Female Migraines Dr Muhammad El Hennawy Ob/gyn specialist Rass el barr central hospital and dumyat specialised hospital Dumyatt – EGYPT www.geocities.com/mmhennawy Female with Migraines Prevalence of migraines Twenty-five percent of women Ten percent of women have the onset of their migraines at menarche 1.5 to 15% of women suffer from migraine only with the menses 60% present migraine at other times in the menstrual cycle Gender --70 percent of all migraine sufferers are women Women are three times more likely to experience migraine headaches than men Age --variable Socioeconomic Groups are found among various socioeconomic groups . In many women, migraine headaches are clearly linked to estrogen levels at the menarche the incidence rises because it is clearly linked to estrogen levels before menses attacks may be precipitated by falling estrogen levels (premenstrual migraine) menstruation-associated migraine The falling estradiol level rather than the absolute level provides the trigger for migraine (menstrual migraine) ovulation or mid cycle migraine is infrequent during pregnancy symptoms usually improve temporary when there are noncyclic high levels of estrogen at first trimester , Absence of migraine noted in second & third trimesters of pregnancy. during lactation Decreased estrogen production may trigger an exacerbation of migraine and make lactation difficult Birt control pills make headache worse specially in week off , stop pills may give some relief in the climacteric phase Decreased estrogen production may trigger an exacerbation of migraine after menopause when estrogen levels are noncyclic and low, there may be an improvement in migraine migraine It is a type of a vascular headache Of unknown aetiology In which final step of pathology of pain is constriction (producing the neurological symptoms of the prodroma and the aura) followed by diltation of one or more of branches of carotid artery or vertebrobasilar arteries Leading to stimulation of pain nerve endings surrounding artery by stretching -- producing the headache). Pain is prolonged by surrounding muscle contraction Diagnostic criteria Headache attacks lasting 4-72 hours (from several minutes to several days). Headache has at least two of the following four Unilateral location (on one side of the head only ) Pulsating quality Moderate or severe intensity (inhibits or prohibits daily activities). Aggravation by walking stairs or similar routine physical activity. During headache at least one of the following accompaniments: Nausea and/or vomiting photophobia and phonophobia It could be triggering an attack by the types of food they choose to eat during this time include red wine, some types of cheese, caffeine and the flavour enhancer monosodium glutamate. Other headache types not suggested or confirmed-- No evidence of Organic Headache. in premenstrual or menstrual migraine, It is not usually preceded by (aura) visual , sensory and speech disturbances as classic migraine , also it is familial NB It is necessary to assume that headache is physical in origin until sufficient time and repeated examination has excluded an organic origin The only sign of migraine can be seen is dilatation of external carotid arteryon one side recognised by visible pulsation in superficial temporal artery Pain is temporary relieved by compression of common carotid artery and return op pain with increase of severity when compression is released Common Triggers for Migraine Hormonal Menstruation, ovulation, oral contraceptive agents, hormonal replacement therapy Dietary nitrite-laden meat, monosodium glutamate, aspartame, chocolate, aged cheese, missing a meal Beverages Caffeinated beverages, beers, wines (especially red wine ) Psychological Stress, post-stress (weekends or vacation), anxiety, worry, depression Environmental Glare, flashing lights, visual stimulation, fluorescent lighting, odors , weather changes, high altitude Sleep-related Lack of sleep, excessive sleep Drugs Nitroglycerin, histamine, reserpine, hydralazine, ranitidine, estrogen Miscellaneous Head trauma, physical exertion, fatigue Types of female migraines 1 - without relation to menstruation a - classic migraine (with aura) b – common migraine(without aura) 2 - with relation