Endogenous Testosterone Predicts Cognitive Function in Women with Epilepsy of Child-Bearing Age

Hormonal disruptions due to seizures and antiseizure medications (ASMs) might be responsible for the cognitive dysfunction in people with epilepsy. This study investigated the association between reproductive hormones and Cognitive Impairment (CI) in women with epilepsy (WWE).  A cross-sectional study was conducted on 150 WWE aged 18-45 years. Epilepsy diagnosis was clinical and supported by electroencephalography (EEG). Cognitive function was evaluated using the Community Screening Instrument for Dementia (CSID). Serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), progesterone, estradiol, prolactin, and testosterone were measured during the follicular and luteal menstrual phases. Analyses included Age group, which examined CI distribution across different age ranges, Mann-Whitney U tests for group comparisons, logistic regression for predictors, and receiver operating characteristic (ROC) curve analysis for diagnostic accuracy (p < 0.05). Of the participants, 28% had CI. The CI group exhibited higher follicular-phase LH (p = 0.002) and testosterone (p < 0.001), as well as luteal-phase LH (p = 0.039) and LH/FSH ratio (p = 0.046), but lower luteal-phase progesterone (p = 0.039), estradiol (p = 0.042), and prolactin (p = 0.023) compared to the non-CI group. Logistic regression identified testosterone as the sole significant predictor (p = 0.004; odds ratio = 0.555; 95% confidence interval, 0.373-0.825), indicating a 44.5% reduction in CI odds per unit increase. ROC analysis demonstrated moderate predictive accuracy for testosterone (area under the curve = 0.708; p < 0.001). Elevated follicular-phase LH and testosterone, luteal-phase LH alongside LH/ FSH, are associated with CI in WWE, with testosterone emerging as a key predictor. These findings indicate that hormonal factors play a role in cognitive impairment among individuals with epilepsy and suggest that focusing on hormone-based therapies might augment ASMs to improve treatment outcomes. Keywords: Cognitive impairment, women with epilepsy, luteinizing hormone, testosterone, Mann-Whitney U test, logistic regression.