PROTECTION OF THE GERMINAL EPITHELIUM IN THE RAT FROM THE CYTOTOXIC EFFECTS OF CHEMOTHERAPY BY A LUTEINIZING-HORMONE-RELEASING HORMONE AGONIST AND ANTIANDROGEN THERAPY

Objectives. The protection of spermatogenesis during chemotherapy usin g an antiandrogen and a luteinizing hormone-releasing hormone (LHRH) a gonist was examined in the rat. Previous studies using LHRH agonists a lone have been inconclusive, as both protective and deleterious effect s on the germinal epithelium have been reported. Flutamide has not pre viously been used in this manner but theoretically should protect the germinal epithelium, since flutamide rapidly blocks testosterone at th e cellular level and also minimizes the testosterone ''flare'' when LH RH agonist therapy is initiated. Methods. Mature Sprague-Dawley rats w ere pretreated with flutamide, sustained-release goserelin acetate (Zo ladex), or a combination of flutamide and sustained-release goserelin acetate for 14 days before 4 weekly doses of procarbazine were initiat ed. The seminiferous tubules were evaluated histologically after a 90- day regeneration period using the stem cell assay test. Results. After treatment with procarbazine alone, only 43% of the seminiferous tubul es were active; however, 80% were active if protected with flutamide, 91% if protected with sustained-release goserelin acetate, and 95% if protected with both flutamide and goserelin acetate. Conclusions. Flut amide, sustained-release goserelin acetate, and a combination of these agents were effective in protecting the germinal epithelium of the ra t during chemotherapy. A combination of flutamide and goserelin acetat e provided the best protection. This study demonstrates for the first time the protective effect of flutamide and flutamide with goserelin a cetate on the germinal epithelium during chemotherapy.