The role of LHRH-analogues in protecting gonadal functions during chemotherapy and irradiation.

Abstract

Therapeutic success has focused attention on late effects in patients with testicular cancer, Hodgkin's disease, non-Hodgkin's lymphoma, and acute leukaemia. Since most patients with testicular cancer are young, the impact of cytotoxic chemotherapy on fertility and hormone deficiency has become particularly important. It has been shown that pulsatile secretion of luteinizing hormone releasing hormone (LHRH) is a prerequisite for normal gonadal function. In contrast, non-pulsatile, chronic treatment with supraphysiological doses of LHRH-analogues (LHRHA) results in suppression of the pituitary-gonadal axis. It has been suggested that inhibition of spermatogenesis during exposure to cytotoxic drugs might reduce gonadal toxicity. The protective effects of LHRHA during chemotherapy or irradiation has been examined in 11 preclinical studies. In only 6 out of 11 models could protection be demonstrated. Four clinical trials have been performed using LHRHA as a gonadal protector. In none of these trials could LHRHA significantly influence severity and duration of germ cell impairment. New approaches are needed to minimize or even prevent gonadal toxicity during chemotherapy or irradiation, such as reduction of courses, alternative schedules, or new drugs.