An examination of sex hormone levels in epilepsy patients taking antiepileptic treatment
Examination of sex hormone levels in epilepsy patients taking antiepileptic treatment
Keywords:epilepsy, antiepileptic drugs, sex hormones
Reproductive adverse events may be observed in patients with epilepsy associated with antiepileptic drugs. This study aimed to evaluate changes in sex hormone levels in patients receiving antiepileptic treatment as monotherapy and polytherapy.
In this case-control study, the sex hormone levels and free androgen indexes were evaluated in 83 patients and 40 controls. In the hormone evaluations, measurements were performed for dehydroepiandrosterone sulfate, sex hormone-binding globulin, follicle-stimulating hormone, luteinizing hormone, total and free testosterone, prolactin and estradiol levels.
A total of 83 patients (42 males, 41 females) with a mean age of 28±7.2 years and a control group of 40 healthy subjects (14 males, 26 females) with a mean age of 33±8.7 years were included. In the patient group, 45 were receiving monotherapy and 38 polytherapy, 13 (15.7%) patients had focal onset seizures, 68 (81.9%) had generalized onset seizure and 2 (2.4%) had seizure type of unknown origin. In the males of the study group, no difference was determined in the hormone levels. In the females of the study group, the free androgen index was determined to be significantly low in the carbamazepine group compared to the control group (p=0.04) and the sex hormone-binding globulin values were significantly high (p=0.01). In males, a significant positive correlation was determined between serum carbamazepine and follicle-stimulating hormone (p=0.046) and prolactin (p=0.035) and a significant negative correlation was determined with the free androgen index (p=0.032). In females, a statistically significant positive correlation was determined between carbamazepine and prolactin (p=0.036).
The use of antiepileptic drugs creates changes in the sex hormone levels in males, and associated reproductive side-effects may be seen. In the management of patients with epilepsy, an awareness of these side-effects and individual evaluation could have a positive effect on treatment compliance and patient satisfaction.
Kwan P, Arzimanoglou A, Berg AT, Brodie MJ, Allen Hauser W, Mathern G, et al. Definition of drug resistant epilepsy: consensus proposal by the ad hoc task force of the ILAE commission on therapeutic strategies. Epilepsia 2010; 51: 1069-77.
Isojärvi JI, Laatikainen TJ, Pakarinen AJ, Juntunen KT, Myllylä VV. Polycystic ovaries and hyperandrogenism in women taking valproate for epilepsy. N Engl J Med 1993; 329: 1383-8.
Herzog AG, Seibel MM, Schomer DL, Vaitukaitis JL, Geschwind N. Reproductive endocrine disorders in men with partial seizures of temporal lobe origin. Arch Neurol 1986; 43: 347-50.
Artama M, Isojärvi JI, Auvinen A. Antiepileptic drug use and birth rate in patients with epilepsy--a population-based cohort study in Finland. Hum Reprod 2006; 21: 2290-5.
Calabrò RS, Marino S, Bramanti P. Sexual and reproductive dysfunction associated with antiepileptic drug use in men with epilepsy. Expert Rev Neurother 2011; 11: 887-95.
Verrotti A, D'Egidio C, Mohn A, Coppola G, Parisi P, Chiarelli F. Antiepileptic drugs, sex hormones, and PCOS. Epilepsia 2011; 52: 199-211.
Gorkemli H, Genc BO, Dogan EA, Genc E, Ozdemir S. Long-term effects of valproic acid on reproductive endocrine functions in Turkish women with epilepsy. Gynecol Obstet Invest 2009; 67: 223-7.
Bauer J, Cooper-Mahkorn D. Reproductive dysfunction in women with epilepsy: menstrual cycle abnormalities, fertility, and polycystic ovary syndrome. Int Rev Neurobiol 2008; 83: 135-55.
Isojärvi JI, Löfgren E, Juntunen KS, Pakarinen AJ, Päivänsalo M, Rautakorpi I, et al. Effect of epilepsy and antiepileptic drugs on male reproductive health. Neurology 2004; 62: 247-53.
Røste LS, Taubøll E, Haugen TB, Bjørnenak T, Saetre ER, Gjerstad L. Alterations in semen parameters in men with epilepsy treated with valproate or carbamazepine monotherapy. Eur J Neurol 2003; 10: 501-6.
