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Women and Migraine: The Hormonal Link Womens Health in Primary Care Orlando, Florida March 2011 Norma Jo Waxman MD Associate Professor of Family and Community Medicine Faculty in the Bixby Center for Global Reproductive Health University of California San Francisco [email protected] Learning Objectives At the end of this talk participants will be able to: Define migraine with and without aura, menstrually related migraine, and true menstrual migraine Utilize pharmacologic and behavioral options for acute and prophylactic management of migraine Understand when hormonal medication is helpful and safe for women with migraine Recognize and decrease incidence of chronic daily headache in your practice Faculty Disclosure No pharmaceutical support or commercial disclosures Member of ARHP expert advisory committee on Hormonal Migraines and developed slide set. Many used in this presentation “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.” Carolyn Bernstein, MD The Migraine Brain Why Care About Migraine? Very Common neurologic disorder • Underrecognized • Undertreated Produces severe disability 1,2 Overuse of any drug may lead to chronic daily HAs3,4 IHS. Headache Classification Subcommittee of the International Headache Society (IHS). The International Classification of Headache Disorders. 2nd ed. Cephalalgia. 2004;24(Suppl.1):139-41. 1. Lipton RB, et al. Headache. 2001;41:646–657 2. Bigal ME, et al. Cephalalgia. 2006; 26:43–49 3. Scher AI, et al. Pain. 2003;16:81–89 4. Bigal ME, Lipton RB. Headache 2006;46:1334–1343 5. Kruit MC. et al. JAMA 2004;291:427–434; 6. Kurth T, et al. JAMA 2006;296:283–291. Migraine in USA 30 million migraine sufferers 1 in 10 persons a migraineur 1 of 4 households include a migraineur 9th 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;41:646–657 Migraine Co-morbidities • • • • • • • • PMS Depression Anxiety disorders (generalized, panic, bipolar, OCD) Abuse/PTSD Stroke Irritable bowel syndrome Epilepsy Fibromyalgia 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 Lipton RB. Headache. 2001. Lipton RB. Neurology. 2007. Stewart. Cephalalgia. 2008. 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 four symptoms: • 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):S24-26. more… IHS Diagnostic Criteria for Migraine Without Aura (cont’d) And at least 1 of the following 2 symptoms: • Nausea and/or vomiting • Photophobia and/or phonophobia Not attributed to organic disease Adapted from IHS, Cephalalgia. 2004. 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. 2004. IHS Diagnostic Criteria for Migraine with Aura (cont’d) • Symptoms of aura develop gradually over >5min or different symptoms occur in succession over >5 min • Each symptom last >5 and <60 min • Migraine begins with aura or within <60 min • Symptoms are fully reversible • No organic disease Adapted from IHS, Cephalalgia. 2004. Prevalence of Migraine by Age and Sex 30 Females Males 25 20 Migraine Prevalence 15 (%) 10 5 0 20 30 40 50 Age (years) Lipton RB, et al. Headache. 2001. 60 70 80 100 Headaches and the Menstrual Cycle Patients with HA (%) 12 Migraine without aura Tension type 10 Migraine with aura 8 6 4 2 0 −16 −14 −12 −10 −8 −6 −4 −2 HA = headache 0 2 4 6 8 Day of Menstrual Cycle Adapted from Stewart WF, et al. Neurology. 2000. 10 12 14 16 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 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. 2004. Distribution of Migraine Types in Women • 40% non-menstrual migraine • 60% menstrual migraine Pure MM 14% MRM 46% – MRM comprises the majority of MM (46% of 60%) Non-menstrual Migraine 40% Female Migraineurs MRM = menstrually related migraine; MM = menstrual migraine. Mannix LK, Calhoun AH. Curr Treat Options Neurol. 2004. Menstrual Migraines Compared with attacks at other times of the cycle, menstrual attacks are: • • • • More disabling Longer in duration Less responsive to acute treatment More likely to relapse MacGregor EA, Hackshaw A. Neurology. 2004. Dowson AJ, et al. Headache. 2005. Non-Hormonal Migraine Triggers • Hunger • Certain Foods • Dehydration • Sleep • Head and neck pains • Emotional • Environmental: smoke, bright lights, change in weather • Concomitant disease • Sex Hormonal Migraine Triggers • Estrogen withdrawal, or change in level Menstruation Placebo days with combined hormonal contraceptives Pregnancy Peri-menopause Hormone replacement therapy 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. 