title: Androgen metabolism in hirsute patients treated with cyproterone acetate.
abstract: Cyproterone acetate (CPA) in association with percutaneously administered estradiol has been used for the treatment of 150 hirsute patients for periods ranging from 6 months to 3 years. A spectacular clinical improvement ensued. Plasma testosterone (T) and androstenedione (A) fell from 69.0 +/- 24 to 33.0 +/- 8 and 210 +/- 103 to 119 +/- 25 ng/dl (mean +/- SD) respectively after 3 months of treatment and remained low thereafter. In contrast, T glucuronide (TG) and 3 alpha-androstanediol (Adiol) remained high during the whole course of treatment: 37 +/- 9 and 115 +/- 43 micrograms/24 h respectively. In vitro T 5 alpha-reductase activity (5 alpha-R) in pubic skin decreased from 147 +/- 34 to 79 +/- 17 fmol/mg skin after 1 year of treatment. To elucidate the discrepancy between plasma and urinary androgens levels, T production rate (PR) and metabolic clearance rate (MCR) were measured with the constant infusion technique in 7 patients before and after 6 months of treatment. PR decreased from 988 +/- 205 to 380 +/- 140 micrograms/24 h (mean +/- SD). In contrast MCRT increased from 1275 +/- 200 to 1632 +/- 360 1/24 h; this increase in MCRT explains the striking plasma T concentration fall and the high TG and Adiol excretion relative to the decrease in PR. Antipyrine clearance rate (n = 8) increased from 36.3 +/- 5.2 to 51.5 +/- 7.4 ml/min whereas 6 beta hydroxycortisol remained unchanged. In conclusion, CPA acts through several mechanisms: (1) it lowers the androgen input to the target cells by (a) depressing T production through its antigonadotropic effect and (b) accelerating T metabolic inactivation due to a partial enzymatic inducer effect on the liver; (2) at the target cell level it competes with any remaining T for the receptor binding sites; (3) the decrease in the androgen-dependent skin 5 alpha-R is a consequence of both actions of androgen suppression and androgen receptor blockade; it reinforces the antiandrogenic effect of CPA.
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism; D000726:Androgen Antagonists / Q000627:therapeutic use*; D000728:Androgens / Q000378:metabolism*; D000735:Androstenedione / Q000097:blood; D002986:Clinical Trials as Topic; D003534:Cyproterone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D017373:Cyproterone Acetate; D005260:Female; D005500:Follow-Up Studies; D006628:Hirsutism / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D012016:Reference Values; D012867:Skin / Q000201:enzymology; D013739:Testosterone / Q000097:blood
chemical_list: D000726:Androgen Antagonists; D000728:Androgens; D013739:Testosterone; D000735:Androstenedione; D017373:Cyproterone Acetate; D003534:Cyproterone; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase