Transcript Title in Initial Caps: 40-point Arial

Women and Migraine:
The Hormonal Link
Womens Health in Primary Care
Orlando, Florida March 2011
Norma Jo Waxman MD
Associate Professor of Family and Community Medicine
Faculty in the Bixby Center for Global Reproductive Health
University of California San Francisco
[email protected]
Learning Objectives
At the end of this talk participants will be able to:

Define migraine with and without aura, menstrually
related migraine, and true menstrual migraine

Utilize pharmacologic and behavioral options for acute
and prophylactic management of migraine

Understand when hormonal medication is helpful and
safe for women with migraine

Recognize and decrease incidence of chronic daily
headache in your practice
Faculty Disclosure
No pharmaceutical
support or commercial
disclosures
Member of ARHP
expert advisory
committee on
Hormonal Migraines
and developed slide
set. Many used in this
presentation
“Despite the fact that it is so
common and has so much impact on
society, migraine is one of the most
misunderstood, misdiagnosed and
undertreated diseases on earth.”
Carolyn Bernstein, MD The Migraine Brain
Why Care About Migraine?

Very Common neurologic
disorder
• Underrecognized
• Undertreated

Produces severe disability 1,2

Overuse of any drug may lead
to chronic daily HAs3,4
IHS. Headache Classification Subcommittee of the International Headache Society (IHS). The
International Classification of Headache Disorders. 2nd ed. Cephalalgia. 2004;24(Suppl.1):139-41.
1. Lipton RB, et al. Headache. 2001;41:646–657 2. Bigal ME, et al. Cephalalgia. 2006; 26:43–49
3. Scher AI, et al. Pain. 2003;16:81–89 4. Bigal ME, Lipton RB. Headache 2006;46:1334–1343 5.
Kruit MC. et al. JAMA 2004;291:427–434; 6. Kurth T, et al. JAMA 2006;296:283–291.
Migraine in USA

30 million migraine sufferers
 1 in 10 persons a migraineur
 1 of 4 households include a migraineur
 9th leading disability, more common than
diabetes or asthma
• 30% of migraineurs have 3+ attacks/mo.
• 75% have reduced ability to function
• 50% are severely impaired
Lipton RB, et al. Headache. 2001;41:646–657
Migraine Co-morbidities
•
•
•
•
•
•
•
•
PMS
Depression
Anxiety disorders (generalized, panic,
bipolar, OCD)
Abuse/PTSD
Stroke
Irritable bowel syndrome
Epilepsy
Fibromyalgia
Epidemiology of Migraine in
Women
Women are affected 3x more than men
 20 million women in USA
 40% of women in their lifetime
•
•
•
•
Before puberty: equally prevalent in both sexes
After puberty: 3x more women than men
Peaks in midlife
↓ after menopause
Lipton RB. Headache. 2001.
Lipton RB. Neurology. 2007.
Stewart. Cephalalgia. 2008.
ICHD Diagnostic Criteria for
Migraine Without Aura
At least 5 attacks with:
 Headache lasts 4–72 hours w/o treatment
or without successful treatment
 At least 2 of the following four symptoms:

• Unilateral pain (60%)
• Throbbing (70%)
• Aggravation by movement
• Moderate to severe pain
ICHD = International Classification of Hreadache Disorders
Adapted from , Cephalalgia. 2004;8(suppl 1):S24-26.
more…
IHS Diagnostic Criteria for
Migraine Without Aura (cont’d)
 And
at least 1 of the following 2 symptoms:
• Nausea and/or vomiting
• Photophobia and/or phonophobia
 Not
attributed to organic disease
Adapted from IHS, Cephalalgia. 2004.
ICHD Diagnostic Criteria for
Migraine with Aura
At least 2 attacks with
 At least 1 fully reversible symptom w/o motor

Visual (flickering lights, zigzags, spots or lines, and/or
loss of vision) + and/or

