Women and Migraine: The Hormonal Link

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1 Women and Migraine: The Hormonal Link March 1, 2012 Norma Jo Waxman, M.D. Associate Professor of Family and Community Medicine Bixby Center for Global Reproductive Health University of California San Francisco Tools you can use Feedback Toolbar Raise Hand Feedback Results Yes No Emoticons 2 Floating Toolbar Use the floating toolbar to communicate in today s session. Participant List Q&A Drop Down Menu for additional options 3 1

2 Q&A Click Send 4 File Transfer 2 Press Download Click File Name 1 5 Women and Migraine: The Hormonal Link March 1, 2012 Norma Jo Waxman, M.D. Associate Professor of Family and Community Medicine Bixby Center for Global Reproductive Health University of California San Francisco njwaxman@fcm.ucsf.edu 2

3 Faculty Disclosure Credit to ARHP for many slides I have no pharmaceutical support for this lecture 7 Learning Objectives At the end of this presentation participants will be able to: Diagnose migraine with and without aura, menstrually related migraine, and true menstrual migraine Prescribe pharmacologic options for acute and prophylactic management of migraine Understand when hormonal medication is dangerous, and when it is helpful and safe for women with migraine 8 Despite the fact that it is so common and has so much impact on society, migraine is one of the most misunderstood, misdiagnosed and undertreated diseases on earth. 1. American Migraine Prevalence and Prevention Study (AMPP). Diamond S, et al. Headache Carolyn Bernstein, MD The Migraine Brain 9 3

4 Why Care About Migraine? Very Common neurologic disorder Underrecognized Undertreated Produces severe disability 1,2 Suboptimal acute quick-fixes & overuse of any drug may lead to chronic daily HAs 3,4 1. Lipton RB, et al. Headache. 2001;41: Bigal ME, et al. Cephalalgia. 2006; 26: Scher AI, et al. Pain. 2003;16: Bigal ME, Lipton RB. Headache 2006;46: Migraine in USA 30 million migraine sufferers 1 in 10 persons is a migraineur 1 of 4 households include a migraineur 9 th leading disability, more common than diabetes or asthma 30% of migraineurs have 3+ attacks/mo. 75% have reduced ability to function 50% are severely impaired Lipton RB, et al. Headache. 2001;41: Migraine Comorbidities PMS Depression Anxiety disorders (generalized, panic, bipolar, OCD) Abuse/PTSD Stroke Irritable bowel syndrome Epilepsy Fibromyalgia 12 4

5 Epidemiology of Migraine in Women Women are affected 3x more than men 20 million women in USA 40% of women in their lifetime Before puberty: equally prevalent in both sexes After puberty: 3x more women than men Peaks in midlife after menopause more Lipton RB. Headache Lipton RB. Neurology Stewart. Cephalalgia Epidemiology of Migraine in Women (cont d) incidence 2 days before to 3 days after menstruation Perimenstrual attacks: more severe more disabling less responsive to treatment MacGregor EA, Hackshaw A. Neurology Dowson AJ, et al. Headache ICHD Diagnostic Criteria for Migraine Without Aura At least 5 attacks with: Headache lasts 4 72 hours w/o treatment or without successful treatment At least 2 of the following: Unilateral pain (60%) Throbbing (70%) Aggravation by movement Moderate to severe pain ICHD = International Classification of Hreadache Disorders Adapted from, Cephalalgia. 2004;8(suppl 1):S more 15 5

6 IHS Diagnostic Criteria for Migraine Without Aura (cont d) And at least 1 of the following: Nausea and/or vomiting Photophobia and/or phonophobia Not attributed to organic disease Adapted from IHS, Cephalalgia ICHD Diagnostic Criteria for Migraine with Aura At least 2 attacks with; At least 1 fully reversible symptom w/o motor Visual (flickering lights, zigzags, spots or lines, and/or loss of vision) + and/or Sensory ( pins and needles and/or numbness) + and/or Dysphasic speech more Adapted from IHS, Cephalalgia IHS Diagnostic Criteria for Migraine with Aura (cont d) Symptoms of aura develop gradually over >5 min or different symptoms occur in succession over >5 min Each symptom lasts >5 and <60 min Migraine begins with aura or within <60 min Symptoms are fully reversible No organic disease Adapted from IHS, Cephalalgia

