Effect of chlorambucil on spermatogenesis in the human with malignant lymphoma

Abstract

A group of 8 patients with malignant lymphomas received chlorambucil as the sole medication. It was observed that although an individual susceptibility to this drug exists, an increasingly serious lesion of the germinal epithelium develops with an increase in the accumulated dose of the drug. The germinal cell line disappears, only Sertoli cells remain, and a moderate peritubular fibrosis develops. There was neither morphological evidence of injury to the interstitial cells nor of the vascular apparatus at microscopical level. The degree of injury was found to be dose dependent; the minimum total dose necessary for azoospermia was 400 mg. Recovery from azoospermia could not be observed, as most of the patients continued treatment with other drugs at a later period; recovery from oligospermia did occur if the drug was suspended prior to the threshold dose mentioned. From the data presented, it can be seen that there is a probability of azoospermia developing after ingestion of determined amounts of chlorambucil. Since this condition is probably permanent, due to the extent of the germinal injury, it has to be taken into consideration when such treatment is indicated in patients at reproductive age.