Gastaut H, Collomb H. Etude du comportement sexuel chez les epileptiques psychomoteurs [Sexual behavior in psychomotor epileptics]. Ann Med Psychol (Paris) 1954; 112: 657-696. French.
Jensen P, Jensen SB, Sørensen PS, Bjerre BD, Rizzi DA, Sørensen AS, et al. Sexual dysfunction in male and female patients with epilepsy: a study of 86 outpatients. Arch Sex Behav 1990; 19: 1-14.
Zhao S, Tang Z, Xie Q, Wang J, Luo L, Liu Y, et al. Association between epilepsy and risk of sexual dysfunction: a meta-analysis. Seizure 2019; 65: 80-8.
Edwards HE, Burnham WM, Ng MM, Asa S, MacLusky NJ. Limbic seizures alter reproductive function in the female rat. Epilepsia 1999; 40: 1370-7.
Morrell MJ, Montouris GD. Reproductive disturbances in patients with epilepsy. Cleve Clin J Med 2004; 71 Suppl 2: S19-24.
Luef G, Madersbacher H. Sexual dysfunction in patients with epilepsy. Handb Clin Neurol 2015; 130: 383-94.
Kuba R, Pohanka M, Zákopcan J, Novotná I, Rektor I. Sexual dysfunctions and blood hormonal profile in men with focal epilepsy. Epilepsia 2006; 47: 2135-40.
Du AT, Schuff N, Kramer JH, Ganzer S, Zhu XP, Jagust WJ, et al. Higher atrophy rate of entorhinal cortex than hippocampus in AD. Neurology 2004; 62: 422-7.
Klüver H, Bucy PC. Preliminary analysis of functions of the temporal lobes in monkeys. 1939. J Neuropsychiatry Clin Neurosci 1997; 9: 606-20.
Svalheim S, Taubøll E, Luef G, Lossius A, Rauchenzauner M, Sandvand F, et al. Differential effects of levetiracetam, carbamazepine, and lamotrigine on reproductive endocrine function in adults. Epilepsy Behav 2009; 16: 281-7.
Rättyä J, Turkka J, Pakarinen AJ, Knip M, Kotila MA, Lukkarinen O, et al. Reproductive effects of valproate, carbamazepine, and oxcarbazepine in men with epilepsy. Neurology 2001; 56: 31-6.
Isojärvi JI, Repo M, Pakarinen AJ, Lukkarinen O, Myllylä VV. Carbamazepine, phenytoin, sex hormones, and sexual function in men with epilepsy. Epilepsia 1995; 36: 366-70.
Isojärvi JI, Taubøll E, Herzog AG. Effect of antiepileptic drugs on reproductive endocrine function in individuals with epilepsy. CNS Drugs 2005;19: 207-23.
Duncan S, Blacklaw J, Beastall GH, Brodie MJ. Antiepileptic drug therapy and sexual function in men with epilepsy. Epilepsia 1999; 40: 197-204.
Verrotti A, Mencaroni E, Cofini M, Castagnino M, Leo A, Russo E, et al. Valproic acid metabolism and its consequences on sexual functions. Curr Drug Metab 2016; 17: 573-81.
Stephen LJ, Sills GJ, Leach JP, Butler E, Parker P, Hitiris N, et al. Sodium valproate versus lamotrigine: a randomised comparison of efficacy, tolerability and effects on circulating androgenic hormones in newly diagnosed epilepsy. Epilepsy Res 2007; 75: 122-9.
Kwan P, Yip FP, Hui AC, Leung H, Ng PW, Hui KF, et al. Effects of valproate or lamotrigine monotherapy on the reproductive endocrine and insulin-related metabolic profile in Chinese adults with epilepsy: a prospective randomized study. Epilepsy Behav 2009; 14: 610-6.
Taubøll E, Gregoraszczuk EL, Tworzydø A, Wójtowicz AK, Ropstad E. Comparison of reproductive effects of levetiracetam and valproate studied in prepubertal porcine ovarian follicular cells. Epilepsia 2006; 47: 1580-3.
Galimberti CA, Magri F, Copello F, Arbasino C, Cravello L, Casu M, et al. Seizure frequency and cortisol and dehydroepiandrosterone sulfate (DHEAS) levels in women with epilepsy receiving antiepileptic drug treatment. Epilepsia 2005; 46: 517-23.
How to Cite
Copyright (c) 2022 Kastamonu Medical Journal
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.