SUN-144 Initiating Estradiol Hormone Therapy in a Transgender Woman With Multifocal Idiopathic Localization-Related Epilepsy

Abstract Disclosure: T. Sia: None. J.J. Chang: None. Introduction: In cis-gender women with epilepsy, estrogen is a potent epileptogenic that decreases the seizure threshold. Estrogen also decreases the serum concentration of lamotrigine, an antiepileptic drug (AED). Data on epilepsy in transgender women on estrogen for gender-affirming hormone therapy (GAHT) remain scarce. Here, we report a case of estradiol (E2) initiation in a transgender woman with epilepsy Case Description A 51-year-old transgender woman with refractory, multifocal idiopathic localization-related epilepsy presented to discuss GAHT. Her seizures were not responsive to ≥5 different AEDs. At the time of presentation, she was on lamotrigine 150 mg and brivaracetam 50 mg twice daily for epilepsy. After discussing the risks and benefits of E2 with the patient and her neurologist, the patient was started on low-dose transdermal E2 0.05 mg/day twice-weekly patch to relieve ongoing gender dysphoria while closely monitoring for seizures. Baseline E2 was 12 pg/mL, and testosterone was 459 ng/dL. At two-month follow up, she noted nipple enlargement. She denied any seizures since starting E2. Mid-cycle E2 levels had elevated to 50 pg/mL. E2 patch was increased to 0.1 mg/day. Four months later, the patient noted breast enlargement, softer skin, and less unwanted hair growth. She noted only one seizure, though the patient noted missing her AEDs. E2 levels increased modestly to 46-79 pg/mL, and testosterone ranged from 257-474 ng/dL. Then, E2 patch was increased to 0.15 mg/day. The patient had increased seizures, so lamotrigine was increased to 200 mg twice daily. Eight months after starting E2, the patient noted continued breast growth and less unwanted hair growth. Her seizures persisted despite increased lamotrigine. E2 was 124 pg/mL, and testosterone was 140 ng/dL. Given that progesterone has been shown to reduce seizures and may further reduce testosterone, the patient was started on progesterone 100 mg daily. She continued to experience seizures, so lamotrigine was increased to 225 mg twice daily. At 1 year from GAHT initiation, the patient reported fat redistribution, finer body hair, and softer skin. She noted some seizures since starting progesterone, though not worse than prior. Interestingly, E2 decreased to 44-83 pg/mL, but testosterone was sufficiently suppressed at 32 ng/dL. At this point, the patient noted that she was overall very satisfied with her progress on GAHT with significantly reduced gender dysphoria. Her neurologist continues to work with her on her seizures. Discussion: GAHT is a life-saving therapy for transgender individuals. Through careful monitoring and management of GAHT and close communication with neurology, the patient has achieved personally satisfactory outcomes with GAHT with her epilepsy overall stable. Our case highlights the importance of multidisciplinary care and safety in starting E2 GAHT in transgender patients with epilepsy. Presentation: Sunday, July 13, 2025