Sensory (“pins and needles” and/or numbness) +
and/or

Dysphasic speech

more…
Adapted from IHS, Cephalalgia. 2004.
IHS Diagnostic Criteria for
Migraine with Aura (cont’d)
• Symptoms of aura develop gradually over
>5min or different symptoms occur in
succession over >5 min
• Each symptom last >5 and <60 min
• Migraine begins with aura or within <60 min
• Symptoms are fully reversible
• No organic disease
Adapted from IHS, Cephalalgia. 2004.
Prevalence of Migraine
by Age and Sex
30
Females
Males
25
20
Migraine
Prevalence 15
(%)
10
5
0
20
30
40
50
Age (years)
Lipton RB, et al. Headache. 2001.
60
70
80
100
Headaches and the Menstrual
Cycle
Patients with HA (%)
12
Migraine without aura
Tension type
10
Migraine with aura
8
6
4
2
0
−16 −14 −12 −10 −8 −6 −4 −2
HA = headache
0
2
4
6
8
Day of Menstrual Cycle
Adapted from Stewart WF, et al. Neurology. 2000.
10 12 14 16
Menstrual Migraines Subtypes
(ICHD-2)
Menstrually Related Migraine (MRM)
 Attacks fulfill criteria for 1.1 Migraine without aura
 Attacks occur days 1 ± 2 (i.e., days -2 to +3) of
menstruation in at least 2 out of 3 menstrual cycles and
additionally at other times of the cycle
 ~46% of women with migraine
Pure Menstrual Migraine (MM)
 Attacks fulfill criteria for 1.1 Migraine without aura
 Attacks occur days 1 ± 2 (i.e., days -2 to +3) of
menstruation in at least 2/3 cycles, and at no other time of
the cycle
 ~14% of women with migraine
IHS, Cephalalgia. 2004.
Distribution of Migraine Types in
Women
• 40% non-menstrual
migraine
• 60% menstrual migraine
Pure
MM 14%
MRM 46%
– MRM comprises the
majority of MM
(46% of 60%)
Non-menstrual
Migraine
40%
Female Migraineurs
MRM = menstrually related migraine; MM = menstrual migraine.
Mannix LK, Calhoun AH. Curr Treat Options Neurol. 2004.
Menstrual Migraines
 Compared
with attacks at other times of
the cycle, menstrual attacks are:
•
•
•
•
More disabling
Longer in duration
Less responsive to acute treatment
More likely to relapse
MacGregor EA, Hackshaw A. Neurology. 2004. Dowson AJ, et al. Headache. 2005.
Non-Hormonal
Migraine Triggers
• Hunger
• Certain Foods
• Dehydration
• Sleep
• Head and neck
pains
• Emotional
• Environmental: smoke,
bright lights, change in
weather
• Concomitant disease
• Sex
Hormonal Migraine Triggers
• Estrogen withdrawal, or change in level
Menstruation
 Placebo days with combined hormonal
contraceptives
 Pregnancy
 Peri-menopause
 Hormone replacement therapy

Case 1: Sarah
New Patient Visit
24-year-old non-smoker
 Sexually active
 On intake: checks off
“headaches,” which she
says are worse with her
periods
 Presents for contraception

Does Sarah have migraine?...
Use “PIN” for Diagnosis of
Migraine
Photophobia: Does light bother you?
Impairment: Do your headaches limit you?
Nausea: Do you feel nauseated?
Based on Lipton RB, et al. Neurology. 2003.
Case 1: Sarah
Accurate diagnosis of migraine aura is
essential for the safe prescribing of
estrogen-containing contraception.
Sarah has migraine without aura. She has no
other risk factors for stroke.
Case 1: Sarah
 Is
Sarah eligible for estrogencontaining contraception?
A) Yes
B) No
Case 1: Sarah
• Is Sarah eligible for estrogen-containing
contraceptives? Might she opt for a patch or
ring?
A) Yes: Low-dose estrogen contraception can be
used in women under age 35 who have migraine
without aura and no other risk factors for stroke.
B) No: OCPs should never be used in women who
have migraine.
MEC: Headaches and CHC
Initiate Continue
Non-migrainous (mild or severe) 1
2
Migraine
(i) without focal neurologic symptoms
Age < 35
2
Age > 35
3
(ii) with focal neurologic symptoms 4
(at any age)
3
4
4
photo/phonophobia, N/V are not focal symptoms
Focal symptoms = vision changes, numbness, parasthesias
http://www.who.int/reproductive-health/publications/RHR_00_2_medical_eligibility_criteria_3rd/
Treatment of Migraines
 Education

