Menstrual Migraine Anne MacGregor [email protected].
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Transcript of Menstrual Migraine Anne MacGregor [email protected].
Role of hormones
• Migraine affects 1 in 5 women compared to 1 in 13 men
Rate of change of migraine prevalence over age continuum in females
1.horizontal line at 0 on the y-axis indicates no change in the rate. 2.during childhood and early adolescence, the rate is accelerating quickly.
3. rate begins to slow its acceleration. 4. Rate is decelerating
Victor et al. Cephalalgia 2010;30(9):1065–72
2
1
3
4
Role of hormones
• 50% of women with migraine report an association between migraine and menstruation
Wöber et al. Cephalalgia 2007;27:304-314
Hazard ratios: headache & migraine:menstrual vs non-menstrual attacks
1.43**
1.96***
0
1
2
3
days -2 to -1 days +1 to +3 days 4+
Haz
ard
Rat
io
*P < 0.01**P < 0.001
** P < 0.00001
1.50***1.83***1.21*
HeadacheMigraine
Population based
MacGregor EA, Hackshaw A. Neurology 2004;63:351-3
Relative risk of migraine:menstrual vs non-menstrual attacks
2.19**2.5**
1.71**
1.25*
0
1
2
3
days -5 to -1 days -2 to -1 days +1 to +3 days +1 to +6
Rel
ativ
e R
isk
[95%
CI]
*P < 0.001** P < 0.0001
Clinic based
Menstrual vs non-menstrual attacks
More severeLonger duration Less responsive to
acute treatmentGreater relapseGreater disability
Couturier et al. Cephalalgia 2003;23:302-308 MacGregor EA, Hackshaw A. Neurology 2004;63:351-3
Granella et al. Cephalalgia 2004;24:707-16 Dowson et al. Headache 2005;45:274-82
Diagnosis
• Prospective diary for at least three consecutive cycles
• Attacks on or between days -2 to +3 in 2/3 cycles
ICHD (2nd edition). Cephalalgia 2004;24(suppl 1):1–160
Migraine and menstruation
MacGregor EA et al Headache Quarterly 1997;8:126-136MacGregor EA et al Cephalalgia 1990;10(6):305-10
• Symptomatic treatment• Standard prophylaxis• Perimenstrual
prophylaxis• Continuous hormonal
contraception
Management
Pathophysiology
• No consistent biochemical or hormonal abnormalities have been identified in patients
• Increased sensitivity to NORMAL hormonal changes
Oestrogen ‘withdrawal’
• Migraine associated with – Hormone-free interval of combined hormonal
contraceptives
– Late-luteal decline in oestrogen
– Decline in oestrogen levels following oestrogen challenge in postmenopausal women
Occurs in the absence of ovulation
Occurs in the absence of progesterone
oestrogen
progesterone
0
10
20
30
40
50
0
10
20
30
40
day of cycle-15 -10 -5 1 5 10 15
% d
ays
with
rep
orte
d m
igra
ine
hormone m
etabolite concn ng/ml E
1G and µ
g/ml P
dG
Inverse relationship between oestrogen
and migraine
MacGregor EA et al. Neurology 2006; 67: 2154-8
Day +2minimum oestrogen level
MacGregor et al. Neurology 2006;67:2159-63
Bridging luteal phase oestrogen
Evidence-based treatment of menstrual migraine: perimenstrual oestrogen
• Transcutaneous estrogen 1.5mg daily– de Lignières et al, 1986 (day -2 to day +5)
– Dennerstein et al, 1988 (7 days perimenstrually)
– MacGregor et al, 2006 (day -5 to day +2)
Pringsheim et al. Neurology 2008;70:1555-63
Recommendation B “We recommend that clinicians routinely offer estradiol gel 1.5 mg perimenstrually to women with PMM or MRM for the prevention of
migraine. We found fair evidence that transdermal estradiol applied perimenstrually provides substantial reduction in the occurrence of
PMM and moderate reduction in the occurrence of MRM.”
