1. Callum Duncan Consultant Neurologist Aberdeen Royal Infirmary
Migraine and Hormones
Migraine Trust Public Meeting: September 2011
Callum Duncan
Consultant Neurologist
Aberdeen Royal Infirmary

2. Hormones and migraine Pre-puberty boys = girls
1st year of menstrual period
15% of women develop their 1st migraine
Fertile years
women:men 3:1
50% women with migraine report an association between migraine and menstruation
Menopause (Migraine without aura)
Commonly worsens during menopause
may improve after menopause

3. Migraine frequency and menstrual cycle

4. Definitions Pure Menstrual Migraine Menstrually-related Migraine
Migraine without aura
Only during menstrual period
Can start anytime from 2 days before bleeding starts to 3 days after
Menstrually-related Migraine
As Pure Menstrual Migraine but additional attacks with or without aura at other times of the cycle

6. Menstrual vs non-menstrual attacks
Menstrual attacks are:
More severe
Last longer
Acute treatment is not as effective
Greater relapse
Greater disability

7. Menstrual Migraine Women with menstrual migraine have
increased sensitivity to NORMAL hormonal
changes during their menstrual cycle

8. How to treat menstrual migraine:
Modifiable lifestyle triggers
Acute treatment
Set limits to avoid MOH
MOH less likely if short spells of frequent headache around menstruation and infrequent or no headache at other times of the month
Regular preventative treatment
Preventative treatment taken around period time

9. Specific Anti inflammatories
Mefenamic acid 500 mg 3 times per day
Naproxen 500mg 2 times per day
Work on prostaglandins produced by the womb
Can be used whether periods are regular or irregular
Useful if periods are heavy or painful
If regular cycle:
Start treatment a few days before expected first day of period and continue until period stops
If irregular cycle:
Start treatment on first day of period

10. The oestrogen drop in the few days before bleeding triggers migraine

11. Oestrogen to prevent menstrual migraine
Only useful when periods are regular and predictable
Counter acts fall in oestrogen levels that happen a few days before period starts

12. Which oestrogens? Gel applied to the skin (arm or hip)
Oestradiol gel 1.5 mg applied daily from 2–3 days before expected first day of period for 7 days
Patch
Oestrogen 100 μg patch can be used from 2–3 days before expected menstruation up to day 4 or 5
two twice-weekly patches or
one 7-day patch

13. Women using the combined oral contaceptive pill: Migraine during the pill free week
Typically migraine without aura
Oestrogen ‘withdrawal’
Prevention
Long cycle
“Tricycle” 3 packs continuously
followed by a pill free week
Oestrogen to cover pill free week
100mcg oestradiol patches on last day of contraceptive hormones, replace after 3½ days and remove on 1st day of next pack

14. Long acting triptans to prevent menstrual migraine
Menstrual migraine is more severe, prolonged and more likely to recur
Rapid onset short duration triptans
Almotriptan 12.5mg
Eletriptan 40mg or 80mg
Rizatriptan 10mg
Sumatriptan 100mg
Zolmatriptan 5mg
Slow onset long duration triptans
Frovatriptan 2.5mg
Naratriptan 2.5mg
Frovatriptan has longest duration of action and can be taken once per day
Naratiptan has to be taken twice per day

15. Long acting triptans to prevent menstrual migraine
Rational: menstrual migraine is more severe, prolonged and more likely to recur
Only useful when periods are regular and predictable
Frovatriptan 2.5mg daily
2 days before expected migraine for 6 days
Naratriptan 1mg (½ 2.5mg tablet) morning and night
2 days before expected migraine for 5 days
If rebound headache after triptan is stopped can take tablets for up to 8 days

16. Summary Heavy and painful periods Mefenamic acid or Naproxen
Periods unpredictable
Periods predictable
Frovatriptan or Naratriptan
Oestrogen
On Combined Oral Contraceptive Pill: Headache during pill free week
3 packs in a row

17. Combined Oral Contraceptive Pill and Migraine
Often has no effect
on migraine frequency
Can make migraine worse
More likely to occur with
migraine with aura
Rarely makes migraine better
Progesterone only contraceptives should have no effect on migraine
pill, implant, injection, coil

18. Migraine aura and stroke
Small increased risk of stroke in people who have migraine aura
Increased risk in
Women
Age less than 45
Smokers
Use of contraceptive oestrogens
No increased risk with contraceptive progestrogens }
Where usual stroke risk
are factors less common

19. Contraception in Migraine: (1) Combined Oral Contraceptive
Migraine with aura
Contra-indicated in migraine with aura
If no aura for >5years it is ok to use the combined pill, BUT must stop immediately if aura returns
Migraine without aura
Safe to use at any age
If first migraine aura happens after starting the combined pill, it must be stopped again