and behavior modification
Identify and avoid or modify triggers
 Acute
treatment
 Prophylactic
• Short-term
• Long-term
treatment
Treatment of Migraines

Triptans more effective than NSAIDs and
combination analgesics- warn about SEs

NSAIDS can act synergistically with Triptans

Phenothiazines, PO or PR, great for nausea & pain

Think non-oral meds with nausea & vomiting

Sleep can abolishes headache
Options for Acute Therapy
 Aspirin
 Ibuprofen
 Naproxen
sodium
 Combination Analgesics

Acetaminophen, aspirin and caffeine
 Triptans
 Phenothiazines
Rescue or Emergency
Treatment of Migraine
 When
acute tx fails
 When
H/A returns in <24 hrs or continues
for days
 IV/IM
phenothiazines in addition to DHE or
a triptan work better than narcotics-
Prophylaxis of Migraines

Consider prophylaxis if acute meds used >
4x/mo, rescue meds > 1x/mo, or headaches are
functionally limiting

Start prophylaxis at low dose and titrate up over
2-3 months

TCAs are effective independent of their
antidepressant effect

Limited studies show biofeedback, relaxation
training, spinal manipulation and physical
therapy may be helpful
Medications for Prophylaxis
Consider hx, co-morbidities and hormonal state
 TCAs- Amitrip best studied, but most side effects
 SNRIs (more effective then SSRIs)
 Beta- blockers
Propranolol most studied and successful- Nadolol and
Timolol too
Valproate, Topiramate, Gabapentin and other “anticonvulsants” and “mood stabilizers”
 Botox
 Verapamil and CCB- less effective
 Hormonal Tx

Preventive Options with
Non-pharmacologic Modalities
Supplements
Magnesium
Vitamin
B2- riboflavin
Feverfew
 Butterbur
(Petadolex)
 Coenzyme Q10
 Omega-3 Fatty Acids
 Isoflavones
chelated magnesium at 400-600 mg/d for 3-4 months works as prophylaxis
(best in pt. w/ aura or perimenstrual migraine, and those not responding to
triptans). Riboflavin, 400mg/d for 3 months decrease migraine frequency.
Preventive Options with
Non-pharmacologic Modalities
Cognitive/behavioral Modalities



􀂃 Meditation
Recognize and Avoid Triggers
Headache Diary
Physical Modalities





Massage
Yoga
Acupuncture
􀂃 Osteopathic manipulation
Peppermint oil (? Helpful for acute)
Evaluating Migraine
 Lab
tests?
 Hormone
Tests?
 Cat
Scan?
 Headache
Diary
Red Flags
 Headaches
begin after age 50
 Very sudden onset of Headache
 First or worst
 Change in frequency or severity
 Immunosuppression
 Fever, stiff neck, rash, trauma
 Focal neurologic symptoms or signs
 Papilledema
Case 1: Sarah
Recommended Approach
Migraine
diary
Counseling
about migraine triggers and nonpharmacologic treatment options
Her
choice of hormonal / non-hormonal
contraception
Acute
treatment with triptan
Schedule
2-3 mo f/u to review diary
Case 1: Sarah
Return Visit
 Headache
diary confirms menstrual
related migraine
 2–3 attacks/mo. without aura
 Severe attack during pill-free week
What do you do next?...
Options for Pharmacologic
Treatment for MRM
Rescue/Emergency treatments
 IM/IV phenothiazines or DHE
Prophylactic perimenstrual treatments
 NSAIDs
 Supplemental estrogen
 Triptans
 Extended cycle combined hormonal
contraceptives
Prophylactic Treatments for MM and
MRM with Continuous hormonal therapy
Continuous combined contraceptives
Dedicated product
 Monophasic product throw away placebo
 Continuous cycling with ring

