Leah Palmquist migraine

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Leah Palmquist

Migraine Review Paper

Dr. Strand

27 April 2009

       Migraine is an episodic headache disorder which affects otherwise healthy individuals.

This prevalent disorder has been deemed by the World Health Organization as 19th among all

causes of years lived with disability, 12th in women. Thus, a great deal of research has been

conducted on migraine triggers and forms of treatment for migraines. Migraine headaches can be

divided into two categories based on the aura associated with one type. Migraines without aura

are the most common, and include episodic disabling attacks of headache associated with nausea

and photophobia. These symptoms can last anywhere between a couple of hours to about three

days. The other category of migraine, migraine with aura, can be recognized by different

symptoms over a shorter time range. Specific neurological symptoms gradually develop over 5-

20 minutes, last under an hour and almost always discontinue with the onset of the headache

itself. Homonymous visual symptoms are the most common symptom of migraine with aura and

are experienced in 99% of migraine cases (MacGregor, 2009).

       The symptoms of migraine without aura can be very severe and can also include nausea,

numbness and tingling sensation in various parts of the body (especially the face). Migraine is

often debilitating, uncomfortable and therefore life altering. Since this is such a widespread,

devitalizing condition, the National Headache Foundation (NHF) published a list of some of the

most common migraine triggers. They suggest foods high in tyramine, an organic compound

occurring naturally in plants and animals, may trigger migraines. Unfortunately, tyramine is

widespread in foods such as ripened cheeses, sourdough bread, lima beans, processed meats such
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as salami and pepperoni, etc. Alcohol is another migraine trigger. For some, the vasodilating

effects and consequently a drop in blood pressure cause the headache. A combination of the

dehydrating effect of alcohol and the resulting imbalance of electrolytes can also contribute to

migraine onset. The NHF has mixed reviews about caffeine’s effect on migraines. Avid caffeine

users can trigger a migraine by not consuming caffeine. On the other hand, the vasoconstricting

affect of caffeine can actually help relieve headache pain.

       The American Headache Society (AHS) suggests an entirely new set of migraine triggers.

In a recent survey of 200 patients with successive migraines, more than 90% identified one or

more migraine triggers. Among these triggers were physical and emotional stress (77%), menses

(72% of actively cycling females), exposure to bright or flickering light (65%), and various odors

(61%). The AHS also suggests a change in one’s usual sleep pattern or weather changes may

also cause migraine onset. One trigger may cause a migraine for one victim, while having no

effect on the next. Likewise, migraine onset may not always occur in conjunction with the

trigger, or one or more triggers may be needed to induce a migraine. Migraine triggers are

various, circumstantial and also vary from individual to individual.

       It seems as though migraine symptoms are difficult to control since triggers are so

various. However, one major migraine trigger is incredibly predictable—menses. “Around 50%

of women report an association between migraine and menstruation during the reproductive

years” (MacGregor, 2009). This is not surprising, since four out of every ten women, and only

two out of every ten men experience migraines. Ovarian hormones elicit varying effects on

neurons which may explain association with migraine. “Estrogen withdrawl, prostaglandin

release, and magnesium deficiency during the late luteal and early follicular phases of the

menstrual cycle all may contribute to the risk of migraine” (Newman, 2007).
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       To further understand the role of menses in migraine onset, a study was conducted to

compare the characteristics between menstrually related and nonmenstrually related migraines.

The researchers describe women with menstrually related migraines (MRMs) as occurring in at

least two out of three menstrual cycles. An MRM is defined as occurring in the 5-day period

from 2 days before to 2 days after the first day of menstrual flow. A nonMRM is defined as

occurring from the eighth day of the menstrual cycle to 3 days before the onset of menstrual

bleeding with the next cycle. Out of 64 women who referred to a specialty headache center, those

with MRMs experienced significantly greater pain intensity than those with nonMRMs. Another

survey of 21 women who kept daily headache diaries reported greater pain intensity in the

menstruation interval from the first to sixth day of menstruation. This demonstrates that women

are more likely to have severe MRMs on the first day of menstruation and during the following

two days. (Diamond et al, 2008). This sudden increase in pain intensity suggests a correlation

with the sudden change in estrogen levels that occurs with the first days of menstruation.