20. Contraception in Migraine: (2) Progesterone
Safe to use
Pill
Implant
Injection
Coil
Not associated with an increased risk of stroke

21. Migraine and Pregnancy

22. Effect of Pregnancy on Migraine
Migraine without aura
Migraine gets better or stops during pregnancy in most women
Migraine is more likely to stop if it is triggered by menstruation
Migraine with aura
More likely for attacks to continue during pregnancy
Migraine aura can start for the 1st time during pregnancy
1st ever attack of migraine
In person who already has migraine without aura

23. Acute treatment in Pregnancy
Pain killers
Paracetamol
Aspirin/NSAIDs
avoid from 30 weeks (3rd trimester)
avoid aspirin during breastfeeding
Codeine
Anti-sickness tablets
Domperidone
Prochlorperazine

24. Can triptans be used in pregnancy?
Risk of birth defects in the general population = 3-5%
Women with migraine 3.4% (95%CI )
Sumatriptan Pregnancy Registry
1st January1996 – 31 October 2010
594 pregnancies
Birth defects following exposure in 1st trimester 4.3%
Birth defects following exposure in any trimester 4.3%
Other triptans - insufficient data
Sumatriptan/Naratriptan/Treximet Pregnancy Registry Spring

25. Can triptans be used in pregnancy?
Not enough evidence to be certain
Best to use as few medications as possible in pregnancy
If triptans used in early pregnancy (before a woman knows she is pregnant) it is unlikely to have caused harm
If attacks are very severe, especially if there is significant vomiting, it may be reasonable to use Sumatriptan

26. Triptans and breast-feeding
Risk is likely to be very small
Sumatriptan
Low levels of sumatriptan in breastmilk and amounts ingested by the infant are small
BNF recommends withhold breast-feeding for 12 hours
Others triptans
BNF recommends withholding breasr-feeding for 24 hours
Practically
Either mix breast and bottle or have expressed milk available
Express for 12 hours after Sumatriptan or 24 hours after other tripans and discard expressed milk

27. Other Acute Treatments
Paracetamol and Ibuprofen are safe
Aspirin should not be used during breast-feeding
Risk of Reye’s Syndrome in infant

28. Preventative treatment in Pregnancy and Breast-feeding (1)
Most migraine improves during pregnancy
Preventative treatment should be avoided if possible
If required use lowest dose possible and withdraw in last weeks of pregnancy
Amitriptyline
Has been widely used for many years
No reports of limb deformities at low doses (10-50mg)
Beta-blockers
Risk of babies heart rate going slowly in late pregnancy (3rd trimester) and baby having low sugar levels in the first few days after birth
Propranolol 10-20mg 2 times daily

29. Preventative treatment in Pregnancy and Breast-feeding (2)
Antiepileptics
Should not be used in pregnancy
All women of child bearing age should be counselled about risk of birth defects when prescribing an anti-epileptic for migraine prevention and must use adequate contraception
Sodium Valproate contra-indicated in pregnancy
Topiramate (epilepsy data):
birth defects in 4.8% when on Topiramate alone
birth defects in 11.2% when Topiramate given with other anti-epileptics
Others migraine preventatives
No evidence

30. Investigations in pregnancy
Most migraine does not require investigation
Migraine symptoms that change during pregnancy or are not typical may need investigation
Investigations are the same as for women who are not pregnant
CT brain
most radiation is to the head and the rest of the body is exposed to very limited amounts
can cover the tummy with a lead blanket to protect baby
MRI: safe after 1st trimester
Lumbar puncture: safe

31. Migraine and the Menopause
In the menopause hormones fluctuate erratically
Migraine and menstrual migraine often worsen during the menopause
This persists until oestrogen levels stabilise after the menopause stops
Migraine often improves after a natural menopause, but may worsen after a hysterectomy

32. Prevention for menstrual migraine during the menopause
Mefenamic acid and Naproxen can be helpful
BUT
Long acting triptans and oestrogen are not useful because:
Ovulation must occur for oestrogen to be used and the menopause is associated with cycles where no oestrogen is produced
Periods must be regular and the menopause is associated with irregular cycles

33. Hormone Replacement Therapy
HRT may worsen migraine
More likely with tablets than with gel or patches
Probably due to more stable hormone levels associated with gel and patch HRT
HRT is safe in migraine
No evidence of increased risk of stroke in patients with migraine with or without aura

34. Summary Hormones are a common migraine trigger in women
Oestrogen “withdrawal”
Prostaglandins
Not progesterone
Migraine usually improves in pregnancy
Combined Oral Contraceptives are contra-indicated in migraine with aura
HRT is safe in migraine with and without aura
Gel and patch are less likely to aggravate migraine

35. Questions?