Women’s Issues and EpilepsyWomen’s Issues and Epilepsy

Deana M. Gazzola, M.D.Deana M. Gazzola, M.D.Instructor, NYU School of MedicineInstructor, NYU School of MedicineNYU Comprehensive Epilepsy CenterNYU Comprehensive Epilepsy CenterNYU Women’s Epilepsy Center, Co-NYU Women’s Epilepsy Center, Co-DirectorDirector

Lara V. Marcuse, M.D.Lara V. Marcuse, M.D.Instructor, NYU School of MedicineInstructor, NYU School of MedicineNYU Comprehensive Epilepsy CenterNYU Comprehensive Epilepsy Center

TopicsTopics

Dr. Gazzola:Dr. Gazzola: General Overview – HormonesGeneral Overview – Hormones

– Catamenial Epilepsy and treatmentCatamenial Epilepsy and treatment Bone HealthBone Health

Dr. Marcuse:Dr. Marcuse: AED Pregnancy RegistriesAED Pregnancy Registries Breastfeeding Breastfeeding Birth ControlBirth Control

What makes Women with Epilepsy What makes Women with Epilepsy Unique? Why do we give this talk?Unique? Why do we give this talk?

Hormones affect seizures.Hormones affect seizures. Pregnancy can affect seizures and Pregnancy can affect seizures and

antiepileptic drugs.antiepileptic drugs. Antiepileptic drugs can affect Antiepileptic drugs can affect

baby.baby. Antiepileptic drugs can affect bone Antiepileptic drugs can affect bone

health, and women are at health, and women are at increased risk of osteoporosis.increased risk of osteoporosis.

Hormones and the Hormones and the Menstrual Menstrual Cycle Cycle

The Hormonal EffectThe Hormonal Effect

Estrogen = Pro-convulsantEstrogen = Pro-convulsant Progesterone = Anti-convulsantProgesterone = Anti-convulsant Estrogen levels gradually increase Estrogen levels gradually increase

approximately 2-4 years prior to approximately 2-4 years prior to the first menses.the first menses.

Progesterone production increases Progesterone production increases after the first ovulation (about 1-2 after the first ovulation (about 1-2 years after menarche).years after menarche).

The Hormonal EffectThe Hormonal Effect

There is a relative “pro-convulsant” state There is a relative “pro-convulsant” state for several years, during which estrogen for several years, during which estrogen effects outweigh progesterone effects.effects outweigh progesterone effects.

During this period, young women may During this period, young women may experience an increase in seizure experience an increase in seizure frequency.frequency.

Several studies have shown worsened Several studies have shown worsened seizures during puberty or menarche in seizures during puberty or menarche in approximately approximately one-thirdone-third of young of young women. women.

The Hormonal Effect: Catamenial The Hormonal Effect: Catamenial EpilepsyEpilepsy

Catamenial derived from Catamenial derived from “katamenios” (monthly).“katamenios” (monthly).

Seizures increase or occur Seizures increase or occur exclusively during a certain phase exclusively during a certain phase of the menstrual cycle.of the menstrual cycle.

Catamenial Epilepsy: HistoryCatamenial Epilepsy: History

Galen: “(the moon’s) effects Galen: “(the moon’s) effects were weak at half moon, but were weak at half moon, but strong at full moon.”strong at full moon.”

Middle Ages: Vapor arising from Middle Ages: Vapor arising from the uterus thought to induce the uterus thought to induce attacks.attacks.

Sir Charles Locock first described Sir Charles Locock first described the relationship between seizures the relationship between seizures and the menstrual cycle in 1857.and the menstrual cycle in 1857.

•Gowers described the first series of menses-related seizures affecting 46 of 82 women in 1881.

