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Hair Loss Study Abstract: Effects of flutamide, a pure antiandrogen, on endocrine parameters, in the adult female rat.
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Title
Effects of flutamide, a pure antiandrogen, on endocrine parameters, in the adult female
rat. Author
Luthy I; Caron S; Bélanger A; Labrie F
Address
MRC Group in Molecular Endocrinology, Le Centre Hospitalier de l'Université Laval,
Québec, Canada. Source
Gynecol Endocrinol, 1: 2, 1987 Jun, 151-68
Abstract
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.
Language of Publication English
Unique Identifier 89022099
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