Background

Although only women suffer from “hormone headache,” both men’s and women’s headaches are prompted by hormones.

You would not feel pain without them, because it is the hormones that induce the pain response. Actually, the headache may be protecting you or warning you of something more damaging in the same way that touching a hot stove alerts you to the heat and protects you from burning yourself.

The word hormone is derived from a Greek word that means to “set in motion.” Hormones initiate and regulate many of your body’s functions. For example, metabolic hormones regulate the way your body turns food into energy. Growth hormones control childhood development and maintain certain tissue structure in adults. Regulating hormones determine your femininity, masculinity and sexuality.

Hormones are manufactured and secreted by your endocrine glands, which include the pituitary, thyroid, parathyroid, thymus, adrenals, pancreas, gonads and other glandular tissues located in your intestines, kidneys, lungs, heart, and blood vessels. The endocrine system works with your nervous system to keep your body in balance within a constantly changing environment.

As they interact, your endocrine and nervous systems are responsible for the thousands of automatic responses that regulate your bodily functions. They decide, for example, whether you will respond to a potential headache trigger with an actual sensation of pain.

Menstrual Migraine

Women suffer migraines three times more frequently than men do; and, menstrual migraines affect 60 percent of these women. They occur before, during or immediately after the period, or during ovulation.

While it is not the only hormonal culprit, serotonin is the primary hormonal trigger in everyone’s headache. Some researchers believe that migraine is an inherited disorder that somehow affects the way serotonin is metabolized in the body. But, for women, it is also the way the serotonin interacts with uniquely female hormones.

Menstrual migraines are primarily caused by estrogen, the female sex hormone that specifically regulates the menstrual cycle fluctuations throughout the cycle. When the levels of estrogen and progesterone change, women will be more vulnerable to headaches. Because oral contraceptives influence estrogen levels, women on birth control pills may experience more menstrual migraines.

Symptoms

The menstrual migraine’s symptoms are similar to migraine without aura. It begins as a one-sided, throbbing headache accompanied by nausea, vomiting, or sensitivity to bright lights and sounds. An aura may precede the menstrual migraine.

Menstrual Syndrome (PMS) Headaches

The PMS headache occurs before your period and is associated with a variety of symptoms that distinguish it from the typical menstrual headache. The symptoms include headache pain accompanied by fatigue, acne, joint pain, decreased urination, constipation and lack of coordination. You may also experience an increase in appetite and a craving for chocolate, salt, or alcohol.

Treatment – Menstrually Related Migraine

As you review these, remember that all medications have side effects, and you should discuss them with your doctor.

In general, MRM can be effectively managed with strategies similar to those used for non-MRM. Behavioral management is an important concept in menstrual as well as nonmenstrual migraine. Menstruation is one of many factors that puts women at risk for migraine. Hormonal changes are just one of many potential trigger factors.

Most sufferers of menstrually related migraine are treated with acute medications. When attacks are very frequent, severe, or disabling, preventive treatment may be required.

Acute Treatment

Medications that have been proven effective or that are commonly used for the acute treatment of MRM include nonsteroidal anti-inflammatory drugs (NSAIDs), dihydroergotamine (DHE), the triptans, and the combination of aspirin, acetaminophen, and caffeine (AAC). If severe attacks cannot be controlled with these medications, consider treatment with analgesics, corticosteroids, or dihydroergotamine.

Preventive Treatment

Women with very frequent and severe attacks are candidates for preventive therapy. For sufferers taking preventive medications who experience migraine attacks that break through the preventive therapy perimenstrually, the dose can be raised prior to menstruation. For sufferers not taking preventive medication, or for those with true menstrual migraine, short-term prophylaxis taken perimenstrually can be effective. Agents that have been used effectively perimenstrually for short-term prophylaxis include: naproxen sodium (or another NSAID) 550 mg twice a day; a triptan, such as frovatriptan 2.5 mg twice on the first day and then 2.5 mg daily/ naratriptan 1 mg twice a day/ sumatriptan 25 mg twice a day/ or, methylergonovine 0.2 mg twice a day; DHE either via nasal spray or injection 1 mg twice a day; and magnesium, equivalent to 500 mg twice a day.

The triptans, ergotamine, and DHE can be used at the time of menses 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 MRM.

Fluoxetine, especially if the headache is associated with other premenstrual dysphoric disorder (PMDD) symptoms, can be an effective headache preventive between ovulation and menses.

Hormonal Therapy

If standard preventive measures are unsuccessful, hormonal therapy may be indicated. This may involve the use of a supplemental estrogen taken perimenstrually either by mouth or in a transdermal patch. Estradiol (0.5 mg tablet twice a day, or 1 mg patch) is the preferred form of estrogen because it does not convert to the other active forms of estrogen.

For women using traditional estrogen/progesterone oral contraceptives for 21 days per month, the supplemental estrogen may be started on the last day of the pill pack. Another approach for women who take an estrogen/progesterone oral contraceptive is to take it daily – that is, without the monthly break – for 3 to 6 months. This has become accepted as a standard practice, and in Europe this approach has been used for up to a year with safety. The reduction in menstrual periods provides a method of preventive treatment.

