Female migraines

1. Female Migraines
Dr Muhammad El Hennawy
Ob/gyn Consultant
Rass el barr central hospital and
 dumyat specialised hospital
Dumyatt – EGYPT
www. Mmhennawy.co.nr

2. 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 .

3. 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

4. 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

5. 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

6. 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

7. 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

8. 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

9. 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

10. 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

11. 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

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 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

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
igraine-associated nausea and vomiting.

15. 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..

16. 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).

17. 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

18. 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

19. 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
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

20. 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

21. 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.

22. 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

23. 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.

24. 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 ?

25. 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.

26. 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

27. 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.

28. Depot progestogen
as it also inhibits ovulation and can
improve migraine, provided amenorrhoea
is achieved

30. 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.

31. 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

32. 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

33. 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.

34. 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.

35. 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

36. severity last TTT
mild Migraine
Headache
>2hours analgesics (Aspirin,
Acetaminophen , NSAIDS ) ,
Antiemetic
Moderate Migraine
Headache
>4hours refractory to above
give Antiemetic , analgesics ,
Triptan agents .
Severe Migraine
Headache
4-6hours refractory to above
give Other Antiemetic ,
Serotonin Agonist
(Dihydroergotamine , Triptans)
Severe Refractory
Migraine Headache
6 to 72 hours refractory to above
Emergency ttt
status migrainosus over 72 hours
severity

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
 Naratriptan, oral
 Rizatriptan, oral
 DHE, intramuscular or intranasal
 Extremely severe migraine
 Ketorolac (Toradol), 60 mg intramuscularly
 DHE, intravenous, plus metoclopramide
 Dopamine antagonist
 Opioids

39. 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.

40. Tension
headache
migraine
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

42. Until researchers discover a cure,
individuals can take precautions and
communicate their symptoms to their
healthcare providers to find relief from
migraine attacks.