7 Prevalence of Migraine by Age and Sex Females Males 15 Migraine 10 Prevalence 5 (%) Age (years) Lipton RB, et al. Headache Stages of Hormonal Change During the Female Lifetime Birth Menarche Menopause 12.5 yr 1 Menstrual Cycle yrs 2 Low sex hormone levels Estrogen and progesterone fluctuate Fluctuations may be greater in perimenopause 3 Low sex hormone levels Age (years) 1. Anderson SE, et al. Pediatrics McKinlay SM. Maturitas Santoro N, et al. JCEM Patients with HA (%) Headaches and the Menstrual Cycle Migraine without aura Tension type Migraine with aura HA = headache Day of Menstrual Cycle Adapted from Stewart WF, et al. Neurology

8 Menstrual Migraines Subtypes (ICHD-2) Menstrually Related Migraine (MRM) Attacks fulfill criteria for 1.1 Migraine without aura Attacks occur days 1 ± 2 (i.e., days -2 to +3) of menstruation in at least 2 out of 3 menstrual cycles and additionally at other times of the cycle ~46% of women with migraine IHS, Cephalalgia Menstrual Migraines Subtypes (ICHD-2) Pure Menstrual Migraine (MM) Attacks fulfill criteria for 1.1 Migraine without aura Attacks occur days 1 ± 2 (i.e., days -2 to +3) of menstruation in at least 2/3 cycles, and at no other time of the cycle ~14% of women with migraine IHS, Cephalalgia Distribution of Migraine Types in Women 40% non-menstrual migraine 60% menstrual migraine MRM comprises the majority of MM (46% of 60%) MRM 46% Pure MM 14% Non-menstrual Migraine 40% Female Migraineurs MRM = menstrually related migraine; MM = menstrual migraine. Mannix LK, Calhoun AH. Curr Treat Options Neurol

9 Migraines during menses Compared with migraine at other times of the cycle, menstrual attacks are: More severe Longer in duration Less responsive to acute treatment More likely to relapse 25 Non-Hormonal Migraine Triggers Hunger Certain Foods Dehydration Sleep Head and neck pains Emotional Environmental: smoke, bright lights, change in weather Concomitant disease Sex 26 Hormonal Migraine Triggers Estrogen withdrawal, or change in serum level Menstruation Cyclic combined hormonal contraceptives Pregnancy Peri-menopause Hormone replacement therapy 27 9

10 Case 1: Sarah New Patient Visit 24-year-old non-smoker Sexually active On intake: checks off headaches, which she says are worse with her periods Presents for contraception Does Sarah have migraine? Use PIN for Diagnosis of Migraine Photophobia: Does light bother you? Impairment: Do your headaches limit you? Nausea: Do you feel nauseated? Based on Lipton RB, et al. Neurology Case 1: Sarah Accurate diagnosis of migraine aura is essential for the safe prescribing of estrogencontaining OCPs. Sarah has migraine without aura. She has no other risk factors for stroke. OCP = oral contraceptive pills 30 10

11 Case 1: Sarah Is Sarah eligible for estrogen-containing OCPs? A) Yes B) No 31 Case 1: Sarah Is Sarah eligible for estrogen-containing contraceptives? Might she opt for a patch or ring? A) Yes: Low-dose estrogen contraception can be used in women under age 35 who have migraine without aura and no other risk factors for stroke. B) No: OCPs should never be used in women who have migraine. 32 CDC: Headaches and CHC Initiate Continue Non-migrainous (mild or severe) 1 2 Migraine (i) without focal neurologic symptoms Age < Age > (ii) with focal neurologic symptoms 4 4 (at any age) Prodrome = photo/phonophobia, N/V These are not focal Focal symptoms = vision changes, numbness, parasthesias

12 Case 1: Sarah What if Sarah did not need contraception? 34 Treatment of Migraines Education and behavior modification Identify and avoid or modify triggers Acute treatment Prophylactic treatment Short-term Long-term 35 Treatment of Migraines Triptans more effective than NSAIDs and combination analgesics- warn about SEs NSAIDS can act synergistically with Triptans PO or PR phenothiazines helpful in the outpt setting for both nausea and HA pain. Consider non-oral meds w/ nausea & vomiting Sleep often abolishes the headache

