Patterns of Migraine in Postmenopausal Women: A Systematic Review

Abstract

Introduction: Migraine prevalence is higher in fertile than in postmenopausal women. However, few literature data are available on the prevalence and characteristics of migraine after the menopause and on the effect of hormones in postmenopausal women with migraine. Methods: We performed a systematic literature review of studies available on Scopus and Web of Science from the beginning off indexing until October 18th, 2020. We included both randomized trials and observational studies. Results: We included 12 papers, six of which assessed the prevalence and characteristics of migraine in postmenopausal women, while the other six assessed the effect of hormones on migraine after the menopause. One of the studies was a randomized trial, while the remaining 11 were observational studies. Ten studies were clinic-based, while the remaining two were population-based. Studies assessing the prevalence and characteristics of migraine after the menopause reported inconsistent findings; in studies performed in headache clinics, likely affected by selection bias towards the most severe cases, a relevant proportion of women reported migraine worsening after the menopause. Studies assessing the effect of hormones on migraine after the menopause showed that postmenopausal hormone replacement therapy was invariably associated with migraine worsening, if containing estrogen. Conclusion: Our systematic review showed that migraine could be a relevant health problem in postmenopausal women, mostly in headache clinics. However, the available studies allow a limited assessment of the prevalence and characteristics of postmenopausal migraine. Further large studies are needed to better determine the burden of migraine after the menopause according to migraine characteristics and the impact of hormonal treatments.

Migraine: A Review on Its History, Global Epidemiology, Risk Factors, and Comorbidities

“…Migraine occurrence can be affected by menstruation, pregnancy, and menopause, in addition to the use of hormonal contraceptives and hormone replacement therapies ( 39 ). In this regard, a recent systematic review of 12 studies showed that high-estrogen levels, high estrogen fluctuations, and hormonal replacement therapy were associated with the worst migraine outcomes ( 42 ).…”

Is There a Gender Difference in the Response to onabotulinumtoxinA in Chronic Migraine? Insights from a Real-Life European Multicenter Study on 2879 Patients

“…Gender differences in migraine primarily depend on sex hormones. The high fluctuations in estrogen levels that accompany the menstrual cycle and perimenopause are associated with a possible exacerbation of migraine, leading to the particularly higher prevalence of migraine in women than in men during the female fertile period [ 39 – 41 ]. On the other hand, male sex hormones are likely protective against migraine, as suggested by the cessation of migraine in women treated with testosterone for reasons other than their migraines [ 7 ].…”

Acute and Preventive Management of Migraine during Menstruation and Menopause

“…After natural menopause, migraine usually improves [ 28 , 29 ], while women undergoing surgical menopause have a high risk of migraine worsening, possibly due to a sudden fall in estrogen levels [ 30 , 31 ]. The proportion of women reporting postmenopausal migraine worsening is particularly high in headache clinics, possibly due to selection bias [ 9 , 32 ]. Therefore, headache clinics likely provide care to a high proportion of women with perimenopausal migraine worsening, and women with previously rare migraines can come to the attention of a headache center for the first time because of a perimenopausal worsening.…”

“…HRT is usually prescribed to reduce the vasomotor symptoms associated with the menopausal transition [ 100 , 101 ]. However, population-based studies suggest that HRT worsens migraine [ 32 , 102 , 103 ]. To limit migraine worsening after the menopause, different strategies are viable based on the estrogen withdrawal hypothesis, including the continuous rather than intermittent administration of combined hormonal treatments [ 104 ], the intrauterine or transdermal rather than oral administration of estrogen [ 105 ], and the administration of non-estrogen compounds such as tibolone [ 106 ].…”