Common misconceptions in diagnosing and treating menstrual migraine

Fortunately, in recent years, migraine has gained wider public and provider recognition as a complex and serious, chronic neurological disease that can profoundly impact a person’s quality of life.

Importantly, new evidence is emerging about the biological mechanisms underlying migraine, as well as the pathophysiology of different forms of the disease — including menstrual migraine (MM).

Three times more women live with migraine than men, and MM affects a significant subset — about 20% to 25% — of women and girls with the disease. MM can be divided even further into two types: attacks that occur only with menstruation and attacks that occur both during menstruation as well as during the rest of the cycle. Both types are more severe, longer lasting and tend to be more resistant to treatment due to the effects of hormones, particularly estrogen.

Unfortunately, the current diagnostic criteria for MM leave a lot to be desired, especially for OB/GYNs and primary care physicians who treat a variety of conditions. Some of the biggest diagnostic concerns I hear from these providers are:

• There are no diagnostic tests or biomarkers to help me confirm a MM diagnosis.
• My patients have a hard time keeping a migraine diary linked to their cycle, especially for extended periods of time.
• My patients aren’t as forthcoming as they should be about their symptoms out of fear of being taken off their preferred birth control.

In addition, hesitation to diagnose and treat this specific form of migraine can be linked to a few persisting myths. Let’s review:

Myth: Estrogen is solely responsible for menstrual migraine

Women with MM develop headaches anywhere from 2 days before to 3 days after the start of menstruation. It is believed that when estrogen levels rapidly drop before menstruation, there is an increased likelihood of developing migraine headaches. In fact, the fluctuating level of estrogen, rather than the level itself, is believed to be the main trigger. While estrogen plays a key role in MM pathogenesis, there are likely other contributing factors, including prostaglandin release and alterations in serum magnesium levels. Recent studies also show that estrogen seems to affect patients in different ways depending on their medical history, age and use of hormonal therapy.

Myth: Treating patients on birth control compounds cardiovascular risks

For some women with MM, continuous (skipped placebo tablets) birth control pills might help prevent attacks by keeping estrogen levels stable throughout the menstrual cycle. Standard noncontinuous use of birth control pills results in only subtle differences in the course of menstrual migraine, as abrupt estrogen withdrawal occurs when active pills are switched to placebo. Thus, many women still need to be treated with migraine-specific medication. But there can be a reluctance to prescribe certain classes of migraine medication to women with migraine, especially those on hormonal birth control, due to concern over increased cardiovascular risk, especially stroke.

First, it’s important to note that increased vascular risk is explicitly related to migraine with aura (twofold higher stroke risk at baseline). The use of oral contraceptives increases that risk. Secondly, providers should understand that the risk for stroke from estrogen-containing birth control is mainly due to blood clots, and the risk for stroke with certain migraine medications is due to vasoconstriction. These two risks are not interlinked; therefore, providers should take a patient’s complete medical history into account when evaluating birth control and migraine treatment options.

Myth: Prescribing migraine medication for those planning pregnancy or during pregnancy is risky

Unfortunately, migraine is prevalent during pregnancy, and the use of acute and preventative migraine therapies has not been extensively studied in this patient population. However, data suggests that some migraine medications, such as triptans, are relatively safe during pregnancy, particularly after the first trimester. Plans to become pregnant or being pregnant should not automatically preclude prescribing a migraine-specific treatment. Severe untreated pain can also have adverse effects on maternal and fetal well-being.

Now that we demystified some of the main concerns with treating MM, what should providers consider when evaluating treatment options?

Limitations of common management strategies

Migraine affects approximately 39 million people in the United States, and of those diagnosed, only about 4 million are on a prescription treatment. For decades, triptans have been the first-line therapy in treating acute migraine attacks and still account for almost 70% of migraine therapies; however, a large subset of these patients — approximately 30% to 40% — do not respond adequately to triptan therapy. This could be due to a variety of factors, including that triptans are only effective when taken early in an attack and tend to promote headache recurrence that results in poor adherence and discontinuation.

Oral therapies may not work for many patients

Almost 50% of patients with acute migraine experience frequent nausea that contributes to the burden of migraine and leads to anxiety about taking oral medication during an attack. Despite recent FDA approvals of new classes of oral therapies, it is important to recognize that many patients living with migraine have related gastrointestinal disorders and are often unable to achieve relief with oral routes of administration. Conditions such as gastroparesis and functional dyspepsia are both associated with delayed gastric emptying, while cyclic vomiting syndrome is marked by nausea and vomiting, which commonly occur with migraine attacks. These comorbidities can render oral therapies ineffective or inadequate, so alternate administration routes are needed for these patients.

The reemergence of dihydroergotamine

Because of the aforementioned reasons, there has been a renewed appreciation for dihydroergotamine (DHE) and the need for non-oral, non-injected delivery options. DHE has been considered to be an effective option in treating migraine since 1945 for a few reasons:

Unlike triptans, calcitonin gene-related peptide, or CGRP, inhibitors, or a class of drugs known as “ditans,” DHE is known to interact with a broad range of receptors that are theorized to be implicated in migraine onset and duration. DHE has a chemical structure similar to many naturally occurring neurotransmitters, for instance, epinephrine, norepinephrine, dopamine and serotonin.

DHE has a rapid onset and sustained effects lasting up to 48 hours and may be used at any time point after migraine onset, from early (within 2 hours) and up to 8 hours after onset.

DHE has been shown to be highly effective in patients who wake with migraine, are triptan resistant, have MM, allodynia or severe and/or prolonged migraine, and even in those who have cluster headache.

MM attacks tend to be particularly burdensome and refractory to treatment. Recurrence tends to be a major issue impacting more than 50% of those with MM. DHE not only acts quickly and provides long-lasting relief but can reduce the risk of migraine recurrence, which is hugely impactful.

A new at-home DHE therapy utilizing an improved nasal delivery system was approved by the FDA in 2021 (Trudhesa; Impel Pharmaceuticals) and there is another program in clinical development by Satsuma Pharmaceuticals.

Fortunately, our knowledge of migraine and its distinct forms continues to evolve with an influx of industry and academic research in this area. Given how common and debilitating MM is, more research investment is welcomed by clinicians to expand understanding of its pathophysiology and to elucidate the most effective treatment strategies.

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