The anticancer drug megestrol acetate (MA) is suspected to cause adrenal insufficiency. Several clinical reports indicated that suppressed adrenal function might be possible in long term administration of MA . The present study was designed to evaluate this issue by using the histological, histochemical and ultrastructural techniques. The data obtained from the present study indicated that MA caused various cellular and subcellular damages in most of the cells of the three zones of adrenal cortex. Histochemical investigations indicated increased lipid content associated with increased storage of ascorbic acid and acid phosphatase, and all these data might reflect a state of suppressed steroidogenesis. The results also indicated that selenium might have a protective role against the cytotoxicity of megestrol acetate on adrenocortical cells. All the results were discussed and it is concluded that more followup of adrenal function should be
done during the long term treatment with MA, and an additional protective supplement .