to menstruation ( Menstrually associated migraines (MAM)) (usually migraine without aura ) a - premenstrual migraine 2 to 7 days before the onset of menses ,it considered as a part of PMTS b - menstrual migraine when 90% of all attacks occur between the two days before and the last day of their menstrual periods. occurs regularly, each month the character of menstrually-associated migraine tends to differ from other migraines it lasts longer generally more resistant to treatment more likely to reoccur. But this is not true? they have a better chance to prevent or treat it Classification of migraine by the International Headache Society, 1988 (with code numbers) 1.1 Migraine without aura 1.2 Migraine with aura 1.2.1 Migraine with typical aura 1.2.2 Migraine with prolonged aura 1.2.3 Familial hemiplegic migraine 1.2.4 Basilar migraine 1.2.5 Migraine aura without headache 1.2.6 Migraine with acute onset aura 1.3 Ophthalmoplegic migraine 1.4 Retinal migraine 1.5 Childhood periodic syndromes that may be precursors to or associated with migraine 1.5.1 Benign paroxysmal vertigo 1.5.2 Alternating hemiplegia 1.6 Complications of migraine 1.6.1 Status migrainosus 1.6.2 Migrainous infarction 1.7 Migrainous disorder not fulfilling above criteria The cause of migraines remains unresolved Hormonal theory Estrogen cyclic withdrawal is thought to be the trigger for the migrainous attack ,is accompanied by a decrease in central opioid tone, dopamine-receptor hypersensitivity, and an increase in cerebral vasoreactivity to serotonin Estradiol vasodilates small-diameter cerebral vessels in healthy women. Prostaglandin secretion reaches maximal concentrations at the time of menstruation in response to the withdrawal of estradiol and progesterone. Prostaglandins increase uterine contractions, causing the pain of dysmenorrhea. The prostaglandin F2-alpha (PGF2- alpha) is thought to stimulate the intense vasospasm and vasoconstriction that cause necrotic ischemia of the endometrium Prostaglandins inhibit norepinephrine release in the central nervous system and antagonize electrical and morphine analgesia PGF2-alpha may induce intracerebral vasoconstriction, and PGE1 may cause dilation of external carotid arteries. Prostaglandins sensitize pain receptors and increase neurogenic inflammation Traditional theory the veins and arteries outside of the skull expand and the veins and arteries inside the skull contract, causing pressure and pain Central theory an attack is initiated by low magnesium levels in the body that eventually create abnormal electrical activity and a disturbance in the hormone called serotonin in the brain. Neurogenic theory reaction between the nerves and arteries that control the face, eyes, nose, mouth, and jaws (the trigeminovascular system). Unifying theory a disturbance in the electrical activity in the brain, which causes changes in the brain stem and the trigeminovascular system decrease estrogen (cyclic) decrease magnesium increase prostaglandin E disturbance in electrical activity Decrease Vitamin B2 decrease serotinin in brain vasodiltation of cerebral artery Decrease pain threshold in periarterial nerve ending stimulation of pain nerve ending surrounding artery pain of migraine Serotinin receptors the various families of serotonin receptors (5-HT1), 5-HT2 and 5-HT3 receptor subtypes 5-HT1receptors 5-HT1A 5-HT1B serotinin agonist---used in acute migraine 5-HT1D serotinin agonist --- used in acute migraine –selective agonist –Triptan - non selective agonist—ergot alkaloid Selective 5-HT1F agonist -- under development 5-HT2 receptors 5-HT2 serotinin receptor antagonist ---propranolol ,methylsergide 5-HT3 receptors 5-HT3 serotinin receptor antagonist---- metoclopramide The 5-HT1B receptors are postsynaptic receptors on blood vessels. Intracranial blood vessels have a rich supply of these receptors. They are also, to a small degree, in the coronary arteries, which accounts for the reason selective serotonin receptor agonists are contraindicated in patients with occlusive coronary artery disease. The 5-HT1D receptors, on the other hand, are presynaptic receptors on the trigeminal nerve endings. Stimulation causes a reduction in the release of vasoactive polypeptides, such as calcitonin