The objective of this prospective randomized study was to evaluate and compare the hormonal and clinical effects of long-acting gonadotropin-releasing hormone (GnRH) agonist and a combination of GnRH agonist with combined oral contraceptive (COC) or flutamide in women with polycystic ovary syndrome (PCOS). Thirty-five hirsute women with PCOS, ranging in age from 19-27 years, were randomly divided into three groups: group A treated with GnRH agonist (n = 12), group B (n = 12) treated with GnRH agonist plus COC and group C (n = 11) treated with GnRH agonist plus flutamide for 6 months. Before, at the end and 6 months after the end of treatment, blood samples were drawn from all women (in early follicular phase in those with menstrual cycles) to measure ovarian and adrenal androgens, gonadotropins luteinizing hormone (LH) and follicle-stimulating hormone (FSH), estradiol and estrone plasma levels. The results showed that all three protocols had good therapeutic efficacy. A significant reduction in hirsutism was observed in all patients after 6 months of therapy, the Ferriman-Gallwey scores dropping to 9 +/- 3 in group A, 10 +/- 4 in group B and 11 +/- 5 in group C. Six months after the end of therapy, the hirsutism score continued to be significantly reduced in all groups. After 6 months of therapy, a reduction in plasma levels of LH, FSH, estrone, estradiol, testosterone, free testosterone, androstenedione and dehydroepiandrosterone sulfate (DHEAS) was observed in all groups although this was more pronounced in group B and group C. These therapies may be the basis of future treatments that quickly reduce hirsutism and remove its causes by reducing the secretion of ovarian and adrenal androgens and by blocking androgen receptors.