Acute Effects of Aminoglutethimide on Testicular Steroidogenesis in Normal Men

Abstract

Aminoglutethimide (AG), a known adrenal inhibitor, was administered acutely to normalmen in order to study its effects on testicular steroidogenesis. Sixteen subjects between the agesof 21–30 yr received either placebo or 1250 mg AG in divided doses during a 24-h period. To reducethe contribution of adrenal steroids, adrenal function was inhibited in both groups of men by the administration of dexamethasone (2 mg) on the night of the experiment. As a result, mean morning plasma cortisol levels fell to <2 µg/100 ml.

AG blunted the normal diurnal rise in testosterone, which was observed in men receiving placebo, and significantly suppressed the levels of this androgen at 0700 and 0900 h. Estradiol concentr tions fell to a greater extent than those of testosterone. The differences between the placebo anddrug treatment groups were significant at all time points except 1900 h. A pattern similar to that of estradiol was observed for plasma estrone. When the overall effect of AG administration was examined by analysis of variance, the differences in the levels of all three steroids produced by treatment were highly significant (P < 0.01 to <0.001). After the inhibition of testosterone and estradiol levels, LH and FSH concentrations were significantly (P< 0.01 and P < 0.001, respectively) higher in men receiving AG than in those given placebo. However, the data exhibited a large variance due to pulsatile gonadotropin secretion. These observations suggested that AG induces an acute inhibition of testicular steroidogenesis and probably also of the aromatization of testosterone to estradiol. {J Clin Endocrinol Metab49: 631, 1979)