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Menstrual Migraine

Menstrual Migraine. Anne MacGregor www.migraineclinic.org.uk anne.macgregor@migraineclinic.org.uk. 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.

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Menstrual Migraine

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  1. Menstrual Migraine Anne MacGregor www.migraineclinic.org.uk anne.macgregor@migraineclinic.org.uk

  2. Role of hormones • Migraine affects 1 in 5 women compared to 1 in 13 men

  3. 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 accelerating 2 3 1 4 Victor et al. Cephalalgia 2010;30(9):1065–72

  4. Role of hormones • 50% of women with migraine report an association between migraine and menstruation

  5. 3 1.96*** 2 1.43** Hazard Ratio 1 0 days 4+ days -2 to -1 days +1 to +3 Hazard ratios: headache & migraine:menstrual vs non-menstrual attacks Population based *P < 0.01 **P < 0.001 ** P < 0.00001 1.50*** 1.83*** 1.21* Headache Migraine Wöber et al. Cephalalgia 2007;27:304-314

  6. 3 2.5** 2.19** 2 1.71** Relative Risk [95% CI] 1.25* 1 0 days -5 to -1 days -2 to -1 days +1 to +3 days +1 to +6 Relative risk of migraine:menstrual vs non-menstrual attacks Clinic based *P < 0.001 ** P < 0.0001 MacGregor EA, Hackshaw A. Neurology 2004;63:351-3

  7. Menstrual vs non-menstrual attacks • More severe • Longer duration • Less responsive to acute treatment • Greater relapse • Greater 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

  8. 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

  9. Migraine and menstruation MacGregor EA et al Headache Quarterly 1997;8:126-136 MacGregor EA et al Cephalalgia 1990;10(6):305-10

  10. Symptomatic treatment Standard prophylaxis Perimenstrual prophylaxis Continuous hormonal contraception Management

  11. Pathophysiology • No consistent biochemical or hormonal abnormalities have been identified in patients • Increased sensitivity to NORMAL hormonal changes

  12. 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

  13. Inverse relationship between oestrogen and migraine 40 50 oestrogen 40 progesterone 30 % days with reported migraine 30 hormone metabolite concn ng/ml E1G and µg/ml PdG 20 20 10 10 0 0 -15 -10 -5 1 5 10 15 day of cycle MacGregor EA et al. Neurology 2006; 67: 2154-8

  14. 40 50 40 30 % days with reported migraine 30 20 concn ng/ml E1G and µg/ml PdG 20 10 Day +2 minimum oestrogen level 10 0 0 Bridging luteal phase oestrogen MacGregor et al. Neurology 2006;67:2159-63

  15. 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) 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 Pringsheim et al. Neurology 2008;70:1555-63

  16. Relative Risk of migraine: estradiol vs placebo n=35 MacGregor et al. Neurology 2006;67:2159-63

  17. Relative Risk of migraine: estradiol vs placebo n=35 *peak increase day 3 post gel MacGregor et al. Neurology 2006;67:2159-63

  18. 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

  19. 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?

  20. 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 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 Pringsheim et al. Neurology 2008;70:1555-63

  21. Short-term prevention with frovatriptan:no evidence of delayed headache 100 Frovatriptan 2.5 mg bid Frovatriptan 2.5 mg qd Placebo 80 60 % of Patients Without Migraine 40 20 0 1 2 3 4 5 6 7 8 9 10 11 12 Treatment Day (Last Day of Treatment = 6) Silberstein et al. Neurology 2004;63:261-9

  22. Short-term prevention with naratriptan:evidence of delayed headache Study 1 Study 2 100 100 Naratriptan Naratriptan Placebo Placebo 90 90 n=290 n=365 80 80 70 70 60 60 % of Patients Without Attack % of Patients Without Attack 50 50 40 40 30 30 20 20 10 10 0 0 1 5 10 15 20 25 0 5 10 15 20 25 Treatment Day(Last Day of Treatment = 6) Treatment Day(Last Day of Treatment = 6) Mannix et al. Headache 2007;47:1037-49

  23. Headache nausea & vomiting MenstRual cramps max release during first 48hrs menstruation Uterine prostaglandin release Prostaglandin inhibitors provide relief

  24. 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

  25. 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

  26. Contraceptive options • Maintain stable oestrogen levels • Continuous combined contraception • Transdermal oestrogens + Mirena IUS • Inhibit prostaglandin release • Mirena IUS

  27. 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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