Abstract
The effects of ketoconazole on pituitary-ovarian function and adrenal function were evaluated in nine hirsute women treated with 400-1200 mg/day for 1-6 months. High dose (800-1200 mg/day) ketoconazole treatment decreased serum androstenedione, dehydroepiandrosterone, and testosterone (T) concentrations, while that of 17 alpha-hydroxyprogesterone increased, suggesting a steroidogenic block at the level of 17,20-desmolase. The decreased serum T and increased sex hormone-binding globulin concentrations led to a significant decrease in the free androgen index. Serum estradiol, cortisol, and dehydroepiandrosterone sulfate concentrations did not change. The serum LH concentration and the LH to FSH ratio increased during treatment, suggesting a negative feedback effect of T on pituitary LH secretion. The hormonal changes that occurred during high dose ketoconazole therapy persisted during subsequent low dose (400 mg/day) treatment. The therapeutic effect of ketoconazole on hirsutism manifested itself at 6 months. We conclude that ketoconazole reduces excessive androgen production in a dose-dependent manner and decreases the free androgen index in hirsute women; these changes are accompanied by significant alleviation of hirsutism.
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