Overview of Hormones and Epilepsy


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by Joyce Liporace, M.D.
Women's and Men's Conference
May 1, 2010

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Overview of Hormones and Epilepsy

  1. 1. Overview of Hormones and Epilepsy Joyce Liporace, M.D. Women’s and Men’s Conference May 1, 2010
  2. 2. Topics <ul><li>Review of Hormones </li></ul><ul><li>Seizures and the menstrual cycle </li></ul><ul><li>Birth control </li></ul><ul><li>Pre-menstrual syndrome and epilepsy </li></ul><ul><li>Polycystic Ovarian Syndrome </li></ul>
  3. 3. Hormones <ul><li>Hormones are chemical messengers </li></ul><ul><li>Two major female hormones: estrogen and progesterone </li></ul><ul><li>Both made from cholesterol </li></ul><ul><li>Both easily enter the brain </li></ul>
  4. 4. Estrogen <ul><li>Lowers seizure threshold </li></ul><ul><li>May increase seizures </li></ul><ul><li>Binds neurons (brain cells) and increases excitation </li></ul>
  5. 5. Estrogen <ul><li>If you drip estrogen on the brain of a healthy animal, it will have a seizure </li></ul><ul><li>Estrogen changes the shape of neurons in animal studies-increased growth and branching </li></ul>
  6. 6. Progesterone <ul><li>Lowers the seizure threshold </li></ul><ul><li>May reduce seizures </li></ul><ul><li>Binds to neurons and increases inhibition </li></ul>
  7. 7. Progesterone <ul><li>Decreases abnormal brain waves </li></ul><ul><li>Changes the shape of neurons in animals-decreases the branching seen with estrogen </li></ul>
  8. 8. Anatomic Changes with Estrogen-Dendritic spines Neurons from a rat embryo Left: Estrogen supplement Right: Control
  9. 9. Seizures and Hormones <ul><li>Yes! Seizures can be linked to hormones. Called catamenial epilepsy. </li></ul><ul><li>First described over 120 years ago </li></ul><ul><li>Still, not completely recognized </li></ul>
  10. 10. Seizures and Hormones <ul><li>Normally, the pituitary gland in the brain provides the signal to the ovaries to release different hormones </li></ul><ul><li>With epilepsy, especially temporal lobe epilepsy, there may be abnormal signals because of the seizures </li></ul>
  11. 11. Menstrual cycle: Three phases <ul><li>1. Follicular phase : First 2 weeks after bleeding, estrogen increasing </li></ul><ul><li>2. Luteal phase : Second half of cycle, progesterone increasing </li></ul><ul><li>3. Bleeding ( Menstrual phase ): Signal to begin bleeding is drop in progesterone </li></ul>
  12. 12. Normal cycles 21-35 days, bleeding 2-6 days Day 1 = First day of bleeding
  13. 13. Hormones and seizures <ul><li>It it probably the ratio of estrogen to progesterone that is important in seizure control for some women </li></ul><ul><li>Testosterone (male hormone) has inconsistent links to seizures </li></ul>
  14. 14. Menstrual cycle <ul><li>10% of the time healthy women do not ovulate (no egg released) </li></ul><ul><li>Without ovulation, no progesterone is formed during the second half of the menstrual cycle </li></ul><ul><li>For women with temporal lobe epilepsy, 35% of cycles are without ovulation </li></ul>
  15. 15. Three Patterns-Catamenial Seizures <ul><li>1. Seizures just before and with bleeding (drop in progesterone) </li></ul><ul><li>2. Seizures mid-cycle with ovulation (increase in estrogen) </li></ul><ul><li>3. For anovulatory cycles, seizure throughout second half of cycle </li></ul>
  16. 16. Determine if your seizures are linked to menstrual cycle <ul><li>Chart menstrual cycle and seizures for at least four months </li></ul><ul><li>Look for one of the three patterns </li></ul><ul><li>Discuss treatment options with your doctor </li></ul>
  17. 17. Treatment options <ul><li>Increased epilepsy medications at expected time of increased seizures </li></ul><ul><li>Progesterone supplements </li></ul><ul><li>Ganaxolone-progesterone “like” medication, under investigation </li></ul>
  18. 18. Progesterone Supplements <ul><li>Synthetic progesterone not very helpful </li></ul><ul><li>Natural progesterone may reduce seizures </li></ul><ul><li>Optimal dosage and timing of supplements are unclear, controlled trials are on-going </li></ul>
  19. 19. Natural Progesterone Options <ul><li>Natural Progesterone cream -need to use a compounding pharmacy </li></ul><ul><li>Prometrium, linked with menstrual </li></ul><ul><li>Daily Prometrium </li></ul>
  20. 20. Birth Control <ul><li>Some epilepsy medications can make low dose birth control pills less effective. </li></ul><ul><li>You can still take the pill, but you may need a higher estrogen dose pill (50 ug) </li></ul><ul><li>Be careful-most doctors are not aware of this problem </li></ul>
  21. 21. Medications that reduce the effectiveness of the pill <ul><li>Tegretol, Trileptal, Carbatrol </li></ul><ul><li>Dilantin </li></ul><ul><li>Zonisamide </li></ul><ul><li>Phenobarbital/Primidone </li></ul><ul><li>Topamax (above 200 mg a day) </li></ul><ul><li>Gabitril (high doses) </li></ul>
