Sex and Gender Considerations in Episodic Migraine

We seek to update readers on recent advances in our understanding of sex and gender in episodic migraine with a two part series. In part 1, we examine migraine epidemiology in the context of sex and gender, differences in symptomatology, and the influence of sex hormones on migraine pathophysiology (including CGRP). In part 2, we focus on practical clinical considerations for sex and gender in episodic migraine by addressing menstrual migraine and the controversial topic of hormone-containing therapies. We make note of data applicable to gender minority populations, when available, and summarize knowledge on gender affirming hormone therapy and migraine management in transgender individuals. Finally, we briefly address health disparities, socioeconomic considerations, and research bias.

Migraine is known to be more prevalent, frequent, and disabling in women. There are also differences in migraine co-morbidities and symptomatology. For instance, women are likely to experience more migraine associated symptoms such as nausea, photophobia, and phonophobia. Migraine pathophysiology is influenced by sex hormones, e.g., estrogen withdrawal as a known trigger for migraine. Other hormones such as progesterone and testosterone are less well studied. Relationships between CGRP (the target of new acute and preventive migraine treatments) and sex hormones have been established with both animal and human model studies. The natural course of migraine throughout the lifetime suggests a contribution from hormonal changes, from puberty to pregnancy to menopause/post-menopause. Treatment of menstrual migraine and the use of hormone-containing therapies remains controversial. Re-evaluation of the data reveals that stroke risk is an estrogen dose- and aura frequency-dependent phenomenon. There are limited data on episodic migraine in gender minorities. Gender affirming hormone therapy may be associated with a change in migraine and unique risks (including ischemic stroke with high dose estrogen).

There are key differences in migraine epidemiology and symptomatology, thought to be driven at least in part by sex hormones which influence migraine pathophysiology and the natural course of migraine throughout the lifetime. More effective and specific treatments for menstrual migraine are needed. A careful examination of the data on estrogen and stroke risk suggests a nuanced approach to the issue of estrogen-containing contraception and hormone replacement therapy is warranted. Our understanding of sex and gender is evolving, with limited but growing research on the relationship between gender affirming therapy and migraine, and treatment considerations for transgender people with migraine.