Kitahara S, Umeda H, Yano M, Koga F, Sumi S, Moriguchi H, Hosoya Y, Honda M, Yoshida K
Department of Urology, Dokkyo University School of Medicine, Mibu, Tochigi, Japan.
Endocr J. 1999 Oct;46(5):659-64. doi: 10.1507/endocrj.46.659.
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.
本研究的目的是阐明磷酸己烯雌酚（DES-DP）对激素治疗难治性前列腺癌患者血清睾酮（T）进一步抑制作用的潜在机制。这些患者在接受DES-DP治疗前，接受了促性腺激素释放激素（LHRH）激动剂，联合或不联合非甾体类雄激素受体阻滞剂或孕激素治疗。我们在静脉注射高剂量DES-DP（500或1000mg/天）之前和期间，测量了血清总睾酮、游离睾酮、双氢睾酮（DHT）、雌二醇（E2）、硫酸脱氢表雄酮（DHEA-S）、脱氢表雄酮（DHEA）、雄烯二酮、皮质醇、醛固酮的水平。给予DES-DP后，血清促卵泡生成素（FSH）水平（p=0.04）和总睾酮水平（p=0.02）受到抑制，血清游离睾酮（p=0.04）和E2（p=0.04）被清除，同时血清DHEA-S水平降至治疗前水平的约三分之二（p=0.03）。相反，给予DES-DP后，血清性激素结合球蛋白（SHBG）水平（p=0.02）和皮质醇水平（p=0.02）显著升高。后者对血清黄体生成素、DHT、促肾上腺皮质激素、17α-羟孕烯醇酮、17α-羟孕酮、DHEA、雄烯二酮或醛固酮水平无显著影响。结果表明，DES-DP对循环总睾酮的有效抑制作用部分是由DES-DP对血清DHEA-S水平的抑制作用引起的。在大多数患者中，高剂量DES-DP治疗可完全抑制血清游离睾酮水平，同时可能升高血清SHBG水平并降低血清总睾酮水平。DES-DP治疗期间维持血清DHT水平的机制有待进一步阐明。