gene-related peptide (CGRP) and substance P, and, hence, a reduction in the degree of neurogenic inflammation. The excitatory 5-HT2 receptors are also important in the pathogenesis of migraine. Preventive medications, such as methysergide and propranolol, are 5-HT2 receptor antagonists. The 5-HT3 family of receptors is also relevant in migraine pharmacotherapy. The nausea and vomiting associated with migraine may be partly due to stimulation of 5-HT3 receptors in the nausea and vomiting center of the brain stem. 5-HT3 antagonists such as metoclopramide can provide relief of igraine-associated nausea and vomiting. serotonin reuptake inhibitors (SSRIs Antidepressants such as tricyclic compounds and selective serotonin reuptake inhibitors (SSRIs) may act synergistically with other agents used in migraine prophylaxis. The combination of a tricyclic antidepressant, particularly amitriptyline, and a beta blocker is a very practical approach in patients with frequent headaches, especially if migraine is associated with depression, stress, anxiety and sleep problems. An antidepressant and a beta blocker are also commonly used in patients with refractory headache disorders.. dopamine antagonists Effective for the treatment of acute migraine include chlorpromazine (Thorazine), 12.5 mg; prochlorperazine, 5 to 10 mg; metoclopramide, 5 mg with DHE; and droperidol (Inapsine), 2.5 These agents serve as alternatives to 5-HT1 agonists in patients who present to the emergency department for the treatment of migraine. They are good choices for patients in whom the triptans are contraindicated. Intravenous diphenhydramine (50 mg) may also be useful in the emergency department setting, as may intravenous valproate (300 to 500mg). Characteristics of Migraine Headaches Migraine without aura Migraine with aura (classic (common migraine) migraine) At least five attacks per year At least two attacks per year last 4 — 72 hours At least three of the following symptoms: At least two of the following One or more aura symptoms that symptoms: later subside. Aura symptoms Pain on one side of the head only include: alterations in vision; Pulsing pain numbness or tingling in the face, arm, or hand on one side of the Moderate-to-severe intensity that body; muscular weakness or mild inhibits or prohibits one’s ability paralysis on one side of the body; to function and/or difficulty speaking or loss of Aggravating pain caused by speech. physical activity, such as Gradual development of at least climbing stairs one aura symptom over more than four minutes or two or more At least one of the following symptoms that occur at the same symptoms: time Nausea and/or vomiting Aura symptoms that last no more Light sensitivity or sound than 60 minutes sensitivity Headache that occurs simultaneously with aura symptoms or follows aura within 60 minutes Migraine Phases Prodrome it occurs within hours or up to days before a migraine attack. Many physical and psychological symptoms are associated with prodrome. These symptoms may vary between individuals, but they usually remain consistent for an individual. Aura (+ or - ) it develops 5 — 20 minutes before a migraine attack and lasts no longer than an hour. Aura symptoms usually effect the senses, especially sight, but they can also effect muscle strength. Migraine headacheSymptoms that distinguish migraines from other headaches, include: Headache on one side of the head (unilateral), behind the eyes (retrorbital), or around the eyes (periorbital) Pain intensity that is moderate to markedly severe and worsened by physical activity Some migraines may develop on both of sides of the head and then shift to one side of the head. In other individuals, the pain may develop on one side of the head and then become more generalized. Postdrome (headache termination) While migraines subside during the postdrome phase, individuals will experience the following symptoms: Fatigue ,Irritability,Impaired concentration ,Scalp tenderness Mood changes prophylaxis Treatment To minimize the onset and the effects of migraines a cure has not yet been Non-Drug Prevention avoiding these trigger factors found Modify life style After exclusion of visual disturbances , Prevention using medication short-term rather than