Women suffer migraines three times more frequently than men do, and menstrual migraines affect 60 percent of these women. Such a headache has rather significant impact on a woman's life, so plenty of researches were made to find the effective relief for this kind of migraine.

Menstrual migraines (or PMS headaches) are migraines that occur before, during or immediately after the period, or during ovulation. While this is not the only reason, serotonin is the primary hormonal trigger in everyone's headache. For women it is also the serotonin interacts with female hormones.

Menstrual migraines are primarily caused by female hormone – estrogen, which specifically regulates the menstrual cycle fluctuations throughout the cycle. Any time the levels of estrogen fall (it happens in the late phase of the menstrual cycle, just before the onset of the period) a women will be more vulnerable to headaches, especially the one who is predisposed to migraine. This is the reason, why women on birth control pills experience more menstrual migraines, as oral contraceptives influence estrogen levels a lot. However, this is not the only factor involved in menstrual-associated migraine.The density and sensitivity of receptors in the central nervous system that respond to opiate drugs (such as morphine, codeine) also changes throughout the menstrual cycle.

What is this migraine feels like?

Menstrual migraine is different from nonmenstrual one. It has the symptoms that are similar to migraine without aura: begins as a one-sided, throbbing headache. Menstrual migraine is often accompanied by nausea, vomiting, and sensitivity to bright lights and loud sounds. Some may even experience an increase in appetite and a craving for chocolate, salt, or alcohol.

It may affect a woman each month between the 2nd day before the start of the menstrual period and the end of it. In most cases it occurs during the first 3 days of the cycle and compared with other times it is more than three times as likely to be severe. But it actually, may occur in other time as much frequent, but the menstrual cramping and fatigue during woman’s periods reduce the tolerance of headache and she doesn’t pay any attention to other shorter, milder headaches that occur at other times.

In some cases treatment for the condition can be very successful, in some – more like a disaster. It depends on the patient and, what is more important, onan accurate diagnosis. Treatment inculdes non-hormonal, hormonal, and preventive methods. Most sufferers of menstrual migraine are treated with acute medications. In case attacks happen very frequent, are severe, or disabling, preventive treatment may be required.

Among acute treatment, the following medications have proved its effectiveness:

• nonsteroidal anti-inflammatory drugs (NSAIDs),
• dihydroergotamine (DHE),
• the triptans,
• and the combination of aspirin, acetaminophen, and caffeine (AAC).

In case severe attacks cannot be controlled with these medications analgesics, corticosteroids, or dihydroergotamine may help.

Women with very frequent and severe attacks can get rid from menstrual headaches only through preventive therapy. The only way for them is to try to prevent the migraine rather than to treat. For sufferers taking preventive method as a treatment the following medications (short-term prophylaxis) taken perimenstrually can be effective:  

• naproxen sodium (or another NSAID),
• a triptan, such as frovatriptan (or Frova) on the first day and then naratriptan,
• methylergonovine,
• DHE,
• and magnesium supplements.

The triptans, DHE, and ergotamine can be used at the time of periods without significant risk of developing dependence.  As with the NSAIDs, these drugs will also be more effective as preventive medications if started 24 to 48 hours before the onset of the expected menstrual migraine.

Hormonal therapy is used when standard preventive measures are unsuccessful. Among such medications are:

• a supplemental estrogen taken perimenstrually (taken by mouth or in a transdermal patch),
• estradiol (in estrogen form),
• one more method (especially if you are on birth control pills) is to take it daily - that is, without the monthly break - for 3 to 6 months (ore up to year, what is considered to be rather safe). In Europe this has become accepted as a standard practice.

Preventive method is rather effective in fighting the menstrually related migraines. Prophylactic treatment with a triptan is commonly used by many women all over the world and have been found to be effective in aborting menstrual migraines. The triptans act as agonists for 5-hydroxytryptamine (5-HT) receptors and include:

1. sumatriptan (Imitrex),
2. zolmitriptan (Zomig),
3. rizatriptan (Maxalt),
4. naratriptan (Amerge),
5. eletriptan (Relpax),
6. lmotriptan (Axert),
7. frovatriptan (Frova).

1. They reduce inflammation of certain blood vessels in the brain thought to cause pain.
2. They block the release of irritating chemicals in the nerve endings.
3. They prevent transmission of pain signals from the lining of the brain to the brain itself.

Triptans are taken for 6 days beginning 2 days before the anticipated start of the menstrual migraine. This structure reduces the incidence of migraine by at least a half. Triptans are especially effective in controlling the associated nausea and vomiting. However, some women respond to the triptans and others don't, so further study is needed to be made in order to understand why. It could be because of the age, the frequency of their attacks, or the duration of their attacks.

Frova^® (or  frovatriptan) was approved by the FDA in 2001 "for the acute treatment of Migraine attacks with or without aura in adults where a clear diagnosis of Migraine has been established", and Frova is the only triptan indicated in the US for the prevention of menstrual migraines. It is currently approved only in the United States for the acute or preventive treatment (where a clear diagnosis of migraine has been established).

In October 2002, positive study data were first presented from a study of more than 500 menstrual migraine sufferers in the U.S., suggesting that six days treatment per month with Frova® (according to the mentioned scheme) was effective in preventing migraine headaches triggered by menstruation. The data demonstrated statistically significant improvement in the numbers of patients who were headache-free during their menstrual cycles for both once and twice-daily dose regimens of Frova® compared to placebo (p ‹ 0.0001).

In December 2005 the higher dose of Frova® were investigated. Women were administered Frova® for six days each month. The study results indicated that Frova® was well-tolerated when used as a six-day dosing regimen for up to 12 menstrual periods as preventive therapy for menstrual migraines.

In May 2006, Vernalis announced positve data from a second Phase III study. Endo Pharmaceuticals (Vernalis partner) has released data from the second Phase III study of Frova^® (frovatriptan succinate) for the short-term (six days per month) prevention of menstrual migraine. The researches give positive results in two successful Phase III trials. Silberstein led a three-month study of the triptan known as Frova (frovatriptan), enrolling 545 women who had suffered from menstrual migraine headaches for an average of 12 years. For six days (starting two days before their period) women were given either placebo, a 2.5 milligram dose of Frova or a 5 milligram dose of the drug. The received result was that headaches disappeared in half of patients treated with the higher dose of Frova. More than that, headaches stopped in over a third of patients taking the lower dose of Frova (in comparison with those, taking placebo). As for the side effects, they were common with frovatriptan and with placebo (the frequency was also the same), and include nausea, dizziness, headache, and fatigue (there were no serious adverse effects in the researches). Study participants also reported a reduction in the use of rescue medication. According to Silberstein, triptans are a relatively new class of designer drugs that work directly to turn off migraines.

 In 2H 2007, Vernalis’ European partner, Menarini, plans to submit an application to extend the current indication to include prevention of menstrual migraine throughout Europe under the mutual recognition procedure with France.

Frova acts like all triptans. Among other actions it prevents transmission of pain signals from the lining of the brain to the brain itself. But for good lifelong result taking medications are not enough in menstrual migraines treatment. For better result along with medications you should monitor and identify aggravating factors of migraines, such as stress, foods (red wine or coffee, or just regular use of a diary), skipping medications, and sleep pattern changes. Avoiding these factors will also help in menstrual headaches treatment.Perhaps you may need to be careful about getting enough sleep, eating regular meals and avoiding alcohol prior to the start of menstruation if you know you are more vulnerable to headaches at this time. Good news, however, is that women with menstrualmigraine headaches now have choices.

Valentyna Ant.