Estrogen back in hormone-free interval
Mircette
 Yaz
 Supplemental estrogen

Migraine, OCPs, and Stroke



6 per 100,000 ♀ / year – healthy
12 per 100,000 ♀ / year – migraine
18 per 100,000 ♀ / year – migraine with aura

12 per 100,000 ♀ / year – healthy and COC
19 per 100,000 ♀ / year – migraine and COC
30 per 100,000 ♀ / year – migraine with aura and COC

34 per 100,000 ♀ / year – stroke in pregnancy


Attributable risk: 7-19 per 100,000 women per year ~ 4000 / year
So, What about estrogen containing contraception in women with Migraine?
• IHS: low-dose estrogen in women with simple visual aura
• ACOG: progestin only, intrauterine or barrier contraception
• WHO: absolute contraindication in all women with aura
Prescribing Contraception in
Women with Migraines
 Use
a Progesterone Only method with aura
 Lowest
estrogen levels with ring
 Consider
20 or 25 mcg pills
 Consider
eliminating the placebo week
 Follow-up
 Stress
in 1-3 months after initial Rx
need to discontinue method if
Migraines worsen
Case 1: Sarah
Treatment and Outcome
Change 21-day OCPs to continuous
hormonal therapy
For symptomatic treatment of migraine,
continue therapy with nsaids and triptans
Lifestyle modifications
More regular meals
More sleep and exercise
Stress-reduction techniques
Follow up in 1-3 months
Case 2: Pam
35-year-old woman
6th week of pregnancy
Menstrual migraine diagnosed 10 years ago
Migraine more frequent and severe since
she became pregnant
Migraine and MRM in Pregnancy
60% – 70% of migraineurs improve
during pregnancy
Non-pharmacologic treatment is
preferred
Biofeedback
Relaxation therapy
Cognitive-behavioral therapy
Magnesium
MacGregor EA. J Fam Plann Reprod Health Care. 2007.
Migraine Drug Use During Pregnancy and
Lactation (Analgesics and Ergots)
Drug
1st Trimester
2nd Trimester
3rd Trimester
Lactation
Y
Y
Acetaminophen
Y
Y
Codeine
(Y)
(Y)
(Y)
Y
Aspirin
(Y)
(Y)
Avoid
Avoid
Diclofenac
Ibuprofen
Naproxen
(Y)
(Y)
Avoid
Y
Dihydroergotamine
Ergotamine
CI
CI
CI
CI
Y = no evidence of harm
(Y) = data suggest unlikely to cause harm
?(Y) = limited data but probably safe
CI = contraindicated
ID = insufficient data
* = for emergency treatment of migraine
not responding to standard measures
MacGregor EA. J Fam Reprod Health Care.
2007
Drug use during pregnancy and lactation
(Triptans, magnesium, prednisolone)
Drug
1st Trimester
2nd Trimester
3rd Trimester
Lactation
Almotriptan
Frovatriptan
ID
ID
ID
ID
Eletriptan
ID
ID
ID
Y
Naratriptan
Rizatriptan
?(Y)
?(Y)
?(Y)
(Y)
Sumatriptan
?(Y)
?(Y)
?(Y)
Y
Zolmatriptan
ID
ID
ID
(Y)
Magnesium
sulphate*
(Y)
(Y)
(Y)
(Y)
Prednisolone*
(Y)
(Y)
(Y)
(Y)
MacGregor EA. J Fam Reprod Health Care. 2007
Case 2: Pam
Treatment and Outcome

