[Effects of valproate on sexual development].
BACKGROUND
Valproate use in young girls has been associated with the adverse endocrinological effects of weight gain and hyperandrogenism. Furthermore, polycystic ovaries and hyperinsulinism have been described in adult women. In men and young boys, however, the possible adverse endocrinological effects of valproate have scarcely been analyzed.


OBJECTIVE
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.


METHODS
Twenty-three girls and 15 boys (aged 8-16 years old) who were undergoing valproate treatment for epilepsy were compared with 15 control girls and 10 control boys of the same age range. Anthropometric indexes, sexual maturation, and hirsutism scores were evaluated. Serum concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, androstenedione, dehydroepiandrosterone, estradiol, and insulin were measured. Ultrasound examination of ovaries and estimation of bone age 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 0.001). This finding was independent of valproate dose and treatment duration. Hyperandrogenism was not found in valproate-treated boys.


CONCLUSIONS
Valproate may induce hyperandrogenism in epileptic girls but not in boys. This is an early adverse effect and is independent of the dose used. No changes in normal pubertal development or physical repercussions were found in epileptic patients.
Servicio de Pediatría. Hospital Clínic Universitari. Universidad de Valencia. España.
J V
JV
Balaguer Martínez
M J
MJ
López García
M
M
Andrés Celma
A
A
Contell Villagrasa
M L
ML
Castelló Pomares
D000365:Age Determination by Skeleton; D000886:Anthropometry; D000927:Anticonvulsants / Q000009:adverse effects* / Q000627:therapeutic use; D002648:Child; D004827:Epilepsy / Q000188:drug therapy*; D005260:Female; D012739:Gonadal Steroid Hormones / Q000097:blood / Q000378:metabolism*; D006801:Humans; D017588:Hyperandrogenism / Q000139:chemically induced*; D008297:Male; D011627:Puberty / Q000187:drug effects*; D012737:Sex Factors; D014635:Valproic Acid / Q000009:adverse effects* / Q000627:therapeutic use
D000927:Anticonvulsants; D012739:Gonadal Steroid Hormones; D014635:Valproic Acid