       To test this correlation, another study was performed primarily to determine if the

symptoms of migraine differ between different intervals of the menstrual cycle. Their second

objective was to determine if differing hormone levels correlated with the severity of migraine

symptoms during these stages of the menstrual cycle. They hoped to distinguish “hormonally

defined” intervals throughout the menstrual cycle. By dividing the menstrual cycle into intervals,

they were able to compare hormone levels in each interval. The two ovarian hormones of interest

were estrogen and progesterone. They hypothesized that “the frequency, severity, and disability

of headache would differ in female migraineurs between hormonally defined intervals of the

menstrual cycle and that headache outcome measures would be greatest during perimenstrual

time intervals” (Martin et al, 2005).
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       To test this hypothesis, 21 women age 21 to 45 years of age were asked to document their

migraine headaches in a diary during three menstrual cycles. Ovarian hormone levels were

obtained through measuring estrogen and progesterone metabolites in the urine. Thus, daily urine

samples were collected and assessed during the three menstrual cycles. The research group was,

in fact, able to define menstrual intervals based on differing levels of progesterone and estrogen

and was therefore able to compare this to the diaries of the participants. They were able to

conclude that both headache symptoms and levels of ovarian hormones varied among the

different menstrual intervals. They could not confidently conclude, however, that the differing

ovarian hormone levels directly caused the varying migraine symptoms. They explain their study

“suggested that progesterone metabolites play a role in the modulation of migraine headache

during luteal intervals of the menstrual cycle” (Martin et al, 2005). Since more direct correlations

and mechanisms are yet to be discovered, they admit “future studies are needed to define the

precise mechanisms through which ovarian hormones modulate and trigger migraine headaches”

(Martin et al, 2005).

       Another conclusion was made in this experiment. The two abovementioned studies were

not related or conducted in conjunction. Though different groups of females were asked to

document their menstrual cycles, their results are similar. In this study they found “the first six

days of the menstrual cycle represented a time period during which headaches were more

frequent, disabling, and severe in the patient population” (Martin et al, 2005). It is important to

note that both groups of women reported a greater intensity of migraine symptoms during the

beginning of the menstrual cycle.

       It seems abnormal that the human body has an adverse reaction to such a normal

physiological process. Severe and debilitating symptoms are arising in otherwise perfectly
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healthy women simply due to their menstruation cycle. A group of researchers at the Roby

Institute in Austin, Texas hypothesized there is a “connection between symptoms associated with

hormone changes to a hormone antibody response” (Roby et al, 2006). This hormone antibody

response was thought to induce allergy, thus resulting in adverse symptoms. Since menstruation

is an obvious time of hormone fluctuation, 270 patients who experience changes in symptoms

during menstruation were examined. The symptoms of interest were not only those associated

with migraine, but joint pain and asthma as well.

       As in the previously mentioned studies, the ovarian hormones of interest were

progesterone and estrogen. The participants were divided into two groups—symptomatic and

asymptomatic. Blood levels of IgG, IgM and IgE antibodies to progesterone and IgE antibodies

to both progesterone and estrogen were measured in both groups. Their hypothesis was

supported by evidence of increased blood levels of antibodies during menstruation in the

symptomatic group. The asymptomatic group was not without these antibodies of interest,

however their blood levels of IgG, IgM and IgE were significantly lower than the symptomatic

group. Therefore, they were able to conclude there was, in fact, evidence of antibodies to

estrogen and progesterone. They suggest “progesterone, estrogen and their metabolites, after

binding to human tissue proteins, such as albumin or globulin, may act as antigens and promote

Type 2 helper cell development, thereby regulating antibody synthesis and allergy”(Roby et al,

2006). This resulting allergy is thought to be the cause of symptoms relating to hormone

fluctuation during the menstrual cycle—joint pain, asthma and MRM. If this is the case, health

care professionals may be able to provide relief to suffering patients through “determining the

presence of hormone allergy and (using) hormones as antigens to diminish symptoms by

desensitization” (Roby et al, 2006).
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       There are many hypotheses regarding the etiology of MRM. The symptoms associated

with MRM, however, are not only obvious but life altering. So, whatever the cause of these

unfortunate occurrences, finding a cure is crucial for migraine sufferers. Using hormones as

antigens may be one way to help treat MRM. As shown earlier, however, migraine symptoms

and triggers vary greatly among individuals. Fluctuating hormone levels during menstruation

may elicit a completely different set of symptoms for two individuals. This makes treating

MRMs and their symptoms a difficult task. NSAIDs such as aspirin and ibuprofen and

acetaminophen are often used to treat migraine symptoms. A problem arises, however, when

desensitization occurs due to regular use and an unhealthy dosage is needed to relieve migraine

symptoms. These drugs also do not treat all symptoms relating to migraine. Photophobia may or

may not be alleviated and nausea may actually be worsened by NSAIDs.

       Currently, a heavily marketed drug for acute migraine relief with or without aura is

IMITREX ( sumatriptan succinate). The primary mechanism of action of IMITREX is

vasoconstriction. According to the FDA, this is effective in relieving migraine pain due to

vasoconstriction in the basilar artery. Certain animal trials have shown IMITREX binds to 5-HT1

receptors which is thought to diminish certain migranous symptoms such as photophobia.

IMITREX has provided migraine relief for some patients, however has provided little to no relief

for others. Some patients actually reported adverse side effects; paresthesia and warm and cold

sensations being the most common. These side effects occurred in less than 10% of IMITREX

users (FDA, 2000).

