An investigation into the effects of ketoconazole on testicular function in Wistar rats

Ketoconazole was administered orally to sexually mature Wistar rats and testicular function assessed. A single oral dose of 24 mg ketoconazole/kg body weight lowered plasma testosterone and DHT levels by 83 and 50%, respectively within 2 h, without altering gonadotrophin levels. Treatment for up to 7 days decreased epididymal sperm number and motility and increased the proportion of abnormal sperm. The sperm appeared to be most affected 3 days after a single dose of ketoconazole and recovery had taken place by the seventh day. Daily treatment for up to 90 days also decreased sperm number and motility and increased the proportion of abnormal sperm, but did not affect testicular germ cells. No significant change was noted in the weights of the testis, epididymis, seminal vesicle and prostate; nor was there a change in testicular DNA, RNA and protein contents. Although fertility appeared to be impaired by long-term treatment, some of the treated rats mated successfully.