2003. Case 1: Sarah Accurate diagnosis of migraine aura is essential for the safe prescribing of estrogen-containing contraception. Sarah has migraine without aura. She has no other risk factors for stroke. Case 1: Sarah Is Sarah eligible for estrogencontaining contraception? A) Yes B) No 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. MEC: Headaches and CHC Initiate Continue Non-migrainous (mild or severe) 1 2 Migraine (i) without focal neurologic symptoms Age < 35 2 Age > 35 3 (ii) with focal neurologic symptoms 4 (at any age) 3 4 4 photo/phonophobia, N/V are not focal symptoms Focal symptoms = vision changes, numbness, parasthesias http://www.who.int/reproductive-health/publications/RHR_00_2_medical_eligibility_criteria_3rd/ Treatment of Migraines Education and behavior modification Identify and avoid or modify triggers Acute treatment Prophylactic • Short-term • Long-term treatment Treatment of Migraines Triptans more effective than NSAIDs and combination analgesics- warn about SEs NSAIDS can act synergistically with Triptans Phenothiazines, PO or PR, great for nausea & pain Think non-oral meds with nausea & vomiting Sleep can abolishes headache Options for Acute Therapy Aspirin Ibuprofen Naproxen sodium Combination Analgesics Acetaminophen, aspirin and caffeine Triptans Phenothiazines 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- Prophylaxis of Migraines Consider prophylaxis if acute meds used > 4x/mo, rescue meds > 1x/mo, or headaches are functionally limiting Start prophylaxis at low dose and titrate up over 2-3 months TCAs are effective independent of their antidepressant effect Limited studies show biofeedback, relaxation training, spinal manipulation and physical therapy may be helpful Medications for Prophylaxis Consider hx, co-morbidities and hormonal state TCAs- Amitrip best studied, but most side effects SNRIs (more effective then SSRIs) Beta- blockers Propranolol most studied and successful- Nadolol and Timolol too Valproate, Topiramate, Gabapentin and other “anticonvulsants” and “mood stabilizers” Botox Verapamil and CCB- less effective Hormonal Tx Preventive Options with Non-pharmacologic Modalities Supplements Magnesium Vitamin B2- riboflavin Feverfew Butterbur (Petadolex) Coenzyme Q10 Omega-3 Fatty Acids Isoflavones chelated magnesium at 400-600 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. Preventive Options with Non-pharmacologic Modalities Cognitive/behavioral Modalities Meditation Recognize and Avoid Triggers Headache Diary Physical Modalities Massage Yoga Acupuncture Osteopathic manipulation Peppermint oil (? Helpful for acute) Evaluating Migraine Lab tests? Hormone Tests? Cat Scan? Headache Diary 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 Case 1: Sarah Recommended Approach Migraine diary Counseling about migraine triggers and nonpharmacologic treatment options Her choice of hormonal / non-hormonal contraception Acute treatment with triptan Schedule 2-3 mo f/u to review diary Case 1: Sarah Return Visit Headache diary confirms menstrual related migraine 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 IM/IV phenothiazines or DHE Prophylactic perimenstrual treatments NSAIDs Supplemental estrogen Triptans Extended cycle combined hormonal contraceptives Prophylactic Treatments for MM and MRM with Continuous hormonal therapy Continuous combined contraceptives Dedicated product Monophasic product throw away placebo Continuous cycling with ring Estrogen back in hormone-free interval Mircette Yaz Supplemental estrogen 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 estrogen containing contraception 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 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 the placebo week Follow-up Stress in 1-3 months after initial Rx need to discontinue method if Migraines worsen Case 1: Sarah Treatment and Outcome Change 21-day OCPs to continuous hormonal therapy For symptomatic treatment of migraine, continue therapy with nsaids and triptans Lifestyle modifications More regular meals More sleep and exercise Stress-reduction techniques Follow up in 1-3 months 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 Migraine and MRM in Pregnancy 60% – 70% of migraineurs improve during pregnancy Non-pharmacologic treatment is preferred Biofeedback Relaxation therapy Cognitive-behavioral therapy Magnesium MacGregor EA. J Fam Plann Reprod Health Care. 2007. Migraine Drug Use During Pregnancy and Lactation (Analgesics and Ergots) Drug 1st Trimester 2nd Trimester 3rd Trimester Lactation Y Y Acetaminophen Y Y Codeine (Y) (Y) (Y) Y Aspirin (Y) (Y) Avoid Avoid Diclofenac Ibuprofen Naproxen (Y) (Y) Avoid Y Dihydroergotamine Ergotamine CI CI CI CI Y = no evidence of harm (Y) = data suggest unlikely to cause harm ?