This document provides information about migraine in women. Some key points: - Migraine is 3 times more common in women than men. Hormonally-associated migraines affect 12 million women in the US. - Migraines are often associated with changes in hormone levels, such as during menstruation, pregnancy, use of oral contraceptives, and menopause. - Diagnosis of migraine involves evaluating symptoms such as headache duration/intensity, nausea, light/sound sensitivity, visual/sensory disturbances (aura). - Treatment involves both acute symptomatic relief and preventive medications, though choices are more limited during pregnancy/breastfeeding due to safety.

1. Migraine in Women
Deborah Friedman, MD,
MPH
Professor, Neurology and
Ophthalmology
University of Texas
Southwestern Medical
Center
Dallas, Texas

2. Disclosure:
Consultant: Iroko, MAP Pharmaceuticals,
Zogenix
Grant Support: AGA Pharmaceuticals,
Merck, Pfizer, MAP Pharmaceuticals,
Quark Pharmaceuticals
Honoraria: Allergan
Other: Neurology News Editorial Board

3. Migraine is a Female Disorder
Average lifetime percent of population
with migraine:
22.6% women (range 13-32%)
10.5% men (range 5.7-9%)
Women are roughly 3 times as likely as
men to have migraine
Hormonally associated migraine affect 12
million women in the U.S.

4. Is it Migraine?
Migraine without Aura
At least 5 attacks
Headache lasts 4-72 hours (untreated) in adults,
1-72 hours in children
At least 2 of the following:
Unilateral location
Pulsating quality
Moderate or severe intensity
Aggravated by routine physical activity
During the headache, at least 1 of the following:
Nausea and/or vomiting
Photophobia and phonophobia

5. Migraine with Aura
At least 2 attacks Scintillating scotoma
At least 3 of the following:
Fully reversible aura symptoms explained
by focal brain dysfunction
At least one aura symptoms evolving over
at least 4 minutes or two or more
symptoms in succession
Each symptom lasts less than 60 minutes
Headache usually begins during or follows
the aura

6. Sensory
Paresthesias (tongue; hand-mouth)
Motor
Unilateral or bilateral weakness (spreads)
Olfactory
Gustatory hallucinations
Vertigo/dizziness
Common (50%) but does not distinguish
migraine with/without aura
Fortification spectra

7. Speech
Dysarthria
Aphasia
Behavioral
Depersonalization
Automatic behavior
Transient global amnesia
Emotional (anxiety, euphoria)
Déjà vu (strange things look familiar)
Jamais vu (familiar things look strange)

8. Other
Diplopia
Ptosis
Altered level of consciousness
Ataxia
Unilateral episodic mydriasis
Auditory
What’s not aura
Blurred vision
Premonitory photophobia, phonophobia,
nausea

9. Quick and Easy Migraine Diagnosis:
“I.D. Migraine”
1. Headache related
disability
2. Photophobia
3. Nausea
93% of migraineurs have 2 of 3 features
81% sensitivity, 75% specificity
Aura 100% sensitive

10. Phases of Migraine
Pre-Headache Headache Post-Headache
Premonitory Aura Postdrome
symptoms*
Mild Moderate Severe
*Yawning, mood
change, sleepiness,
food cravings,
excessive thirst or
urination

11. Taking the History: The American
Migraine Communication Study
60 visits (approximately 12 minutes each)
between healthcare professionals (primary
care, neurologists, NP) and patients were
video and audio-recorded
Post-visit interviews were conducted
separately with patients and healthcare
professionals
All interviews were transcribed and analyzed
looking for discordance

12. Findings
91% of the questions asked were closed-
ended or short-answer
90% of visits did not address impairment
in any way (60% were severely impaired
during attacks; average frequency
5/month)
Of the 50 patients, 35 were not on a
preventive medication after the first visit
Prevention was only mentioned in 50% of
the 25 patients who would qualify for
one based on standard guidelines

13. Suggestions for Improving
Communication
Patient-centered interviewing focused on
disability:
“How do migraines affect your daily life?”
“How does migraine affect your work and
family?”
“How does migraine make you feel – even
when you aren’t having one?”

