:progesterone ratio)

11. Periovulatory Perimenstrual Luteal phase (Ovulation) Menses Also refer to image at: http://www.epilepsyfoundation.org/answerplace/Life/adults/women/Professional/hormone.cfm Hormone Levels Day of Cycle Estrogen levelProgesterone Level

12. Catamenial Epilepsy: Treatment Acetazolamide Acetazolamide –Unclear how it works. –Little data documenting efficacy. –One study (referenced in Foldvary et al, Cleveland Clinic Study) of 20 women showed that seizure frequency was significantly reduced in 40% patients, and seizure severity in 30% of patients.

13. Problems with acetazolamide: Problems with acetazolamide: –Side effects –Tolerance Catamenial Epilepsy: Treatment

14. Cyclic Antiepileptic Drug Use: Cyclic Antiepileptic Drug Use: –Feely et al. studied in clobazam use (benzodiazepine) –Administered to 24 women for 10 days beginning 2-4 days before menses. –Sustained effects were seen in 13 women over 6-13 months. –10 were seizure-free perimenstrually. –Side effects of depression, lethargy The cyclic increase in dosage of other antiepileptic drugs has not yet been adequately studied. The cyclic increase in dosage of other antiepileptic drugs has not yet been adequately studied. Catamenial Epilepsy: Treatment

15. Hormonal Therapy: Hormonal Therapy: –Isolated anecdotal cases of improved seizure control in women treated with birth control have been described. –Sparse literature –Natural progesterone in the form of lozenges has been shown to be helpful in some cases (Herzog et al) Of 15 women followed for 3 years, 20% became seizure-free Of 15 women followed for 3 years, 20% became seizure-free There was an overall seizure reduction of 62% for partial seizures and 74% for convulsions in these 15 patients. There was an overall seizure reduction of 62% for partial seizures and 74% for convulsions in these 15 patients. Catamenial Epilepsy: Treatment

16. We Need Your Help! We need more, and better-designed, trials to find answers to these questions. We need more, and better-designed, trials to find answers to these questions.

17. Bone Health Certain antiepileptic drugs (AEDs) affect bone mineral density. Certain antiepileptic drugs (AEDs) affect bone mineral density. Increased risk of fracture in patients on AEDs. Increased risk of fracture in patients on AEDs. Certain AEDs decrease vitamin D and calcium levels. Certain AEDs decrease vitamin D and calcium levels.

18. AEDs that can affect bone health: Carbamazepine (Tegretol) Carbamazepine (Tegretol) Oxcarbazepine (Trileptal) Oxcarbazepine (Trileptal) Phenobarbital (Luminal) Phenobarbital (Luminal) Phenytoin (Dilantin) Phenytoin (Dilantin) Valproic acid (Depakote) Valproic acid (Depakote) No studies/unclear results in Topiramate, Zonisamide, Levetiracetam and Lamotrigine. No studies/unclear results in Topiramate, Zonisamide, Levetiracetam and Lamotrigine.

19. Bone Health: Screening We currently have no standard recommendations for screening. We currently have no standard recommendations for screening. Protocol: Protocol: –Obtain baseline DEXA scan. –If normal, screen every 3 years unless at high risk. –If abnormal, closer monitoring (yearly).

20. Vitamin D and Calcium Supplementation Vitamin D is needed for calcium to be absorbed from the intestines. Vitamin D is needed for calcium to be absorbed from the intestines. Vitamin D also plays an important role in bone formation. Vitamin D also plays an important role in bone formation. Therefore it is important to take BOTH calcium and Vitamin D supplementation. Therefore it is important to take BOTH calcium and Vitamin D supplementation.

21. Remember to take care of your bones!