(Y) = limited data but probably safe CI = contraindicated ID = insufficient data * = for emergency treatment of migraine not responding to standard measures MacGregor EA. J Fam Reprod Health Care. 2007 Drug use during pregnancy and lactation (Triptans, magnesium, prednisolone) Drug 1st Trimester 2nd Trimester 3rd Trimester Lactation Almotriptan Frovatriptan ID ID ID ID Eletriptan ID ID ID Y Naratriptan Rizatriptan ?(Y) ?(Y) ?(Y) (Y) Sumatriptan ?(Y) ?(Y) ?(Y) Y Zolmatriptan ID ID ID (Y) Magnesium sulphate* (Y) (Y) (Y) (Y) Prednisolone* (Y) (Y) (Y) (Y) MacGregor EA. J Fam Reprod Health Care. 2007 Case 2: Pam Treatment and Outcome Reassurance • Migraine may improve by the 2nd trimester, particularly in women w/ history of menstrual migraine • No evidence migraine will affect pregnancy outcome Acute • Acetaminophen, NSAIDS, • Triptans ??? (1-2nd trimester- may be safe- need more studies) Prophylactic • If possible, delay treatment until 2nd trimester Case 2: Pam Treatment and Outcome (cont’d) Propranolol safe and effective and 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 Amitriptyline is another option (FDA C) 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 Menstrual Migraine and Hormone Therapy (HT) Lowest and Non oral routes are best Evaluate risk factors for stroke and CAD Migraine with aura is not a contraindication to HT in low risk women (no RCTs, expert opinion) If aura 1st appears after start of HT, reduce estrogen and consider work up for TIA Macgregor EA. Migraine, the menopause and hormone replacement therapy: a clinical review. J Fam Plann Reprod Health Care. 2007;33(4):245-9.. Macgregor EA. Estrogen replacement and Migraine, Maturitas Volume 63, Issue 1, 20 May 2009, Pages 51-55 Case 3: Hannah Treatment and Outcome Acute treatment with NSAIDS & triptans Low-dose non-oral estradiol AND continuous progestin (if needed) Hannah’s migraine attacks increase when HT is initiated but improve with continued use Fluoxetine & venlafaxime useful migraine prophylaxis and treat hot flashes Chronic Daily Headache (CDH) Diagnostic Criteria: Headache 15 or more days/month for at least 6 months Preventable Speaks with accurate medication history to early use of prophylaxis Depression, anxiety and drug abuse may complicate presentation 1. Cephalalgia. 2004;8 (suppl 1):S24–26; 2. Bigal ME, et al. Cephalalgia. 2007;27:568. Chronic Daily Headache (CDH) AKA: rebound headache, chronic tensiontype, medication induced, transformed migraine CDH caused by overuse of acute meds Unrecognized epidemic: majority of referrals to headache clinics Disabling and expensive Chronic Daily Headache (CDH) Taper off acute medications Overuse of NSAIDs, tylenol, narcotics typical May require hospitalization 6 RCTs showed sig improvement w/ Amitriptyline The longer one has CDH, the harder it is to treat Steroids may be helpful during taper Creating a Supportive Office Environment Educate patients and entire healthcare team Make adjustments in your office • • • • Light Odor/smells Noise Chemical 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 Summary: Pharmacologic Tx Acute treatment (NSAIDs, triptans) Rescue Tx- DHE, phenothiazines Prophylactic treatment Perimenstrual (NSAIDs, estrogen, triptan) if: Response to acute tx inadequate Regular, predictable periods Continuous (extended cycle contraception) if: Patient needs contraception Patient has irregular periods Other strategies fail Take-Home Points Migraine is a neurological illness caused by abnormality in brain chemistry A range of behavioral and drug options exist for the management of severe migraine A substantial proportion of women with migraine experience increased incidence around onset of menses Short-term prevention is the best approach for these women if they have regular menses