Catamenial Epilepsy: HistoryCatamenial Epilepsy: History

Catamenial epilepsy: Catamenial epilepsy: CategoriesCategories

Periovulatory (about 2 weeks before Periovulatory (about 2 weeks before ovulation) ovulation) *high estrogen:progesterone ratio)*high estrogen:progesterone ratio)

Perimenstrual (within the week Perimenstrual (within the week before and during menses) before and during menses) *high *high estrogen:progesterone ratio)estrogen:progesterone ratio)

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 level Progesterone Level

Catamenial Epilepsy: Catamenial Epilepsy: TreatmentTreatment

AcetazolamideAcetazolamide– Unclear how it works.Unclear how it works.– Little data documenting efficacy.Little data documenting efficacy.– One study (referenced in Foldvary et One study (referenced in Foldvary et

al, Cleveland Clinic Study) of 20 al, Cleveland Clinic Study) of 20 women showed that seizure women showed that seizure frequency was significantly reduced frequency was significantly reduced in 40% patients, and seizure severity in 40% patients, and seizure severity in 30% of patients. in 30% of patients.

Problems with acetazolamide:Problems with acetazolamide:

– Side effectsSide effects

– ToleranceTolerance

Catamenial Epilepsy: Catamenial Epilepsy: TreatmentTreatment

Cyclic Antiepileptic Drug Use:Cyclic Antiepileptic Drug Use:– Feely et al. studied in clobazam use Feely et al. studied in clobazam use

(benzodiazepine)(benzodiazepine)– Administered to 24 women for 10 days beginning 2-Administered to 24 women for 10 days beginning 2-

4 days before menses.4 days before menses.– Sustained effects were seen in 13 women over 6-13 Sustained effects were seen in 13 women over 6-13

months.months.– 10 were seizure-free perimenstrually10 were seizure-free perimenstrually..– Side effects of depression, lethargySide effects of depression, lethargy

The cyclic increase in dosage of other The cyclic increase in dosage of other antiepileptic drugs has not yet been antiepileptic drugs has not yet been adequately studied.adequately studied.

Catamenial Epilepsy: Catamenial Epilepsy: TreatmentTreatment

Hormonal Therapy:Hormonal Therapy:– Isolated anecdotal cases of improved Isolated anecdotal cases of improved

seizure control in women treated with birth seizure control in women treated with birth control have been described.control have been described.

– Sparse literatureSparse literature– Natural progesterone in the form of Natural progesterone in the form of

lozenges has been shown to be helpful in lozenges has been shown to be helpful in some cases (Herzog et al)some cases (Herzog et al)

Of 15 women followed for 3 years, 20% became Of 15 women followed for 3 years, 20% became seizure-freeseizure-free

There was an overall seizure reduction of 62% There was an overall seizure reduction of 62% for partial seizures and 74% for convulsions in for partial seizures and 74% for convulsions in these 15 patients.these 15 patients.

Catamenial Epilepsy: Catamenial Epilepsy: TreatmentTreatment

We Need Your Help!We Need Your Help!

We need more, and better-We need more, and better-designed, trials to find answers to designed, trials to find answers to these questions.these questions.

Bone HealthBone Health

Certain antiepileptic drugs (AEDs) Certain antiepileptic drugs (AEDs) affect bone mineral density.affect bone mineral density.

Increased risk of fracture in Increased risk of fracture in patients on AEDs.patients on AEDs.

Certain AEDs decrease vitamin D Certain AEDs decrease vitamin D and calcium levels.and calcium levels.

AEDs that can affect AEDs that can affect bone health: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, No studies/unclear results in Topiramate, Zonisamide, Levetiracetam and Zonisamide, Levetiracetam and Lamotrigine.Lamotrigine.

Bone Health: Bone Health: ScreeningScreening We currently have no standard We currently have no standard

recommendations for screening.recommendations for screening.

Protocol:Protocol:– Obtain baseline DEXA scan.Obtain baseline DEXA scan.– If normal, screen every 3 years If normal, screen every 3 years

unless at high risk.unless at high risk.– If abnormal, closer monitoring If abnormal, closer monitoring

(yearly).(yearly).

Vitamin D and Vitamin D and Calcium SupplementationCalcium Supplementation

Vitamin D is needed for calcium to Vitamin D is needed for calcium to be absorbed from the intestines.be absorbed from the intestines.

Vitamin D also plays an important Vitamin D also plays an important role in bone formation.role in bone formation.

Therefore it is important to take Therefore it is important to take BOTH calcium and Vitamin D BOTH calcium and Vitamin D supplementation.supplementation.

Remember to take Remember to take care of your bones!care of your bones!