Corticosteroid-induced inhibition of adrenal androgen production in selected patients with prostate cancer.
OBJECTIVE
To determine the effect of administration of corticosteroids on adrenal androgen production and the serologic markers of prostate cancer.


METHODS
Six patients with prostate cancer who had a serum testosterone concentration that exceeded 20 ng/dL despite treatment with medical or surgical castration were treated with dexamethasone. All patients were asymptomatic, but four were demonstrating progressive increases in serum prostate-specific antigen (PSA) concentrations. Dexamethasone, 1 mg at bedtime, was given initially and then increased to 1 mg twice daily if serum testosterone concentrations remained > or =10 ng/dL. The effect of treatment on PSA concentration was monitored.


RESULTS
The mean testosterone concentration (and standard error of the mean) was 47.5 +/- 7.9 ng/dL before administration of dexamethasone; this decreased to 5.2 +/- 3.0 ng/dL during therapy (P = 0.002). The effect was rapid (overnight) and sustainable (for 6 months). Although the duration of follow-up is limited, PSA concentrations generally stabilized (23.5 +/- 6.1 ng/mL at baseline in comparison with 15.6 +/- 1.1 ng/mL approximately 2 months after initiation of dexamethasone therapy; P = 0.24). Two patients required 1 mg of dexamethasone twice daily to suppress serum testosterone levels to <10 ng/dL.


CONCLUSIONS
Administration of corticosteroids in a manner opposing the normal circadian glucocorticoid production effectively and rapidly decreases adrenal androgen production in patients with prostate cancer treated with orchiectomy or luteinizing hormone-releasing hormone agonists. This reduction of androgen production was generally associated with a decrease or stabilization of PSA concentrations in all patients with increased PSA levels. Overnight dexamethasone suppression testing is useful in determining the minimal effective dose.
Khandwala
H M
HM
Section of Endocrine Neoplasia and Hormonal Disorders, University of Texas, M. D. Anderson Cancer Center, Houston 77030, USA.
Vassilopoulou-Sellin
R
R
Logethetis
C J
CJ
Friend
K E
KE
D000311:Adrenal Glands / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000368:Aged; D000728:Androgens / Q000096:biosynthesis*; D000735:Androstenedione / Q000097:blood; D002940:Circadian Rhythm; D003907:Dexamethasone / Q000008:administration & dosage / Q000627:therapeutic use; D005938:Glucocorticoids / Q000008:administration & dosage / Q000627:therapeutic use*; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists; D006801:Humans; D008297:Male; D008875:Middle Aged; D009919:Orchiectomy; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000601:surgery; D013739:Testosterone / Q000097:blood
D000728:Androgens; D005938:Glucocorticoids; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D000735:Androstenedione; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D017430:Prostate-Specific Antigen