Title: Female Migraines
1Female Migraines
- Dr Muhammad El Hennawy
- Ob/gyn specialist
- Rass el barr central hospital and
- dumyat specialised hospital
- Dumyatt EGYPT
- www.geocities.com/mmhennawy
2Female 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 .
3In 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
4migraine
- 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
5Diagnostic 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
6NB
- 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
7Common 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
8Types 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
9the 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
10Classification 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
11The cause of migraines remains unresolved
- Hormonal theory
- Estrogen cyclic withdrawalis 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 secretionreaches 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
12- 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
13- 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 agonistergot 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
14- 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
15serotonin 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..
16dopamine 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).
17Characteristics 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 ones 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
18Migraine 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
19- Treatment
- a cure has not yet been found
- After 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
- prophylaxis
- To minimize the onset and the effects of
migraines - Non-Drug Prevention
- avoiding these trigger factors
- Modify life style
- Prevention using medication
- short-term rather than continuous treatment
- Short 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
20Indications 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 gt2 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
21Migraine 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.
22Migraine 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
23non-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.
24the 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 ?
25A 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.
26Estrogen
- 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
27NSAIDs
- 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.
28Depot progestogen
- as it also inhibits ovulation and can improve
migraine, provided amenorrhoea is achieved
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30Abortive 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.
315-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
-
32Triptans
- 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
33Ergot 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.
34Contraindications 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.
35Symptomatic 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 painNSAIDsSumatriptan
succinate (Imitrex - DHE, dihydroergotamine mesylate
- Agents for severe episodesOpioid agonists
and antagonists - narcotics
- neuroleptics (eg, chlorpromazine
hydrochloride - Antiemeticsused to relieve nausea and vomiting
- Sedatives
- Steroids
- Ergot-containing substances
- Serotonin agonists
36severity
37- 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
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39resistant 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.
40- There is much overlap between symptoms of
migraine and tension headache - And many patient suffer from both
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42- Until researchers discover a cure, individuals
can take precautions and communicate their
symptoms to their healthcare providers to find
relief from migraine attacks.
43