Perimenopause and Menopause Are Associated with High Frequency Headache in Women with Migraine: Results of the American Migraine Prevalence and Prevention Study

Objectives To examine the relationship of headache frequency to the stages of the menopausal transition in mid-life women with migraine. Background Past studies suggest that the perimenopause is associated with an increased prevalence of migraine, particularly in those with a history of premenstrual syndrome. The effect of the menopausal transition on the frequency of headache attacks in women with migraine has not been explored. Methods This was a cross-sectional observational study. Using data from the 2006 American Migraine, Prevalence and Prevention study survey, women meeting modified ICHD-3 beta criteria for migraine between the ages of 35-65 years were included in analyses. Women who had never menstruated or were pregnant, breastfeeding, or using exogenous sex hormones were excluded. The 2006 survey was selected because it included detailed questions on the menstrual cycle. The stages of the menopausal transition were defined based upon the self-reported cycle length and/or duration of amenorrhea. The primary outcome, high vs low headache frequency, was defined using a cut score of ≥10 headache days per month. Binary logistic regression models were used to assess the influence of menopausal stage on headache frequency category using premenopause as the reference group. Adjustments for stage of menopausal transition and sociodemographics (eg, age and income) were included in the first model, while the second model included sociodemographics, depression, body mass index, preventative medications, and medication overuse. Results The study sample included 3664 women at a mean age of 46 years. Among women who were premenopausal, 8.0% (99/1242) were in the high frequency headache group in comparison with 12.2% (154/1266) of perimenopausal and 12.0% (131/1095) of postmenopausal women. Compared with premenopausal women, the adjusted odds of being in the high frequency headache group was 1.62 (95% CI = 1.23, 2.12) for perimenopausal and 1.76 (95% CI = 1.23, 2.52) for postmenopausal women (Model 1). In model 2, high frequency headache was only increased in perimenopausal women with an OR of 1.42 (95% CI = 1.03, 1.94). Conclusions The risk of high frequency headache is increased in women during the perimenopause compared to premenopause in the fully adjusted model. The fact that the increased risk of high frequency headache was not statistically significant for menopause in the fully adjusted models suggests that different mechanisms might account for the increased risk for this stage of the menopausal transition. 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.