13 Options for Acute Therapy Aspirin Ibuprofen Naproxen sodium Combination Analgesics Acetaminophen, aspirin and caffeine Triptans Phenothiazines 37 Rescue or Emergency Treatment of Migraine When acute tx fails When H/A returns in <24 hrs or continues for days IV/IM phenothiazines in addition to DHE or a triptan work better than narcotics 38 Prophylaxis of Migraines Consider prophylaxis if acute medications used > 4x/mo, when rescue medications are necessary > 1x/mo, or if headaches are functionally limiting Prophylaxis should be started at low doses and titrated up over 2-3 months TCAs are effective independent of their antidepressant effect Limited studies have shown biofeedback, relaxation training, spinal manipulation and physical therapy as helpful tx

14 Medications for Prophylaxis Consider history, co-morbidities and hormonal state TCAs Beta- blockers- Propranolol most studied and successful Verapamil Gabapentin, Valproate and some of the newer mood stabilizers Hormonal Tx 40 Management Options with Non-pharmacologic Modalities Supplements Magnesium Vitamin B2- riboflavin Feverfew Butterbur Coenzyme Q10 Isoflavones chelated magnesium at mg/d for 3-4 months works as prophylaxis (best in pt. w/ aura or perimenstrual migraine, and those not responding to triptans). Riboflavin, 400mg/d for 3 months decrease migraine frequency. 41 Management Options with Non-pharmacologic Modalities Cognitive/behavioral Modalities Meditation Recognize and Avoid Triggers Headache Diary Physical Modalities Massage Yoga Acupuncture Osteopathic manipulation 42 14

15 Evaluating Migraine Lab tests? Hormone Tests? Cat Scan? Headache Diary 43 Red Flags Headaches begin after age 50 Very sudden onset of Headache First or worst Change in frequency or severity Immunosuppression Fever, stiff neck, rash, trauma Focal neurologic symptoms or signs Papilledema 44 Case 1: Sarah Recommended Approach Migraine diary Counseling about migraine triggers and non-pharmacologic tx options Her choice of hormonal / nonhormonal contraception Acute treatment with triptan Schedule 3 mo f/u to review diary 45 15

16 Case 1: Sarah Return Visit Headache diary confirms MRM: 2 3 attacks/mo. without aura Severe attack during pill-free week What do you do next? Options for Pharmacologic Treatment for MRM Rescue/Emergency treatments IV/IM phenothiazines Prophylactic perimenstrual treatments NSAIDs Supplemental estrogen Triptans Extended-cycle combined hormonal contraception Unclear if usual prophylactic treatments successful in woman with MRM 47 Summary Recommendations: Short-term Prophylactic Treatments for MRM Medication Transdermal estradiol Frovatriptan Naratriptan Levels of evidence 4 RCTs; inconsistent 1 RCT; good 1 RCT; fair Dosing regimen 1.5 mg perimenstruall y 2.5 mg BID permenstrually 1 mg BID perimenstruall y Recommendati on B B B Pringsheim, T. Neurology

17 Prophylactic Treatments for MM and MRM (long-term) Continuous hormonal therapy Without aura Continuous combined contraceptives Dedicated product Monophasic product throw away placebo Continuous cycling with ring Estrogen supplements in hormone-free interval Mircette Yaz Supplemental estrogen 49 Migraine, OCPs, and Stroke 6 per 100,000 / year healthy 12 per 100,000 / year migraine 18 per 100,000 / year migraine with aura 12 per 100,000 / year healthy and COC 19 per 100,000 / year migraine and COC 30 per 100,000 / year migraine with aura and COC 34 per 100,000 / year stroke in pregnancy Attributable risk: 7-19 per 100,000 women per year ~ 4000 / year So, What about OCPs in women with Migraine? IHS: low-dose estrogen in women with simple visual aura ACOG: progestin only, intrauterine or barrier contraception WHO: absolute contraindication in all women with aura 50 Migraine, OCPs, and Stroke Stroke risk is 2-3 fold in migraineurs with aura (MA) Stroke risk is 8-fold in MA plus OCP Absolute risk is low 17-19/year/100,000 women years 4000 / year What about OCPs alone in women with MA? IHS: low-dose oestrogen in women with simple visual aura ACOG: progestin only, intrauterine or barrier contraception WHO: absolute contraindication in all women with aura ACOG, American College of Obstetricians and Gynecologists; IHS, International Headache Society; WHO, World Health Organization 51 17

