PROTECTION OF THE GERMINAL EPITHELIUM IN THE RAT FROM THE CYTOTOXIC EFFECTS OF CHEMOTHERAPY BY A LUTEINIZING-HORMONE-RELEASING HORMONE AGONIST AND ANTIANDROGEN THERAPY
Rd. Cespedes et al., PROTECTION OF THE GERMINAL EPITHELIUM IN THE RAT FROM THE CYTOTOXIC EFFECTS OF CHEMOTHERAPY BY A LUTEINIZING-HORMONE-RELEASING HORMONE AGONIST AND ANTIANDROGEN THERAPY, Urology, 46(5), 1995, pp. 688-691
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.