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Effects of flutamide, a pure antiandrogen, on endocrine parameters, in the adult female rat


Since antiandrogens having mixed agonistic-antagonistic activities on the androgen receptor have shown benefits in the treatment of hirsutism, the availability of a pure antiandrogen is of particular interest. As a first step, we have thus investigated in detail the effect of the pure antiandrogen Flutamide on endocrine parameters in the female rat. Treatment with the antiandrogen (5 mg, twice daily) for 4 cycles did not affect the 4-day estrous cycle. The antiandrogen had no significant effect on the ovarian level of cytosolic total and available as well as nuclear estrogen receptors in the uterus, and did not affect the concentration of LH and FSH ovarian receptors. The ovarian level of progestins was minimally affected or unchanged on estrus and diestrus I, while an increase was observed under treatment with Flutamide on diestrus II and proestrus. In the plasma, however, there was small or no effect of Flutamide treatment on the concentration of pregnenolone, 17-OH pregnenolone, progesterone and 17-OH-progesterone. The ovarian levels of testosterone (T) and of its two metabolites androstane-3 alpha,17 beta-diol and androstane-3 beta,17 beta-diol were increased by treatment with Flutamide on the morning of diestrus II and proestrus. This was reflected by a 30-100% increase of the levels of plasma T on proestrus. The increase in the ovarian concentration of 5-androstene-3 beta,17 beta-diol (delta 5-diol) and androstenedione observed on diestrus II and on proestrus did not lead to any change in the plasma level of these steroids, which remained normal throughout the estrous cycle during treatment with Flutamide. The ovarian and plasma levels of 17 beta-estradiol were not affected by treatment with the antiandrogen. The present data show that treatment of intact adult female rats with the pure antiandrogen Flutamide has no effect on the estrous cycle, with no significant change in the plasma concentration of the most important estrogenic compound in the rat, namely, 17 beta-estradiol. The present observation of minor endocrine effects of Flutamide in the intact adult female rat supports clinical trials on the use of this antiandrogen, a potential drug of choice for the treatment of hirsutism, acne and alopecia in women.



Pavone-Macaluso M; Serretta V; Pavone C; Romano C; Daricello G;



MRC Group in Molecular Endocrinology, Le Centre Hospitalier de l’Université Laval, Québec, Canada.



Luthy I; Caron S; Bélanger A; Labrie F





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