Perimenopause marks a period of increased prevalence of migraine in women and many of them also report problematic vasomotor symptoms. Migraine is affected by fluctuating estrogen levels with evidence supporting estrogen ’withdrawal’ as a trigger for menstrual migraine attacks without aura, while high estrogen levels can trigger migraine aura.
Unlike contraceptive doses of ethinyl estradiol, migraine aura does not contraindicate the use of physiological doses of natural estrogen. In women with migraine with or without aura, using only the lowest doses of transdermal estrogen necessary to control vasomotor symptoms minimizes the risk of unwanted side effects.
Cyclic progestins may have an adverse effect on migraine, so continuous progestins, provided by the levonorgestrel intrauterine system or in continuous combined transdermal preparation, are preferred.
There are no data on the effect of micronized progesterone on migraine, whether cyclical or continuous. Non-hormonal options for both conditions are limited, but there is evidence of the effectiveness of escitalopram and venlafaxine.
Although migraine affects both sexes, it is predominantly a female disorder, with a lifetime cumulative incidence of 43% in women and 18% in men. These sex differences are generally attributed to the differential effects of male and female sex hormones on migraine pathophysiology.
In particular, the prevalence of migraine is very similar in children, but after puberty the prevalence increases more in women than in men, reaching a three-fold difference in the prevalence proportion during the fourth decade.
- Migraine without aura is the most prevalent type of migraine whose main symptoms are headache associated with nausea and/or vomiting, photophobia and phonophobia, requiring bed rest.
- Migraine with aura, in which the headache is preceded by transient and completely reversible neurological symptoms, is less common, affecting one in four people with migraine.
- Migraine without headache affects only one in every hundred people with migraine.
Migraine types are not mutually exclusive and the prevalence of each type changes with age; Migraine aura attacks without headache are more common in adulthood after a previous history of migraine with or without aura.
| ? A simple screening for migraine with aura. |
1. Does the patient have visual disturbances that begin before the headache?
2. Do they last up to an hour?
3. Do they resolve before the headache?
If the answer to all three questions is "YES", you are likely to be diagnosed with migraine with aura.
| Effects of hormonal changes on migraine |
Throughout the reproductive years, menstruation is one of the most important risk factors for migraine without aura with the highest incidence of attacks during the five days of the cycle, beginning two days before menstruation and during the first three days of bleeding.
Research suggests that one of the triggers of menstrual migraine is the natural drop or ’withdrawal’ of estrogen in the late luteal phase of the menstrual cycle.
Estrogen ’ withdrawal ’ also explains the higher incidence of headache and migraine during the hormone-free interval of combined hormonal contraception. Migraine with aura has a different hormonal response, with high estrogen states such as pregnancy, combined hormonal contraception or hormone replacement therapy (HRT), associated with a higher incidence of migraine with aura.
During perimenopause , migraine attacks without aura often become more frequent and severe, in part because menstrual periods are more frequent. Therefore, maintaining a stable hormonal milieu should be associated with fewer migraine attacks.
Consequently, several studies have used perimenstrual estrogen supplementation in women with regular periods in order to maintain midluteal levels until follicular estrogen surge, successfully preventing menstrual migraine. Continuous combined hormonal contraception or progestin-only contraceptives, desogestrel, are an option.
| Alternatives to HRT in women with migraine |
For women in whom estrogen is contraindicated, there is some evidence supporting the efficacy of escitalopram and venlafaxine for the control of vasomotor symptoms and for migraine prophylaxis. As with hormone therapy, an initial migraine exacerbation may occur in the first few weeks of treatment; Therefore, it is important not to stop treatment too soon.
Clonidine (50-75 micrograms twice daily) is approved for menopausal hot flashes and migraine prophylaxis. However, trial data supporting its effectiveness as a migraine prophylactic is limited.
Practice Points
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Perimenopause is a time of peak prevalence of migraine, particularly perimenstrual attacks of migraine without aura.
Perimenopausal women should be routinely asked about headache and migraine so that appropriate counseling can be offered. However, there is a paucity of research on the treatment of migraine in perimenopausal women.
From the limited data available, a stable estrogen environment may benefit migraine, either with appropriate contraceptive hormones to suppress endogenous ovarian activity or with estrogen replacement therapy to maintain constant levels. Non-oral routes of administration, which use the lowest effective dose necessary to control vasomotor symptoms, are associated with the most favorable outcomes.
For women with an intact uterus, transdermal estrogen along with the levonorgestrel intrauterine system is appropriate during perimenopause and postmenopause, while continuous combined transdermal HRT is an additional option in postmenopause.
The presence of migraine aura contraindicates the use of contraceptive synthetic estrogens, which are themselves an independent risk factor for ischemic stroke, but does not contraindicate the use of physiological doses of transdermal estrogens.
There are data supporting the use of escitalopram SSRI or venlafaxine SNRI for both migraine prophylaxis and treatment of vasomotor symptoms if estrogens are contraindicated.
