Worsening Migraine During HRT Tied to Increased Stroke Risk

Megan Brooks

February 18, 2016

LOS ANGELES — Women who have worsening migraine headaches while receiving hormone replacement therapy (HRT) are at increased risk for ischemic stroke, a large observational study suggests.

Researchers found that current HRT users who reported more severe migraines while receiving HRT were 30% more likely to experience ischemic stroke, relative to women who never used HRT and past users of HRT who were also coping with worsening migraine headaches.

The study was presented here at the International Stroke Conference (ISC) 2016 by lead investigator Haseeb A. Rahman, MD, from the Zeenat Qureshi Stroke Institute, Minneapolis, Minnesota, and neurology resident at Houston Methodist Hospital in Texas.

There has been a "long-standing debate" about the role of HRT and migraines in stroke, Dr Rahman noted during a press briefing. HRT is considered a risk factor for migraines and patients with a history of migraines may experience worsening migraines while receiving HRT.

But this new analysis is believed to be the first to assess whether changes in migraine severity with HRT are a risk factor for ischemic stroke, he explained.

Significant Link

The researchers analyzed data for 82,208 women aged 50 to 79 years from the Women's Health Initiative Study who had migraines at baseline. Of these, 37,680 (45.8%) were current users of HRT, which included unopposed estrogen and/or estrogen plus progesterone, and 44,528 (54.2%) were past users or had never used HRT.

The researchers compared stroke risk in current HRT users vs never users or past users of HRT and further dichotomized the women by change in migraine severity from baseline to the 3-year follow-up visit.

During 12 years of follow-up, 2063 of the women had an ischemic stroke. The rate of increase in migraine severity was significantly higher in women who were current HRT users relative to never and past HRT users (20.6% vs 17.3% and 18.7%, respectively; P .0001).

There was about a 10% increase in ischemic stroke risk in women on HRT who did not have worsening of migraine severity (odds ratio [OR], 0.91; confidence interval [CI], 0.88 - 0.94; P < .001), Dr Rahman reported.

However, current HRT users who did experience an increase in migraine severity of one grade or more from baseline to 3 years had a 30% increase in ischemic stroke risk (OR, 1.3; [CI, 1.1 - 1.5]; P < .001). That was the "real significant finding," Dr Rahman said.

The results were adjusted for well-known risk factors for stroke, including age, hypertension, hypercholesterolemia, diabetes, and smoking.

Dr Rahman said physicians and patients need to "sit down and discuss the risks and benefits" of HRT. If a patient starting HRT has had a history of migraines, "it's important keep a close watch" on migraine severity.

"Kudos to the Authors"

Commenting on the findings, American Stroke Association spokesperson Brian Silver, MD, said, "Kudos to the authors" for thinking about not just whether taking HRT or having migraines could lead to stroke, "but how the two would interact together."

"There's always some concerns amongst stroke neurologists when an older person is taking hormone placement therapy," said Dr Silver, director of the Stroke Center at Rhode Island Hospital and associate professor of neurology at The Warren Alpert Medical School of Brown University in Providence, Rhode Island. "[W]hat these authors are suggesting is that if your migraines are increasing while you're on hormone replacement therapy, you may want to consider finding an alternative treatment to the hormone replacement therapy."

Noah Rosen, MD, director, Northwell Health's Headache Center in Great Neck, New York, who wasn't involved in the study, told Medscape Medical News, "There have been a couple of studies linking migraine (and particularly migraine with aura) to an increased risk for stroke. Tobias Kurth's study on this was particularly enlightening and led to further concern over migraine as a risk factor for stroke."

Dr Rosen also noted that previous work has shown that hormonal treatment may increase the risk for stroke in addition to the risk associated with migraine. "However, it has not been shown that increased severity of migraine in the context of hormone use has increased the risk of stroke," he noted.

Having a history of migraine is "not a modifiable risk factor, meaning it cannot be altered or changed. However, it needs to be considered when risk stratifying an individual as to their actual stroke risk," Dr Rosen said.

This new study, Dr Rosen added, is "limited by the fact it is retrospective and using a large-scale database not designed to specifically look at this question and (presumably) all hormonal therapies were lumped together. In the future, further prospective studies looking at only one form of oral hormone would be useful."

The study had no commercial funding. The authors have disclosed no relevant financial relationships.

International Stroke Conference (ISC) 2016. Poster WMP57. Presented February 17, 2016.

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