Effects of ketoconazole in hirsute women.

To determine the efficacy of ketoconazole in the treatment of hirsutism, clinical and hormonal effects of this agent were evaluated with a randomized, placebo-controlled, double-blind cross-over study design. Nine hirsute women were given ketoconazole (600 mg/day) or placebo for 6 months and then crossed over. The severity of hirsutism was assessed according to the scale of Ferriman & Gallwey. Baseline serum testosterone, dehydroepiandrosterone sulphate, progesterone, estradiol, basal and stimulated cortisol and 17-alpha hydroxyprogesterone were measured. Blood was also drawn for FSH and LH levels at 0, 30, 60, and 90 min of a GnRH stimulation test. The same parameters were determined following administration of placebo or ketoconazole for 6 months. The pretreatment (28.3 +/- 0.9) and post-placebo (27.7 +/- 1.4) Ferriman-Gallwey scores were significantly higher than the post-ketoconazole score (16.6 +/- 1.3, p less than or equal to 0.01). Basal and stimulated cortisol levels were not blunted after ketoconazole, but basal and stimulated 17-hydroxyprogesterone levels were significantly higher, indicating sufficient enzymatic inhibition. Serum dehydroepiandrosterone sulphate and testosterone levels were significantly lowered following ketoconazole (p less than or equal to 0.05). Although E2 levels did not change significantly at any time, E2:testosterone ratios were significantly higher after ketoconazole (p less than or equal to 0.01), and the LH:FSH area ratio was also significantly greater than 3 after ketoconazole. It is concluded that ketoconazole significantly alleviates hirsutism by inhibiting steroid synthesis.