female migraines
TRANSCRIPT
Female Migraines
Dr Muhammad El HennawyOb/gyn ConsultantRass el barr central hospital and dumyat specialised hospitalDumyatt – EGYPTwww. Mmhennawy.co.nr
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 headacheOf unknown aetiologyIn 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 aura1.2 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 aura1.3 Ophthalmoplegic migraine1.4 Retinal migraine1.5 Childhood periodic syndromes that may be precursors to or associated with migraine 1.5.1 Benign paroxysmal vertigo 1.5.2 Alternating hemiplegia1.6 Complications of migraine 1.6.1 Status migrainosus 1.6.2 Migrainous infarction1.7 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 arteryDecrease 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 bloodvessels. Intracranial blood vessels have a rich supply of thesereceptors. They are also, to a small degree, in the coronaryarteries, which accounts for the reason selective serotoninreceptor agonists are contraindicated in patients with occlusivecoronary artery disease. The 5-HT1D receptors, on the other hand, are presynapticreceptors on the trigeminal nerve endings. Stimulation causes areduction in the release of vasoactive polypeptides, such ascalcitonin 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 thepathogenesis of migraine. Preventive medications, such asmethysergide and propranolol, are 5-HT2 receptor antagonists. The 5-HT3 family of receptors is also relevant in migrainepharmacotherapy. The nausea and vomiting associated withmigraine may be partly due to stimulation of 5-HT3 receptors inthe nausea and vomiting center of the brain stem. 5-HT3antagonists such as metoclopramide can provide relief ofigraine-associated nausea and vomiting.
serotonin reuptake inhibitors (SSRIsAntidepressants 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
(common migraine) At least five attacks per year last 4 — 72 hours At least two of the following
symptoms: Pain on one side of the head only Pulsing pain Moderate-to-severe intensity
that inhibits or prohibits one’s ability to function
Aggravating pain caused by physical activity, such as climbing stairs
At least one of the following symptoms:
Nausea and/or vomiting Light sensitivity or sound
sensitivity
Migraine with aura (classic migraine)
At least two attacks per year At least three of the following
symptoms: One or more aura symptoms that
later subside. Aura symptoms include: alterations in vision; numbness or tingling in the face, arm, or hand on one side of the body; muscular weakness or mild paralysis on one side of the body; and/or difficulty speaking or loss of speech.
Gradual development of at least one aura symptom over more than four minutes or two or more symptoms that occur at the same time
Aura symptoms that last no more than 60 minutes
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 To minimize the onset and the effects of
migraines Non-Drug Prevention avoiding these trigger factorsModify life stylePrevention using medicationshort-term rather than continuous treatmentShort ttt Estrogen (establishment of a stable
estrogen state ) NSAIDs start 1 wk before expected headache during luteal
phase) Continuous ttt also beta blockers or calcium channel
blockers, taking continuously , the dose can be increased in the premenstrual or menstrual phase.
NB: premenstrual migraine is considered as a part of PMTS –ttt of PMTS to prevent it
Treatmenta cure has not yet been
foundAfter exclusion of visual disturbances ,
sinusitis and dental diseases
acute abortive measures focuses on stopping the migraine as it progresses.
symptomatic measures focuses on treating the symptoms that result 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 prophylaxisthe 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 sleepdiscontinue smoking.
EstrogenBecause 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
TriptansTriptans 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 derivativesThe 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
NSAIDsSumatriptan 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
severitylastTTT
mild Migraine Headache
<2 hoursanalgesics (Aspirin, Acetaminophen , NSAIDS ) ,
Antiemetic
Moderate Migraine
Headache <4 hoursrefractory to above
give Antiemetic , analgesics , Triptan agents .
Severe Migraine Headache
4-6 hoursrefractory to above give Other Antiemetic ,
Serotonin Agonist (Dihydroergotamine , Triptans)
Severe Refractory Migraine Headache
6 to 72 hoursrefractory to aboveEmergency ttt
status migrainosusover 72 hours
severity
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 headache
migraine
Family history positivesiteUni or bilateralunilateral
Character Dull achingThrobbing
Nausea, vomiting rarleyFrequently 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.