18 Prescribing Contraception in Women with Migraines Use a Progesterone Only method with aura Lowest estrogen levels with ring Consider 20 or 25 mcg pills Consider eliminating placebo week in women who have migraines triggered by withdrawal of estrogen Regular follow-up in 1-3 months after initial Rx Stress need to discontinue method if Migraines worsen 52 Case 1: Sarah Treatment and Outcome Change 21-day OCPs to continuous hormonal therapy For symptomatic treatment of migraine, continue standard therapy with triptan Lifestyle modifications More regular meals More sleep Stress-reduction techniques 53 Case 2: Pam 35-year-old woman 6th week of pregnancy Menstrual migraine diagnosed 10 years ago Migraine more frequent and severe since she became pregnant 54 18

19 Migraine and MRM in Pregnancy 60% 70% of migraineurs improve during pregnancy Non-pharmacologic treatment is preferred Biofeedback Relaxation therapy Cognitive-behavioral therapy MacGregor EA. J Fam Plann Reprod Health Care Case 2: Pam Treatment and Outcome Reassurance Migraine may improve by the 2 nd trimester, particularly in women w/ history of menstrual migraine No evidence migraine affects pregnancy outcome Acute Acetaminophen, NSAIDS, Triptans??? (1-2nd trimester- may be safeneed more studies) Prophylactic If possible, delay treatment until 2 nd trimester 56 Case 2: Pam Treatment and Outcome (cont d) Propranolol Can be used postpartum and during lactation (FDA C) Use lowest effective dose Stop 2 to 3 days before delivery Manage with neurologist or headache specialist Nortriptyline is another option (FDA C) 57 19

20 Acute Summary of Managing Migraine During Pregnancy acetaminophen, NSAIDS (1-2 nd trimester), metaclopramide, prochlorperazine, opioids Triptans (?? need more studies) Prevention Delay treatment until 2 nd trimester Very low dose Propranolol or Tricyclic best combination of safety and efficacy can be used postpartum and during lactation 58 Case 3: Hannah 52-year-old woman Presents with headache 5-year history of menstrual migraine and occasional attacks of migraine with aura Hot flashes, mood swings Asks about hormone therapy 59 Menstrual Migraine and Hormone Therapy (HT) Evaluate risk factors for stroke and CAD Migraine aura is not a contraindication to use of HT in low risk women (no RCTs, expert opinion) If aura appears after beginning HT, reduce estrogen and consider changing delivery route If progestin required, continuous delivery best Macgregor EA. Migraine, the menopause and hormone replacement therapy: a clinical review. J Fam Plann Reprod Health Care. 2007;33(4):

21 Case 3: Hannah Treatment and Outcome Low-dose non-oral estradiol AND continuous progestin For symptomatic and prophylactic treatment of migraine, standard prophylactic therapy Hannah s migraine attacks increase when HT is initiated but improve with continued use SSRIs and SNRIs may be useful migraine prophylaxis and help treat hot flashes. 61 Chronic Daily Headache (CDH) Diagnostic Criteria: Headache 15 or more days/month for at least 6 months. Emphasizes why careful medication history is mandatory, Speaks to early use of prophylaxis Depression, anxiety and drug abuse may complicate presentation 1. Cephalalgia. 2004;8 (suppl 1) 2. Bigal ME, et al. Cephalalgia Chronic Daily Headache (CDH) Also Called: rebound headache, chronic tension-type, medication induced, transformed migraine CDH associated with overuse of acute medications. Unrecognized epidemic: majority of referrals to headache clinics Disabling and expensive syndrome 63 21

22 Chronic Daily Headache (CDH) Taper off acute medications May require hospitalization 6 RCTs found significant improvement with Amitriptyline. The longer one has CDH, the harder it is to treat 64 Creating a Supportive Environment Educate patients and entire healthcare team Make adjustments in your office Light Odor/smells Noise Chemical 65 Summary: Behavioral and Lifestyle Modifications Avoid dietary, emotional, and environmental triggers Eat regular, healthful meals Get the right amount of sleep Get regular exercise Learn stress management techniques 66 22

23 Summary: Pharmacologic Treatments Acute treatment (NSAIDs, triptans) Rescue Tx Prophylactic treatment Perimenstrual (NSAIDs, estrogen, triptans) if: --Response to acute treatment is inadequate --Patient has regular, predictable periods Continuous (extended cycle contraception) if: --Patient needs contraception --Patient has irregular periods --Other strategies fail 67 QUESTIONS? 68 Evaluation and Other Forms At the conclusion of session complete: 1. Evaluation Form 2. Sign-in Sheet 3. Continuing Education Forms (if applicable) o Post-Test o CE Application Forms can be downloaded at the end of this session by file transfer. Fax to Those without web access can get forms by calling FAMPACT Thank You! 69 23

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