Sex Differences in Epilepsy Risk Factors and Outcomes in U.S. Veterans
Madeline Evans1, Andrea Hildebrand1, Julie Lynch2, Tia Dinatale2, Mary Jo Pugh2, Zulfi Haneef3, Andrea Schneider4, Nishant Mishra5, Jessica Minnier1, Anh Huan Vo6, Marissa Kellogg1
1Oregon Health and Science University/VA Portland Healthcare System, 2Salt Lake City VA, 3Houston VA, 4University of Pennsylvania, 5West Haven VA, 6Oregon Health and Science University
Objective:
To compare the prevalence of epilepsy-related characteristics among male and female veterans in the VA’s Million Veteran Program (MVP) genetic research biobank.
Background:
Civilian studies describe sexual dimorphism in certain epilepsy-related outcomes (e.g. lower incidence of status epilepticus and higher incidence of genetic generalized epilepsy in women), which suggest genetic factors may modify epilepsy risk. This preliminary epidemiological analysis of epilepsy-related sex differences in MVP lays the foundation for future genetic epidemiology studies.
Design/Methods:
This retrospective cohort study included all Veterans enrolled in MVP by 10/1/2024. Epilepsy-related risk factors and outcomes by sex at birth were determined using diagnostic coding and prescription data extracted from the VA EMR. Logistic regression was performed in R to calculate age-adjusted odds ratios (OR).
Results:
Of the 1,016,584 Veterans enrolled in MVP, 10.49% (n=106,642) were female and 4.14% (n=42,073) developed epilepsy. Median age at enrollment was 58 years in females and 71 in males. Compared to males, female Veterans were more likely to have epilepsy (OR=1.14, 95%CI=1.11-1.18) and benign brain tumors (OR=1.88, 95%CI=1.78-1.98), but less likely to have strokes (OR=0.86, 95%CI=0.84-0.88) and traumatic brain injury (TBI, OR=0.74, 95%CI=0.72-0.75). Females with epilepsy were more likely prescribed three or more anti-seizure medications (ASMs, OR=1.45, 95%CI=1.37-1.55) and undergo neurostimulator placement (OR=1.72, 95%CI=1.37-2.14), but less likely to develop status epilepticus (OR=0.78, 95%CI=0.70-0.86) than males.
Conclusions:
Among Veterans in MVP, females were more likely to develop epilepsy and benign brain tumors than men, but less likely to develop stroke or TBI. Among Veterans with epilepsy, females were more likely to undergo multiple ASM trials and neurostimulation and less likely to develop status epilepticus, which suggests female Veterans may have more refractory epilepsy or are more willing to try different treatments than male Veterans. Future studies will analyze the influence of various risk factors, additional covariates, and genotypes on epilepsy outcomes.
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