continuous treatment sinusitis and dental diseases Short ttt Estrogen (establishment of a stable acute abortive measures estrogen state ) NSAIDs focuses on stopping the start 1 wk before expected headache during migraine as it luteal phase) Continuous ttt progresses. also beta blockers or calcium channel blockers, taking continuously , the dose can symptomatic measures be increased in the premenstrual or menstrual phase. focuses on treating the NB: premenstrual migraine is considered as a part of PMTS –ttt of symptoms that result PMTS to prevent it from migraines Indications of prophylactic drugs A - Consider in any patient desiring Migraine prophylaxis B - Headache frequency Two or more Headaches monthly Absolutely indicated for 2 Headache days per week C - Headache duration Prolonged Headaches >2 days with Disability D - Headache response to Migraine Abortive Treatment Refractory to current abortive agents Intolerance to abortive agents Overuse of abortive agents Protocol Effective prophylaxis reduces Headache frequency by 50% Trial of prophylactic agent for 2-3 months Keep Headache diary Start prophylaxis at low dose and gradually increase Migraine prophylaxis the treatments used for the prophylaxis of non- menstrual related migraine are used, with the additional of hormonal therapy short-term prophylaxis (Intermittent Prophylaxis ) -- when the association between migraine and menses has been confirmed with prospective records kept with a diary for a minimum of three cycles ---start 1 wk before expected headache during luteal phase) long-term prophylaxis (Daily Prophylaxis) --- when migraine occur at menses and also occur in the non- menstrual period -- taking drugs continuously , but the dose should be increased in the premenstrual or menstrual phase. Migraine prophylaxis To minimize the onset and the effects of migraines Non-Drug Prevention avoiding these trigger factors (Foods , Medications , Hormonal Factors , Lifestyle Factors , Environmental Changes )could reduce the frequency of migraine attacks by half. individuals should exercise, get plenty of sleep, form regular sleeping habits, avoid missing meals, and discontinue smoking. Individuals may also find that relaxation, and stress management help to prevent migraines. Prevention using medication (prophylactic treatment) is only recommended in individuals when: Migraines occur twice a month, producing disability that lasts three days or longer Medication that treats symptoms or tries to stop an attack are not best for patients or are not working Pattern of migraine attacks are predictable, such as premenstrual and menstrual migraines Drugs--- short-term rather than continuous treatment Estrogen (establishment of a stable estrogen state ) NSAIDs start 1 wk before expected headache during luteal phase) Depot progestogen continuous oral contraceptive Triptans have also been studied for use in short-term prophylaxis. In an open-label trial, sumatriptan proved to be effective also Beta-blockers (Most commonly used. Approximately 60 — 80% effective in reducing attacks by 50%.) Calcium Channel Blockers , Serotonin Antagonists , Tricyclic Antidepressants , Anticonvulsants , Monoamine Oxidase Inhibitors (MAOIs) , Selective Serotonin-reuptake Inhibitors (SSRIs) , Alpha-adrenergic Blockers taking continuously , the dose can be increased in the premenstrual or menstrual phase. Treating underlying causes—as high blood pressure Stress management – bec arteries can be affected by emotional state non-pharmacological methods to control either the frequency or severity of their migraines, these include – biofeedback, relaxation therapy hypnosis, meditation, osteopathy, acupuncture, cognitive behavioural training and lifestyle changes such as identifying the possible aggravating factors e.g. stress, alcohol, coffee, cheese and chocolate. the Migraine Diet Women who suffer ,she must follow a migraine diet She may find that they feel better by eating five or six small meals at regular three-hour intervals. limiting caffeine avoiding red wine, some types of cheese, caffeine and the flavour enhancer monosodium glutamate. vitamin (B2 ,B6 ,E )and mineral (magnesium)supplements both before and during menstruation ? A healthy lifestyle a helpful preventive