Testosterone-estradiol binding globulin (TeBG) in hirsute patients treated with cyproterone acetate (CPA) and percutaneous estradiol.
Testosterone-estradiol binding globulin (TeBG) was studied in 50 hirsute women, before and after 6-month treatment with cyproterone acetate (CPA). 50 mg CPA was administered orally from the 5th to the 25th day of the menstrual cycle and combined with 3 mg 17 beta-estradiol (E2) administered percutaneously from days 16-25 of the cycle. TeBG was evaluated by a filter assay measuring [3H]-DHT binding capacity. Before treatment, the mean plasma TeBG level was 40 +/- 12 nM in hirsute patients, which is significantly lower than TeBG value in normal women (60 +/- 9 nM, n = 20, P less than 0.01) and intermediate between normal women and normal men (30 +/- 8 nM, n = 20). After a 6-month treatment, TeBG strikingly decreased to 22 +/- 8 nM, which is significantly lower than pretreatment values (P less than 0.01) and even less than TeBG level in normal men. Parallel TeBG assay by immunoelectrodiffusion in 8 of these hirsute patients provided similar results. With this treatment, plasma testosterone and delta 4-androstenedione, measured between the 20th and 25th days of the cycle, decreased from 68 +/- 21 to 25 +/- 8 ng/dl, and 210 +/- 95 to 98 +/- 31 ng/dl respectively. Plasma estradiol decreased from 150 +/- 62 pg/ml to 75 +/- 25 pg/ml. In contrast, urinary 3 alpha-androstanediol glucuronide remained high: 112 +/- 51 and 123 +/- 55 micrograms/24 h respectively before and with CPA treatment. Three mechanisms have been proposed to explain TeBG decrease under CPA + E2perc. treatment (1) relative competition of CPA with labelled DHT in the TeBG-binding capacity assay, (2) relative hypoestrogenism with this treatment, (3) a progestagen or even a partial agonistic androgen effect of CPA on TeBG synthesis in the liver. The third mechanism appears to be predominant. In any case. TeBG decrease combined with the partial enzymatic induction effect of CPA on the liver contributes to the increase in the metabolic clearance rate of T and the high urinary Adiol levels previously reported with CPA treatment.
Vincens
M
M
Department of Endrocrinology and Reproductive Medicine, Hôpital Necker, Paris, France.
Mercier-Bodard
C
C
Mowszowicz
I
I
Kuttenn
F
F
Mauvais-Jarvis
P
P
D000293:Adolescent; D000328:Adult; D000726:Androgen Antagonists / Q000627:therapeutic use*; D003534:Cyproterone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D017373:Cyproterone Acetate; D004359:Drug Therapy, Combination; D004958:Estradiol / Q000008:administration & dosage; D005260:Female; D006628:Hirsutism / Q000097:blood* / Q000188:drug therapy; D006801:Humans; D012738:Sex Hormone-Binding Globulin / Q000187:drug effects*
D000726:Androgen Antagonists; D012738:Sex Hormone-Binding Globulin; D017373:Cyproterone Acetate; D004958:Estradiol; D003534:Cyproterone