Effect of antiepileptic drug monotherapy on endogenous sex hormonal profile in men and women with epilepsy

Neha Kanojia; Debleena Guin; Nitin Machahary; Sarita Thakran; Samiksha Kukal; Jyotika Thakur; Biswajit Panda; Priyanka Singh; Ankit Srivastava; Pooja Singh; Sandeep Grover; Anju Singh; Viren Sardana; Luciano Saso; Shrikant Kukreti; Ritushree Kukreti

doi:10.1016/j.yebeh.2024.110220

Effect of antiepileptic drug monotherapy on endogenous sex hormonal profile in men and women with epilepsy

Epilepsy Behav. 2024 Dec 17:163:110220. doi: 10.1016/j.yebeh.2024.110220. Online ahead of print.

Authors

Affiliations

¹ Council of Scientific and Industrial Research -Institute of Genomics and Integrative Biology (CSIR-IGIB), Delhi 110007, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.
² Council of Scientific and Industrial Research -Institute of Genomics and Integrative Biology (CSIR-IGIB), Delhi 110007, India; Department of Biotechnology, Delhi Technological University, Shahbad Daulatpur, Delhi 110042, India.
³ Council of Scientific and Industrial Research -Institute of Genomics and Integrative Biology (CSIR-IGIB), Delhi 110007, India.
⁴ Council of Scientific and Industrial Research -Institute of Genomics and Integrative Biology (CSIR-IGIB), Delhi 110007, India; Department of Pharmacology, Department of Pharmacology, School of Pharmaceutical Education and Research, Jamia Hamdard (Hamdard University), New Delhi 110062, India.
⁵ Centre for Genetic Epidemiology, Institute for Clinical Epidemiology and Applied Biometry, University of Tübingen, Tübingen, Germany.
⁶ Nucleic Acids Research Laboratory, Department of Chemistry, University of Delhi (North Campus), Delhi 110007, India; Department of Chemistry, Ramjas College, University of Delhi, Delhi 110007, India.
⁷ Department of Physiology and Pharmacology "Vittorio Erspamer", Sapienza University of Rome, P. le Aldo Moro 5, 00185 Rome, Italy.
⁸ Nucleic Acids Research Laboratory, Department of Chemistry, University of Delhi (North Campus), Delhi 110007, India.
⁹ Council of Scientific and Industrial Research -Institute of Genomics and Integrative Biology (CSIR-IGIB), Delhi 110007, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India. Electronic address: ritus@igib.res.in.

PMID: 39693860
DOI: 10.1016/j.yebeh.2024.110220

Abstract

Objective: To assess the alterations of endogenous sex hormone profiles in patients with epilepsy (PWE) on different antiepileptic drug (AED) monotherapies compared to healthy controls and drug naïve PWE (DNPWE).

Methods: Four databases MEDLINE, EMBASE, SCOPUS, and CENTRAL were searched for analytical observational/intervention studies on the assessment of endogenous sex hormones in PWE compared to healthy controls and DNPWE. Two researchers reviewed the title/abstract, and full-text articles for the selection of the studies independently. Extracted data included information on study details, participant demographics, interventions, method of assessment and study results. The study outcomes were used to calculate the standard mean differences (SMD) and 95% confidence interval (CI) as effect size for assessing differences in the endogenous sex hormone levels between the treatment group and control/DNPWE.

Results: Among 5888 publications retrieved, 33 studies were included. Enzyme-inducing AEDs (EIAEDs) such as phenytoin (men: SMD = 1.36; 95%CI = 1.06,1.66) and carbamazepine (men: SMD = 0.71; 95%CI = 0.39, 1.04 and women: SMD = 0.54; 95%CI = 0.25, 0.83) and weak-EIAED oxcarbazepine (men: SMD = 0.62; 95%CI = 0.26,0.99) increased the SHBG levels in PWE compared to control. The same trend was observed when comparing it to DNPWE. No significant changes in SHBG were observed for non-EIAEDs valproic acid, lamotrigine and levetiracetam in men. Lamotrigine significantly reduced SHBG in women (SMD = -0.50; 95%CI = -0.85, -0.16) compared to controls. Testosterone (T) levels were significantly reduced for both carbamazepine (SMD = -0.39; 95%CI = -0.67, -0.11) and valproic acid (SMD = -0.48; 95%CI = -0.74, -0.21) treated men compared to control.

Significance: Our findings emphasize the importance of screening the endogenous sex hormonal profile in PWE on AED monotherapies to evaluate the associated endocrine-related perturbations which may impact reproductive functions.

Keywords: Antiepileptic drugs; Gonadal hormone; Gonadotropins; Meta-analysis; Sex hormone binding globulin; Sex steroid; Sex steroid precursor.