What makes women’s migraines different

There’s a good reason three times as many women suffer migraines as men: hormones. A clinician lays out a plan for avoiding these disabling attacks.

Growing up in the 1960s, I watched many sitcom bedroom scenes—with twin beds, of course—in which the wife would rebuff her husband’s amatory advances by declaring, “Not tonight, dear, I have a headache.”

The writers of those old scripts may have been ahead of their time. If the woman was a migraineur, the physical exertion of sex would indeed have been something she’d want to avoid. Many activities can trigger these debilitating headaches. In addition to causing terrible, throbbing pain, migraines can cause a range of symptoms (Table 1), including nausea and sensitivity to light and sound. About 15% of patients develop an aura, a feeling or series of sensations, before a migraine attack.

These sensations can include vision changes, such as seeing bright lights, jagged lines, or blind spots. Untreated migraines can last a few hours to several days.

Hormone connections

According to the American Migraine Study II, 21 million American women suffer from migraines—three times the number of men. The prevalence of migraine in women appears related to levels of estrogen and, to a lesser extent, progesterone. Indeed, the frequency, duration, and severity of migraines change in direct relationship to the female hormonal milestones of menarche, pregnancy, and menopause.

Menstruation. Between 7% and 14% of female migraine sufferers have menstrual migraines, experiencing headaches two days before through the first three days of their periods. (See “Leah: Menarche-related migraine.”) Approximately 60% of women have menstrually-related migraines. Besides having headaches during the two days prior through the third day of menstruation in at least two thirds of their cycles, these women also experience headaches at other times of the month.

Pregnancy. During the second and third trimesters, most migraineurs experience fewer headaches, probably because estrogen levels rise at this time. Improvement is more likely if a woman’s migraines were menstrually-related before pregnancy (see “Barbara: Pregnancy and migraine”). Rarely, women have their first migraine during the first trimester. If this happens, rule out other causes of headache, such as tumor, eclampsia, subarachnoid hemorrhage, and hypothyroidism. Once a migraine diagnosis has been made, reassurance that a woman’s headaches are likely to decrease as pregnancy progresses often helps. Postdelivery, a drop in estrogen levels may cause migraines to return.

Menopause. Headaches starting after age 45 should always be evaluated for secondary causes since migraine onset usually occurs earlier in life (see “Maria: Migraine during perimenopause”). In established migraineurs, however, the hormonal fluctuations of perimenopause can trigger an increase in headache frequency and severity. In the years following menopause, most women will experience an improvement in symptoms. By age 60, the annual incidence of migraines decreases to about 8%. However, two thirds of women who have surgically-induced menopause complain of migraine symptoms. Migraines beginning after age 65 are extremely rare. Women in this category must be thoroughly evaluated for other causes of head pain (up to one third of headaches in this older population are due to secondary causes).

Acute-care treatment

Migraine therapy can be broken down to acute-care and preventative (Table 2). Triptans are considered first-line therapy for acute migraine. These medications are most effective if taken within one to two hours of onset; once cutaneous allodynia has occurred, they are less effective. Recent evidence suggests that combining a triptan with a nonsteroidal anti-inflammatory drug (NSAID), such as naproxen 500 mg, may be more beneficial than either therapy alone. Triptans are contraindicated in patients with cardiovascular disease, however.

NSAIDs work best if taken before nausea and vomiting occur. Naproxen or ibuprofen started two to three days before menses begins has had variable success in reducing the number of menstrual and menstrually-related migraines. Dihydroergotamine, an ergot alkaloid, is an older, migraine-specific medication.

Though effective, ergot alkaloids are not used very often because of their high side-effect profile. Dihydroergotamine is usually provided as a nasal spray. In most cases, medication for acute migraine should not be used more than twice a week; excessive use can increase the risk of rebound headaches. If a patient’s migraines occur more frequently, consider therapeutic prevention.

