Sex and Gender Considerations in Episodic Migraine

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Abstract

Purpose of Review

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.

Recent Findings

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).

Summary

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.

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Most cited references 83

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Pathophysiology of Migraine: A Disorder of Sensory Processing.

Peter J Goadsby, Philip Holland, Margarida Martins-Oliveira … (2017)

Plaguing humans for more than two millennia, manifest on every continent studied, and with more than one billion patients having an attack in any year, migraine stands as the sixth most common cause of disability on the planet. The pathophysiology of migraine has emerged from a historical consideration of the "humors" through mid-20th century distraction of the now defunct Vascular Theory to a clear place as a neurological disorder. It could be said there are three questions: why, how, and when? Why: migraine is largely accepted to be an inherited tendency for the brain to lose control of its inputs. How: the now classical trigeminal durovascular afferent pathway has been explored in laboratory and clinic; interrogated with immunohistochemistry to functional brain imaging to offer a roadmap of the attack. When: migraine attacks emerge due to a disorder of brain sensory processing that itself likely cycles, influenced by genetics and the environment. In the first, premonitory, phase that precedes headache, brain stem and diencephalic systems modulating afferent signals, light-photophobia or sound-phonophobia, begin to dysfunction and eventually to evolve to the pain phase and with time the resolution or postdromal phase. Understanding the biology of migraine through careful bench-based research has led to major classes of therapeutics being identified: triptans, serotonin 5-HT1B/1D receptor agonists; gepants, calcitonin gene-related peptide (CGRP) receptor antagonists; ditans, 5-HT1F receptor agonists, CGRP mechanisms monoclonal antibodies; and glurants, mGlu5 modulators; with the promise of more to come. Investment in understanding migraine has been very successful and leaves us at a new dawn, able to transform its impact on a global scale, as well as understand fundamental aspects of human biology.

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Sex differences in the prevalence, symptoms, and associated features of migraine, probable migraine and other severe headache: results of the American Migraine Prevalence and Prevention (AMPP) Study.

Dawn Buse, Elizabeth W Loder, Jennifer A Gorman … (2013)

The strikingly higher prevalence of migraine in females compared with males is one of the hallmarks of migraine. A large global body of evidence exists on the sex differences in the prevalence of migraine with female to male ratios ranging from 2:1 to 3:1 and peaking in midlife. Some data are available on sex differences in associated symptoms, headache-related disability and impairment, and healthcare resource utilization in migraine. Few data are available on corresponding sex differences in probable migraine (PM) and other severe headache (ie, nonmigraine-spectrum severe headache). Gaining a clear understanding of sex differences in a range of severe headache disorders may help differentiate the range of headache types. Herein, we compare sexes on prevalence and a range of clinical variables for migraine, PM, and other severe headache in a large sample from the US population. This study analyzed data from the 2004 American Migraine Prevalence and Prevention Study. Total and demographic-stratified sex-specific, prevalence estimates of headache subtypes (migraine, PM, and other severe headache) are reported. Log-binomial models are used to calculate sex-specific adjusted prevalence ratios and 95% confidence intervals for each across demographic strata. A smoothed sex prevalence ratio (female to male) figure is presented for migraine and PM. One hundred sixty-two thousand seven hundred fifty-six individuals aged 12 and older responded to the 2004 American Migraine Prevalence and Prevention Study survey (64.9% response rate). Twenty-eight thousand two hundred sixty-one (17.4%) reported "severe headache" in the preceding year (23.5% of females and 10.6% of males), 11.8% met International Classification of Headache Disorders-2 criteria for migraine (17.3% of females and 5.7% of males), 4.6% met criteria for PM (5.3% of females and 3.9% of males), and 1.0% were categorized with other severe headache (0.9% of females and 1.0% of males). Sex differences were observed in the prevalence of migraine and PM, but not for other severe headache. Adjusted female to male prevalence ratios ranged from 1.48 to 3.25 across the lifetime for migraine and from 1.22 to 1.53 for PM. Sex differences were also observed in associated symptomology, aura, headache-related disability, healthcare resource utilization, and diagnosis for migraine and PM. Despite higher rates of migraine diagnosis by a healthcare professional, females with migraine were less likely than males to be using preventive pharmacologic treatment for headache. In this large, US population sample, both migraine and PM were more common among females, but a sex difference was not observed in the prevalence of other severe headache. The sex difference in migraine and PM held true across age and for most other sociodemographic variables with the exception of race for PM. Females with migraine and PM had higher rates of most migraine symptoms, aura, greater associated impairment, and higher healthcare resource utilization than males. Corresponding sex differences were not observed among individuals with other severe headache on the majority of these comparisons. Results suggest that PM is part of the migraine spectrum whereas other severe headache types are not. Results also substantiate existing literature on sex differences in primary headaches and extend results to additional headache types and related factors. © 2013 American Headache Society.

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Migraine prevalence by age and sex in the United States: a life-span study.

TW Victor, X. Hu, JC Campbell … (2010)

The present study assessed age- and sex-specific patterns of migraine prevalence in a US population of 40,892 men, women, and children who participated in the 2003 National Health Interview Survey. Gaussian mixture models characterised the relationship between migraine, age, and sex. Migraine prevalence was 8.6% (males), 17.5% (females), and 13.2% (overall) and showed a bimodal distribution in both sexes (peaking in the late teens and 20s and around 50 years of age). Rate of change in migraine prevalence for both sexes increased the fastest from age 3 years to the mid-20s. Beyond the age of 10 years, females had a higher prevalence of migraine than males. The prevalence ratio for females versus males was highest during the female reproductive/child-bearing years, consistent with a relationship between menstruation and migraine. After age 42 years, the prevalence ratio was approximately 2-fold higher in women.

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Author and article information

Contributors

Sarah R. Ahmad:

ORCID: http://orcid.org/0000-0001-5500-3100

Sarah.Ahmad@ucsf.edu

Nicole Rosendale:

ORCID: http://orcid.org/0000-0002-2431-5440

Nicole.Rosendale@ucsf.edu

Journal

Journal ID (nlm-ta): Curr Pain Headache Rep

Journal ID (iso-abbrev): Curr Pain Headache Rep

Title: Current Pain and Headache Reports

Publisher: Springer US (New York )

ISSN (Print): 1531-3433

ISSN (Electronic): 1534-3081

Publication date (Electronic): 9 June 2022

Publication date PMC-release: 9 June 2022

Publication date (Print): 2022

Volume: 26

Issue: 7

Pages: 505-516

Affiliations

[1 ]GRID grid.266102.1, ISNI 0000 0001 2297 6811, Headache Division, , University of California, ; San Francisco, CA USA

[2 ]GRID grid.266102.1, ISNI 0000 0001 2297 6811, Neurohospitalist Division, , University of California, ; San Francisco, CA USA

Author information

Sarah R. Ahmad http://orcid.org/0000-0001-5500-3100

Nicole Rosendale http://orcid.org/0000-0002-2431-5440

Article

Publisher ID: 1052

DOI: 10.1007/s11916-022-01052-8

PMC ID: 9325838

PubMed ID: 35679008

SO-VID: 627d8ef5-1fa2-49a3-8f58-d87c9114d1f6

License:

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