Objective: Efficacy and tolerability of three doses of flutamide (125, 250, 375 mg) combined with a triphasic oral contraceptive (ethynylestradiol / levonorgestrel) during 12 months to treat moderate to severe hirsutism in patients with polycystic ovary syndrome (PCOS) or idiopathic hirsutism.

Design: Randomized, double blind, placebo-controlled, parallel clinical trial.

Patients: 131 premenopausal women, suffering from moderate to severe hirsutism were randomized to placebo or flutamide 125, 250, 375 mg daily associated with a triphasic oral contraceptive (OC) pill. Hirsutism (Ferriman-Gallwey), acne and seborrhea (Cremoncini), and hormone serum levels were monitored at baseline, 3 (except hormone serum levels), 6 and 12 months. Side effects and biochemical, haematological and hepatic parameters were assessed.

Methods: Three-way analysis of variance (subject, dose, visit) with Scheffé adjustment for multiple comparisons, or non-parametrical Friedman test and Least Square Means (paired data), and Kruskall-Wallis test for unpaired data analyses. Chi-square or Fisher's test for categorical data.

Results: One-hundred and nineteen patients were included in the intention to treat analysis. All flutamide doses induced a significant decrease in hirsutism, acne and seborrhea scores after 12 months compared to placebo; without differences among dose levels. Similar related side effects were observed with placebo and flutamide 125 mg (12.5%), and slightly higher with 250 mg (17.3%) and 375 mg (21.2%). No statistically significant differences were observed either among doses or compared to placebo.

Conclusions: Flutamide 125 mg daily during 12 months was the minimum effective dose to diminish hirsutism in patients with polycystic ovary syndrome or with idiopathic hirsutism.