ReviewEstrogen replacement and migraine
Introduction
Migraine is prevalent episodic headache disorder affecting otherwise healthy individuals. It is an important target for public health interventions as it is highly prevalent and disabling. The World Health Organization (WHO), recognizes migraine as 19th among all causes of years lived with disability (YLDs), 12th in women [1]. Headache disorders impose recognizable burden on sufferers including sometimes substantial individual suffering, impaired quality of life and financial cost [2]. Four of every 10 women and two of every 10 men will contract migraine in their lifetime. This sex difference is recognized to be the result of the additional hormonal triggers affecting women. The median age at onset is 25 years but prevalence does not peak until middle life [3].
Of the two main types of migraine seen in clinical practice, migraine without aura is most prevalent, particularly in women [4]. In migraine without aura, typical symptoms are of episodic disabling attacks of headache associated with nausea and photophobia, which last between part of a day and three days. Migraine with aura is characterized by specific neurological symptoms that gradually develop over 5–20 min, last under 1 h, and usually completely resolve before the onset of headache [5]. Homonymous visual symptoms are most common, experienced in 99% of auras [6].
Both menopause and hormone replacement therapy (HT) can have significant effects on migraine. Given the high prevalence of migraine, it is important for all healthcare professionals to understand the association between migraine and estrogen in order to develop effective management strategies for their patients.
Section snippets
Role of estrogen in migraine pathophysiology
Around 50% of women report an association between migraine and menstruation during the reproductive years [7], [8], [9], [10]. Evidence supports estrogen ‘withdrawal’ in the late luteal phase of the menstrual cycle as one of the important triggers of menstrual migraine, which are typically attacks of migraine without aura [11], [12], [13]. Somerville found that migraine could be postponed by maintaining high plasma estradiol levels with an intramuscular injection of long-acting estradiol
Effect of the perimenopause on migraine
Few studies have specifically addressed how migraine changes through the perimenopause, but they support the clinical impression that migraine without aura deteriorates with time since menopause being a significant factor in improvement [25], [26].
A study of 1436 women showed a migraine prevalence of 10.5% in spontaneous menopausal women compared with 16.7% in premenopausal and perimenopausal women (OR 0.6, 95%CI 0.4–0.9, p = 0.03) [27]. This improvement is generally attributed to the absence of
Effect of estrogen replacement on migraine
There are few data on the association between headache and current use of hormone replacement therapy (HT), particularly with respect to the effect of specific doses of HT on migraine. Of 120 women attending a headache clinic, 64.1% of responders reported improvement or complete remission of headache associated with HT use, 22.5% reported no change, and 13.3% reporting worsening headache.[31] In contrast, a cross-sectional questionnaire of 6007 postmenopausal women showed a significant
Estrogen replacement and migraine aura
In contrast to the effects of menopause on migraine without aura, prevalence of migraine with aura does not improve with menopause [26].
Limited evidence from the Women's Health Study suggests that the association between migraine with aura and ischemic stroke is not statistically significantly modified by use of postmenopausal HT [40].
However, at an individual level, estrogen replacement therapy can have an adverse effect on migraine aura. Of ten women seen in an ophthalmology clinic who were
Migraine aura and ischemic stroke
All the recent studies suggest that women with migraine without aura are not at increased risk of ischemic stroke [40], [44], [45], [46]. In contrast there is a body of evidence of support an association between ischemic stroke and migraine with aura [40], [44], [47], [48], [49], [50], [51], [52], [53], [54], [55]. Hence there is potential concern regarding the effect that HT might have on risk of stroke in this group of women. Although estrogen has favourable long-term effects on
Practical guidance on estrogen replacement in women with migraine
Treatment of menopausal symptoms in women with migraine should differ from standard recommendations, including use of HT. For women with migraine, low-dose non-oral preparations of estradiol should be recommended as first choice. Migraine aura is not a contraindication to use of non-oral HT on the basis that physiologic doses of natural estrogens are used. This is in contrast to high doses of synthetic contraceptive estrogens necessary to inhibit ovulation. New onset headache should be
Conclusion
Migraine is a common disorder, particularly prevalent in women. Perimenstrual estrogen ‘withdrawal’ is a recognized trigger for migraine without aura. During the perimenopause, unpredictable fluctuating estrogen is associated with deterioration in migraine without aura, which typically improves postmenopause.
Migraine with aura is a recognized marker of increased risk of ischemic stroke. Estrogen replacement therapy should not be contraindicated for women with migraine, with or without aura.
Conflict of interest statement
Dr. MacGregor has no relevant conflicts of interest to declare.
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