Epilepsy and

Women’s health

OlgicaOlgica Laban-GrantLaban-Grant, , MDMD

Northeast Regional Epilepsy Group

NEREG 2011

Epilepsy in Women Role of hormones in epilepsy Contraception and AED’s

Pregnancy and epilepsy Postpartum period and epilepsy Bone health and epilepsy

Epilepsy in adolescence Epilepsy in menopause

Epilepsy in Women Hormones and Seizures

Female hormones change the excitability of the brain and alter the threshold for seizures

Estrogen –decreases thresholdPorgesteron- increases threshold

Hormon sensitive seizuresCatamenial epilepsy

In 1/3 of female patients there is substantial relationship between seizures and menstrual cycle.

Catamenial EpilepsySeizures that tend to cluster in relationship to

menstrual periods

High levels of estrogen Low levels of progesterone Fluid and electrolyte imbalance Psychological Stress Decrease in levels of AEDs

Epilepsy in Women Catamenial Epilepsy

Catamenial epilepsy

Pattern 1 – just before menstruation (steep decline in progesterone)

Pattern 2 – just before ovulation ~day 14 (steep elevation in estrogen)

Catamenial epilepsy Pattern 3- in second half of

menstrual cycle Anovulatory cycles (ovulation does

not occur) are more frequent in women with epilepsy

There is no elevation of progesterone

Catamenial epilepsy What should you do:

Keep diary of your seizures and menstrual periods

Discuss with your neurologist possibility of catamenial epilepsy

Management of Catamenial Seizures

Your doctor may treat you with

Increase in doses of antiseizure medications during particular time of menstrual cycle

Supplementation with reproductive hormones-natural progesterone

Management of catamenial epilepsy

Cyclic Natural progesterone seems to work

better

Suppressive Depo-provera

Birth control and epilepsy

Some of the antiseizure medication decrease efficacy of birth control pills and other hormonal birth control

This may result in birth control failure and unplanned pregnancy

Birth control pills and epilepsy

Antiseizure medications that interfere with birth control are:

Carbamazepine (Tegretol) Phenobarbital Phenytoin (Dilantin) Primidone Rufinamide (Banzel) Topiramate (Topamax) *higher doses Oxcarbazepine (Trileptal) *higher doses

Contraception AED’s that have no influence on

levels of steroids Gabapentin (Neurontin) Lamotrigine (Lamictal) Levetiracetam (Keppra) Tiagabine (Gabatril) Zonisamide (Zonegran) Pregabalin (Lyrica)

Lamictal

Does not lower efficacy of oral birth control pills, but oral birth control pill can decrease levels of Lamictal

Contraception Solutions: Using antiseizure medications

that do not interact with birth control pills

Using alternative birth control methods

Using birth control pills with higher dose of estrogen

Contraception OCP with higher doses of estrogen (50

micrograms) Depo-Provera - more frequent (6-8 weeks) If breakthrough bleeding

Increase dose of estrogen add barrier method

• Condoms• Cervical diaphragm or cervical cap• Spermacides

Fertility and Epilepsy

Women with epilepsy have fewer children

Possible explanations: Choice (fear of having child with birth defect) Sexual dysfunction Women with epilepsy have more frequent

anovulatory cycles (cycles where there is no egg released from ovary)

Polycystic Ovary Syndrome (PCOS)

Polycystic Ovary Syndrome (PCOS) and epilepsy

Definition of syndrome– two out of three of following:

Multiple cysts in ovaries High male hormone levels Excessive facial hair and acne

Other features Obesity Irregular menstrual periods More frequent anovulatory cycles

Polycystic Ovary Syndrome (PCOS) and epilepsy

Syndrome is twice as common in women with epilepsy

Possible explanations: Seizure activity in brain alters the

production of hormones Valproic acid (depakote) causes

features similar to PCOS

Epilepsy and Pregnancy

Over 90% of babies born to women with epilepsy will be healthy.

This number may be higher if pregnancies are planned.

Although low, birth defect rate is still about twice (4-7%) of rate in general population (1.6-3.2%).

Epilepsy in Women Pregnancy

Higher risk is due to:

Seizures Antiseizure medications Genetic

Epilepsy in Women Pregnancy

Plan pregnancy!

May need to change AED drug/dosage Folic Acid: start before pregnant Close supervision with neurologist High-risk pregnancy OB is preferred

Seizures in Pregnancy

What can you do about seizures:

Women who have better control of seizures prior to pregnancy usually have fewer seizures during pregnancy.

AED’s in pregnancy

More birth defects with: Polypharmacy (two or more AED’s) Higher levels of medications

AED’s in pregnancy

What can you do about antiseizure medications:

Your neurologist/epileptologist will consider: Reducing your medications to single medication

(monotherapy) Changing your medication Decreasing dose of your medication Stopping your medication

Pregnancy Category

A In human studies, pregnant women used the medicine and their babies did not have any problems related to using the medicine.

