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 f urther suppression of serum testosterone (T) by diethylstilbestrol diphosph ate (DES-DP) in patients with prostate cancer refractory to hormonal treatm ent. These patients received an LHRH agonist with or without a non-steroida l androgen-receptor blocker or a gestagen before DES-DP. We measured serum levels of total and free T, dihydrotestosterone (DHT), estradiol (E-2), deh ydroepiandrosterone sulfate (DHEA-S), dehydroepiandrosterone (DHEA), andros tenedione, cortisol, aldosterone before and during intravenous administrati on of high doses of DES-DP (500 or 1000 mg/day). DES-DP administration supp ressed the serum levels of FSH (p=0.04) and total T (p=0.02), and eliminate d free T (p=0.04) and E-2 (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 increas ed after DES-DP administration. The latter had no significant effect on ser um levels of LH, DHT, ACTH, 17 alpha-hydroxypregnenolone, 17 alpha-hydroxyp rogesterone, DHEA, androstenedione, or aldosterone. The results suggest tha t the potent suppression of circulating total T by DES-DP is caused, in par t, by the inhibitory effect of DES-DP on serum DHEA-S level. In most patien ts, high-dose DES-DP treatment completely suppressed the serum level of fre e T, while possibly elevating serum SHBG and decreasing serum total T. The mechanisms that maintain the serum level of serum DHT during DES-DP treatme nt require further elucidation.