PMID: 6409130Jan 1, 1983Paper

The inhibiting effect of trilostane on testosterone synthesis. Hormonal and morphologic alterations induced by subchronic trilostane treatment in rats and healthy volunteers

Arzneimittel-Forschung
E JungmannK Schöffling

Abstract

(2 alpha, 4 alpha, 5 alpha, 17 beta)-4, 5-[Epoxy-17-hydroxy-3-oxo-androstane-2-carbonitrile (Trilostane, Win 24450) is a new, orally active, competitive inhibitor of 3 beta-hydroxysteroid dehydrogenase currently being introduced into therapy of Cushing's disease and primary aldosteronism and being investigated in the treatment of low-renin essential hypertension. In adult male rats and in healthy, young, male volunteers the effect of trilostane on testosterone production was studied. Rats were treated with trilostane 150 mg or 300 mg/kg/d for 7 or 14 days. Testosterone in serum was measured by radioimmunoassay, testes were weighed and Leydig cell nuclear volume determined. In healthy volunteers, dehydroepiandrosterone sulphate (DHEAS) and responses of luteinizing hormone (LH), follicle stimulating hormone (FSH) and testosterone to luteinizing hormone releasing hormone (LHRH) stimulation were measured by radioimmunoassay before and during trilostane treatment (240 mg/d). In rats, trilostane treatment decreases testosterone and increases Leydig cell nuclear volumes without affecting testicular weight. In volunteers, basal testosterone is not changed during trilostane treatment but testosterone response to LHRH is impaired. DHEAS ...Continue Reading

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