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Twenty-six preadolescent children ( 16 boys and 10 girls) with minimal lesion nephrotic syndrome, who were either unresponsive to or dependent on corticosteroid therapy, were treated exclusively with chlorambucil. Evaluation of chlorambucil toxicity on the reproductive system was based on penile and testicular size, serum testosterone values, and sperm count. Nine boys had azoospermia and one had oligospermia. The other six, who received a mean cumulative dose of 10.2 mg/kg of chlorambucil, had a normal sperm count. However, we consider that the total safe dose of chlorambucil should not exceed 8.2 mg/kg, equivalent to six weeks treatment at a daily dose of 0.2 mg/kg. In the ten girls, pubertal development was normal; axillary and pubic hair, breast development, age at onset of menarche, and length of the menstrual cycle were all normal; however, the possibility of abnormalities in ovarian functions cannot be excluded.
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