Influence of valproic acid on the gonadotropin-releasing hormone test in puberty

Twelve epileptic adolescents on valproate (VPA) treatment were studied by means of clinical observation and gonadotropin-releasing hormone stimulation (GnRH) tests. Five patients were investigated before and during VPA treatment. Before treatment the basal and peak levels of gonadotropins were appropriate for age; during treatment both levels were depressed and the areas under the curves were significantly decreased. The long-term effect of VPA was studied in an additional seven patients. The basal levels of gonadotropins were as low and their response to GnRH as poor as in the second test of the first five patients--i.e., during VPA treatment. No recovery was noted in two patients after dose reduction or in a further two patients 10 months after the discontinuation of VPA treatment. In all the patients, however, the usual clinical signs of pubertal development and maturity were unaffected by VPA treatment. The significance of the results for sexual development and fertility is therefore uncertain.