Headache in Transgender and Gender-diverse Patients

A Narrative Review

Jennifer A. Hranilovich MD; Eric A. Kaiser MD, PhD; Anna Pace MD; Mark Barber MD, MPH; Jason Ziplow MD


Headache. 2021;61(7):1040-1050. 

In This Article

Abstract and Introduction


Objective: To summarize the unique aspects of managing headache in gender minorities and current research in this area including the potential relationship between gender-affirming hormone therapy (GAHT) and headache.

Background: The study of headache in gender minorities is intrinsically important. Gender minorities are medically underserved, and their medical care to date has been limited by socioeconomic disadvantages including stigma and an unsupportive clinical environment. Despite the rising population of transgender and gender-diverse adults and youth, headache research has also been limited. Knowledge of hormonal effects on headache in cisgender patients raises the question of possible effects of GAHT on transgender patients.

Methods/Results: The manuscript is a narrative review of current best practices in treating transgender patients, including the use of appropriate terminology and ways to create a supportive environment. It also contains current guidelines on GAHT and reviews drug–drug interactions and secondary headache related to hormone therapy. We also review transgender headache research and related research on hormonal effects on headache in cisgender individuals.

Conclusion: Creating a supportive environment for transgender and gender-diverse patients and being knowledgeable about GAHT are key to providing quality headache care. This review identifies further research needs for this population including the epidemiology of headache disorders in sexual minorities and the potential effects of GAHT on headache disorders in transgender patients.


In 2016, almost 3 billion people were estimated to have a headache disorder. Headache is ranked as the second highest cause of years lived with disability worldwide.[1–3] The peak prevalence of headache is more than 20% higher in adult women than in men,[1,4] and estrogen is known to play a key role in this sex difference.[5] However, we do not know the prevalence of primary headache disorders in transgender men or women (see Table 1 regarding terminology) or how this compares to prevalence of primary headache disorders in cisgender men and women. Although hormones likely influence headache disorders in transgender patients, we have little research in this area.

With a rising population of transgender adults and youth, the Institute of Medicine has identified transgender-specific health needs as a research priority.[6] However, transgender patients are a medically underserved population due to stigma and an unsupportive environment.[7] The precise numbers of individuals who identify as transgender, or the subset of those receiving gender-affirming hormone therapy (GAHT), are difficult to estimate.[7] Population estimates range from 1:11,900 to 1:45,000 for transgender women and 1:30,400 to 1:200,000 for transgender men.[8] These represent worldwide figures over the last 40 years. Further, most agree the proportion of transgender persons receiving GAHT has been increasing.[7,8] In particular, the number of transgender youth treated with histrelin for GAHT, as a percentage of all histrelin implants in youth, has increased from 0% in 2010 to 11% in 2016 in a large multihospital study.[9]

The epidemiology of headache as a condition in transgender individuals is complicated by a lack of population-based studies. One study estimating the prevalence of headache in trans women who had received GAHT from a 50-patient sample in the Netherlands found it to be similar to that of cisgender female adults in the Dutch general population, or 25%.[10] Another that compiled migraine-related Twitter postings over 1 week reported a gender breakdown of self-reported gender of 0.01% (2/14,028) suggesting that transgender individuals may actually be overrepresented compared with cisgender individuals in the population of those who posted on migraine.[11] Although this is a small population, primary headache disorders are common and likely affect a significant proportion of transgender patients.

The aim of this review is twofold. First, we discuss the management of headache in the transgender population, including potential causes of secondary headache and important drug–drug interactions. Second, we summarize GAHT-related headache research. Although clinical studies of headache in transgender persons are scarce, two studies have shown GAHT to worsen headache in transgender women and improve headache in transgender men.[10,12] Prospective trials of the effects of GAHT on headache in adults and children are needed. Until this occurs, recommendations for treatment considerations for this population and the research to date in this area are summarized here as expert opinion (class IV evidence).