Male Wistar rats were treated for three weeks with cyproterone (1·7 or 5·1 mg/day) or cyproterone acetate (2 or 6 mg/day). The adrenal weights of animals treated with either dose of cyproterone acetate were significantly less (P < 0·001) than those of untreated animals. In contrast, the adrenal weights of animals treated with cyproterone did not differ from those of the controls. The concentrations of corticosterone in the plasma were significantly less (P < 0·001) in both groups treated with cyproterone acetate compared with those of the controls; only the higher dose of cyproterone reduced the plasma concentration of corticosterone (P < 0·001).
Cyproterone acetate inhibited the rat adrenal 3β-hydroxysteroid dehydrogenase–5-ene,4-ene-isomerase complex in vitro, with both pregnenolone and dehydroepiandrosterone as substrates. Analysis of the reaction rates suggested an uncompetitive mode of inhibition.
These results suggest that in rats the antiandrogens cyproterone and cyproterone acetate may provoke adrenal insufficiency by inhibition of steroid biosynthesis. Furthermore, indirect evidence from the mass and morphology of the adrenal suggests that cyproterone acetate may also suppress production or secretion of ACTH by the pituitary gland.
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