       Many drugs used for migraine symptom treatment are either specific to one symptom,

ineffective for some patients, or elicit undesirable side effects. These undesirable qualities of

synthetic drugs make a study on the effect of vitamin E on MRM especially interesting. The
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purpose of the study was to determine “the effect of vitamin E as a prophylactic agent on women

with menstrual migraine” (Ziaei, 2009). 165 women age 20-30 with at least a six month history

of menstrually related migraine participated in this double-blind placebo-controlled trial. In the

past three months, they had not undergone any preventative strategies for migraine relief. The

women were divided into two groups—one group receiving a placebo and the other receiving a

vitamin E supplement. Both agents were in the form of a pill and similar in appearance. The

participants were evaluated by a neurologist and were asked to rate the severity of the following

symptoms: headache, photophobia, phonophobia, nausea and functional disability. Only the

women who had a MRM according to the criteria of he International Headache Society (an

attack of migraine without aura occurring on day 1 of menstruation (day-2 to day + 3) in two of

three menstrual cycles) were identified as having a MRM.

       The results showed “statistically significant reductions in pain severity, functional

disability and ibuprofen consumption dose in both treatment methods, but the magnitude of the

reduction was significantly greater in the vitamin E treatment group than in the placebo group”

(Ziaei, 2009). Though the placebo group was receiving only a placebo, they still experienced a

decrease in these migraine symptoms. However, “vitamin E was superior to placebo regarding

photophobia, phonophobia, and nausea in women with menstrual migraines” (Ziaei, 2009).

These results are exciting to health care providers and migraine sufferers. If relief from

menstrual migraine could be obtained from a vitamin E supplement, this could provide a

relatively inexpensive, simple treatment method. Also, no negative side effects due to the

vitamin E supplement were discussed in this study. This is not surprising since vitamin E is

present in many common foods and therefore is not a foreign substance to the body. A substance

not found in the diet—NSAIDs are briefly discussed in this paper and compared to vitamin E
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with regards to menstrual migraine relief. They explain that NSAIDs reduce headache

temporarily, but “many patients experience an increase in headaches when the short-term

preventative treatment is stopped. However, the patients did not experience breakthrough

headache when five days of vitamin E was stopped” (Ziaei, 2009). This information provides

another potential benefit of using vitamin E for menstrual migraine relief over commonly used

synthetic drugs.

       Migraines are experienced by a very significant amount of people. This potentially

debilitating condition can be life altering and unpredictable. MRMs allow us to more accurately

predict when a migraine is going to occur, and to explore the physiological changes that occur

during the migraine. Numerous hypotheses exist regarding which specific physiological changes

associated with menstruation trigger a menstrual migraine. Since various symptoms are

associated with menstrual migraine, it is difficult to pinpoint which alteration is causing which

symptom. It would be helpful to isolate menstrual migraine patients who experience one

predominant symptom and monitor bodily changes during an attack. This could lead us to

information regarding treatment of the migraine itself, instead of solely the symptoms. It could

potentially lead us to information about not only menstrual migraines, but nonmenstrually related

migraines as well. This is an important condition that debilitates many people; more research

needs to be done on the root of the problem and how to treat it.
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8 things you need to know about nutrition & your aching head.(2008). Tufts University Health &

    Nutrition Letter, 26(4), 6-6.

Diamond, M. L., Cady, R. K., Mao, L., Biondi, D. M., Finlayson, G., Greenberg, S. J., et al.

    (2008). Characteristics of migraine attacks and responses to almotriptan treatment: A

    comparison of menstrually related and nonmenstrually related migraines. Headache, 48(2),


Diamond, M., & Cady, R. (2005). Initiating and optimizing acute therapy for migraine: The role

    of patient-centered stratified care. American Journal of Medicine Supplement,

    118(Supplement 1), 18-27.

Food and Drug Administration. (2000). IMITREX product information.

MacGregor, E. A. Estrogen replacement and migraine. Maturitas, In Press, Corrected Proof

Martin, V. T., Wernke, S., Mandell, K., Ramadan, N., Kao, L., Bean, J., et al. (2005). Defining

    the relationship between ovarian hormones and migraine headache. Headache, 45(9), 1190-


Newman, L. C. (2007). Understanding the causes and prevention of menstrual migraine: The role

    of estrogen. Headache, 47 Suppl 2, S86-94.

Roby, R. R., Richardson, R. H., & Vojdani, A. (2006). Hormone allergy. American Journal of

    Reproductive Immunology (New York, N.Y.: 1989), 55(4), 307-313.
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The truth about triggers.(2008). Headache: The Journal of Head & Face Pain, 48(3), 499-500.

Ziaei, S., Kazemnejad, A., & Sedighi, A. (2009). The effect of vitamin E on the treatment of

    menstrual migraine. Medical Science Monitor : International Medical Journal of

    Experimental and Clinical Research, 15(1), CR16-9.