measure. Physical activities and exercise may be valuable in decreasing stress in addition to contributing to fitness and well-being. Early identification and monitoring of the signs of physical and psychological stress, such as tight neck muscles or an anxious feeling, will lead to early intervention and possible prevention of migraine get plenty of sleep discontinue smoking. Estrogen Because menstrual migraine can be triggered by falling estrogen levels that are either endogenously or exogenously induced (by week-off oral contraceptive or hormonal replacement therapy), prevention can be attempted by providing a more stable estrogen state Percutaneous estrogen in gel form applied for 7 days, beginning at least 2 days before the expected migraine, has been shown to decrease the frequency and severity of menstrual migraine The estradiol cutaneous patch may be less effective than gel but is used in many headache clinics, either alone or in combination with a small dose (20 mg) of methyltestosterone the birth control pill If used continuously (no break), it may also occasionally be effective NSAIDs Prostaglandins may play a role in the initial vasoconstriction phase of migraine and in the pain and sensitization to the pain of headache and of dysmenorrhea, if present. Nonsteroidal anti- inflammatory drugs (NSAIDs) are valuable both for prophylaxis of menstrual migraine and for analgesia; the agents inhibit prostaglandin synthesis and block neurogenic inflammation. Naproxen has been used effectively for prophylaxis (Typically, the drugs are started 7 days before the expected menses. Effective doses vary, but naproxen, 550 mg twice a day; ketoprofen (Orudis), 75 mg three times a day (or extended-release form [Oruvail], 200 mg once a day); ibuprofen, 300 mg two or three times a day; or mefenamic acid (Ponstel), 250 mg two or three times a day, may be helpful for prophylaxis If one class of NSAID is not effective, another should be tried. Depot progestogen as it also inhibits ovulation and can improve migraine, provided amenorrhoea is achieved Abortive therapy the treatment of acute menstrual migraine is currently similar to any other type of acute migraine focuses on stopping the migraine as it progresses. The earlier the treatment is given,the better the result All drugs should be considered on basis of therapeutic trial because responses of each individual women vary Rest in dark , quiet room Analgesic – antiemetic drugs-- Dopamine antagonist antiemetics, such as metoclopramide and prochlorperazine, are effective, even if nausea is not prominent. Vasoconstrictor drugs (if prolonged , severe attack) caffeine (cerebral vessels vasoconstrictor) 5-HT1 agonists a class of new drugs called Triptans a class of old drugs eg ergot alkaloid agents all work by cerebral vasoconstriction Acute migraine headaches are self-limited and respond well to placebos, so many therapies are effective. 5-HT1D receptor agonist (serotonin analogue ) An old class of drugs -- The ergot derivatives-- ergotamine tartrate and Dihydroergotamine (DHE) A new class of drugs --a selective 5-HT1D receptor agonist --- Triptans-- Stimulation of the 5-HT1D (serotonin )receptors can inhibit release of vasodilatory peptides such as CGRP and substance P and can block neurogenic inflammation ,thus induce vasoconstriction of extracerebral blood vessels and also reduce neurogenic inflammation . can abort migraine pain in about 70% of patients Triptans Triptans can be divided into 2 groups: Group I: fast onset, relatively high headache response and pain free rates at 2 hours sumatriptan (Imitrex, Imigran), zolmitriptan (Zomig, Zomigon, Ascotop), rizatriptan (Maxalt), almotriptan (Axert, Almogran), and eletriptan (Relpax). Group II: slower onset and lower efficacy rates. naratriptan (Amerge, Naramig) and frovatriptan. Precautions: NOT to be given to pregnant or lactating women. Contraindicated in Ischemic heart disease, Prinzmetal angina Uncontrolled hypertension Decreased arterial flow, Raynaud's disease Impaired hepatic function Ingestion of any ergotamine-containing medication. within 24 hours (DHE, methysergide, ergotamine tartrate etc). MAO inhibitor use within 2 weeks Hypersensitivity to sumatriptan Basilar or hemiplegic migraine Age over 