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Background: The anti-androgen (flutamide) is widely used nowadays in the treatment of cancer prostate either alone or in combination with Luteinizing Hormone Releasing Hormone (LHRH) analogues. These drugs block androgen receptors, thus prevent growth of cancer cells. Meanwhile, gonadotroph cells of the anterior pituitary may be affected. Aim of the work: To study the effects induced by flutamide administration in the presence or absence of concomitant use of LHRH analogue on gonadotrophs. Materials and methods: Twelve adult male albino rats were divided into three groups: Group (I) rats were served as controls, Group (II) rats were given flutamide orally while Group (III) rats were given flutamide combined with LHRH analogue. The experiment lasted for 20 days after which the rats were sacrificed and pituitary glands were collected. Samples were processed for Hx.&E., immunohistochemistry and electron microscope examination. Results: Gonadotrophs of Group (II) rats showed cytoplasmic vacuolation, castration cells, increased vascularization and decreased immunoreactive cells. E/M examination revealed reduction of secretory granules and dilatation of rER. Morphological changes of nuclei and disappearance of cell membrane were demonstrated. In rats of Group (III), some cells appeared normal while others showed cytoplasmic vacuolation with increased immunoreactive cells compared to Group (II). In E/M examination, most of the rER returned to normal appearance with partial sparing of secretory granules. Most cells showed normal nuclei. Conclusion: Flutamide produced marked histological, immunohistochemical and ultrastructural changes of pituitary gonadotroph cells similar to castration effects which were improved by concomitant use of LHRH analogue.

Background: It was previously documented that hypogonadal men suffer from learning and memory impairment. Recent researches proved the role of the hippocampus in controlling learning and memory functions mediated by the action of gonadal hormones. However, the mechanism of this action is debatable. Aim of the Work: To verify the effects of castration and testosterone substitution on the neuronal structure of the hippocampus in adult male albino rats. Material and Methods: Twenty adult male albino rats were divided into 4 groups : control (group I), castrated nontreated rats (group II), castrated rats provided with immediate daily injections of dihydrotestosterone (group III) and castrated rats injected with daily dihydrotestosterone 3 weeks post surgery (group IV). Six weeks post surgery, all rats were sacrificed and their hippocampi were processed to be examined with the light microscope and transmission electron microscope. Results: Significant structural changes of the hippocampi obtained from Groups II and IV were noticed. Meanwhile, rats of group III showed restoration of the normal hippocampal structure compared to that of the control. Conclusion: Castration affected the structure of the hippocampus which may explain learning and memory impairment in cases of hypogonadism. Early testosterone substitution would prevent these effects. However, late substitution showed no protective role which may indicate that hippocampal damage, when occurs, is irreversible.