14. Other General Features
Migraine changes throughout life
Migraine may change with hormones
You can have a migraine without a
headache
Children get migraines too
People with migraine often get other
kinds of headaches as well
It runs in the family

15. Occurs in the peak productive
years
Migraine affects:
18% of women
6.5% of men
7% of children

16. Estrogen Paradox
Being female increases the likelihood of
having migraine (estrogen)
Sudden decreases in estrogen can trigger
migraine headaches
Fall in estrogen
Prior to menses
Pill free week of oral contraceptives
Perimenopause
Postpartum

17. Migraine Throughout
the (Hormonal) Life Cycle
Children
Adolescence – Puberty
Menstruation
Pregnancy
Menopause
Other:
Hormone replacement therapy
Oral contraceptives

18. Migraine in Children
Boys=girls prior to puberty
Peak incidence of
migraine with aura
Boys – age 5
Girls – age 12-13
Peak incidence of migraine
without aura
Boys – age 10-11
Girls – age 14-17
After puberty ratio is 3 to 1
(girls to boys)
Boys often outgrow them

19. Migraine in Childhood
Under-diagnosed
Young children may not be
able to describe pain or
associated features
Nausea, vomiting, sensitivity
to light and noise is inferred
Headaches are often shorter than
in adults

20. Think about migraine in children with:
Episodes of unexplained vomiting and
abdominal pain lasting an hour or more
Attacks of imbalance or dizziness lasting
minutes
Recurring attacks of head tilt, vomiting,
imbalance lasting hours to days
Alternating one-sided weakness
Headaches followed by droopy eyelid and
double vision (lasting days to weeks)

21. Migraine and Menstruation
60-70% of women with migraine have
them with menstruation
Pure Menstrual Migraine
2 days prior to menses to 4th day of
menses only (14% of women) for 2 of 3
cycles
Menstrually-Related Migraine
Within the above window and at other
times of the month
Perimenstrual Migraine
Attacks 2-7 days prior to menses
Keep a diary! Compare menstrual and
non-menstrual attacks.

23. May Be Associated with Other
Features of PMS
(DSM-4: 5 days before to 4 days into menses,
interfere with activities)
Affective Physical
Depression Breast tenderness
Angry outbursts Abdominal bloating
Irritability Headache
Anxiety Peripheral edema
Confusion Acne
Social withdrawal Cramping
Food cravings
Increased appetite
Sexual disinterest

24. What’s Different During Menses?
No difference in sex hormones
between migraineurs and
controls (testosterone, LH, FSH)
Headaches more severe, more
nausea and vomiting
Treatments may not
be as effective during
menses (?)
Loder E. Neurol Sci 2005;26:S121-124

25. Treatment of Menstrual Migraine
Acute symptomatic treatment
Migraine specific, anti-inflammatories
Standard preventive treatment
Short-term preventive treatment (“mini-
prevention”)
Non-steroidal anti-inflammatories
Long-acting triptans (frova) or ergots
Magnesium
Hormonal therapy (estradiol gel)
Increase usual preventative
Non-pharmacologic therapy
**Pringsheim T, et al. Acute treatment and prevention of menstrually
related migraine headache. Neurology 2008;70:1555-1563

26. Use of Oral Contraceptives to
Prevent Menstrual Migraine
1. Extended cycle OCs
Suppress ovulation for months
May have breakthrough bleeding in first few
months (accompanied by migraine)
2. Reduce monthly decline in estrogen
Use low-dose estrogen instead of 7 placebo pills
each month
3. Contraceptive patch + vaginal ring
Less daily fluctuation in estrogen level

27. Migraine and Pregnancy
Better (50-60+%)
Worse (15-%)
The Same (25%)
May worsen during the first trimester
May only occur during pregnancy
May be headache free in last trimester

28. New Onset of Headaches During
Pregnancy
Increased intracranial pressure
Tension-type headache
Cerebral venous sinus thrombosis
Stroke
Tumor
Vasculitis
Intracranial hemorrhage
Reversible cerebrovasoconstrictive
syndrome (RCVS)

29. Headache Medications and
Pregnancy – General Concepts
Pharmakokinetics vary during gestation
Increased plasma volume – increase
unbound drug
Decreasing albumin – increase free
fraction (total assays unreliable)
Increased renal clearance
Changes in CYP and glucuronidation
**Lucas S. Medication Use in the Treatment of Migraine
During Pregnancy and Lactation. Curr Pain Headache
Rep 2009;13:392-398.