Not licensed for short-term prevention of menstrual migraine
MacGregor et al. Neurology 2006;67:2159-63
Relative Risk of migraine: estradiol vs placebo n=35
RR [95%CI] P
During gel 0.78 [0.62 to 0.99] <0.05
Days 1-5 post gel* 1.40 [1.03 to 1.92] <0.05
Days 6-10 post gel 1.04 [0.67 to 1.62] NS
Relative Risk of migraine: estradiol vs placebo n=35
*peak increase day 3 post gel
MacGregor et al. Neurology 2006;67:2159-63
RR [95%CI] P
During gel 0.78 [0.62 to 0.99] <0.05
Days 1-5 post gel* 1.40 [1.03 to 1.92] <0.05
Days 6-10 post gel 1.04 [0.67 to 1.62] NS
Practical guidance: perimenstrual oestrogen
• Need plasma levels >70 pg/ml
• 100mcg patches/1.5 mg gel
• Start 2-5 days before onset of period
• Continue to 5th day of period
• Taper off 6th/7th day• Try for 3 cycles
Oestrogen and serotonin
• Oestrogen ‘withdrawal’ associated with– Decreased serotonin production
– Increased serotonin reuptake
– Increased serotonin elimination
• Can specific serotonin agonists, i.e. triptans prevent menstrual migraine?
Evidence-based treatment of menstrual migraine: perimenstrual triptans
• Frovatriptan 2.5mg daily– 2 days before expected migraine for 6 days
• Naratriptan 1mg daily– 2 days before expected migraine for 5 days
Pringsheim et al. Neurology 2008;70:1555-63
Recommendation B “We recommend that clinicians routinely offer estradiol gel 1.5 mg perimenstrually to women with PMM or MRM for the prevention of
migraine. We found fair evidence that transdermal estradiol applied perimenstrually provides substantial reduction in the occurrence of
PMM and moderate reduction in the occurrence of MRM.”
Not licensed for short-term prevention of menstrual migraine
Short-term prevention with frovatriptan:no evidence of delayed headache
Silberstein et al. Neurology 2004;63:261-9
95
% o
f P
atie
nts
Wit
ho
ut
Mig
rain
e
100
60
40
20
0
80
Treatment Day (Last Day of Treatment = 6)
12731 84 1162 10
Frovatriptan 2.5 mg qd
Frovatriptan 2.5 mg bid
Placebo
Short-term prevention with naratriptan:evidence of delayed headache
Mannix et al. Headache 2007;47:1037-49
Study 1 Study 2
1 50
60
100
40
20
90
80
50
30
10
70
Treatment Day(Last Day of Treatment = 6)
2515 2010 00
60
100
40
20
90
80
50
30
10
70
Treatment Day(Last Day of Treatment = 6)
% o
f P
atie
nts
Wit
ho
ut
Att
ack
5 2515 2010
Naratriptan
Placebo
n=290
Naratriptan
Placebo
n=365
% o
f P
atie
nts
Wit
ho
ut
Att
ack
Uterine prostaglandin release
max release during first 48hrs menstruation
HEADACHE
NAUSEA & VOMITING
MENSTRUAL CRAMPS
Prostaglandin inhibitors provide relief
Short-term prevention with naproxen sodium
• Double-blind placebo-controlled study (n=40)– 550mg or placebo 12 hrly– Day -7 to day +6 (start of menses = day 1)– Reduced headache intensity, duration, and number
of headache days– 33% were headache free (none with placebo)
• Open-label study (n=25) – Day -7 to days +7 or day -5 to day +5– Reduced number of attacks, intensity, and duration
Sances et al. Headache 1990;30:705-9; Allais et al. Neurol Sci 2007;28(suppl):S225-8
Evidence-based treatment of menstrual migraine: perimenstrual naproxen
• Evidence is insufficient to recommend for or against routinely offering naproxen to patients with menstrual migraine as short-term preventive therapy
• Balance of benefits and harms cannot be determined
Pringsheim et al. Neurology 2008;70:1555-63
Contraceptive options
• Maintain stable oestrogen levels– Continuous combined contraception
– Transdermal oestrogens + Mirena IUS
• Inhibit prostaglandin release– Mirena IUS
Conclusions
• Many women report migraine associated with menstruation
• Menstrual attacks are more disabling than non-menstrual attacks
• Correct diagnosis is important to enable optimal management
• Diary cards confirm the diagnosis• Tailor treatment to individual patient needs
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