Rennie P S, Bruchovsky N, Goldenberg S L, Lawson D, Fletcher T, Foekens J A
Department of Cancer Endocrinology, Cancer Control Agency of British Columbia, Vancouver, Canada.
J Urol. 1988 Jun;139(6):1337-42. doi: 10.1016/s0022-5347(17)42914-4.
From a large number of potentially effective androgen withdrawal regimens including bilateral orchiectomy, estrogens, antiandrogens and LHRH agonists alone or in combinations, we compared the ability of 12 different treatment options to mimic the acute results of surgical castration on the rat prostate. Agents were administered s.c. in clinical doses to groups of male rats daily for three days. On day 4 the prostatic tissue was removed and analyzed by conventional methods for whole-tissue and nuclear concentrations of dihydrotestosterone, nuclear androgen receptor and cytoplasmic androgen receptor. Castration-like changes were most pronounced with the synergistic combinations of cyproterone acetate + low-dose diethylstilbestrol, and megestrol acetate + low-dose diethylstilbestrol. Comparing the effectiveness of single agents, low-dose diethylstilbestrol was superior to cyproterone acetate, megestrol acetate, flutamide, leuprolide and RU23908. Leuprolide combined with flutamide was superior to leuprolide + cyproterone acetate, leuprolide + cyproterone acetate + low-dose diethylstilbestrol or leuprolide + RU23908 after three days of administration; however, this advantage disappeared when the treatments were extended to seven days. The observations indicate that the most potent androgen withdrawal therapies such as cyproterone acetate + low-dose diethylstilbestrol and megestrol acetate + low-dose diethylstilbestrol at best approximate but do not surpass the early effects of surgical castration. During the same time course, other regimens are characterized by a slower onset of action and a lesser degree of suppression of androgenic mechanisms within the cell.
在众多可能有效的雄激素去除方案中，包括双侧睾丸切除术、雌激素、抗雄激素药物以及单独或联合使用的促性腺激素释放激素（LHRH）激动剂，我们比较了12种不同治疗方案模拟手术去势对大鼠前列腺急性影响的能力。将药物以临床剂量皮下注射给雄性大鼠组，每日一次，持续三天。在第4天，取出前列腺组织，通过常规方法分析全组织和细胞核中二氢睾酮、细胞核雄激素受体和细胞质雄激素受体的浓度。醋酸环丙孕酮+低剂量己烯雌酚以及醋酸甲地孕酮+低剂量己烯雌酚的协同组合产生的去势样变化最为明显。比较单一药物的有效性，低剂量己烯雌酚优于醋酸环丙孕酮、醋酸甲地孕酮、氟他胺、亮丙瑞林和RU23908。给药三天后，亮丙瑞林联合氟他胺优于亮丙瑞林+醋酸环丙孕酮、亮丙瑞林+醋酸环丙孕酮+低剂量己烯雌酚或亮丙瑞林+RU23908；然而，当治疗延长至七天时，这种优势消失。这些观察结果表明，最有效的雄激素去除疗法，如醋酸环丙孕酮+低剂量己烯雌酚和醋酸甲地孕酮+低剂量己烯雌酚，充其量只能接近但不能超过手术去势的早期效果。在相同的时间进程中，其他方案的特点是起效较慢，对细胞内雄激素机制的抑制程度较小。
