Overview of Hormones and Epilepsy

Overview of Hormones and Epilepsy Joyce Liporace, M.D. Women’s and Men’s Conference May 1, 2010

Topics
Review of Hormones
Seizures and the menstrual cycle
Birth control
Pre-menstrual syndrome and epilepsy
Polycystic Ovarian Syndrome

Hormones
Hormones are chemical messengers
Two major female hormones: estrogen and progesterone
Both made from cholesterol
Both easily enter the brain

Estrogen
Lowers seizure threshold
May increase seizures
Binds neurons (brain cells) and increases excitation

Estrogen
If you drip estrogen on the brain of a healthy animal, it will have a seizure
Estrogen changes the shape of neurons in animal studies-increased growth and branching

Progesterone
Lowers the seizure threshold
May reduce seizures
Binds to neurons and increases inhibition

Progesterone
Decreases abnormal brain waves
Changes the shape of neurons in animals-decreases the branching seen with estrogen

Anatomic Changes with Estrogen-Dendritic spines Neurons from a rat embryo Left: Estrogen supplement Right: Control

Seizures and Hormones
Yes! Seizures can be linked to hormones. Called catamenial epilepsy.
First described over 120 years ago
Still, not completely recognized

Seizures and Hormones
Normally, the pituitary gland in the brain provides the signal to the ovaries to release different hormones
With epilepsy, especially temporal lobe epilepsy, there may be abnormal signals because of the seizures

Menstrual cycle: Three phases
1. Follicular phase : First 2 weeks after bleeding, estrogen increasing
2. Luteal phase : Second half of cycle, progesterone increasing
3. Bleeding ( Menstrual phase ): Signal to begin bleeding is drop in progesterone

Normal cycles 21-35 days, bleeding 2-6 days Day 1 = First day of bleeding

Hormones and seizures
It it probably the ratio of estrogen to progesterone that is important in seizure control for some women
Testosterone (male hormone) has inconsistent links to seizures

Menstrual cycle
10% of the time healthy women do not ovulate (no egg released)
Without ovulation, no progesterone is formed during the second half of the menstrual cycle
For women with temporal lobe epilepsy, 35% of cycles are without ovulation

Three Patterns-Catamenial Seizures
1. Seizures just before and with bleeding (drop in progesterone)
2. Seizures mid-cycle with ovulation (increase in estrogen)
3. For anovulatory cycles, seizure throughout second half of cycle

Determine if your seizures are linked to menstrual cycle
Chart menstrual cycle and seizures for at least four months
Look for one of the three patterns
Discuss treatment options with your doctor

Treatment options
Increased epilepsy medications at expected time of increased seizures
Progesterone supplements
Ganaxolone-progesterone “like” medication, under investigation

Progesterone Supplements
Synthetic progesterone not very helpful
Natural progesterone may reduce seizures
Optimal dosage and timing of supplements are unclear, controlled trials are on-going

Natural Progesterone Options
Natural Progesterone cream -need to use a compounding pharmacy
Prometrium, linked with menstrual
Daily Prometrium

Birth Control
Some epilepsy medications can make low dose birth control pills less effective.
You can still take the pill, but you may need a higher estrogen dose pill (50 ug)
Be careful-most doctors are not aware of this problem

Medications that reduce the effectiveness of the pill
Tegretol, Trileptal, Carbatrol
Dilantin
Zonisamide
Phenobarbital/Primidone
Topamax (above 200 mg a day)
Gabitril (high doses)

Medications that do not affect the pill
Depakote
Neurontin, Lyrica
Lamictal
Keppra
Benzodiazepines (valium, klonopin, ativan, Clobazam)
Vimpat

Depo-provera
Intra-muscular injection of a synthetic progesterone
Helpful for people who have trouble remembering to take daily birth control
Usually given every 10 weeks instead of 12 weeks for women with epilepsy

IUDs
Mirena coil secretes low dose progesterone locally in uterus and remains active for 5 years
Copper IUD, effective for 10 years
Effective with all of the seizure meds