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B In humans, there are no good studies. But in animal studies, pregnant animals received the medicine, and the babies did not show any problems related to the medicine. Or In animal studies, pregnant animals received the medicine, and some babies had problems. But in human studies, pregnant women used the medicine and their babies did not have any problems related to using the medicine.

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C In humans, there are no good studies. In animals, pregnant animals treated with the medicine had some babies with problems. Or No animal studies have been done, and there are no good studies in pregnant women. In some situations the medicine may still help the mothers and babies more than it might harm.

Ethosuximide, Felbamate, Gabapentin, Lacosamide, Lamotrigine, Levetiracetam, Oxcarbazepine, Pregabalin, Rufinamide, Tiagabine, Topiramate, Vigabatrin, Zonisamide

D Studies in humans and other reports show that when pregnant women use the medicine, some babies are born with problems related to the medicine. In some situations, the medicine may still help the mother and the baby more than it might harm.

Carbamazepine, Clonazepam, Lorazepam, Phenobarbital, Phenytoin, Primidone, Valium, Valproic acid

X Studies or reports in humans or animals show that mothers using the medicine during pregnancy may have babies with problems related to the medicine. Risks involved in use of the drug in pregnant women clearly outweigh potential benefits.

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Epilepsy & PregnancyAED National Pregnancy Registry

Tracks use of AEDs and pregnancy outcomes

All information confidential Can greatly improve our knowledge

Epilepsy in WomenPregnancy Registry Resources

North American Pregnancy Registry 888 – 233 - 2334

Epilepsy and PregnancyFetal Risks

Most common major malformations: Neural tube defects Heart abnormalities Orofacial clefts

Folic acid Folic deficiency is associated with

increase risk of neural tube defects. Aed’s that are linked to folic acid

malabsorbtion/metabolism are Phentoin (Dilantin) Carbamazepine (Tegretol) Barbiturates Valproate (Depakote)

Prenatal care Take extra folic acid (1-4mg per day)

while trying to conceive Take prenatal vitamins while trying

to conceive. Discuss possibility of genetic

counseling, especially if there is history of birth defects in family.

Epilepsy in Women Prenatal Testing

Testing that may be done to detect some of birth defects:

Maternal serum alpha-fetoprotein at 15-22 weeks of gestation

Level II ultrasound (structural) at 16-20 weeks of gestation

Amniocentesis at 15-20 weeks of pregnancy

Epilepsy in womenPregnancy

Epilepsy in Women Postpartum issues AED levels may rise – close

monitoring of levels is necessary Sleep deprivation and stress may

increase frequency of seizures Child safety/lifestyle adaptation

Epilepsy in Women Breastfeeding

Benefits of breastfeeding are felt to outweigh potential risk of continued exposure of neonate and infant to AEDs (AAN and AAP)

Protein bound drugs have low concentrations in breast milk

Observe breastfeeding infant for irritability, poor sleep patterns, or inadequate weight gain

Epilepsy in adolescence Most seizure disorders are not

altered by onset of puberty Certain types of epilepsy start at

approximate age (JME) or improve (benign rolandic epilepsy, absence epilepsy)

Rapid growth may account for poor seizure control

Epilepsy in adolescence Menarche (first period)

Discuss hormon sensitive seizures Interactions of AED’s with contraceptive

pills Start folic acid supplementation Discuss planning of pregnancy

Epilepsy in adolescence Discuss

Choice of medications Substance abuse Sleep deprivation Compliance to medications Driving Sports safety Choice of profession

Epilepsy and menopause Premature menopause is more

common in WWE Effect on seizure frequency is

unclear as both estrogen and progesterone levels drop

Catamenial epilepsy seems to improve

Epilepsy and menopause Doses of AED’s may need to be

changed due to changes in metabolism

Polypharmacy due to other medical conditions may affect efficacy of AED’s and seizure

Hormone replacement therapy Bone health

Epilepsy & HRT HRT increases estrogen levels and

may increase seizure frequency – concomitant use of natural progesterone may help

AED’s may affect HRT efficacy

Epilepsy & Bone health Fractures are more likely in people

with epilepsy due to: Falls due to seizures and due to side

effects of AED’s, and Altered bone density due to certain

AED’s

Epilepsy & Bone health Altered bone density due to AED’s is

associated with: Phenytoin (dilantin) Carbamazepine (tegretol) Barbiturates Valproate (depakote)

Epilepsy & Bone health

Prevention and therapy >6mo AEDs-exercise, balanced diet, stop smoking,

moderate alcohol, moderate caffeine-calcium and vitamin D supplements-measure Ca, ALP, 25-hydroxy vit D

yearly- Baseline DXA scan

Epilepsy & Bone health

Refer for possible treatment to endocrinologist if:

- osteopenia/osteoporosis- Abnormal calcium or vit D levels- fracture

THANK YOU!

Northeast Regional Epilepsy Groupepilepsygroup.com