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.