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Endocrine effects of high-dose ketoconazole therapy in advanced prostatic cancer.
- Source :
-
Acta endocrinologica [Acta Endocrinol (Copenh)] 1985 Oct; Vol. 110 (2), pp. 276-83. - Publication Year :
- 1985
-
Abstract
- The endocrine effects of ketoconazole (400 mg orally every 8 h) were studied in 9 previously untreated patients with advanced prostatic cancer. Five of these patients were followed for 12 months. A rapid fall in the serum concentration of testosterone was noted in all patients studied. Minimal values were observed on day 4 of treatment but thereafter serum testosterone increased slowly. The effect of the drug on unbound testosterone was relatively more important, since sex hormone binding globulin increased markedly during treatment. An increase in progesterone and LH was observed in all patients. This suggests that ketoconazole limits the conversion of C21-precursors into androgens. This block is compensated in part by activation of the hypothalamo-hypophyseal feedback system. Urinary 17-ketosteroids were decreased but 17-hydroxysteroids were unaffected by the treatment. In 5 patients followed monthly over a period of 12 months the mean testosterone concentration ranged from 69 ng/100 ml in one patient to 428 ng/100 ml in another. An excellent inverse correlation could be demonstrated between the mean serum concentration of testosterone and the mean concentration of ketoconazole. The change of serum dehydroepiandrosterone sulphate also correlated inversely with the mean ketoconazole level. Increased concentrations of oestradiol were noted in 2 patients with slight gynaecomastia. It is concluded that long-term suppression of androgen production can be realized by high-dose ketoconazole treatment and that the degree of suppression is proportional to the serum levels of the drug.
- Subjects :
- 17-Ketosteroids urine
Dose-Response Relationship, Drug
Estradiol blood
Follicle Stimulating Hormone blood
Humans
Hydrocortisone blood
Hydroxysteroids urine
Luteinizing Hormone blood
Male
Progesterone blood
Prolactin blood
Prostatic Neoplasms metabolism
Testosterone blood
Transcortin blood
Ketoconazole administration & dosage
Prostatic Neoplasms drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 0001-5598
- Volume :
- 110
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Acta endocrinologica
- Publication Type :
- Academic Journal
- Accession number :
- 3933237
- Full Text :
- https://doi.org/10.1530/acta.0.1100276