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Migraine, menstruation and the menopause

In the last of our headache series, specialist Dr Anne MacGregor discusses migraine in relation to the menstrual cycle and the menopause

In the last of our headache series, specialist Dr Anne MacGregor discusses migraine in relation to the menstrual cycle and the menopause

About 25% of women experience migraine at some point during their lives. At least 50% of women with migraine report an association between migraine attacks and menstruation.

Clinical features

For most women with menstrual attacks, migraine also occurs at other times of the month (menstrually related migraine).

41219192• Some 10% of women report migraine exclusively with menstruation and at no other time of the month (pure menstrual migraine – see table).

• A few women report a constant association between migraine and menstruation since menarche.

• Most women report a gradual association between migraine and menstruation developing from their late 30s, with increasing prevalence in the years leading to the menopause.

• Following the menopause, migraine prevalence declines.

• Migraine is most likely to occur on the first day of menstruation or up to two days before or after.

• Menstrual attacks are almost invariably without aura, even in women who have attacks with aura at other times of the cycle.

Attacks occurring at the time of menstruation are more severe and disabling, last longer and are less responsive to symptomatic medication.

Pathophysiology

• Studies have not identified any consistent biochemical or hormonal abnormalities in women with menstrual migraine, compared with control groups.

• The most likely mechanism to account for perimenstrual migraine is falling levels of oestrogen following prolonged oestrogen exposure, such as occurs during the late luteal phase of the normal menstrual cycle.

• Migraine associated with menorrhagia and dysmenorrhoea may be associated with prostaglandins and prostaglandin metabolites in the systemic circulation, which occurs during the first 48 hours of menstruation.

• Hormone fluctuations associated with the perimenopause may account for increased prevalence of menstrual migraine in this group of women.

Diagnosis

Confirm the diagnosis using diary cards to record migraine and menstruation over at least three consecutive cycles (see box below).

Principles of treatment

• There are currently no drugs licensed for the treatment of menstrual migraine in the UK – all drugs must be prescribed off licence.

• It is sensible to try a method for at least three cycles before considering alternative prophylaxis.

• Optimise symptomatic treatment, which may suffice without need for further intervention.

• Consider prophylaxis if response to symptomatic treatment for migraine attacks is inadequate.

• Although many women favour non-drug approaches, these appear to be ineffective for menstrual migraine.

• Users of the combined hormonal contraceptive (CHC) may be helped by long cycle regimes or progestogen-only methods if their attacks only happen in the pill-free week. If the episodes aren't confined to the pill-free week, a change of method may be needed, especially if the problem is increasing.

• Non CHC users might try perimenstrual NSAIDs – or, if contraception is needed, could use a long-cycle CHC regime or progestogen-only methods.

• Perimenstrual NSAIDs are also particularly suitable for women with painful or heavy periods.

• Women not on, or needing, hormonal contraception and not suffering heavy or painful periods could try perimenstrual triptans or estradiol.

Non-steroidal anti-inflammatory drugs

• NSAIDs should be tried as first-line agents for migraine attacks that start on the first to third day of bleeding, particularly in the presence of dysmenorrhoea and menorrhagia.

– Mefenamic acid 500mg three to four times daily. Start two to three days before the expected onset of menstruation and continue for the first two to three days of bleeding. If periods are irregular, start on the first day of bleeding.

– Naproxen 500mg once or twice daily is an alternative.

Perimenstrual oestrogen supplements

41219193• Estradiol gel 1.5mg applied once daily from two to three days before expected menstruation for seven days.

• An alternative is transdermal oestrogen 100µg from two to three days before expected menstruation up to the fourth or fifth day of menstruation.

• Some women responding to oestrogen supplements experience delayed attacks when the supplements are discontinued.

• The duration of supplement use can be extended until day seven of the cycle, tapering the dose by halving it over each of the last two days.

• Oestrogen supplements can be used only when menstruation is regular and predictable.

• No additional progestogens are necessary, provided that the woman is ovulating regularly.

• Ovulation can be confirmed using a home-use fertility monitor, which has the advantage of predicting menstruation.

• There is no evidence of increased risk of thrombosis or cancer in women already producing endogenous oestrogen. Supplemental oestrogens are not recommended for women who have oestrogen-dependent tumours or other oestrogen-dependent conditions, including a history of venous thromboembolism.

Perimenstrual triptans

• Trials using frovatriptan, naratriptan, sumatriptan and zolmitriptan for perimenstrual prophylaxis have suggested efficacy.

• Perimenstrual triptans should be considered for women with menstrual migraine in whom standard strategies fail.

• Frovatriptan has undergone extensive clinical trials using the following six-day regime:

– start perimenstrual prophylaxis two days before the expected menstrual attack

– on the first day of treatment take 5mg frovatriptan twice daily.

– continue frovatriptan 2.5mg twice daily for a further five days.

Other strategies to consider

• Hormonal contraceptives – women who also require contraception may benefit from contraceptives that eliminate the ovarian cycle.

• Gonadotrophin-releasing hormone analogues have been shown to be effective in clinical trials. They have some drawbacks and are expensive, so treatment should be instigated only in specialist departments, but are worth considering if all other options fail.

Migraine and the menopause

• The natural history of migraine is to diminish with increasing age.

• For women who experience menstrual migraine, the problem is likely to get worse perimenopausally with fluctuating oestrogen levels.

• Migraine is more likely to deteriorate after surgical menopause with bilateral oophorectomy.

• HRT is the treatment of choice, particularly when migraine is accompanied by other perimenopausal symptoms (see box left).

• Both oestrogen and progestogen can exacerbate migraine if not optimised. Treatment can be difficult as some women can develop headaches as a result of the therapy. If migraine persists once other menopausal symptoms are controlled, review non-hormonal triggers and management strategies.

Dr Anne MacGregor is director of clinical research at the City of London Migraine Clinic, London

This is an extract from Headache: a Practical Manual, by Dr David Kernick and Dr Peter Goadsby, published by Oxford University Press, ISBN 978-0-19-923259-8. Available from bookshops or from www.oup.com/uk/medicine

Oestrogen supplements can only be used when periods are regular Oestrogen supplements can only be used when periods are regular Diagnostic criteria HRT

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