30. Symptomatic Treatment of Migraine
During Pregnancy (Category B – no
evidence of risk but no studies)
Acetaminophen
Caffeine
Ibuprofen*
Indomethacin*
Naproxen*
Meperidine
Morphine
Prednisone
*Avoid in third trimester

31. Barbiturates, opioids,
benzodiazepines
Neonatal withdrawal syndrome
Opioids are category B
Beware medication overuse
Triptans are all category C
Ergots are contraindicated

32. Treatment of Migraine-Related
Nausea (Category B)
Dimenhydramine
Meclizine
Metoclopramide
Ondansetron
Anticholinergics –
meconium ileus

33. Migraine Prevention During
Pregnancy (Category B/C)
Avoid migraine triggers
Beta blockers (C)
Fluoxetine (C)
Venlafaxine (C)
Vitamin B2 (B)
Coenzyme Q-10 (B)
Magnesium (B)
Avoid valproate,
topiramate, AEDs,
lithium (D)

34. Breast Feeding – General Principles
No evidence that
lactation worsens
migraine
Safe in pregnancy ≠ safe
in lactation
Amount passed to breast
milk depends on:
• average plasma
concentration
• amount excreted into
breast milk
• volume of milk
ingested

35. Is the drug necessary?
Use the safest one
Consider measuring blood levels in
the infant
Take medication after completing a
breast feeding to minimize
exposure to the baby

36. Symptomatic Treatment While Breast
Feeding
Concern
Compatible Benzodiazepines
Acetaminophen, Contraindicated
caffeine, NSAID Antihistamines
Caution Ergotamine/DHE
Aspirin,
barbiturates
Triptans

37. Preventive Treatment While Breast
Feeding
Concern
Compatible Tricyclic
Beta blockers antidepressants
Calcium blockers Verapamil
Valproate Contraindicated
Corticosteroids Bromocriptine
Amitriptyline
**Hale TW. Medications and
Caution Mother’s Milk. Amarillo, TX, Hale
Publishing, 2008.
SSRI

38. Perimenopause
Women with a history of menstrual
migraine (“hormonally sensitive”)
may have worsening of migraines in
peri-menopause
Treatment:
Hormone replacement therapy
Low dose OC (without placebo week)
Standard migraine therapies

39. Menopause
Migraine and natural
menopause:
20-40% worsen
20-30% improve
30-50% unchanged
Effect of surgical menopause:
(hysterectomy, oophorectomy)
38-87% worsen
Some women develop migraines
for the first time at menopause

40. Hormone Replacement Therapy?
Conflicting data regarding migraine
Considerations:
Delivery (patch*, cream, pill, injection)
Need for continuous use
Type and dosage
Natural estrogens (estradiol) are better
tolerated than conjugated estrogen
One size does not fit all
Risk-benefit ratio

41. Migraine and Stroke
Women under 45
Posterior circulation strokes and white
matter lesions more likely in MWA and
high attack frequency of migraine than
controls
Women 45 years and older
MWA twice as likely to develop ischemic
stroke and MI over 10 years of follow-up

42. Ferrari M, et al. Brain 2005

43. Migraine and Stroke
Numerous studies document increase
risk:
National Health and Nutrition Examination
Survey – prospective (11,777 men and
women; RR 2.1)
Meta-analysis of 14 observational studies
Risk among all migraineurs, OR = 2
MWA, OR = 2.9
MWOA, OR = 1.6

44. Women’s Health Study
Prospective cohort study of 39,754 health
professionals ages 45 and older
No migraine or MWOA – no increased risk
MWA – Adjusted hazards ratio
1.53 for total stroke
1.71 for ischemic stroke
No increased risk for hemorrhagic stroke
Women < 55 with MWA had greatest risk:
1.75 for total stroke
2.25 for ischemic stroke

45. Stroke Risk: Low Dose OCs
Meta analysis of 16 studies (Gillum)
RR = 1.92 (1.4-2.7) controlling for
smoking and hypertension = 1
additional stroke per 24,000
Meta analysis of 14 studies (Baillargeon)
RR 1.84 (1.4-2.4) with low dose OC use
Also risk of 2nd and 3rd generation OC
use

46. Risk of Stroke Varies by Age:
Women
9 per 100,000 in 20-year-old MWA
3 per 100,000 in 20-year-old w/o migraine
80 per 100,000 in 40-year-old MWA
11 per 100,000 in 40 year-old w/o migraine

47. Summary of Risk
Migraine increases risk of stroke, OR = 2-3
Aura, female sex, age > 45, high
frequency, migraine duration – higher
risk > 12 attacks/year, > 12 years of
migraine)
OC increases risk of ischemic stroke,
OR = 2
OC increase risk of venous sinus
thrombosis, OR = 22
OC increase risk of subarachnoid
hemorrhage, OR = 1.6

