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Menstrually Associated Migraine
Marianne Mallon
Posted May 2000
Staff Writer at PA Today

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.