Women in perimenopause are at increased risk of high-frequency headache, compared with premenopausal women, according to data published online ahead of print January 21 in Headache. Women in menopause also are at increased risk of high-frequency headache, but the effect of menopause on headache frequency may be mediated or confounded by medication overuse or depression.
“Our results confirm the commonly held belief that the perimenopause worsens headache, but challenge the idea that migraine ‘always’ improves during the menopause,” said Vincent T. Martin, MD, Professor of Internal Medicine in the University of Cincinnati’s (UC) Division of General Internal Medicine and codirector of the Headache and Facial Pain Program at the UC Neuroscience Institute. “Recognition of the increased risk of high-frequency headache during the menopausal transition suggests a need for optimized preventive treatment of migraine during this time of women’s life.”
Research has suggested a lower prevalence of headache or migraine during menopause, compared with premenopause. No previous studies have analyzed whether frequency of headache attacks changes during the menopausal transition among women with migraine, however. Dr. Martin and colleagues sought to determine whether the percentage of female migraineurs with high-frequency headache, defined as 10 or more days/month, is greater during the perimenopausal and menopausal time periods, compared with the premenopausal period. The researchers also set out to examine whether any increase in high-frequency headache during a particular reproductive phase was restricted to the early or late stages of the phase.
An Analysis of AMPP Data
To answer their questions, the investigators conducted a cross-sectional study using data from the American Migraine Prevalence and Prevention (AMPP) study. The AMPP researchers elicited data about headache from 162,756 respondents age 12 or older in 2004 and invited a random subset of 24,000 people age 18 or older with self-reported severe headache to participate in annual follow-up surveys for the subsequent five years. Follow-up surveys included questions about sociodemographics (eg, BMI, smoking, and household income) and headache types and characteristics, in addition to the Migraine Disability Assessment Score. Dr. Martin and colleagues examined data from the 2006 follow-up survey because it contained questions on the menstrual cycle.
Eligible participants in the cross-sectional study were women with a diagnosis of migraine between ages 35 and 65. Women who were pregnant, breastfeeding, had a history of hysterectomy or oophorectomy, or used hormonal therapies were excluded from the analysis. The investigators classified respondents as premenopause, perimenopause, and menopause according to Stages of Reproductive Aging Workshop criteria.
Late Perimenopause and Headache Frequency
The analysis included 3,664 women, of whom 3,454 had episodic migraine and 210 had chronic migraine. In all, 1,263 women were classified as premenopausal, 1,283 as perimenopausal, and 1,118 as menopausal. Compared with women in premenopause, women in perimenopause and menopause used more migraine preventives and were more likely to overuse medication.
Approximately 8% of premenopausal women had high-frequency headache, compared with 12.2% of perimenopausal women and 12.0% of postmenopausal women. After adjustments for sociodemographics alone, the odds ratios (ORs) of high-frequency headache were 1.62 for perimenopausal women and 1.76 for menopausal women, compared with premenopausal women. After adjustment for BMI, current migraine preventive use, medication overuse, and depression, the OR decreased, but remained significant in the perimenopausal group (OR, 1.42) and lost significance for the menopausal group (OR, 1.27). Depression and medication overuse significantly increased the likelihood of high-frequency headache.
When the researchers examined participants in the early and late stages of perimenopause and adjusted data for all covariates, women in late perimenopause had an increased likelihood of high-frequency headache (OR, 1.72), but women in early perimenopause had a statistically insignificant increased risk of this outcome (OR, 1.22), compared with premenopausal women. When the researchers examined the early and late stages of menopause, compared with premenopause, they found no significant difference in risk of high-frequency headache after controlling for all covariates.
Results Contradict Common Belief
“These results suggest that the hormonal milieu of the late perimenopause is particularly provocative for high-frequency headache among migraineurs,” said Dr. Martin. Because the researchers did not collect data on premenstrual syndrome (PMS) disorder, they could not determine whether the increased risk for high-frequency headache during perimenopause only occurred in female migraineurs with PMS or in the entire population.
Epidemiologic studies have contributed to an impression that migraine prevalence declines in menopausal women, but the current study’s results contradict this impression. “Our study used high-frequency headache as its primary outcome measure, rather than migraine prevalence. It is plausible that during menopause, migraine prevalence decreases and migraine attacks occur more frequently in subgroups of women,” said Dr. Martin. “Women, as they get older, develop lots of aches and pains, joint [pain], and back pain, and it is possible [that] their overuse of pain medications for headache and other conditions might actually drive an increase in headaches for the menopause group,” he added.