Ortho Evra
Combination of norelgestromin and ethinylestradiol
New patch applied weekly for 3 weeks
Menstruation occurs 4 th week, with no patch
It is low dose progestin and may be ineffective with EIAEDs

Morning after pill
It is essentially four birth control pills combined
Two formulations- estrogen and progesterone and then also progesterone only
No studies for women with epilepsy-but may need higher dose

Birth Control may affect blood levels of seizure meds
This seems to be most important with Lamictal but also happens with Depakote
Lamictal levels will drop by as much as 50% with the pill and increase by 80% during hormone free week
May need to have your blood level checked twice in one month

Attention Women with Epilepsy! Despite the importance of birth control to women of reproductive age, there has been little formal investigation of the safety and effectiveness of birth control methods in women with epilepsy. To remedy this, doctors from Harvard and Columbia University Medical Schools have developed a website that offers a survey to help us gain more knowledge and some educational material that will be updated regularly to provide the latest information. The ultimate goal is to develop guidelines for the selection of safe and effective birth control methods and to make sure that the best forms of birth control become available to women with epilepsy in all communities of our society. Go to www.epilepsybirthcontrolregistry.com , take our survey and then catch up on the latest information about birth control for women with epilepsy. LEARN MORE ABOUT YOUR BIRTH CONTROL OPTIONS!

Premenstrual Syndrome
A group of physical and emotional symptoms that women experience linked to menses (anger, irritability, cravings)
Symptoms interfere with life
Range from mild to incapacitating
Occur 7-10 days before bleeding and improve after bleeding

Diagnosis made by daily symptom rating scale (DSR)
Cause is unknown but may be related to hormones or neurotransmitters (? Low serotonin)
Improves with the absence of ovulation

Mild PMS occurs in 75% of women
Moderate PMS occurs in 20-40% of women
Severe PMS occurs in 2-5% of women

PMS and Epilepsy
Does PMS occur more commonly in women with epilepsy?
Some would predict that it would not (because of fewer cycles with ovulation)
Absence of ovulation is linked with improvement in PMS

PMS and Epilepsy
PMS occurs commonly in women with partial epilepsy
Severe PMS occurs more commonly than in the general population
Factors other than low progesterone must play a role

PMS-Treatment
Many different treatments
>300 studies with 115 different treatments
Diet
Exercise
Medication
Stop smoking

PMS-Diet
Balanced diet improves symptoms
Limit Caffeine
Limit salt and refined sugar
Vitamin B6 and magnesium may be helpful

PMS-Medication
Selective serotinin reuptake inhibitors (SSRI)
Prozac, Zoloft, Celexa can reduce symptoms by 50 -80% (especially mood and appetite improvements)
Daily or intermittent treatment is helpful

Polycystic Ovarian Syndrome
The most common endocrine disorder in women
Difficult to diagnose
Infertility, Hirsutism, Obesity
Under diagnosed
.

PCOS
No single cause; Complex disorder, poorly defined
Common: Prevalence 5-10%
Usually begins around menarche
Insulin resistance thought to play direct/indirect role
Obesity often present ( ↑waist:hip ratio)

Vicious Cycle Insulin Resistance Increased Androgen Production Weight Gain Anovulation

PCOS and PCO: General Population and Epilepsy Prevalence (%) PCOS PCO Genton P, et al. Epilepsia . 2001;42:295-304. Dunaif A, et al. Annu Rev Med . 2001;52:401-419. Herzog AG, et al. Epilepsia . 2001;42:311-315. 12% 23% 25% 38% All premenopausal women Women with epilepsy

Epilepsy and PCOS Baseline Epilepsy PCOS Treatment of Epilepsy ?

PCOS
Linked with infertility
Metformin, a diabetes medication may be an effective treatment
Seizure medication choice may affect development of PCOS

Questions???

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Overview of Hormones and Epilepsy

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Overview of Hormones and Epilepsy — Presentation Transcript