Diagnosis and management of menstrual migraine

Transcription

1 Menstrual migraine z Review Diagnosis and management of menstrual migraine E Anne MacGregor MD, MFSRH, MICR The prevalence of migraine is highest during the peak reproductive years and many women report its association with their menstrual periods. In this review, Professor MacGregor discusses the diagnosis, pathophysiology and management of menstrual migraine. Despite affecting one in seven of the UK population, migraine is underdiagnosed and undertreated. 1 Prevalence is highest during the peak reproductive years with a female predilection, affecting one in five women compared with one in 13 men. 1 The diagnosis of migraine is based on recurrent episodic headaches lasting between four and 72 hours associated with photophobia, nausea and limitation of normal function in an otherwise healthy person. 2 Prevalence of menstrual migraine Menstruation is a significant risk factor for attacks of migraine without aura, with per cent of women reporting a link between their menstrual periods and migraine. 3-5 Most women with menstrual exacerbation of migraine also experience attacks at other times of the month ( menstrually-related migraine). 6,7 Fewer than 10 per cent of women report migraine exclusively with menstruation ( pure menstrual migraine). 5-9 Characteristics of menstrual migraine Timing of attacks Compared with all other phases of the menstrual cycle, attacks of migraine without aura are most likely to occur during a five-day window that starts two days before the onset of menses and continues through the first three days of menstruation. 8,10-12 Studies suggest that women are over 70 per cent more likely to have migraine in the two days before menstruation and more than 2.5 times more likely to have attacks during the first three days of bleeding. 12 How attacks differ from non-menstrual attacks Menstrual attacks last longer, are more severe, are more likely to relapse, are less responsive to treatment, and are associated with greater disability when compared with attacks at other times of the cycle. 5,11-19 Diagnosis The International Headache Society (IHS) recognises two types of menstrual migraine: menstrually-related migraine, which is migraine without aura that regularly occurs on or between two days before menstruation and third day of bleeding (days -2 to +3), with additional attacks of migraine with or without aura at other times of the cycle; and pure menstrual migraine, which is migraine without aura that occurs only on or between days -2 to +3, ie with no attacks at any other time during the cycle. 6,20 To confirm the diagnosis, migraine attacks during the day -2 to +3 window must occur in at least two of three menstrual cycles to establish a relationship that is greater than chance alone. Relying on the history to confirm the diagnosis can be misleading. 21 Use of a three-month diary to record migraine patterns can reveal the predictable patterns associated with menstrual migraine, aiding diagnosis. Pathophysiology Research has found an increased risk of migraine associated with oestrogen withdrawal. This occurs during the late luteal phase of the natural menstrual cycle and also during the hormone-free interval of combined hormonal contraceptives. 17,22 Prostaglandins have also been implicated in menstrual migraine. There is a three-fold increase in prostaglandin levels in the uterine endometrium from the follicular to the luteal phase, with a further increase during menstruation. 23 As a result of the withdrawal of oestrogen and progesterone, the endometrium breaks down and prostaglandins are released. When excessive prostaglandins enter the circulation, other systemic symptoms, such as headache and nausea, accompany menorrhagia and/or dysmenorrhoea. 24,25 Management The mainstay of management of menstrual migraine is symptomatic treatment of acute attacks. If this is insufficient for effective control of attacks, a variety of prophylactic options are available depending on individual needs (see Figure 1). Progress in Neurology and Psychiatry 11

2 Confirm diagnosis of migraine Optimise acute treatment Review predisposing factors and triggers Key: COC, combined oral contraceptive; GnRH, gonadotrophinreleasing hormone; HFI, hormone-free interval; HRT, hormone replacement therapy; IUS, intrauterine system Acute treatment adequate? Diary card record of last three cycles available? Continue with acute treatment only Provide diary cards and review as necessary Provide diary cards and Attacks only in HFI? Review suitability of COCs Continue if no evidence of increased migraine on COCs If contraception required, consider progestogenonly or other nonhormonal methods Consider perimenstrual NSAIDs: mefenamic acid/naproxen (day 1 start if periods unpredictable) review after three cycles COC user? Consider longcycle COCs or progestogen-only methods Menstrual attacks in average of two of three cycles? Wants hormonal contraception? Symptoms of perimenopause (flushes, sweats, irregular periods)? Painful or heavy periods Regular and predictable periods Consider standard prophylaxis review as required Consider HRT Consider perimenstrual oestradiol/triptans Continue NSAIDs/consider IUS Continue diary cards and review every three to six cycles Regular periods consider perimenstrual oestradiol/ triptans, or anovulatory progestogens Consider perimenstrual NSAIDs or anovulatory progestogens Continue treatment and diary cards and review every three to six cycles Review diagnosis: if diaries confirm menstrual attacks consider GnRH analogues ± addback HRT; otherwise standard prophylaxis with regular review Continue treatment and diary cards and review every three to six cycles Figure 1. Recommended management of menstrual attacks of migraine. Reproduced with permission from MacGregor EA. Menstrual migraine: a clinical review. J Fam Plan Reprod Health Care 2007;33(1): Progress in Neurology and Psychiatry

