Endogenous Testosterone Predicts Cognitive Function in Women with Epilepsy of Child-Bearing Age
DOI:
https://doi.org/10.54548/چکیده
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
مراجع
1. Hophing L, Kyriakopoulos P, Bui E. Chapter Seven - Sex and gender differences in epilepsy. In: Moro E, Arabia G, Tartaglia MC, Ferretti MT, editors. International Review of Neurobiology [Internet]. Academic Press; 2022 [cited 2025 Oct 2]. p. 235–76. (Sex and Gender Differences in Neurological Disease; vol. 164). Available from: https://www.sciencedirect.com/science/article/pii/S0074774222000708
2. Svalheim S, Sveberg L, Mochol M, Taubøll E. Interactions between antiepileptic drugs and hormones. Seizure - Eur J Epilepsy. 2015 May 1;28:12–7.
3. Eddy CM, Rickards HE, Cavanna AE. The cognitive impact of antiepileptic drugs. Ther Adv Neurol Disord. 2011 Nov;4(6):385.
4. Couper RG, Espino PH, Vicuna MP, Burneo JG. Effects of antiseizure medications on sexual hormones and functions in males with epilepsy: A systematic review and meta-analysis. Epilepsia. 2025 Aug;66(8):2639–56.
5. McEwen BS, Milner TA. Understanding the broad influence of sex hormones and sex differences in the brain. J Neurosci Res. 2017;95(1–2):24–39.
6. Ogunjimi L, Yaria J, Makanjuola A, Alabi A, Osalusi B, Oboh D, et al. Polycystic ovarian syndrome in Nigerian women with epilepsy on carbamazepine/levetiracetam monotherapy. Acta Neurol Scand. 2021 Feb;143(2):146–53.
7. Zhou JQ, Zhou LM, Chen LJ, Han JD, Wang Q, Fang ZY, et al. Polycystic ovary syndrome in patients with epilepsy: A study in 102 Chinese women. Seizure - Eur J Epilepsy. 2012 Nov 1;21(9):729–33.
8. Blair JA, Bhatta S, McGee H, Casadesus G. Luteinizing hormone: Evidence for direct action in the CNS. Horm Behav. 2015 Nov;76:57–62.
9. Stoffel-Wagner B, Bauer J, Flügel D, Brennemann W, Klingmüller D, Elger CE. Serum sex hormones are altered in patients with chronic temporal lobe epilepsy receiving anticonvulsant medication. Epilepsia. 1998 Nov;39(11):1164–73.
10. Höfer P, Lanzenberger R, Kasper S. Testosterone in the brain: Neuroimaging findings and the potential role for neuropsychopharmacology. Eur Neuropsychopharmacol. 2013 Feb 1;23(2):79–88.
11. Li S, Zhang L, Wei N, Tai Z, Yu C, Xu Z. Research Progress on the Effect of Epilepsy and Antiseizure Medications on PCOS Through HPO Axis. Front Endocrinol. 2021 Dec 21;12:787854.
12. Fisher RS, Cross JH, French JA, Higurashi N, Hirsch E, Jansen FE, et al. Operational classification of seizure types by the International League Against Epilepsy: Position Paper of the ILAE Commission for Classification and Terminology. Epilepsia. 2017 Apr;58(4):522–30.
13. Hirsch LJ, Fong MWK, Leitinger M, LaRoche SM, Beniczky S, Abend NS, et al. American Clinical Neurophysiology Society’s Standardized Critical Care EEG Terminology: 2021 Version. J Clin Neurophysiol. 2021 Jan;38(1):1.
14. Herzog AG. Catamenial epilepsy: Update on prevalence, pathophysiology and treatment from the findings of the NIH Progesterone Treatment Trial. Seizure - Eur J Epilepsy. 2015 May 1;28:18–25.
15. Ojo OO, Okubadejo NU, Ojini FI, Danesi MA. Frequency of cognitive impairment and depression in Parkinson’s disease: A preliminary case-control study. Niger Med J J Niger Med Assoc. 2012;53(2):65–70.
16. Ogunjimi L, Yaria J, Makanjuola A, Alabi A, Osalusi B, Oboh D, et al. Polycystic ovarian syndrome in Nigerian women with epilepsy on carbamazepine/levetiracetam monotherapy. Acta Neurol Scand. 2021 Feb;143(2):146–53.
17. Pletzer B, Harris TA, Scheuringer A, Hidalgo-Lopez E. The cycling brain: menstrual cycle related fluctuations in hippocampal and fronto-striatal activation and connectivity during cognitive tasks. Neuropsychopharmacology. 2019 Oct;44(11):1867–75.
18. Lai W, Li X, Zhu H, Zhu X, Tan H, Feng P, et al. Plasma luteinizing hormone level affects the brain activity of patients with polycystic ovary syndrome. Psychoneuroendocrinology. 2020 Feb 1;112:104535.
19. Maguire MJ, Nevitt SJ. Treatments for seizures in catamenial (menstrual‐related) epilepsy. Cochrane Database Syst Rev. 2019 Oct 14;2019(10):CD013225.
20. Velíšková J, DeSantis KA. Sex and Hormonal influences on Seizures and Epilepsy. Horm Behav. 2013 Feb;63(2):267–77.
21. Cutia CA, Christian-Hinman CA. Mechanisms linking neurological disorders with reproductive endocrine dysfunction: insights from epilepsy research. Front Neuroendocrinol. 2023 Oct;71:101084.
22. Wang Q, Geng Y, Li X, Hao Y, Huang S. The Progress of Cognitive Dysfunction Impairment Caused by Temporal Lobe Epilepsy. J Mol Neurosci. 2025;75(3):81.
23. Wahjoepramono EJ, Asih PR, Aniwiyanti V, Taddei K, Dhaliwal SS, Fuller SJ, et al. The Effects of Testosterone Supplementation on Cognitive Functioning in Older Men. CNS Neurol Disord Drug Targets. 2016 Apr;15(3):337–43.
24. Kanojia N, Guin D, Machahary N, Thakran S, Kukal S, Thakur J, et al. Effect of antiepileptic drug monotherapy on endogenous sex hormonal profile in men and women with epilepsy. Epilepsy Behav [Internet]. 2025 Feb 1 [cited 2025 Oct 2];163. Available from: https://www.epilepsybehavior.com/article/S1525-5050%2824%2900602-4/abstract?utm_source=chatgpt.com
25. Reddy DS. Role of hormones and neurosteroids in epileptogenesis. Front Cell Neurosci [Internet]. 2013 July 31 [cited 2025 Oct 4];7. Available from: https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2013.00115/full
26. Sha L, Wu Y, Lai W, Duan Y, Xia Y, Chen L. Heterogeneity in susceptibility to polycystic ovary syndrome among women with epilepsy. Acta Epileptol. 2023 June 19;5(1):14.
27. Li Q, Zhang Z, Fang J. Hormonal Changes in Women with Epilepsy. Neuropsychiatr Dis Treat. 2024 Feb 26;20:373–88.
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حق نشر 2026 Nigerian Journal of Physiological Sciences

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