50, particularly males Cerebrovascular disease Ergot derivatives The ergot derivatives can be effective for both prophylaxis and treatment of menstrual migraine DHE is a serotonin receptor agonist with strong binding at the 5-HT1 receptor subtypes. Stimulation of these receptors constricts cerebral blood vessels, thus relieving headache. Methylergonovine maleate (Methergine), 0.4 mg orally followed by 0.2 mg three times a day for 2 days, may provide prophylaxis Dihydroergotamine (DHE) mesylate DHE is a serotonin receptor agonist with strong binding at the 5-HT1 receptor subtypes. Stimulation of these receptors constricts cerebral blood vessels, thus relieving headache. (D.H.E.) is used for acute moderate to severe pain; it is given parenterally (1 mg subcutaneously or intramuscularly or 0.5 mg intravenously), up to a maximum of 3 mg over 24 hours Metoclopramide (Maxolon, Octamide PFS, Reglan), 10 mg intravenously, can be given before DHE to provide relief from any associated nausea and vomiting. Contraindications to the use of DHE include pregnancy, hypertension, and vascular disease (coronary, cerebral, and peripheral). should not be used within 24 hours of the serotonin analogue sumatriptan succinate (Imitrex), to be discussed next. Symptomatic therapy focuses on treating the symptoms that result from migraines. analgesic For mild to moderate pain Acetaminophen with or without caffeine NSAIDs For moderate to severe pain NSAIDs Sumatriptan succinate (Imitrex DHE, dihydroergotamine mesylate; Agents for severe episodes Opioid agonists and antagonists narcotics neuroleptics (eg, chlorpromazine hydrochloride Antiemetics–used to relieve nausea and vomiting Sedatives Steroids Ergot-containing substances Serotonin agonists severity severity last TTT mild Migraine <2 hours analgesics (Aspirin, Headache Acetaminophen , NSAIDS ) , Antiemetic Moderate Migraine <4 hours refractory to above Headache give Antiemetic , analgesics , Triptan agents . Severe Migraine 4-6 hours refractory to above Headache give Other Antiemetic , Serotonin Agonist (Dihydroergotamine , Triptans) Severe Refractory 6 to 72 hours refractory to above Migraine Headache Emergency ttt status migrainosus over 72 hours Mild migraine Simple analgesics NSAIDs Isometheptene (Midrin, etc.) Metoclopramide (Reglan) may be added to reduce nausea and enhance drug absorption Moderately severe migraine NSAIDs Isometheptene Ergotamine, oral or intranasal Sumpatriptan (Imitrex), oral or intranasal Zolmitriptan (Zomig), oral Naratriptan (Amerge), oral Rizatriptan (Maxalt), oral DHE, intranasal With oral agents, metoclopramide may be added to reduce nausea and enhance drug absorption Severe migraine Ergotamine plus an antiemetic, both administered by suppository Sumatriptan, subcutaneous injection, intranasal or oral Zolmitriptan, oral Naratriptan, oral Rizatriptan, oral DHE, intramuscular or intranasal Extremely severe migraine Ketorolac (Toradol), 60 mg intramuscularly DHE, intravenous, plus metoclopramide Dopamine antagonist Opioids resistant menstrual migraine These include the antiestrogen tamoxifen citrate (Nolvadex), 5 to 15 mg a day for seven to fourteen days at 10 mg. per day the dopaminergic agent bromocryptine mesylate (Parlodel), 2.5 to 5 mg a day the androgen derivative danazol (Danocrine), 200 to 600 mg a day The serotonin reuptake inhibitor fluoxetine hydrochloride (Prozac) has been used selectively in the luteal phase of the cycle in women with PMS. For the most severe cases of menstrual migraine and PMS, gonadotropin-releasing hormone (Gn-RH) agonists with estrogen and progestin replacement may be considered Oophorectomy -- by inducing a hypoestrogenic state, could be instrumental in controlling the worst premenstrual and menstrual migraine attacks in some women. Tension migraine headache Family history positive site Uni or bilateral unilateral Character Dull aching Throbbing Nausea, vomiting rarley Frequently Awaken from sleep Positive Response to ergot Favourable There is much overlap between symptoms of migraine and tension headache And many patient suffer from both Until researchers discover a cure, individuals can take precautions and communicate their symptoms to their healthcare providers to find relief from migraine attacks.