Primary Hypogonadism Associated with O,P′ DDD (mitotane) Therapy

Abstract

Mitotane is a drug which is concentrated largely in adipose tissue and the adrenal glands. It has a remarkable specificity for the adrenal cortex and can produce necrosis of that organ; consequently, it has been used as a therapeutic agent for adrenocortical carcinoma. Because of the similarity between adrenocortical and testicular tissue, mitotane could be expected to cause testicular damage; however, there is sparse support for this in the literature. We recently studied a patient who developed impotency due to primary testicular failure at the time that he was treated with mitotane. A testicular biopsy, performed about four months after the drug was discontinued, showed normal appearing Leydig cells and atrophy of the seminiferous tubules with the picture of a maturation arrest. In the four and one half years since he last received mitotane, the patient's libido has slowly improved and his plasma testosterone, gonadotropins and LH response to gonadotropin-releasing hormone have become essentially normal. We propose that mitotane can be cytotoxic to the testis as it is to the adrenal cortex.