48. Recommendations (ACOG, WHO, IHS)
Women with migraine should minimize
other vascular risks
Women with MWOA on hormone therapy
should stop if aura develops or
headache worsens
Women with migraine over 35 who smoke
should not use OCs
Women with a history of stroke or venous
clot should not use OCs
Controversy: Women with MWA should
not use hormonal therapy

49. Migraine and Cardiovascular
Disease (Women’s Health Study)
580 major CVD events occurred
Active MWA: hazard ratio 2.15 overall
1.91 for ischemic stroke
2.08 for MI
1.74 for coronary revascularization
1.71 for angina
2.33 for ischemic CVD death
18 additional major CVD events/10,000
women per year, after adjusting for age
MWOA: No increased risk

50. Migraine as a Clinically
Progressive Disorder
Episodic migraine evolves over time in
some patients, AKA “transformed
migraine”
Attacks increase in frequency (medication
overuse)
Chronic daily headache (>180 days yearly)
with superimposed migraine
Development of allodynia

51. Risk Factors for Development of
Chronic Daily Headache
Definition: Headache on more days than
not (> 15 days monthly X 3 months
Case-control, cross sectional population
study
Longitudinal follow-up for progression
800 people with episodic headache
3% developed CDH
6% developed 105-179 HA days

52. Predictors of Progression
Medication overuse
Especially OTC with caffeine
combinations, narcotic combinations,
barbiturate combinations
Weight: Overweight = 2X, Obesity = 5X!!
Baseline headache frequency (>1/wk)
Low socioeconomic status
Head injury
Lipton RB, Bigal M. Headache 2005; 45 (suppl 1) S3-S13
Goadsby PJ. Med J Austr 2005;182(3):103-4

53. Stressful life events (moving, death in
family, work-related changes)
Snoring

54. Risk Factors and Development of CDH
Not readily modifiable Modifiable
Migraine as a disorder Attack frequency
(predisposition) Obesity
Female sex Medication overuse
Low SES Stressful life events
Head injury Snoring (OSA and
other sleep disorders)

55. Central Sensitization and Allodynia
Allodynia – a normally non-painful
stimulus becomes painful
Occurs in 75% of migraineurs during
migraine
Usually takes years to develop

56. Allodynia – Taking the History
Positive in 70%
Peripheral sensitization
Throbbing quality
Hair / eye glasses / earrings hurt
Hurts to touch: shave, sleep, wash
Central sensitization
Pain is worse with coughing, sneezing
Triptans less likely to work when central
allodynia is present

57. Implications for Treatment
Stratified care based on disability
Reduce environmental triggers, if present
Weight management
Investigate for sleep disorder when
appropriate
Prophylaxis
Reduce modifiable cardiovascular risk

58. Stratified Care by Overall
Disability
Little to none “Low end” Triptans
Moderate Combination treatments
Triptans Anti-emetics
Prophylaxis
Severe “High end” Triptans
Prophylaxis Narcotics
Anti-emetics Ergots
Refer to specialist

59. Summary
Women are different.
Migraines change
throughout the
reproductive cycle.
Estrogen is
important.
Migraine may be
progressive –
consider preventive
treatment.

61. Additional Recommended Reading
Dodick DW. Chronic daily headache. NEJM
2008;354:158-165
Elliott D. Migraine and stroke: current
perspectives. Curr Pain Headache Rep
2008;30(8):801-12
Ferrante E, Tassorelli C, Rossi P, et al. Focus
on the management of thunderclap headache:
from nosography to treatment. J Headache
Pain 2011;12:251-258
Klein AM, Loder E. Postpartum headache. Int J
Obstet Anesth. 2010;19:422-30

62. Kurth T, Gaziano JM, Cook NR, et al. Migraine
and risk of cardiovascular disease in women.
JAMA 2006;296;283-291
Lipton RB, Bigal ME. Ten lessons on the
epidemiology of migraine. Headache
207;46(Suppl1):S2-S9
McGregor EA. Prevention and treatment of
menstrual migraine. Drugs 2010;70:1799-818
Sullivan E, Bushnell C. Management of
menstrual migraine: a review of current
abortive and prophylactic therapies. Curr Pain
Headache Rep 2010;14:376-84