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Vol. 58. Issue 5.
Pages 443-448 (1 May 2003)
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Vol. 58. Issue 5.
Pages 443-448 (1 May 2003)
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Efectos del ácido valproico sobre el desarrollo sexual
Effects of valproate on sexual development
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J.V. Balaguer Martíneza, M.J. López Garcíaa,
Corresponding author
lopez_margar@gva.es

Correspondencia: Servicio de Pediatría. Hospital Clínic Universitari de València.Avda. Blasco Ibáñez, 17. 46010 Valencia. España.
, M. Andrés Celmaa, A. Contell Villagrasab, M.L. Castelló Pomaresa
A Servicio de Pediatría Hospital Clínic Universitari. Universidad de Valencia. España.
b Laboratorio de Bioquímica. Hospital Clínic Universitari. Universidad de Valencia. España.
Related content
An Pediatr (Barc). 2003;59:1210.1016/S1695-4033(03)78141-7
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Introducción

La utilización del ácido valproico se ha relacionado enniñas y adolescentes con efectos adversos endocrinológicos: ganancia de peso e hiperandrogenismo. Además, enmujeres adultas se han descrito ovarios poliquísticos e hiperinsulinismo. En varones apenas se han estudiado losposibles efectos adversos endocrinológicos.

Objetivos

El objetivo de este estudio fue evaluar los efectos del ácido valproico en el desarrollo puberal en chicas y en chicosepilépticos, en especial relación con su posible efecto hiperandrogénico.

Material y métodos

Se incluyeron 23 chicas y 15 chicos (entre 8 y 16 años)epilépticos, tratados con ácido valproico, se compararoncon 15 niñas control y 10 niños control del mismo rangode edad. Se valoraron índices antropométricos y lasescalas de desarrollo sexual e hiperandrogenismo. Semidieron las concentraciones séricas de hormona foliculostimulante (FSH) y luteinizante (LH), testosterona, androstendiona, deshidroepiandrosterona, estradiol e insulina. Se valoraron los ovarios mediante ecografía y la edadósea mediante radiografía de la mano izquierda.

Resultados

El ácido valproico no afectó el desarrollo puberal en elgrupo estudio. No se apreció hirsutismo ni ovarios poliquísticos. Se observó un aumento de peso, peso relativo eíndice de masa corporal, pero sin que existieran diferencias estadísticamente significativas respecto al grupo control. La testosterona plasmática en las niñas tratadas(0,71 ± 0,51 ng/ml) fue mayor que en el grupo control(0,35 ± 0,15) (p50,001) y este hallazgo fue independiente del tiempo de tratamiento o de la dosis empleada. En loschicos tratados no se encontró hiperandrogenismo.

Conclusiones

El ácido valproico induce hiperandrogenismo analíticoen niñas epilépticas, pero no en niños. Este es un efectoadverso precoz e independiente de la dosis. No hay cambios en el desarrollo puberal normal ni repercusión clínica en los/as pacientes epilépticos/as.

Palabras clave:
Ácido valproico
Pubertad
Hiperandrogenismo
Testos-terona
Introduction

Valproate use in young girls has been associated with theadverse endocrinological effects of weight gain and hyperandrogenism. Furthermore, polycystic ovaries and hyperinsulinism have been described in adult women. In menand young boys, however, the possible adverse endocrinological effects of valproate have scarcely been analyzed.

Objectives

The aim of this study was to evaluate the effects of valproate treatment on pubertal development, especially the possible hyperandrogenic effects, in girls and boys with epilepsy.

Material and methods

Twenty-three girls and 15 boys (aged 8–16 years old) whowere undergoing valproate treatment for epilepsy were compared with 15 control girls and 10 control boys of thesame age range. Anthropometric indexes, sexual maturation, and hirsutism scores were evaluated. Serum concentrations of folliclestimulating hormone (FSH), luteinizinghormone (LH), testosterone, androstenedione, dehydroepiandrosterone, estradiol, and insulin were measured. Ultrasound examination of ovaries and estimation of boneage through X-ray of the left hand were also performed.

Results

Valproate did not affect pubertal development in the study group. No hirsutism or polycystic ovaries were found. Increases in weight, relative weight, and body mass index were observed in the group undergoing valproate treatment, but no statistically significant differences compared with the control group were found. Plasma testosterone was higher in valproate-treated girls (0.71 ±0.51 ng/ml) than in control girls (0.35± 0.15) (p = 5 0.001). This finding was independent of valproate dose and treatment duration. Hyperandrogenism was not found in valproate-treated boys.

Key words:
Valproic acid
Puberty
Hyperandrogenism
Testos-terone
Body weight
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