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Effects of high dose ketoconazole therapy on the main plasma testicular and adrenal steroids in previously untreated prostatic cancer patients.
- Source :
-
Clinical endocrinology [Clin Endocrinol (Oxf)] 1986 Jun; Vol. 24 (6), pp. 657-64. - Publication Year :
- 1986
-
Abstract
- In vitro, ketoconazole has been shown to block testicular and adrenal 17,20-lyase, which converts progestins to androgens. At higher concentrations, it also inhibits 11 beta-hydroxylase, 20,22-desmolase and 17 alpha-hydroxylase. To determine the differential hormonal effects of a 2-week ketoconazole high-dose therapy, the plasma levels of 10 major androgens, gluco- and mineralocorticoids were measured in 14 previously untreated patients with metastatic prostate cancer. Within 24 h, plasma testosterone fell from 14.6 +/- 1.4 nmol/l (mean +/- SEM) to 3.7 +/- 0.7 nmol/l. Thereafter, it decreased to about 2.5 nmol/l and remained at that level. Plasma androstenedione and dehydroepiandrosterone decreased more gradually, respectively from 3.1 +/- 0.4 nmol/l to 0.64 +/- 0.17 nmol/l and from 6.6 +/- 1.0 nmol/l to 2.82 +/- 0.55 nmol/l (on day 14). In contrast, 17 alpha-hydroxyprogesterone and progesterone rose respectively 2- and 5-fold. Plasma cortisol and aldosterone levels remained unchanged whereas 11-deoxycorticosterone and 11-deoxycortisol rose by factors of 14 and 6.7 respectively. Plasma corticosterone also increased, but to a much lesser extent (3-fold). These results demonstrate that ketoconazole high dose therapy blocks mainly the 17,20-lyase of both adrenal and testis. In addition it inhibits mitochondrial 11 beta-hydroxylase to a lesser extent. The inhibition of 20,22-desmolase also seems to be of little clinical relevance. However, since clinical or laboratory symptoms suggestive of hypo-adrenalism have been reported in a small minority of patients, replacement therapy should be considered in such cases.
- Subjects :
- 17-alpha-Hydroxyprogesterone
Aged
Androstenedione blood
Corticosterone blood
Cortodoxone blood
Dehydroepiandrosterone blood
Desoxycorticosterone blood
Humans
Hydroxyprogesterones blood
Ketoconazole therapeutic use
Male
Progesterone blood
Testosterone blood
Adrenal Cortex Hormones blood
Androgens blood
Ketoconazole administration & dosage
Prostatic Neoplasms drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 0300-0664
- Volume :
- 24
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Clinical endocrinology
- Publication Type :
- Academic Journal
- Accession number :
- 2947757
- Full Text :
- https://doi.org/10.1111/j.1365-2265.1986.tb01662.x