Abstract
Of the 26 million adult Americans who suffer from migraine headaches, between 18 and 20 million of them are women. Approximately 60% of these women associate the migraines with their menstrual cycles. However, of that 60%, only 10% to 14% experience what is called "true menstrual migraine." The strict definition
of true menstrual migraine is a migraine that occurs within the time frame of 2 days before and 3 days after the onset of menses. Women with true menstrual migraine have the migraine only during that limited period of time and at no other times during the month. Menstrually associated migraine is a term that includes women who typically expereince a migraine of the greatest severity
around the time of their periods, but who also may have migraines at other times of the month.
"True menstrual migraine where women do not get migraines the rest of the month is relatively unusual," says Lawrence Robbins, MD, author of Management of Headache and Headache Medications, 2nd edition, (Springer-Verlag, 2000) and director of the Robbins Headache Clinic in Northbrook, IL. Excluding women whose migraines occur around the time of their menstrual periods but do not fall into the strict day minus 2 through day plus 3 time frame is "missing the boat," he says, "because clearly, hormonal
influences are involved." In this article, the less restrictive term, menstrually associated migraine, will be used; however, discussion of diagnoses, causes, and treatments will also apply to the true menstrual migraine.
Women of childbearing age comprise the majority of migraine sufferers (all types). Menstrually associated migraines are considered more severe and disabling than other migraines and often less responsive to treatment. The JAMA Migraine
Information Center reports that untreated or poorly managed migraine is associated with morbidity and economic and social consequences that take a substantial toll on women at a time when many are trying to balance the demands of family and work.
Robbins reports that migraines in general, cost the United States a conservative estimate of $16 billion last year, mostly in lost work, and that menstrually associated migraines, in particular, are a major reason for missing work, lost mothering time, and broken relationships. "Many women have told me how
bad they feel for their kids who will remember the image of their mothers so often lying in a dark room in bed, holding their heads, or with an icepack, saying 'I can't do anything. I have a headache,'" says Robbins.
Triggers: Estrogen withdrawal is believed to be an important trigger of menstrually associated migraines. Early in the menstrual cycle, prior to the onset of menses, an elevation in estrogen levels occurs, only to be followed by a precipitous drop just before the period begins. Estrogen has vasodilatory
properties in both the coronary and cerebral vessels (possibley through nitric oxide production), and it also alters vascular responsiveness to various neurotransmitters such as serotonin and dopamine.
Prostaglandins are also thought to play a role because they activate CNS pain receptors and stimulate development of neurogenic inflammation. Prostaglandin levels fluctuate during the mesntrual cycle and may act independently or with estrogen to induce the migraine. Prostaglandin levels are at their highest at the time of menstruation.
Another mechanism that has been proposed in recent research involves dysfunctional opioid control in the hypothalamic-pituitary-adrenal axis. Robbins is of similar thinking in his belief that menstrually associated migraines are not a simple estrogen problem but are more likely attributable to activity in the hypothalamus.
As in the case of other kinds of migraines, there are nonhormonal triggers that must also be considered, some of which can be avoided by lifestyle changes. They include too much or too little sleep, consumption of migraine-triggering foods (eg, some alcohol, chocolate, foods containing tyramine, nitrates, or MSG), weather changes, and high stress.
"Routine is also extremely important in preventing migraines," says Christine Lay, MD, FRCPC, director of the Women's Comprehensive Headache Center at St. Luke's-Roosevelt Hospital Center in Manhattan. "Women can often reduce their migraine frequency by developing a routine that includes regular exercise, eating at regular intervals, and regular sleep hours."
Diagnosis: According to Lay, thorough history-taking is the key to accurate diagnosis of all types of headaches, including menstrually associated migraine. Required are pointed, directed questions that get to specifics of the headache and must include, but are not limited to:
- When it occurs
- Exact location of the pain
- Associated features
- Duration of the migraine
- What treatments have been tried
- How successful or unsuccessful have treatments been
- If there is a family history of migraine
"The neurological examination is normal in the majority of patients with primary or benign headache disorders, so one must rely on a thorough history to make the diagnosis," adds Lay. Extensive workups including brain scan, CT scan, MRI, or blood work are indicated only when the history is atypical or there is evidence of a neurologic deficit.
Medication Choices: Many of the therapies used to treat non-ormonally influenced migraine are also used to treat menstrually associated migraine. Treatments are classified as either abortive or prophylactic, but in some cases may be both. Many clinicians choose abortive therapy because it is generally
less expensive and doesn't pose as great a patient compliance problem as prophylactic therapy.
