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

The majority of transgender and nonbinary individuals receiving gender-affirming hormone therapy reported experiencing headaches.

• Of 160 participants, 102 (63.7%; 95% CI 56.1%-70.8%) reported experiencing headaches.
• The study used a cross-sectional, observational design with an anonymous online survey conducted in Argentina from October 2023 to February 2024.
• Eligible participants were aged ≥18 years and receiving gender-affirming hormone therapy (GAHT).
• Of those reporting headaches, 86.3% (n=88) were receiving testosterone, 11.8% (n=12) estrogens, and 2.0% (n=2) were receiving other GAHT.

A substantial proportion of participants screened positive for migraine-like headaches, far exceeding the rate of prior formal migraine diagnoses.

• Based on the validated Migraine Screen Questionnaire (MS-Q), 46.1% (n=47) of those reporting headaches screened positive for migraine-like headaches.
• Only 24.5% (n=24) of headache reporters reported a prior headache diagnosis.
• Only 18 participants (17.6%; 95% CI 11.3%-26.2%) had a prior diagnosis of migraine.
• This gap between MS-Q-identified migraine-like headache (46.1%) and prior diagnosed migraine (17.6%) indicates a high rate of underdiagnosed headache disorders in this population.

Estrogen-based GAHT was associated with a higher proportion of individuals reporting new or worsening headaches compared to testosterone-based GAHT.

• New headache or worsening of headache was reported by 66.6% of estrogen users.
• New headache or worsening of headache was reported by 27.2% of testosterone users.
• These findings align with the study's hypothesis that estrogen-based GAHT would be associated with increased risk of headache.

Testosterone-based GAHT was more frequently associated with headache improvement or resolution compared to estrogen-based GAHT.

• Improvement or resolution of headaches was reported by 26.1% of testosterone users.
• Improvement or resolution of headaches was reported by only 8.3% of estrogen users.
• These findings align with the study's hypothesis that testosterone-based GAHT would be associated with reduced headache burden.

Migraine disproportionately affects cisgender women, with hormonal fluctuations playing a key role in its pathophysiology, providing the rationale for studying headache in transgender individuals undergoing GAHT.

• The authors note that migraine is a highly disabling headache disorder that disproportionately affects cisgender women.
• Hormonal fluctuations are identified as playing a key role in migraine pathophysiology.
• Despite extensive research in cisgender populations, there is described as a gap in understanding about the prevalence and characteristics of headache disorders in transgender and nonbinary individuals undergoing GAHT.
• The authors state 'there is true urgency to fill this knowledge gap.'