3 Menstrual migraine z Review Acute treatment Factors that enhance the efficacy of treatment of the symptoms of menstrual migraine include the use of appropriate medication, appropriate treatment of associated nausea or vomiting, and adequate doses of medication. It is also important to take medication at a mild stage of the pain, rather than waiting until the headache is severe. It may be necessary to repeat treatment for menstrual attacks over several consecutive days since these attacks typically last longer than attacks at other times of the cycle. However, use of codeine-containing analgesics, ergot or triptans should be limited to a maximum of 10 days a month (15 days of simple analgesics only can be taken) to reduce the risk of medication overuse headache. Contraceptive options Contraceptive strategies may be particularly useful for women with menstrual migraine requiring contraception. Healthy women with migraine without aura can use combined hormonal contraceptives up to the age of 50 years. Contraceptive oestrogens should not be used by women who have migraine with aura because of the synergistic increased risk of ischaemic stroke. 26 Continuous combined oral contraceptives, eliminating the usual monthly hormone-free interval, are a safe and effective method of eliminating menstrual symptoms. 27,28 They are well tolerated, although unscheduled bleeding is a common reason for withdrawal from clinical trials in the first six months of treatment. Continued use induces amenorrhea in 80 to 100 per cent of women by 10 to 12 months of treatment. 29 Women who wish to maintain a monthly period may try combined contraceptives with a twoday hormone-free interval, although data regarding their benefit in headache are limited. Progestogen-only contraceptives can also be effective, particularly those that inhibit ovulation and result in amenorrhoea. 30 This is most likely to be achieved with depot medroxyprogesterone acetate. Although irregular bleeding can occur in early months of treatment, amenorrhoea is usual with continued use. It is therefore important to warn women who use this method that they should persevere until amenorrhoea is achieved. Subdermal or oral etonorgestrel can be tried, although unscheduled bleeding is a common reason for discontinuation. In general, standard oral progestogen-only contraceptives have little place in the management of menstrual migraine, since most do not inhibit ovulation and are associated with a disrupted menstrual cycle. 31 However, unlicensed higher doses of oral progestogen, sufficient to inhibit ovulation, have shown benefit. 32 The levonorgestrel intrauterine system (IUS) is highly effective at reducing menstrual bleeding and associated pain and can be considered for migraine related to menorrhagia. 33 The method is not effective for women who are sensitive to oestrogen withdrawal as a migraine trigger, as the majority of women still ovulate. Perimenstrual prophylaxis None of the drugs recommended below is licensed for management of menstrual migraine, although there are clinical trial data to confirm efficacy. Given that there are no investigations to identify the most effective prophylactic, an empirical approach is necessary, prescribing on a named patient basis. Because of the fluctuating nature of migraine, it is sensible to try a method for at least three cycles before considering alternative prophylaxis. Oestrogen supplements Several trials have confirmed the efficacy of transcutaneous oestradiol for menstrual migraine prophylaxis The effective dose is 100µg oestradiol patches or 1.5mg oestradiol gel, which produce serum oestradiol levels of 75pg per ml. Oestradiol supplements are well tolerated although there may be an increase in the migraine immediately following treatment. 34,40 Although there are no trial data, clinical practice suggests that for these women, the duration of supplement use can be extended until day 7 of the cycle, tapering the dose over the last two days. Menstrual irregularity can occur, probably due to suppression of endogenous oestrogen during treatment. 34 Perimenstrual oestrogen can be used only when menstruation is regular and predictable. If the woman has an intact uterus, no additional progestogens are necessary, provided that she is ovulating regularly. If indicated, ovulation can be confirmed by using a home-use fertility monitor, which has the advantage of predicting menstruation. 41 There is no evidence that supplements increase the risks of cancer or thrombosis in women who are producing endogenous oestrogen. 42 However, supplemental oestrogens are not recommended for women who have oestrogen-dependent tumours or other oestrogen-dependent conditions, including a history of venous thromboembolism. Triptans Triptans are licensed for symptomatic treatment of migraine but several trials have assessed their use to prevent menstrual attacks of migraine. They are not Progress in Neurology and Psychiatry 13

