[A dose-response study of the chronic effect of ketoconazole on androgen and cortisol secretion in women with hyperandrogenism].

We have previously shown that ketoconazole may inhibit the androgen synthesis, but the risk to induce a blockade in the cortisol synthesis and/or hepatic abnormalities makes it mandatory to look for the least dose that is able to inhibit androgen production without inducing other abnormalities. To this end, we studied the levels of 17-alpha-hydroxyprogesterone (17, alpha-OH-P), dehydroepiandrosterone sulphate (DHEA-S), delta 4-androstenedione (delta 4-A), total (tT) and free (fT) testosterone, and the cortisol response to ACTH in 13 women with hyperandrogenism, before and after ketoconazole therapy at dosages of 400, 600, and 800 mg/day. Although with the 400 mg regimen a reduction in the levels of androstenedione and free and total testosterone was already observed, it was of small amount and it was not until the 600 mg regimen that androgen levels became normal. Thus, DHEAS-S was reduced from 3.672 +/- 1.013 to 2.216 +/- 756 ng/ml (p less than 0.05); delta 4-A was reduced from 392 +/- 80 to 283 +/- 79 ng/ml (p less than 0.01); tT was reduced from 1.5 +/- 0.78 to 0.7 +/- 0.1 ng/ml (p less than 0.05), and fT from 5.5 +/- 1.0 to 2.7 +/- 1.3 pg/ml (p less than 0.001). By contrast, 17 alpha-OH-P increased from 1.7 +/- 1.3 to 4.7 +/- 1.3 ng/ml (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)