Short term treatment with ketoconazole: effects on gonadal and adrenal steroidogenesis in women

Ketoconazole, an imidazole derivative, is a large spectrum antifungal agent. The drug is known to cause a decrease in plasma androgens and adrenal steroids in normal men; it is also an active drug in the treatment of malignant tumors of the prostate. To examine the antiandrogenic action of this drug in women, we measured several gonadal and adrenal steroids in 21 normally menstruating women before and after receiving oral ketoconazole (200 mg twice daily) for 5 days. Plasma testosterone (T) decreased from a basal level of 0.35 to 0.25 ng/ml (+/- SEM) (P less than 0.001); dihydrotestosterone (DHT) from a basal level of 190.62 +/- 23.2 to 159.75 +/- 19.43 pg/ml (P less than 0.02); dehydroepiandrosterone sulphate (DHEA-S) from 1.42 +/- 0.44 to 1.15 +/- 0.19 micron/ml (P less than 0.02). Plasma 17 beta-estradiol (E2) decreased from a basal level of 97.42 +/- 29.37 to 54.32 +/- 9.9 pg/ml (P less than 0.05). In contrast, plasma 17-OH-progesterone (17-OHP) levels increased from a basal level of 44.81 +/- 8.21 to 71.81 +/- 15.81 ng/100 ml (P less than 0.05). These results confirm that the ketoconazole blocks the conversion of progestins into androgens. The decrease in the plasma concentration of E2 suggest a direct effect of the ketoconazole on the ovary. It is likely that the effect of the drug, both at the level of the ovaries and of the adrenal gland, is dose-dependent.(ABSTRACT TRUNCATED AT 250 WORDS)