Effect of cyproterone acetate (CPA) on gonadal and adrenal function in men

Abstract

The circadian variation in the levels of biologically active luteinizing hormone (hLH), testosterone (T), dihydrotestosterone (DHT), 17-hydroxyprogesterone (17-0H-P), androstenedione (A), pregnenolone (Δ 5P), 17-hydroxypregnenolone (17-0H-Δ 5P), dehydroepiandrosterone (DHEA) and cortisol (C) was investigated in peripheral plasma collected continuously during 36 hours from 10 healthy male subjects (26 to 55 years) before and during the third week of the oral administration of daily doses of 20 mg of cyproterone acetate (CPA). These hormonal indices, complemented with immunoreactive follicle-stimulating hormone (hFSH) and the sulphurylated (solyolyzable) forms of Δ 5P, 17-0H-Δ 5P, DHEA, T and DHT, were also assessed in conjunction with a standardized dexamethasone - ACTH test carried out both before and during the third week of CPA administration. Administration of CPA suppressed significantly the levels of hLH (mean suppression: 39%), hFSH (66%), T (73%), DHT (51%), 17-OH-P (59%) and A (30%) in all subjects, but did not affect the pattern of circadian variation. The levels of sulphurylated T (34%) and DHT (35%) were also suppressed. There was no correlation between the levels of hLH and T, and the former exhibited no circadian variation. Considerable individual variation was found in the behavior of cortisol (C) and unconjugated Δ 5-steroids during CPA administration; the levels of C were significantly elevated in 2 and diminished in 1 subject, whereas Δ 5P and 17-0H-Δ 5P levels were suppressed in 4, and those of DHEA in 3 of the subjects. Similar changes in the levels of most steroids (including those of C) were observed after the administration of dexamethasone and ACTH before and during the treatment period with CPA. However, dexamethasone induced an increase in hLH and T levels in the pretreatment period, but not during CPA administration, whereas the levels of sulphurylated T, DHT and DHEA were elevated by dexamethasone during CPA treatment, but not in the pretreatment period. ACTH increased significantly unconjugated DHT levels during CPA administration, but not in the pretreatment period. It is concluded that CPA in oral doses of 20 mg administered daily for 3 weeks is a powerful inhibitor of pituitary gonadotrophin and testicular steroid secretion in men, but does not interfere with the secretion of cortisol. In addition, it appears that the administration of CPA gives rise to alterations in the metabolism of several steroid sulphates.