4 currently licensed for perimenstrual prophylaxis. Trials of frovatriptan, naratriptan, sumatriptan and zolmitriptan for perimenstrual prophylaxis show efficacy The most extensive data are available for naratriptan and frovatriptan. The regimen for naratriptan is 1mg twice daily, starting two days before menstruation, continuing for six days in total. Frovatriptan is taken as a loading dose of 5mg twice daily, starting two days before an expected menstrual migraine followed by 2.5mg twice daily for a further five days. Rebound migraine following treatment with naratriptan, but not with frovatriptan, has been noted. 44,47 There are no data reported on rebound following treatment with sumatriptan or zolmi triptan. NSAIDs NSAIDs are effective for prophylaxis of menstrual migraine and have the advantage of treating associated dysmenorrhoea. 52 Naproxen 550mg once or twice daily perimenstrually between days -7 and +6 has shown efficacy with good tolerability. 53 Mefenamic acid 500mg, three to four times daily, may be started two or three days before the expected onset of menstruation and continued through the heaviest days of bleeding. It can be effective even when started on the first day of bleeding, which is useful if periods are irregular. Gonadotrophin-releasing hormone (GnRH) analogues Although effective, adverse effects of oestrogen deficiency, eg hot flushes, restrict their use. 54 The hormones are also associated with a marked reduction in bone density and should not usually be used for longer than six months without regular monitoring and bone densitometry. Add-back continuous combined oestrogen and progestogen can be given to counter these concerns. 55,56 Given these limitations, in addition to increased cost, such treatment should be instigated only in specialist departments. Surgical options Oophorectomy is not recommended as a treatment for menstrual migraine. Migraine is more likely to deteriorate after surgical menopause with bilateral oophorectomy. 57 If other medical problems require surgical menopause, the effects on migraine may be lessened with oestrogen replacement therapy. 58 Conclusion Many women with migraine report an association between migraine and their menstrual periods. This relationship can be confirmed with diary cards, which should be kept for a minimum of three menstrual cycles. Effective symptomatic treatment is the mainstay of management. A variety of prophylactic options are available for women who need contraception or for whom symptomatic treatment alone is not effective. Further information The City of London Migraine Clinic is a research centre and outpatient service for people with migraine and other headaches. It is a registered charity and social enterprise that is independent from the NHS. Anyone can access the service: there is no fee but a donation of 100 towards the cost of the appointment is suggested. Contact: The City of London Migraine Clinic 22 Charterhouse Square, London EC1M 6DX. Tel (09:00-17:00, Monday to Friday). Declaration of interests Professor MacGregor has acted as a paid consultant to and/or her department has received research funding from Addex, Allergan, AstraZeneca, BTG, Endo Pharmaceuticals, GlaxoSmithKline, Menarini, Merck, Pozen and Unipath. Professor MacGregor is Director of Clinical Research, The City of London Migraine Clinic, London; Associate Specialist, Bart s Sexual Health Centre, St Bartholomew s Hospital, London; and Honorary Professor, Centre for Neuroscience and Trauma, Blizard Institute of Cell and Molecular Science, Barts and the London School of Medicine and Dentistry, London References 1. Steiner TJ, Scher AI, Stewart WF, et al. The prevalence and disability burden of adult migraine in England and their relationships to age, gender and ethnicity. Cephalalgia 2003;23(7): Lipton RB, Dodick D, Sadovsky R, et al. A self-administered screener for migraine in primary care: The ID Migraine validation study. Neurology 2003;61(3): Granella F, Sances G, Pucci E, et al. Migraine with aura and reproductive life events: a case control study. Cephalalgia 2000;20(8): Wober C, Brannath W, Schmidt K, et al. Prospective analysis of factors related to migraine attacks: the PAMINA study. 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