The aim of the current study of 18 hyperandrogenic women was to determine the affects of ketoconazole (KTZ), an oral synthetic antifungal imidazole derivative that inhibits gonadal and adrenal steroidogenesis, on lipids, lipoprotein cholesterols, apolipoproteins, endogenous sex steroid hormones, and their interactions. Eighteen hyperandrogenic women, ages 18 to 35, with a history of severe acne and/or hirsutism, were randomly divided into two groups of nine, both receiving KTZ (group 1, 400 mg/d; group 2,800 mg/d) for 10 days. In groups 1 and 2, KTZ therapy reduced cholesterol (10%, P less than or equal to .01; 19%, P less than or equal to .05) and low-density lipoprotein (LDL)-cholesterol (13%, P less than or equal to .05; 33%, P less than or equal to .025), and increased apolipoprotein (apo) A1 (7%, P less than or equal to .005; 13%, P less than or equal to .01). KTZ, 800 mg/d, decreased apo B (21%, P less than or equal to .005), and lowered the ratio of LDL-cholesterol to high-density lipoprotein (HDL)-cholesterol (40%, P less than or equal to .01). KTZ therapy more than doubled the levels of estradiol (E2) in both groups (136%, P less than or equal to .01; 171%, P less than or equal to .01) and, in the high-dose group, decreased the levels of free testosterone (FT) (48%, P less than or equal to .05) and dehydroepiandrosterone-sulfate (DHEA-S) (36%, P less than or equal to .005). The reductions of total and LDL-cholesterol appear to be attributable to the increases in E2 and possibly to the decrease in FT. KTZ therapy may have beneficial effects on atherogenic lipid and lipoprotein patterns in women with hyperandrogenicity.
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