Primary headache disorders frequently present unique clinical challenges across diverse patient populations. Recent epidemiological data highlight that gender identity and exogenous sex steroids fundamentally interact to influence neurovascular biology. Clinicians increasingly evaluate primary headache in transgender men who undergo gender-affirming hormone therapy (GAHT). Most neurological studies traditionally evaluate sex-based biological differences while overlooking social and cultural dimensions of gender. Consequently, significant gaps remain regarding how exogenous testosterone affects headache prevalence, clinical presentation, and overall patient disability.

Neurobiology and Headache in Transgender Men

Sex steroids substantially modulate the trigeminovascular system, cortical spreading depression, and central pain processing pathways. Historically, researchers linked fluctuating estrogen levels to migraine pathophysiology in cisgender women. In contrast, higher circulating androgen levels were thought to confer relative protection against neurovascular inflammation. However, current evidence suggests that endocrine transition introduces a more nuanced neurobiological equilibrium. Transgender men receiving gender-affirming testosterone therapy maintain suppressed endogenous ovarian hormone cycling while establishing stable androgen levels. Therefore, researchers sought to determine whether this hormonal transition shifts headache phenotypes toward masculine or feminine epidemiological patterns. Examining primary headache in this clinical cohort clarifies both biological vulnerabilities and hormonal modulations.

Design of the Brazilian Case-Control Study

Investigators conducted a matched case-control study at the Hospital das Clínicas, Universidade Federal de Pernambuco in Brazil. The research team first completed a pilot study of 50 individuals to determine required statistical power. Subsequently, the investigators enrolled 50 transgender men receiving GAHT, 50 cisgender men, and 50 cisgender women. The team matched both control cohorts by age to the case group. Researchers collected clinical data prospectively between April 2022 and November 2023. They administered semi-structured clinical interviews alongside two validated psychometric instruments: the six-item Headache Impact Test (HIT-6) and the Hospital Anxiety and Depression Scale (HADS). In this study, all transgender men received exogenous testosterone regimens, primarily testosterone cypionate.

Comparative Migraine and Tension-Type Headache Rates

The statistical analyses yielded striking epidemiological observations across the three study cohorts. Transgender men on GAHT exhibited a significantly higher prevalence of migraine compared to cisgender men. Specifically, the odds ratio for any migraine stood at 3.93, while migraine without aura demonstrated an adjusted odds ratio of 3.12 after controlling for affective symptoms. Conversely, transgender men exhibited markedly lower rates of overall headache and tension-type headache compared to cisgender male controls. Interestingly, comparisons between transgender men and cisgender women revealed no statistically significant differences in migraine prevalence or tension-type headache occurrence. Consequently, the neurovascular profile of transgender men on testosterone more closely resembled the female control cohort regarding migraine susceptibility.

Severity Measures and Functional Disability

Beyond headache diagnosis, the investigators meticulously evaluated clinical severity, attack frequency, and everyday functional disability. Adequate statistical power confirmed robust comparisons for tension-type headache frequency and functional impact. Importantly, transgender men demonstrated no significant differences in headache severity metrics compared to cisgender women. The adjusted odds ratio for severe headache frequency of eight or more days per month was 0.54, while moderate-to-severe headache intensity yielded an odds ratio of 1.24. Furthermore, high functional disability, defined by a HIT-6 score of 56 points or higher, showed an adjusted odds ratio of 0.66. Similarly, the study detected no meaningful differences in attack intensity or disability between transgender men and cisgender men.

Clinical Practice Recommendations for Clinicians

These findings provide clear, practical guidance for endocrinologists, neurologists, and primary care physicians managing gender-affirming medical therapies. First, clinicians should actively screen transgender men for migraine before and throughout testosterone administration. Second, healthcare providers must not assume that androgen supplementation automatically eliminates pre-existing migraine syndromes. Third, clinicians should address co-occurring psychological distress, as depression and anxiety frequently exacerbate neurovascular pain. When selecting preventive pharmacotherapy, physicians should choose agents that do not interfere with gender-affirming endocrine regimens. By incorporating routine headache screening into transgender healthcare protocols, practitioners can reduce diagnostic delays, alleviate disability, and optimize long-term clinical outcomes.

What is the prevalence of migraine in transgender men on GAHT?

Transgender men using gender-affirming testosterone therapy exhibit a significantly higher prevalence of migraine compared to cisgender men, with an odds ratio of 3.93. However, their migraine prevalence remains comparable to that observed in cisgender women, indicating persistent neurovascular susceptibility despite active testosterone therapy.

Does testosterone therapy reduce headache disability in transgender men?

Clinical data show that transgender men experience headache disability and attack severity comparable to cisgender controls. Exogenous testosterone therapy does not significantly diminish headache-related disability as measured by the HIT-6 scale, underscoring the ongoing need for standard headache prophylaxis and abortive therapy.

How should physicians screen transgender men for headache disorders?

Physicians should screen transgender men using validated tools like the HIT-6 alongside comprehensive clinical histories before and during hormone therapy. Clinicians must evaluate attack frequency, severity, aura, and comorbid mood disorders to design safe, personalized therapeutic regimens without disrupting gender-affirming endocrine treatments.

Disclaimer: This content is for informational and educational purposes only. It does not constitute medical advice and should not be used as a substitute for professional clinical judgment, diagnosis, or treatment. Medical knowledge and healthcare guidelines continually evolve; readers must verify all information independently against official medical authorities, institutional protocols, and peer-reviewed literature. Pharmaceutical dosages, therapeutic indications, and clinical pathways described herein may change. Healthcare professionals must exercise independent diagnostic and prescribing judgment based on each patient's specific presentation. Neither the authors nor the publishers assume liability for any injury, damage, or clinical decisions made in reliance on this content. Refer to the latest local and national guidelines for clinical practice.

References

1. Trovão Diniz E et al. Headache in transgender men using gender-affirming hormone therapy: A case-control study. Headache. 2025 Sep. doi: 10.1111/head.14944. PMID: 40251852.

2. Hranilovich JA et al. Research needs identified for transgender and gender-diverse patients with headache. Headache. 2021;61(7):1008-1016. doi: 10.1111/head.14167.

3. Rosendal E et al. Headache in individuals undergoing hormone therapy for gender transition: A cross-sectional, observational study. Headache. 2026; doi: 10.1111/head.15076.