Headaches in Women With Migraine Rise in Perimenopause

Ricki Lewis, PhD

February 03, 2016

Many women report increased frequency of headaches as menopause approaches, but few studies have tracked the phenomenon. Now, a new study comparing headache frequency in women with migraine before menopause, during the "transition" (perimenopause), and once menstruation ceases, confirms the largely anecdotal evidence.

"When headaches worsen during the menopausal transition, clinicians can explain the now-established connection with headache severity. This can be reassuring for patients," coauthor Richard B. Lipton, MD, director of the Montefiore Headache Center and the Edwin S. Lowe Chair in Neurology, Albert Einstein College of Medicine, Bronx, New York, told Medscape Medical News.

Their results were published online January 21 in Headache.

Three times as many women as men experience migraines, which affect 12% of the US population. The migraine trigger as menopause approaches is declining estrogen. "During regular menstrual cycles, falling estrogen levels are thought to increase the probability of headache around the time that flow begins. During the menopausal transition, estrogen levels fluctuate and again declining levels may increase the probability of attacks," Dr Lipton explained.

Women who have had premenstrual syndrome, depression, and/or migraine are at higher risk for headache during perimenopause and menopause. Lead author Vincent T. Martin, MD, Department of Internal Medicine, University of Cincinnati College of Medicine, Ohio, and colleagues conducted the cross-sectional observational study analyzing data from the 2006 American Migraine Prevalence and Prevention study on women aged 35 to 65 with diagnosis of migraine.

Participants completed questionnaires that probed details of the menstrual cycle, description and type of headache (including International Classification of Headache Disorders-3 beta criterion for migraine), sociodemographic information such as income and age, history of depression, body mass index, allodynia, preventive medications, and medication overuse. The primary outcome was headache frequency (10 per month dividing high and low). A secondary outcome divided the stages into early or late.

The investigators considered headache frequency among 3664 women with episodic migraine of whom 1263 were premenopausal (normally cycling), 1283 perimenopausal (irregularly cycling), and 1118 menopausal (no cycling). Mean age was 46 years. Further time breakdown yielded 592 and 691 participants in early and late perimenopause, respectively, and 513 and 605 in early and late menopause, respectively.

The researchers parsed the data in several ways: comparing high-frequency headaches in perimenopause and postmenopause to premenopause (model 1), comparing early and late perimenopause to premenopause (model 2), and comparing early and late menopause to premenopause.

Results reveal an upswing in headaches as menopause nears. High-frequency headaches affected 8.0% (99 of 1242) of premenopausal women, 12.2% (154 of 1266) of perimenopausal women, and 12.0% (131 of 1095) of postmenopausal women.

The adjusted odds of high-frequency headache compared with premenopausal women was 1.62 (95% confidence interval [CI], 0.23 - 2.12) for perimenopausal women and 1.76 (95% CI, 1.23 - 2.52) for menopausal women, considering socioeconomic factors alone. High-frequency headache increased in perimenopausal women with an odds ratio [OR] of 1.42 (95% CI, 1.03 - 1.94) adjustment for body mass index, medication overuse, current migraine preventive use, and depression.

Symptoms worsen during perimenopause and wane when menstrual periods permanently cease. Women were more likely to use migraine preventives in late perimenopause compared with premenopause (OR, 1.96; 95% CI, 1.37 - 2.80) but not in early perimenopause compared with premenopause. Medication overuse, smoking, depression, and allodynia were worse in both early and late perimenopause compared with premenopause.

Interestingly, model 3 revealed increased risk for high-frequency headache for early (OR, 1.74; 95% CI, 1.11 - 2.71) and late (OR, 2.07; 95% CI, 1.25 - 3.43) menopause compared with premenopause after adjustment for sociodemographic characteristics, but the risks lost significance after adjustment for all covariates. This may mean that some headaches among the postmenopausal may have causes other than migraine due to declining estrogen, such as depression and medication overuse.

Headaches that increase in frequency with menopause may be less worrisome than those that begin then. "When someone has a new-onset headache in late middle life, we are more suspicious of a secondary cause because migraine rarely begins in the 50s and 60s and other disorders such as stroke and brain tumor become more common," Dr Lipton told Medscape Medical News.

Dr Martin pointed out another explanation for headache increase with menopause: rebound. "Women as they get older develop aches and pains, joints and back pain, and it is possible their overuse of pain medications for headache and other conditions might actually drive an increase in headaches for the menopause group."

Results "Reassuring"

"Those of us who treat women with migraine have been aware that with the onset of perimenopause, there is often an exacerbation of migraine," said Lawrence C. Newman, director, The Headache Institute at Mount Sinai St. Luke’s Roosevelt, New York, New York, and president of the American Headache Society.

"This study focuses on what may happen in the perimenopausal transition period as well as postmenopausally," said Dr Newman. "The authors found increased risk for developing high frequency headaches, defined as more than 10 per month, during this transition phase as compared to premenopausal women with migraine."

The new results should be reassuring for most women approaching menopause. "If the woman is already on prevention, then adjusting the dose or switching to a different medication are options," said Dr Newman. "If she is not on a medication, the physician can consider adding a preventive strategy if headaches worsen. Alternatively, discussing a short-term hormone replacement therapy may have value, but there are risks associated with that approach."

The new results also indicate that preventive treatment might not be required forever. "If headache frequency and severity warrant preventive therapy, doctors can reassure patients that once the menopausal transition is complete, there is a good chance that preventive medicines will no longer be necessary, Dr Lipton said.  

A limitation of the study is inclusion of nonmigraine headaches. But Dr Lipton counters that inclusion of women without migraine would most likely attenuate, not amplify, results. "Migraine is far more likely to be hormonally sensitive than sinus infections or other potential migraine mimics," he said. Other limitations include exclusion of women on hormone replacement therapy, and self-reporting of headache frequency.

The researchers and commentators have disclosed no relevant financial relationships.

Headache. Published online January 21, 2016. Abstract


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