Reassurance
• Migraine may improve by the 2nd trimester,
particularly in women w/ history of menstrual
migraine
• No evidence migraine will affect pregnancy outcome

Acute
• Acetaminophen, NSAIDS,
• Triptans ??? (1-2nd trimester- may be safe- need
more studies)

Prophylactic
• If possible, delay treatment until 2nd trimester
Case 2: Pam
Treatment and Outcome (cont’d)

Propranolol safe and effective and can be used
postpartum and during lactation (FDA C)
• Use lowest effective dose
• Stop 2 to 3 days before delivery
• Manage with neurologist or headache
specialist

Amitriptyline is another option

(FDA C)
Case 3: Hannah
52-year-old woman
Presents with headache
5-year history of menstrual
migraine and occasional attacks
of migraine with aura
Hot flashes, mood swings
Asks about hormone therapy
Menstrual Migraine and
Hormone Therapy (HT)

Lowest and Non oral routes are best

Evaluate risk factors for stroke and CAD

Migraine with aura is not a contraindication to HT in
low risk women (no RCTs, expert opinion)

If aura 1st appears after start of HT, reduce estrogen
and consider work up for TIA
Macgregor EA. Migraine, the menopause and hormone replacement therapy: a clinical
review. J Fam Plann Reprod Health Care. 2007;33(4):245-9.. Macgregor EA. Estrogen
replacement and Migraine, Maturitas Volume 63, Issue 1, 20 May 2009, Pages 51-55
Case 3: Hannah
Treatment and Outcome

Acute treatment with NSAIDS & triptans
Low-dose non-oral estradiol AND continuous
progestin (if needed)

Hannah’s migraine attacks increase when HT is
initiated but improve with continued use

Fluoxetine & venlafaxime useful migraine prophylaxis
and treat hot flashes

Chronic Daily Headache (CDH)
 Diagnostic
Criteria: Headache 15 or more
days/month for at least 6 months
 Preventable
 Speaks
with accurate medication history
to early use of prophylaxis
 Depression,
anxiety and drug abuse may
complicate presentation
1. Cephalalgia. 2004;8 (suppl 1):S24–26; 2. Bigal ME, et al. Cephalalgia. 2007;27:568.
Chronic Daily Headache (CDH)
 AKA:
rebound headache, chronic tensiontype, medication induced, transformed
migraine
 CDH
caused by overuse of acute meds
 Unrecognized
epidemic: majority of
referrals to headache clinics
 Disabling
and expensive
Chronic Daily Headache (CDH)
 Taper
off acute medications
 Overuse of NSAIDs, tylenol, narcotics typical
 May require hospitalization
 6 RCTs showed sig improvement w/
Amitriptyline
 The longer one has CDH, the harder it is to
treat
 Steroids may be helpful during taper
Creating a Supportive Office
Environment
 Educate
patients
and entire
healthcare team
 Make adjustments
in your office
•
•
•
•
Light
Odor/smells
Noise
Chemical
Summary: Behavioral and
Lifestyle Modifications
Avoid dietary, emotional, and
environmental triggers
 Eat regular, healthful meals
 Get the right amount of sleep
 Get regular exercise
 Learn stress management techniques

Summary: Pharmacologic Tx
Acute treatment (NSAIDs, triptans)
Rescue Tx- DHE, phenothiazines
Prophylactic treatment
Perimenstrual (NSAIDs, estrogen, triptan) if:
Response to acute tx inadequate
Regular, predictable periods
Continuous (extended cycle contraception) if:
Patient needs contraception
Patient has irregular periods
Other strategies fail
Take-Home Points
Migraine is a neurological illness caused by abnormality in
brain chemistry
A range of behavioral and drug options exist for the
management of severe migraine
A substantial proportion of women with migraine
experience increased incidence around onset of menses
Short-term prevention is the best approach for these
women if they have regular menses