Epilepsy Management in Transgender Population: More Research for Better Treatment

Abstract

The global transgender population is estimated at approximately 25 million individuals [1]. If epilepsy prevalence in this group mirrors that of the general population, there could be 150,000–450,000 transgender persons with epilepsy worldwide [1]. Despite this significant number, research on this community is notably lacking [1].

This research gap raises concerns about the adequacy of epilepsy treatment for transgender patients, as many aspects of management remains unclear due to the scarcity of observational studies or evidence-based recommendations.

Hormonal changes throughout a woman's life, as well as hormone therapy, may play an important role in the pathogenesis of seizures. However, the limited studies addressing this issue involved cisgender women using hormone therapy for contraception or perimenopausal treatment often with different dosing than that used in gender-affirming hormone therapies (GAHT) [2, 3].

Additionally, significant bidirectional interactions between antiseizure medications (ASMs) and GAHT must be considered in transgender patient treatment [1, 2]. Clinicians should be aware of potential interference from enzyme-inducing ASMs with hormone therapy. Serum levels of lamotrigine or valproic acid should also be monitored when initiating or adjusting estrogen doses, as estrogen can induce the metabolism of these drugs [1, 2].

Transgender individuals with epilepsy also face increased risks for certain comorbidities, including bone mineral density loss and mental health issues, such as depression and suicide [1]. One study revealed that 41% of transgender respondents had attempted suicide, a rate over 25 times higher than that of the general population [1]. Substance abuse is another serious concern, with a meta-analysis showing that 26.7% of transgender women reported illicit drug use, while 43.7% reported alcohol abuse [1]. Moreover, transgender women frequently exhibit low bone density [2]. Eventually, given the increased fracture risk in epilepsy patients and the effects of GAHT and ASMs on bone density, ongoing monitoring and optimization of bone health in this population should be particularly considered [2].

The HIV is a significant concern for transgender, with prevalence rates reaching 12%–16%, higher than in general population [1]. Although data on transgender individuals with both HIV and epilepsy are limited, interactions between antiretroviral therapy and ASMs have been reported [1].

Stigma within healthcare settings presents another challenge. Limited available data indicate that 70% of transgender individuals in the United States have reported discrimination, and 73% hesitate to disclose their identity due to fear of bias [4], potentially leading to significant iatrogenic harm and increased risks for additional health issues.

A survey of Italian neurologists revealed that while many recognized sexual and gender orientation as key health determinants, only few neurologists acknowledged the higher prevalence of health issues in sexual and gender minority populations. The study emphasized the need for specific training and awareness to enhance care for these patients [5].

Considering that no clinical studies have yet addressed epilepsy care in the LGBT+ population, future research should directly evaluate outcomes, focusing on seizure occurrence and control, hormone therapy efficacy, and comorbidity management. As clinicians, we need to have a better understanding on all these aspects to improve our care for this population.

Bruna Nucera: conceptualization, methodology, writing – original draft, writing – review and editing. Francesco Pasini: conceptualization, methodology, writing – original draft, writing – review and editing. Gennarina Arabia: writing – review and editing, supervision. Marianne de Visser: writing – review and editing, supervision. Stephan Rueegg: writing – review and editing, supervision. Bernhard Steinhoff: writing – review and editing, supervision. Isabella Colonna: conceptualization, methodology, writing – original draft, writing – review and editing, supervision.

The authors declare no conflicts of interest.