Some of the most effective and widely-used abortive treatments are the triptan
drugs: sumatriptan (Imitrex), rizatriptan (Maxalt), naratriptan (Amerge),
and zolmitriptan (Zomig). "The triptans are so effective because they were
specifically designed in the laboratory to combat the entire migraine complex,"
explains Lay. "They attack not only the pain, but other features associated
with migraine such as nausea, vomiting, photophobia, phonophobia, and
osmophobia."
Robbins regards Imitrex as the gold standard and the most effective abortive
treatment. It is available by injection, tablets, and nasal spray. Recent
research has shown that the sumatriptan injection and tablets are particularly
effective and well tolerated in the treatment of menstrually associated migraine.
The injectable form comes in a conveniently preloaded pen that is simply
placed on the skin and pressed. Maxalt is very similar to Imitrex but can
be taken in oral melt (MLT) form. It has a pleasant taste and can be taken
without water, which is an advantage.
Robbins describes Amerge as the "kinder, gentler, smoother" triptan, which
has been found to be every effective in treating menstrually associated migraine
and is used often as a prophylactic measure. Available in tablet form, it
can take as long as 2 hours to work, but it does have a long half-life, and
most patients will experience only minimal side effects. While it is
better-tolerated than the other triptans, it is somewhat less effective than
Imitrex. Zomig is also available in tablets and has a similar tolerability
and efficacy profile as other triptans. Lay finds Zomig to be quite useful
in the treatment of menstrually associated migraine.
In cases where patients do not tolerate one of the triptans, Robbins recommends
trying another that may be better tolerated in another version. Lay, too,
supports the use of the triptans as a first-line choice for abortive treatment,
but when they cannot be tolerated, her other first-line choice is nonsteroidal
anti-inflammatories (NSAIDs), specifically Anaprox, meclophenamate, and
flurbiprofen, to name a few. NSAIDs work well because they inhibit prostaglandin
production. Currently, they are being used as both abortive and preventive
treatments. NSAIDs are generally well tolerated, but GI upset is the msot
common side effect.
Also effective in the treatment of menstrually associated migraine are ergotamine
derivatives such as dihydroergotamine (DHE) and ergotamine tartrate/caffeine
tablets (Cafergot). DHE is administered in a nasal spray called Migranal
or by IV, IM, or SQ injection. Many patients can be taught to self-administer
the DHE injection, usually under the skin, but it is clearly not as convenient
as the newer pre-loaded injectables for migraine. Robbins uses Migranal nasal
spray as a first-line abortive treatment and the ergotamine derivatives in
general as preventative therapy for menstrually associated migraines.
Corticosteroids such as Cortisone, Decadron, and Prednisone are other therapeutic
options. Robbins includes them as second-line abortive treatment for migraine
and says that Cortisone is often the most effective treatment for severe,
prolonged migraine, which menstrually associated migraines often are. "There
are many people, not only women, for whom a small amount of Cortisone has
been the only thing that has helped their headaches," says Robbins. Small
doses are recommended to limit the side effects of nausea, anxiety, fatigue,
and insomnia. Robbins has found that most people who have experienced side
effects with Cortisone have been on it for 1 to 2 months or longer. Side
effects after 1 or 2 days of use are unusual but can occur.
Robbins also includes analgesics such as Fiorinal among the most widely used
migraine medications. They have provided relief for many women, some of whom
use them with the triptans.
Over-the-counter analgesics combining aspirin, caffeine, and acetaminophen,
such as Excedrin, have also proven effective in treating the pain of menstrually
associated migraine; however, Lay advises against their use with Fiorinal
or Fioricet.
According to Lay, common prophylactic agents include the triptans, especially
Imitrex and Amerge, NSAIDs, tricyclic antidepressants, the anticonvulsant
Depakote, beta-blockers, and calcium-channel blockers. In standard prophylaxis
for migraine, the patient takes the medication every day but with menstrually
associated migraine, the dosage is increased around the time of the expected
migraine. With true menstrual migraine, a short course of the preventative
drug is taken only around the usual time of the headache.
Robbins sees NSAIDs and Amerge as the most widely-used preventative medications,
and disagrees with the use of Depakote and beta-blockers for menstrually
associated migraines.
The decision of which migraine medications to prescribe is generally made
after considering the patient's comorbidities and age.
