Abstract
Objective To investigate the long-term effects of treatment with low doses of flutamide on clinical and hormonal parameters, as well as on the androgen receptor status, in hirsute women.
Design Eighteen hirsute patients with regular menses were studied basally and during treatment with 125 mg flutamide, three times per day for 12 months. Barrier or intrauterine contraception was used during the study in sexually active women. Safety parameters were assessed throughout the study. Hirsutism, graded by the modified Ferriman-Gallwey score, and hormonal parameters were evaluated basally and at 4-month intervals during treatment. Gonadotropin-releasing hormone and ACTH stimulation tests were performed before and after 3 to 4 months of therapy. In addition, the concentration of androgen receptors in mononuclear leukocytes was measured, in both the follicular and luteal phases of the menstrual cycle, basally and after 4 months of flutamide treatment.
Results Flutamide was well tolerated in all women, with the noticeable exception of one patient who presented increased serum transaminase after 8 months of therapy. Hirsutism markedly improved in all women during the treatment (Ferriman-Gallwey score after 1 year: 4.1 +/- 0.5 versus 14.1 +/- 0.9). A reduction of serum androgens was found, whereas no change was observed in either basal or GnRH-stimulated gonadotropins or in the cortisol and 17 alpha-hydroxyprogesterone response to ACTH. Cycles remained ovulatory. Before treatment, the number of androgen receptors was higher in the luteal than in the follicular phase. This rhythmic differentiation disappeared after the patients had been given the antiandrogen drug.
Conclusions Flutamide is effective in the treatment of hirsutism but requires constant surveillance of liver function. Androgen receptor blockade might be potentiated by a reduction of serum androgens. Flutamide affects androgen receptor behavior during the menstrual cycle. The meaning of this finding remains to be elucidated.
flutamide treatment hirsutism long-term clinical effects, antiandrogen therapy hirsute women Ferriman-Gallwey score, flutamide androgen receptor mononuclear leukocytes menstrual cycle, low dose flutamide serum androgens reduction hirsutism, androgen receptor behavior follicular luteal phase antiandrogen, flutamide liver function transaminase side effects women, GnRH stimulation test ACTH stimulation hirsute patients, Moghetti flutamide androgen receptor blockade hirsutism, antiandrogen drug ovulatory cycles preservation hirsutism treatment, PCOS hyperandrogenism flutamide 125mg clinical trial
PMID 7641903 7641903 DOI 10.1016/s0015-0282(16)57785-1 10.1016/s0015-0282(16)57785-1
Keywords
Acne Vulgaris/drug Therapy, Adult, Androstenedione/blood, Dehydroepiandrosterone/analogs & Derivatives/blood, Dehydroepiandrosterone Sulfate, Female, Flutamide/adverse Effects/therapeutic Use, Hirsutism/drug Therapy, Humans, Leukocytes, Mononuclear/metabolism, Receptors, Androgen/metabolism, Testosterone/blood, Receptors, Androgen, Testosterone, Androstenedione, Dehydroepiandrosterone, Dehydroepiandrosterone Sulfate, Flutamide