LOW-DOSE KETOCONAZOLE TREATMENT IN HIRSUTE WOMEN

Ketoconazole is an orally active antimycotic agent and a potent inhibitor of gonadal and adrenal steroidogenesis. As inhibitor of steroid production, it has been employed in Cushing’s syndrome, prostatic cancer and precocious puberty due to autonomous Leydig-cell hyperfunction. By virtue of its selective action on androgen synthesis at low doses by inhibition of C17–20 lyase, this drug could be of potential therapeutic utility in hirsutism. We evaluated the hormonal and clinical effects of a low-dose regimen (400 mg/day) for 3 months in 16 women with a spectrum of disorders from idiopathic hirsutism to polycystic ovary syndrome. Four of them completed 6-month treatment. At 3 months, DHEA-S decreased from 9.9 ± 1.0 (mean ± SE) to 6.9 ± 1.0 μmol/L (p < 0.01), androstenedione from 13.3 ± 1.5 to 8.3 ± 1.3 nmol/L (p < 0.005), and testosterone from 4.2 ± 0.4 to 3.1 ± 0.4 nmol/L (p < 0.05). No significant changes were observed in LH, FSH, prolactin and estradiol levels. In patients treated for 6 months, androgens were within normal limits at the end of the study. Eleven out of 16 women (about 70%) reported some improvement in their hirsutism. There was a significant decrease in Ferriman-Gallwey’s score (p < 0.001) and mean hair-shaft diameter (p < 0.001). The patients treated for 6 months showed a further improvement. Pelvic ultrasonography, when repeated (n = 8), was either unchanged or improved. Side effects (polymenorrhea, gastrointestinal reaction, somnolence) were generally mild and transient. Of 20 women who entered the study the dropout rate was 20% (n = 4). Although further studies are needed, these results suggest that low-dose ketoconazole may serve as an additional tool in the management of hirsutism. It seems to decrease both gonadal and adrenal androgen excess without major derangements of the pituitary-gonadal axis. © 1990, Italian Society of Endocrinology (SIE). All rights reserved.