Obviously, some divergence of opinion exists on which agents are best. Triptans
and ergotamine derivatives should be used with caution in patients with coronary
disease, peripheral occlusive disorders or hepatic or renal impairment. Lay
also advised using the triptans with caution in menopausal women, as other
cardiac risk factors may have come into play. Robbins deemphasizes age as
a risk factor in triptan use, and sees cardiace history, hypertension that
is not well controlled, and high cholesterol as the greater risks.
Hormonal Approaches: Oral contraceptives (OCs) figure into the picture of
menstrually associated migraine in 2 ways: OCs are considered a hormonal
approach to treatment of menstrually associated migraine; plus, women using
OCs only as contraception may find that the OCs induce or exacerbate menstrually
associated migraines.
How a woman responds to oral contraceptives will depend on which OC is prescribed
and how much estrogen is in it, whether menstrually associated migraine was
present prior to taking the OC, and the kind of cycling being prescribed.
According to Lay, if a woman who has had menstrually associated migraine
takes an OC in the 21 day/placebo week cycle, she will invariably notice
that the migraine recurs during the pill-free week. Recently, some OB/GYNs
have been prescribing the OC pill for such women in a 3-month consecutive
cycle without the placebo week.
Another case scenario is the woman with a very irregular menstrual cycle
who is prescribed OCs and finds that it regulates her hormonal levels and
improves her migraines. At least one major study of the effect of OCs on
migraine has shown that some women experience improvement in their migraine
patterns, other see their migraines worsen, and still others see no change
at all. It is difficult to generalize about the effect of oral contraceptives
on menstrually associated migraine until there is more conclusive research.
Hormonal replacement therapy (HRT) is considered the end-of-the-line treatment
for refractory menstrually associated migraine. Many clinicians wish to avoid
manipulation of hormonal levels in this way, if possible, and will exhaust
all other options first. "There are problems associated with its use, and
it often does not work well," says Robbins. However, HRT is used at times
and, according to Lay, mostly in perimenopausal, menopausal, and postmenopausal
women. It is prescribed in the form of a transdermal estrogen patch, an estrogen
gel, or estrogen tablets with or without progesterone. Gaining popularity
are combined patches and combined pills that contain both estrogen and
progesterone.
Alternative Therapy: Menstrually associated migraine is often less responsive
to treatment than other kinds of migraine. Some women have found no relief
at all in any kind of conventional therapies. Others simply cannot tolerate
any type of conventional medications. For these reasons, many are seeking
treatments from alternative medicine or integrative medicine, an emerging
field that combines conventional Western medicine with alternative practices.
David Edelberg, MD, is chief medical consultant for WholeHealthMD.com and
founder of American Whole Health, Inc., which provides integrative medicine
at healthcare centers of excellence in select cities as well as a network
of alternative medicine practitioners.
Edelberg views treatment of the menstrually associated migraine within the
context of the entire premenstrual syndrome (PMS), which conventional
practitioners often regard as a separate issue. He characterized alternative
and integrative approaches as targeting underlying causes rather than simply
suppressing symptoms. Edelberg's typical treatment approach focuses on diet
and herbs. He begins by cleaning up the diet -- eliminating junk food, reducing
saturated fats, and making sure a woman eats healthful foods on a regular
basis.
According to Edelberg, substantial research has been conducted in Europe
on the efficacy of herbal treatments for PMS. Herbs act in subtle ways on
the pituitary gland, helping it to regulate the levels of estrogen and
progesterone. For PMS, Edelberg commonly uses the herb chasteberry, also
known as Vitex, the Chinese herb dong quai, and black cohosh. Other treatments
include the use of vitamin B6 and magnesium. he also favors feverfew, an
herb that has recently become popular for migraine prophylaxis.
Both Robbins and Lay have used alternative treatments for menstrually associated
migraine but with some reservations.
"In general, menstrually associated migraines are too severe for most herbs
and vitamins," says Robbins, "but we do use alternative treatments for women
who simply do not want to take medication or those who are too sensitive
and cannot tolerate them." Robbins notes that there is insufficient research
on the efficacy of herb and vitamin therapies, but that feverfew, B2, and
magnesium are the 3 that have performed well in at least a few well-controlled
studies.
"Alternative therapies can be very helpful," says Lay. "It really depends
upon the individual. Some women are very open to it and probably have a better
chance of success going in." Just because they can be purchased over the
counter, though, does not mean that treatments like herbs and vitamins are
totally benign. Like conventional medications, alternative therapies that
are used improperly can also exacerbate or complicate a medical condition.
For this reason, Lay strongly advises that alternative treatments only be
taken under the guidance of a physician, or at the very least, someone who
is well versed in alternative medicine.
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