SCOTTSDALE, Arizona — Menstrual migraines that occur in the days following menstrual bleeding may be related to low ferritin caused by blood loss rather than to estrogen fluctuations.

"End menstrual migraine is a common complaint in women evaluated for menstrual related migraine, yet these migraines occur many days after the estrogen withdrawal that precipitates menstrual-related migraine," the authors, led by Anne H. Calhoun, MD, from the University of North Carolina and Carolina Headache Institute–Research, Durham, report.

"[We] believe that end menstrual migraine is not hormonally mediated, but rather that it is causally related to menstrual blood loss, resulting in a brief relative anemia with consequent migraine," the researchers add.

The study, published in Headache, was featured in a session on the "Best" studies of 2017 here at the American Headache Society (AHS) 2017 Scottsdale Headache Symposium.

Menstrual Blood Loss

The study was prompted by the researchers' clinical observations that some patients being treated for regularly occurring menstrual migraine experienced the migraines at the end of menstruation.

"We suspected a relationship to menstrual blood loss and have been routinely checking ferritin levels for this complaint for a few years," they report.

The authors developed their own diagnostic code for those cases — EMM (end menstrual migraine). To further explore the effect, they evaluated data on 119 consecutive patients seen over 6 weeks at the clinic.

The women in the study had a mean age of 36.8 years and had a mean body mass index of 26.6 kg/m2; 88.2% were non-Hispanic white. No significant differences were observed in patients with EMM compared with those with other migraines.

Among 85 women with regular menses who were appropriate for evaluation, 30 (35.3%) had EMM. Their mean EMM duration was 2.6 days, with the headache graded as severe on at least one day.

Of the 30 patients, as many as 28 (93.3%) showed levels of ferritin, an intracellular protein that stores iron and releases it in response to tissue demand, to be below the generally accepted lower desirable limit of 50 ng/mL (mean, 21.9 ng/mL). Of those women, as many as half had levels below 18 ng/mL, the established minimum for women.

"While adequate iron levels are certainly important, adequate iron stores are equally important, [and] with inadequate ferritin, these iron stores can quickly be depleted," the authors note.

The researchers also note that chronic headache is a recognized symptom of low ferritin levels and that it is also associated with anemia, hypoxemia, and hypercapnia, "possibly related to the cerebral vasodilatation that commonly accompanies these conditions."

The authors call for larger epidemiologic studies to confirm the prevalence of EMM and to better characterize the disorder.

They recommend the following diagnostic criteria for EMM: (1) predictable migraine headache (with or without aura) that (2) occurs immediately after or toward the end of menstrual bleeding.

Notable Research

In discussing the study at the session, Thomas N. Ward, MD, editor-in-chief of Headache and active emeritus professor of Neurology at the Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, said the study was notable in shedding light on something that clinicians may commonly see yet not notice.

"This study was interesting because sometimes you run into something like this that you've seen in the clinic, but it just doesn't register because it's not in the literature," said Dr Ward.

Lead author Dr Calhoun said she has seen it — and has taken notice.

"I see this almost daily, but I don't know who else is even looking for it," she told Medscape Medical News.

Dr Calhoun said patients showing such symptoms are usually treated with iron therapy.

"I typically use oral iron, but some levels have been so low that we've used intravenous iron infusions. I usually recheck the ferritin after about 8 to 9 months on oral iron, and it's typically responded to an adequate level, with complete resolution of symptoms," she said.

Also commenting on the research, Elizabeth W. Loder, MD, MPH, associate professor of neurology at Harvard Medical School and chief, Division of Headache and Pain in the Department of Neurology at Brigham and Women's Hospital, Boston, Massachusetts, said the points raised in the study are intriguing but preliminary.

"The authors of the study make an interesting observation about headaches that occur at the end of menstruation, and about the possible connection with menstrual blood loss," she told Medscape Medical News.

"It is important to remember, however, that end-menstrual migraine is not a diagnosis that is yet recognized by the International Classification of Headache Disorders," she noted.

"A great deal more work is needed before we could feel confident about the existence of this entity. Reports from different researchers working in other locations and evaluating different populations of women would be the next step."

The authors and Dr Loder have disclosed no relevant financial relationships.

American Headache Society (AHS) 2017 Scottsdale Headache Symposium

Headache. 2017;57:17-20. Full text

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