Migraine prevention

As of this writing, only five medications have been approved by the FDA for migraine prevention. They are propranolol (Inderal), valproic acid (Depakene), topiramate (Topamax), methysergide (Sansert), and timolol (Blocadren). A number of other medications have been studied and are used off-label.

The triptans can all be effectively used to prevent menstrual and menstrually-related migraines. The longer-acting triptans, frovatriptan (Frova) 2.5 mg and naratriptan (Amerge) 1 mg and 2.5 mg, have also been used to prevent these types of migraine. The medications are typically given b.i.d. for five to six days starting three days before the expected attack. Some experts have cautioned that in addition to being relatively expensive, data regarding the long-term safety of triptans are lacking.

Combination oral contraceptives (COCs) can also be effective, but there are several issues to consider: First, no hormonal treatment regimen has received FDA approval for this indication. Second, results are unpredictable. Most important, clinicians must evaluate each patient’s risk for stroke before prescribing COCs (both migraine and COC use increase the chance of stroke). Other stroke risk factors to keep in mind are migraine with aura; heart disease with risk of emboli; hypertension; BMI >30; hyperlipidemia; diabetes; systemic diseases associated with stroke; a personal or family history of thrombosis, and smoking. Smoking in combination with COCs and migraines increases a woman’s stroke risk 34-fold.

Women at elevated risk for stroke should not be given COCs for migraine, and COCs should always be discontinued if a woman’s migraines worsen, if a secondary cause of headache is suspected, or if there are any neurologic changes, such as the development of atypical aura or a sudden, prolonged headache. When COCs are indicated, opt for low-dose (<35 µg estrogen) monophasic contraceptives.

To keep estrogen levels steady, patients should use just the first three weeks’ pills in a four-week pill pack, skipping the placebo week. This pattern is usually repeated for three or four cycles, allowing for a placebo/menses week at the end of the last cycle. If little or no breakthrough bleeding occurs, some clinicians may extend the patient’s cycle as long as six months.

Seasonale (levonorgestrel/ethinyl estradiol), an extended-cycle contraceptive, operates under the same premise; women taking it have just four periods a year. So far, women using Seasonale report a decrease in menstrually-related symptoms, but they experience more breakthrough bleeding and spotting than women taking traditional OCs. A similar product, Seasonique, is also taken for 12 weeks but with the addition of 10 µg estrogen to the placebo-week tablets to reduce withdrawal symptoms.

The transdermal patch (norelgestromin/ethinyl estradiol [Ortho Evra]) and the vaginal contraceptive ring (etonogestrel/ethinyl estradiol [NuvaRing]) can help maintain steady estrogen levels. Providers should be aware that the FDA added a warning in 2005 that patch users had 60% more exposure to estrogen than users of typical COCs.

Patients on hormone therapy may develop a worsening of migraine or develop an aura. They should be alerted to these possibilities and told to notify you if such symptoms develop. Continuous standard therapy with beta blockers, calcium channel blockers, tricyclic antidepressants, and anticonvulsants have all been shown to reduce headaches in some women and/or improve the efficacy of abortive medications.

Mineral supplementation with magnesium has demonstrated some efficacy. Studies show that 360 mg daily decreases pain associated with menstrually-related migraine when compared with placebo. Biofeedback, massage therapy, chiropractic care, and meditation can also be valuable tools. A headache diary can help chart changes in headache patterns and assess treatment efficacy.

During and after pregnancy

When caring for a pregnant migraineur, the first line of treatment should be avoidance of any known triggers (Table 3), especially alcohol (which all pregnant women obviously should avoid anyway). Medications (Table 4) should be limited and offered only after consultation with the patient’s obstetrician.

The bottom line

A 50% decrease in migraine frequency is considered a successful outcome of prevention therapy. Patients in whom you suspect secondary causes or those not responding to treatment should be referred to a headache specialist or neurologist.

Ms. Vujevich is a family nurse practitioner and adjunct faculty member at the University of Pittsburgh.

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