Headache in individuals undergoing hormone therapy for gender transition: A cross-sectional, observational study

OBJECTIVE: To assess the prevalence, frequency, and characteristics of headache disorders in transgender individuals receiving gender-affirming hormone therapy (GAHT), and to explore the relationship between GAHT and headache pathophysiology. We hypothesized that estrogen-based GAHT would be associated with increased risk of headache, particularly migraine, whereas testosterone-based GAHT would be associated with reduced headache burden.

BACKGROUND: Migraine is a highly disabling headache disorder that disproportionately affects cisgender women, with hormonal fluctuations playing a key role in its pathophysiology. Despite extensive research in cisgender populations, there is a gap in our understanding about the prevalence and characteristics of headache disorders, including migraine, in transgender and nonbinary individuals undergoing GAHT, and there is true urgency to fill this knowledge gap.

METHODS: We conducted a cross-sectional, observational study using an anonymous online survey targeting transgender and nonbinary individuals in Argentina from October 2023 to February 2024. Eligible participants were aged ≥18 years and receiving GAHT. The validated Migraine Screen Questionnaire (MS-Q) was used to identify migraine-like headaches. Additional items assessed changes in headache characteristics associated with GAHT.

RESULTS: Of 160 participants, 102 (63.7%; 95% confidence interval [CI] 56.1%-70.8%) reported experiencing headaches. Of these, 86.3% (number [n] = 88) were receiving testosterone, 11.8% (n = 12) estrogens, and 2.0% (n = 2) were receiving other GAHT. Only 24.5% (n = 24) reported a prior headache diagnosis, including 18 participants (17.6%; 95% CI 11.3%-26.2%) with migraine. Based on the MS-Q, 46.1% (n = 47) screened positive for migraine-like headaches. New headache or worsening of headache was more frequently reported by estrogen users (66.6%) compared to those using testosterone (27.2%). Improvement or resolution of headaches was reported by 26.1% of testosterone users compared to 8.3% of estrogen users.

CONCLUSION: Estrogen-based GAHT was associated with a higher proportion of individuals reporting new or worsening headaches, whereas testosterone-based GAHT was more often associated with headache improvement. These associations underscore the need for further research into how GAHT modulates headache patterns, as well as the high rate of underdiagnosed headache disorders in this population.