Effect of topiramate and traditional antiepileptic drugs on pituitary-sexual gland axis in adult males with epilepsy*

Abstract

Background Some reports indicate that traditional antiepileptic drugs can cause a certain effect on reproductive endocrine system in epileptic patients. However, the effect of topiramate on reproductive endocrine system needs to be further studied. Objective To compare the effects of topiramate and traditional valproic acid and carbamazepine on pituitary-sexual gland axis in adult males with epilepsy. Design Self-contrast and randomly parallel controlled study. Setting Sichuan Academy of Medical Sciences (Department of Neurology, Sichuan Provincial People's Hospital). Participants A total of 54 male epileptic patients aged from 18 to 75 years were selected from Department of Neurology, Sichuan Provincial People's Hospital from January 2004 to June 2006. All patients were diagnosed as epilepsy based on illness history and electroencephalogram (EEG), and types of epilepsy were classified based on the theory of epilepsy and epilepsy syndrome established by International Anti-epilepsy League in 1989 and 2001. The accepted patients and their relatives provided the confirmed consent. Methods ▪ The accepted patients were randomly divided into traditional treatment group [ n =26, mean age of (34±14) years] and topiramate group [ n =28, mean age of (28±17) years]. In addition, based on various kinds of drugs, patients in the traditional treatment group were divided into two subgroups, including carbamazepine group ( n =14) and valproic acid group ( n =12). Patients in both subgroups were respectively treated with carbamazepine (100 mg/table, Shanghai Sanwei Pharmaceutical Factory, batch number: 060705) and valproic acid (200 mg/table, Hunan Xiangzhong Pharmaceutical Co., Ltd., batch number: 061128). Patients in topiramate group were treated with topiramate (25 mg/table, Xi'an Yangsen Pharmaceutical Co., Ltd., batch number: 060215836). Administration: The beginning dosage of topiramate was 25 mg/d, and then increased 25 mg/d per week. The final dosage was 150 mg/d. In addition, the beginning dosage of carbamazepine was 300 mg/d and the beginning dosage of valproic acid was 500 mg/d. All dosages were regulated based on attack frequency. ▪ Effective evaluation: Attack frequency of epilepsy was regarded as apparent effect (decreased 75%-100%), effect (decreased 50%-75%), poor effect (decreased 25%-50%) and no effect (decreased < 25%). ▪ 3 mL blood was collected from fasting patients at 8 o'clock in the morning before administration and at 6 months after administration so as to detect the changes of dihydroxyestrin (E 2), progestogen (P), total testosterone (TT), luteinizing hormone (LH), follicle stimulating hormone (FSH) and prolactin (PRL). Main outcome measures Comparison of the therapeutic effects between topiramate group and traditional antiepileptic drugs group; changes of sex hormone before and after administration. Results All 54 patients were involved in the final analysis. ▪ Efficacy: Among 26 patients in the traditional treatment group, 14 patients had apparent effect (54%, 14/26), 5 effect (19%, 5/26), 4 poor effect (15%, 4/26), and 3 no effect (12%, 3/26). The totally effective rate was 72% (19/26). Among 28 patients in the topiramate group, 20 patients had apparent effect (72%, 20/28), 4 effect (14%, 4/28), and 4 poor effect (14%, 4/28). The totally effective rate was 86% (24/28). ▪ Level of sex hormone: Level of FSH in the valproic acid group was decreased after treatment as compared with that before treatment [(3.09±1.82), (4.61±1.97) IU/L, P < 0.01]; levels of LH were (5.38±1.89) and (4.97±2.43) IU/L, respectively in the carbamazepine group and topiramate group, which were higher than those before treatment [(3.63±2.16), (3.68±2.09) IU/L, P < 0.05]; level of PRL in the topiramate group was decreased after treatment as compared with that before treatment [(192.17±105.69), (250.07±135.11) mIU/L, P < 0.05]; levels of PRL were lower in the valproic acid group and topiramate group than that in the carbamazepine group after treatment [(186.35±102.66), (192.17±105.69), (289.50±192.43) mIU/L, P < 0.05]. Conclusion Both new and traditional antiepileptic drugs have a certain effect on pituitary-sexual gland axis. In addition, a short-term application (about 6 months) of topiramate can mainly influence on pituitary hormone (LH and PRL). Valproic acid has an obvious effect on FSH and carbamazepine also has a certain effect on LH.