Physical Growth and Endocrinal Disorders during Pubertal Maturation in Girls with Epilepsy

Abstract

Summary:Purpose: This study investigated the effect of epilepsy and/or antiepileptic drugs (AEDs) on the physical growth, pubertal development, and androgenic status of girls with epilepsy between ages 8 and 18 years.Methods: Sixty-six female patients with epilepsy, their mean ages 13.47 ± 3.5 years, were included. Anthropometric measurements, staging of pubertal maturation, and clinical manifestations of hyperandrogenism were assessed, as well as measurement of serum levels of testosterone, dehydroepiandrosterone sulfate (DHEAS), sex hormone-binding globulin (SHBG), and free androgen index (FAI). Of the included patients, 44 had transabdominal ultrasonic examination of the ovaries and fasting serum insulin levels were measured. Forty healthy age-matched females served as a control group.Results: Patients showed reduced mean height percentile compared with controls (z = 2.07; p = 0.04), which was negatively correlated with the duration of their epilepsy. Patients showed increased frequency of obesity, especially postpubertal girls taking valproate (VPA; 67%), who also showed higher insulin levels (t = 8.01; p = 0.0003). Patients showed increased frequency of clinical hyperandrogenemia in the different stages of puberty. High levels of testosterone and DHEAS were found in female patients with epilepsy, especially pubertal and postpubertal girls. Hyperandrogenism (clinical and/or laboratory) was most affected by the types of AEDs, with higher incidence in patients taking VPA compared with those taking enzymeinducing AEDs (χ 2 = 9.16; p = 0.01). Eighteen percent of the patients were diagnosed as having polycystic ovary syndrome (PCOS). No difference was found in the types of seizures, degree of seizure control, type of AEDs, or insulin levels between patients with and those without PCOS.Conclusions: Longer duration of the disease has a negative impact on the stature of female patients with epilepsy. Postpubertal girls taking VPA are more liable to obesity, which is associated with increased incidence of hyperinsulinemia. Clinical and/or laboratory evidence of hyperandrogenism is seen at a high frequency in patients, especially with the use of VPA. Furthermore, female patients with epilepsy especially in the postpubertal stage of sexual maturation, have a high prevalence of PCOS, independent of the type of AED or the characteristics of the epilepsy disorder. Key Words: Epilepsy-FemaleAndrogenic hormones-PCOS-Endocrine functions.Reproductive and endocrine functions are of major concerns for clinicians who treat patients with epilepsy. An increased frequency of reproductive endocrine disorders has been reported in women with epilepsy (1). Considerable data pertaining to changes in the hormonal milieu of women with epilepsy and suggest that these individuals are more likely to have derangements of the menstrual cycles and polycystic ovary syndrome (PCOS) (2).A possible role of the seizure disorder or, alternatively, of the use of antiepileptic drugs (AEDs) has been sug-

Endocrine Effects of Valproate versus Carbamazepine in Males with Epilepsy: A Prospective Study

“…These results are compatible with earlier reports of normal height in girls treated with VPA [12,33] and boys treated with diverse antiepileptic drugs for a mean of 3.1 years [33]. By contrast, others reported negative effects of various antiepileptic drugs on height in male adolescents >16 years, regardless of treatment duration [5]. However, the cohort of the latter cross-sectional study was heterogeneous and included patients treated with polytherapy as well as patients with symptomatic epilepsy, and the assessment of shorter height was based on a comparison to healthy age-matched controls.…”

“…It has been associated with an increased frequency of reproductive endocrine disorders in females [2] and abnormal growth and pubertal development in children [3,4,5]. The pathogenic mechanisms underlying the endocrine disorders may be related to impaired hypothalamic regulation of the pituitary by epileptic discharges in the medial temporal lobe [6,7,8] and/or antiepileptic drugs [9,10].…”

Valproate-Induced Insulin Resistance and Obesity in Children

“…The increase in body weight appears to occur most frequently in post-pubertal girls taking VPA [3, 4, 6, 8, 9, 12, 15, 17, 19, 20,25,26,27], although VPA-induced weight gain has also been reported also in pre-pubertal patients [4,5,6,7, 10, 24, 26, 28]. Finally, a recent population-based study reported that increase in body weight is more common in patients treated with VPA during puberty if epilepsy and medication continue into adulthood [16].…”

Massive Carbamazepine Overdose: Any Role of Hemodialysis?: Case Report

“…8 In epi lep tic children, obe sity 12 growth re tar da ti on, hype ran dro genism and polyc ystic ovary syndro me may oc cur du ring the an ti e pi lep tic tre at ment co ur se. 13 The kid ney is ra rely in vol ved, wa ter re ten ti on du e to inap prop ri a te sec re ti on of an ti di u re tic hor mon being the most fre qu ent ad verse re ac ti on. Acu te re nal fa i lu re may appear been related as an ad vers re acti on to CBZ, mostly as a tu bu lo in ters ti ti al nep hri -Özsaraç ve ark.…”