Giving Researchers a Headache – Sex and Gender Differences in Migraine

Abstract

Migraine is a common neurovascular disorder affecting ∼15% of the general population. Ranking second in the list of years lived with disability (YLD), people living with migraine are greatly impacted by this especially burdensome primary headache disorder. In ∼30% of individuals with migraine, transient neurological symptoms occur (migraine aura) that further increase migraine burden. However, migraine burden is differential with respect to sex. Though one-year prevalences in childhood are similar, starting with puberty, migraine incidence increases at a much higher rate in females than males. Thus, migraine over the life course occurs in women three to four times more often than in men. Attacks are also more severe in women, leading to greater disability and a longer recovery period. The sex disparity in migraine is believed to be partly mediated through fluctuations in ovarian steroid hormones, especially estrogen and progesterone, although the exact mechanisms are not yet completely understood. The release of the neuropeptide calcitonin gene-related peptide (CGRP), followed by activation of the trigeminovascular system, is thought to play a key role in the migraine pathophysiology. Given the burden of migraine and its disproportionate distribution, the underlying cause(s) for the observed differences between sexes in the incidence, frequency, and intensity of migraine attacks must be better understood. Relevant biological as well as behavioral differences must be taken into account. To evaluate the scope of the existing knowledge on the issue of biological sex as well as gender differences in migraine, we conducted a systematized review of the currently available research. The review seeks to harmonize existing knowledge on the topic across the domains of biological/preclinical, clinical, and population-level research, which are traditionally synthesized and interpreted in isolation. Ultimately, we identify knowledge gaps and set priorities for further interdisciplinary and informed research on sex and gender differences as well as gender-specific therapies in migraine.

Association between sex hormones and migraine in young Saudi females

“…Control (n=21) MM (n=9) (MIDAS) and the frequency of pain attacks. 9 Thus, the elevated level of the luteal testosterone in our young MM patients might be a protective physiological mechanism and explain the progression of the disease and the increase in the pain frequency and intensity in older females who demonstrated a decrease in testosterone level, as reported by Li et al 9,15 Progesterone levels were not different in any of the studied groups during follicular as well as luteal phases of the menstrual cycle.…”

Metabolic Aspects of Migraine: Association With Obesity and Diabetes Mellitus

“…In view that migraine is a more prevalent disorder in women than in men ( 1 ), it can be suggested that these adipokines could be involved in sexual dimorphism in migraine. On the other hand, considering the importance of sex hormones, including estrogen and testosterone, in migraine pathophysiology ( 152 ) and the role of adipose tissue which serves as an endocrine organ by secreting sex hormones ( 153 ), the association between migraine and obesity might be (partly) attributable to sex hormones. Indeed, the relationship between migraine and obesity has been suggested to be the strongest in women of reproductive age ( 106 , 121 ).…”

Secular Trends in the Incidence of Migraine in China From 1990 to 2019: a Joinpoint and Age-period-cohort Analysis

“…Discussion Prior to this study, no researchers used the age-period-cohort model to explore the secular trends of migraine incidence in China from 1990 and 2019. The burden of migraine is differential with respect to sex and is more common in females than in males [18]. Our study indicated that the evaluation rate of migraine incidence in China is higher in females than in males.…”