Review Underscores Lack of Research on Migraine in Postmenopausal Women

Results of a systematic review show migraine could be a relevant health problem in postmenopausal women. However, authors note that limited studies are available assessing this condition in this population, and future large studies are warranted to better determine the burden of migraine after menopause.

Previous research has found that migraine prevalence and features are influenced by female sex hormones, including fluctuations in estrogen levels, researchers wrote. As variations in estrogen levels occur in women during their reproductive period and during the transition to menopause, the postmenopausal period—characterized by stable, low estrogen levels—is sometimes associated with an improvement or cessation of migraine symptoms.

To better understand migraine patterns in postmenopausal women, researchers conducted a systematic literature review of studies published on Scopus and Web of Science. All relevant articles published in English or Italian until October 18, 2020, were assessed.

A total of 12 studies were included in the final review, all of medium to high quality. Of those included, 6 assessed migraine prevalence and characteristics in postmenopausal women, 4 were performed in headache clinics, 1 in a gynecology clinic, and 1 was a survey of the general population.

In addition, “1 of the studies was a randomized trial, while the remaining 11 were observational studies. Ten studies were clinic-based, while the remaining 2 were population-based.”

Of the studies performed in headache clinics, results showed the postmenopausal period was associated with less frequent and/or less severe migraine in more than half of women.

But another clinic-based study found most women reported migraine worsening after menopause. Notably, “in that same study, migraine worsened in all women with surgical menopause, while the 2 women reporting an improvement in their migraine had undergone natural menopause.”

The last clinic-based study found that 8 of 47 postmenopausal women reported migraine onset in the postmenopausal period, whereas the study performed in the gynecology clinic found postmenopausal migraineurs had a higher prevalence of menopausal and depressive symptoms compared with healthy controls.

Results of the general population study showed that migraine frequency, duration, and associated symptoms were higher in women than in men even after menopause, although it did not compare postmenopausal women with premenopausal women.

Six studies assessed the effect of hormones on postmenopausal migraine but yielded mixed results. For example, “One study found that any type of hormone replacement therapy (HRT) was associated with migraine; the other study found that current and systemic hormonal treatments were associated with increased odds for migraine, while previous and local HRT were not associated with an increased odds of having migraine.”

Yet another study, which looked into the effect of 3 different HRT regimes, showed all 3 worsened migraine frequency, duration, and analgesic use. A single pilot trial found that all postmenopausal women migraineurs treated with subcutaneous testosterone saw their migraines cease within 3 months of follow-up.

Study results on this topic can be affected by potential selection bias, researchers wrote, and available studies often provide incomplete information. As most available data are from studies performed in headache clinics. representing the most severe cases of migraine, results may not be generalizable to the wider population.

“Nevertheless, those data are important as they underline that headache centers usually treat a high number of postmenopausal women with migraine,” authors noted. “Our review also pointed out that postmenopausal migraine can be a relevant issue for gynecologists, as migraine had a high prevalence (about 15%) in women attending a menopause clinic and was associated with a high burden of menopausal symptoms.”

Future collaboration between headache physicians and gynecologists may be useful to assess the burden of disease in this cohort, especially several years after menopause onset.

Researchers underscored that available literature mostly focuses on the menopausal transition period and not on the years after menopause. Migraine worsening during these years may be due to estrogen withdrawal resulting from rapid decreases in estrogen levels. According to authors, “This is the same mechanism which also explains menstrual migraine. The same mechanism can also explain the association between surgical menopause and migraine worsening.”

Future studies should assess the epidemiology of postmenopausal migraine in headache centers and the general population and consider variables such as frequency, duration, and aura presence.

When it comes to HRT, “The available literature data unanimously suggest that any estrogen-progestogen combination used for HRT is associated with migraine worsening.”

The heterogeneous nature of studies included prevented researchers from comparing findings, marking a limitation.

“The population of postmenopausal women with migraine is poorly considered by current literature despite representing a relevant proportion of patients referring to headache centers,” researchers concluded. “Further well-designed and powered observational studies are needed to provide a detailed picture of postmenopausal migraineurs, their characteristics, burden of disease, health resource use, and the effect of different hormonal treatments.”

Reference

Ornello R, Caponnetto V, Frattale I, Sacco S. Patterns of migraine in postmenopausal women: a systematic review. Neuropsychiatr Dis Treat. Published online March 19, 2021. doi: 10.2147/NDT.S285863