Endocrinological and histological changes induced by flutamide treatment on the hypothalamo-hypophyseal testicular axis of the adult male rat and their incidences on fertility.

Adult male Wistar rats were treated with flutamide from 90 to 105 days of age. In a first experiment, testis and accessory sex organs were weighed. In the same animals, hypothalamic LRH content, pituitary gonadotrophin concentrations, plasma LH, FSH, prolactin and testosterone levels, and testicular gonadotrophin receptors were evaluated. In a second experiment, fertility was tested at the end of the treatment, and histology of the testis was performed. All the results were compared to those obtained in control animals of the same age. Accessory glands of genital tract were significantly lower in flutamide-treated animals (P less than 0.01). Hypothalamic LRH, pituitary and plasma FSH, and prolactin concentrations were unchanged, while pituitary and plasma LH level and especially plasma testosterone concentration were increased (P less than 0.001). Flutamide therefore exerted a strong inhibition on testosterone-dependent organs, and blocked the negative feedback of testosterone on the hypothalamo-pituitary axis, increasing the LH levels. Testis weight, intertubular tissue volume, total number and total volume of Leydig cells/testis, as well as total length and diameter of seminiferous tubules were unchanged in flutamide treated rats. However number of LH receptors/Leydig cell, nuclear area of Sertoli cells, number of FSH receptors/Sertoli cell, number of leptotene spermatocytes and of round spermatids per cross section, and yield of spermatogonial divisions were decreased after treatment. Flutamide treatment also decreased fertility by 48% (P less than 0.05). This lowered fertility is likely the result of impaired spermatogenesis and/or a dysfunction of accessory sex organs.