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Vincent T. Martin, MD

Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati Ohio

Two-thirds of premenopausal female migraine sufferers self-report that migraine attacks consistently occur during peri-menstrual time periods.  These headaches have been referred to as “menstrual migraine”.  Interestingly, only attacks of migraine without aura occur more frequently during peri-menstrual time periods. Attacks of menstrual migraine have been found to be more severe, disabling and refractory to abortive medications than those that are non-menstrually related.¹

Definition of Menstrual Migraine 

Menstrual migraine, as defined by the International Headache Society, has two subtypes.  Attacks of menstrually related migraine without aura must have an onset during the peri-menstrual time period (2 days before to 3 days after the onset of menstruation) and this pattern must be confirmed in 2/3 of menstrual cycles, but other attacks may occur at other times of the menstrual cycle.  Attacks of pure menstrual migraine without aura are similar to the above criteria except that migraine headaches are strictly limited to the peri-menstrual time period and do not occur at other times of the month.  The prevalence of menstrually related migraine without aura ranges from 35-51% of females with migraine while that of pure menstrual migraine without aura varies from 7-19%.

Pathophysiology 

The most plausible trigger for menstrual migraine is the decline in serum estradiol levels that occur shortly before and during the peri-menstrual time period.  Other factors may also contribute to its pathophysiology such as: 1) release of prostaglandins from a shedding endometrium that sensitizes peripheral nociceptors, 2) declines in serum magnesium levels and 3) decreases in inhibitory neurotransmitter systems (i.e.,serotonergic, GABAergic, etc.) that modulate neuronal firing rates within second order neurons of the trigeminal system.

Treatments 

Acute and preventative therapies may be utilized for the treatment of menstrual migraine.  Acute therapies are used to abort the migraine attack once it has begun while preventative therapies are employed to prevent the development of menstrual migraine altogether.  Preventative therapies can be subdivided into short- and long-term prophylactic therapies.³  Short-term prophylactic therapies are only given during the peri-menstrual time period.  They are initiated 1-2 days before the start of the anticipated menstrual migraine attack and continued for 4-7 days.  Continuous prophylactic therapies are given every day of the month and can be used to prevent both menstrually-related and menstrually non-related attacks.

Abortive Therapies 

Abortive therapies can be classified as migraine specific and migraine non-specific.  Migraine specific therapies (triptans and ergots) are only effective for migraine and cluster headaches while migraine non-specific therapies (NSAIDS, acetaminophen, narcotics, isometheptane- and butalbital-containing medications) are effective for both migraine and tension-type headaches.   Clinical studies have demonstrated that the triptans (eg. almotriptan, eletriptan, frovatripan, naratriptan, rizatriptan, sumatriptan, zolmitriptan) as well as an aspirin/acetaminophen/caffeine combination (Excedrin™) are effective for the abortive treatment of menstrual migraine.  Efficacy rates of these therapies for the treatment of menstrual migraine are similar to those observed for non-menstrually related attacks.

Short-term Prophylactic Therapies 

Short term prophylactic therapies include NSAIDS, triptans and estrogen transdermal patches/gel.  Naproxen sodium at a dosage of 550 mgs BID given 6 days before to 7 days after menses has demonstrated effectiveness in the prevention of menstrual migraine.  Three triptans (frovatriptan [2.5 QD or BID], naratriptan [1 mg BID] and zolmiptriptan (2.5 mgs BID and 2.5 mgs TID]) when administered for 4-5 days during the peri-menstrual time period are also effective preventative agents.  Estradiol patches and gels can also be employed, but the correct dosage of these medications must be used!  One hundred microgram transdermal estradiol patches were found to be more effective than 25 and 50 mcg patches in one study.

Continuous Prophylactic Therapies 

Continuous prophylactic therapies include hormonal and non-hormonal therapies.  Hormonal therapies include long duration oral contraceptives (OC) and gonadotropin releasing hormone agonists (GnRHa). Long duration OC contain three months of active pills containing both ethinyl estrogen and progestin followed by a placebo week as compared to three weeks of active pills followed by a placebo week with more conventional OC.  Such pills prevent menstrual migraine because they minimize declines in ethinyl estradiol experienced during the placebo week of OC.   GnRHa can be used to induce a medical oophorectomy in rare instances, but estrogen must be added-back to prevent migraine headache in these patients.  However, these medications have many side effects (i.e., menopausal symptoms) and should be reserved for the most refractory patients.  Non-hormonal therapies such as beta-blockers, calcium channel blocker, tricyclic antidepressants and anticonvulsants can also be used particularly in patients with irregular and unpredictable menses.  Some clinicians recommend increasing the dosages of these standard preventatives just during the peri-menstrual time period in an attempt to prevent menstrual migraine although data are lacking for such a practice.

Approach to Treatment of Menstrual Migraine 

All patients with menstrual migraine should be given an abortive medication regardless of whether preventative therapies are employed.  The choice of a given preventative therapy depends upon a number of clinical factors.  If patients are already receiving OC then the easiest intervention would be to use extended duration OC (i.e., omit the placebo week from the first three packs of OC and administer the placebo week with the fourth pack).  A short term prophylactic therapy, such as triptans or an NSAID, may be used for patients with regular menstrual periods.  A continuous standard preventative is considered for patients with irregular menses.  Therefore, an individualized approach to menstrual migraine is necessary to provide optimal treatment to these severe and refractory migraine attacks.

References

1. MacGregor EA, Hackshaw A. Prevalence of migraine on each day of the natural menstrual cycle.

Neurology. Jul 27 2004;63(2):351-353.

2. Martin VT, Behbehani M. Ovarian hormones and migraine headache: understanding mechanisms

and pathogenesis–part 2. Headache. Mar 2006;46(3):365-386.

3. Martin VT. Menstrual