  22. 22. Medications that do not affect the pill <ul><li>Depakote </li></ul><ul><li>Neurontin, Lyrica </li></ul><ul><li>Lamictal </li></ul><ul><li>Keppra </li></ul><ul><li>Benzodiazepines (valium, klonopin, ativan, Clobazam) </li></ul><ul><li>Vimpat </li></ul>
  23. 23. Depo-provera <ul><li>Intra-muscular injection of a synthetic progesterone </li></ul><ul><li>Helpful for people who have trouble remembering to take daily birth control </li></ul><ul><li>Usually given every 10 weeks instead of 12 weeks for women with epilepsy </li></ul>
  24. 24. IUDs <ul><li>Mirena coil secretes low dose progesterone locally in uterus and remains active for 5 years </li></ul><ul><li>Copper IUD, effective for 10 years </li></ul><ul><li>Effective with all of the seizure meds </li></ul>
  25. 25. Ortho Evra <ul><li>Combination of norelgestromin and ethinylestradiol </li></ul><ul><li>New patch applied weekly for 3 weeks </li></ul><ul><li>Menstruation occurs 4 th week, with no patch </li></ul><ul><li>It is low dose progestin and may be ineffective with EIAEDs </li></ul>
  26. 26. Morning after pill <ul><li>It is essentially four birth control pills combined </li></ul><ul><li>Two formulations- estrogen and progesterone and then also progesterone only </li></ul><ul><li>No studies for women with epilepsy-but may need higher dose </li></ul>
  27. 27. Birth Control may affect blood levels of seizure meds <ul><li>This seems to be most important with Lamictal but also happens with Depakote </li></ul><ul><li>Lamictal levels will drop by as much as 50% with the pill and increase by 80% during hormone free week </li></ul><ul><li>May need to have your blood level checked twice in one month </li></ul>
  28. 28. 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!
  29. 29. Premenstrual Syndrome <ul><li>A group of physical and emotional symptoms that women experience linked to menses (anger, irritability, cravings) </li></ul><ul><li>Symptoms interfere with life </li></ul><ul><li>Range from mild to incapacitating </li></ul><ul><li>Occur 7-10 days before bleeding and improve after bleeding </li></ul>
  30. 30. Premenstrual Syndrome <ul><li>Diagnosis made by daily symptom rating scale (DSR) </li></ul><ul><li>Cause is unknown but may be related to hormones or neurotransmitters (? Low serotonin) </li></ul><ul><li>Improves with the absence of ovulation </li></ul>
  31. 31. Premenstrual Syndrome <ul><li>Mild PMS occurs in 75% of women </li></ul><ul><li>Moderate PMS occurs in 20-40% of women </li></ul><ul><li>Severe PMS occurs in 2-5% of women </li></ul>
  32. 32. PMS and Epilepsy <ul><li>Does PMS occur more commonly in women with epilepsy? </li></ul><ul><li>Some would predict that it would not (because of fewer cycles with ovulation) </li></ul><ul><li>Absence of ovulation is linked with improvement in PMS </li></ul>
  33. 33. PMS and Epilepsy <ul><li>PMS occurs commonly in women with partial epilepsy </li></ul><ul><li>Severe PMS occurs more commonly than in the general population </li></ul><ul><li>Factors other than low progesterone must play a role </li></ul>
  34. 34. PMS-Treatment <ul><li>Many different treatments </li></ul><ul><li>>300 studies with 115 different treatments </li></ul><ul><li>Diet </li></ul><ul><li>Exercise </li></ul><ul><li>Medication </li></ul><ul><li>Stop smoking </li></ul>
  35. 35. PMS-Diet <ul><li>Balanced diet improves symptoms </li></ul><ul><li>Limit Caffeine </li></ul><ul><li>Limit salt and refined sugar </li></ul><ul><li>Vitamin B6 and magnesium may be helpful </li></ul>
  36. 36. PMS-Medication <ul><li>Selective serotinin reuptake inhibitors (SSRI) </li></ul><ul><li>Prozac, Zoloft, Celexa can reduce symptoms by 50 -80% (especially mood and appetite improvements) </li></ul><ul><li>Daily or intermittent treatment is helpful </li></ul>
  37. 37. Polycystic Ovarian Syndrome <ul><li>The most common endocrine disorder in women </li></ul><ul><li>Difficult to diagnose </li></ul><ul><li>Infertility, Hirsutism, Obesity </li></ul><ul><li>Under diagnosed </li></ul>.
  38. 38. PCOS <ul><li>No single cause; Complex disorder, poorly defined </li></ul><ul><li>Common: Prevalence 5-10% </li></ul><ul><li>Usually begins around menarche </li></ul><ul><li>Insulin resistance thought to play direct/indirect role </li></ul><ul><li>Obesity often present ( ↑waist:hip ratio) </li></ul>
  39. 39. Vicious Cycle Insulin Resistance Increased Androgen Production Weight Gain Anovulation
  40. 40. 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
  41. 41. Epilepsy and PCOS Baseline Epilepsy PCOS Treatment of Epilepsy ?
  42. 42. PCOS <ul><li>Linked with infertility </li></ul><ul><li>Metformin, a diabetes medication may be an effective treatment </li></ul><ul><li>Seizure medication choice may affect development of PCOS </li></ul>
  43. 43. Questions???