The Impact of Gender-Affirming Hormone Therapy on Seizure Occurrence in Transgender and Gender-Diverse Individuals

<b>Background/Objectives</b>: Gender-affirming hormone therapy (GAHT) is an essential component of care for transgender and gender-diverse (TGD) individuals, yet its impact on seizure occurrence remains unclear. Given the known influence of hormonal fluctuations on seizure activity, this study evaluates whether GAHT affects seizure frequency in TGD individuals with a history of seizures. <b>Methods</b>: We conducted a retrospective cohort study of TGD individuals with a documented history of seizures who initiated GAHT between January 2002 and November 2024. Patients with inadequate follow-up, poor anti-seizure medication adherence, or concurrent feminizing GAHT (FHT) and masculinizing GAHT (MHT) use were excluded. The primary outcome was seizure occurrence before and after GAHT, subdivided into FHT vs. MHT. <b>Results</b>: Of 4391 TGD individuals, 34 met the inclusion criteria. Among 28 patients who had seizures before GAHT, 10 (35.7%) continued to have seizures after, while 18 (64.3%) did not. Seizure occurrence significantly decreased after GAHT: the proportion of individuals who experienced seizures before but not after GAHT was significantly greater than the proportion of individuals who experienced seizures after but not before GAHT (18/34, 52.9%; 6/34, 17.6%; <i>p</i> = 0.025). Among 21 patients on MHT, the proportion of patients who experienced seizures before but not after MHT was greater than the proportion of patients who experienced seizures after but not before MHT, but the difference was not statistically significant (11/21, 52.4%; 3/21, 14.3%; <i>p</i> = 0.06). FHT had no significant impact on seizure occurrence. <b>Conclusions</b>: GAHT was not associated with increased seizure occurrence in this small study. New-onset seizures occurred equally in the FHT and MHT groups, suggesting no disproportionate effect of estrogen-containing regimens. Our results suggest that GAHT might be safe in TGD individuals with epilepsy, though those with poorly controlled seizures may require closer monitoring. Further research may clarify the impact of GAHT on seizure disorders.