Previous research has suggested that changes in estrogen may have a proconvulsant effect due to an increase in neuronal excitability. This poses a theoretical concern for patients who are undergoing feminizing hormone therapy and could have implications for their neurologic care.
We report on a case of a transgender patient with drug resistant right hemispheric focal epilepsy receiving responsive neurostimulation with the RNS® System who underwent gender affirming hormone therapy with the stimulator in place, offering objective data with electrocorticography regarding association of hormonal therapy during the gender change process.   

Our patient is a 40-year-old who transitioned to female in adulthood. In childhood, she developed drug resistant focal epilepsy and underwent implantation of the Neuropace RNS system in January 2019. During the process of transitioning, our patient began receiving transdermal estradiol patches in July 2021. Spironolactone was prescribed in December 2021 and progesterone was added in January 2022. She was switched to intramuscular Estradiol injections in June 2022. No changes were made to the antiseizure medication regimen over this time. We followed subjective descriptions of seizure frequency and objective electrocorticography data between July 2021 to September 2024. 

Our patient’s experience suggests that feminizing hormone therapy may increase seizure frequency. There was an observed increase in RNS detection shortly after estrogen initiation, followed by a delayed increase in clinical seizures after 4-5 months.