Effects of intravenous administration of high dose-diethylstilbestrol diphosphate on serum hormonal levels in patients with hormone-refractory prostate cancer.
The objective of this study was to elucidate the mechanism underlying the further suppression of serum testosterone (T) by diethylstilbestrol diphosphate (DES-DP) in patients with prostate cancer refractory to hormonal treatment. These patients received an LHRH agonist with or without a non-steroidal androgen-receptor blocker or a gestagen before DES-DP. We measured serum levels of total and free T, dihydrotestosterone (DHT), estradiol (E2), dehydroepiandrosterone sulfate (DHEA-S), dehydroepiandrosterone (DHEA), androstenedione, cortisol, aldosterone before and during intravenous administration of high doses of DES-DP (500 or 1000 mg/day). DES-DP administration suppressed the serum levels of FSH (p=0.04) and total T (p=0.02), and eliminated free T (p=0.04) and E2 (p=0.04) from serum, while reducing serum DHEA-S to approximately two-thirds of the pretreatment level (p=0.03). In contrast, serum levels of SHBG (p=0.02) and cortisol (p=0.02) were markedly increased after DES-DP administration. The latter had no significant effect on serum levels of LH, DHT, ACTH, 17alpha-hydroxypregnenolone, 17alpha-hydroxyprogesterone, DHEA, androstenedione, or aldosterone. The results suggest that the potent suppression of circulating total T by DES-DP is caused, in part, by the inhibitory effect of DES-DP on serum DHEA-S level. In most patients, high-dose DES-DP treatment completely suppressed the serum level of free T, while possibly elevating serum SHBG and decreasing serum total T. The mechanisms that maintain the serum level of serum DHT during DES-DP treatment require further elucidation.
Kitahara
S
S
Department of Urology, Dokkyo University School of Medicine, Mibu, Tochigi, Japan.
Umeda
H
H
Yano
M
M
Koga
F
F
Sumi
S
S
Moriguchi
H
H
Hosoya
Y
Y
Honda
M
M
Yoshida
K
K
D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002715:Chlormadinone Acetate / Q000627:therapeutic use; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D004054:Diethylstilbestrol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D004958:Estradiol / Q000097:blood; D005640:Follicle Stimulating Hormone / Q000097:blood; D017273:Goserelin / Q000627:therapeutic use; D006728:Hormones / Q000097:blood*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D016729:Leuprolide / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D045167:Progesterone Congeners / Q000627:therapeutic use; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy*; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D013739:Testosterone / Q000097:blood
D000726:Androgen Antagonists; D000970:Antineoplastic Agents; D006728:Hormones; D045167:Progesterone Congeners; D012738:Sex Hormone-Binding Globulin; D017273:Goserelin; D002715:Chlormadinone Acetate; D013739:Testosterone; D004958:Estradiol; D019314:Dehydroepiandrosterone Sulfate; D004054:Diethylstilbestrol; D005640:Follicle Stimulating Hormone; C004955:fosfestrol; D016729:Leuprolide; D006854:Hydrocortisone