Lycette Jennifer L, Bland Lisa B, Garzotto Mark, Beer Tomasz M
Division of Hematology and Medical Oncology, Department of Medicine, Oregon Health & Science University, Portland, OR 97239, USA.
Clin Genitourin Cancer. 2006 Dec;5(3):198-205. doi: 10.3816/CGC.2006.n.037.
Androgen deprivation therapy (ADT) is the mainstay of management of advanced-stage prostate cancer and recently has been shown to improve survival when administered in earlier stages of the disease. The oncologic benefits of ADT might be partially offset, however, by a reduction in quality of life because of adverse effects. In addition to the well-recognized adverse consequences of ADT, recent evidence suggests that ADT is associated with dyslipidemia, impaired glucose metabolism, adverse body compositional changes, and osteoporosis. Therefore, there is a pressing need to develop less toxic forms of ADT. A novel approach to this problem is the use of estrogen to induce androgen suppression. Whereas oral estrogen therapy is known to be associated with thromboembolic complications, studies of parenteral estrogen in men with prostate cancer suggest that the use of parenteral estrogen achieves target androgen suppression, does not adversely affect prothrombotic protein levels, and is not associated with adverse metabolic, skeletal, and body compositional changes when compared with conventional ADT. Herein, we review the data for parenteral estrogen use in prostate cancer, the antineoplastic mechanisms of action of estrogen in prostate cancer, the potential advantages of parenteral estrogen compared with conventional ADT, and the remaining barriers in the use of parenteral estrogen in prostate cancer.
雄激素剥夺疗法（ADT）是晚期前列腺癌治疗的主要手段，最近研究表明，在疾病早期使用该疗法可提高生存率。然而，由于不良反应导致生活质量下降，ADT在肿瘤学方面的益处可能会被部分抵消。除了ADT广为人知的不良后果外，最近的证据表明，ADT与血脂异常、糖代谢受损、不良的身体成分变化和骨质疏松症有关。因此，迫切需要开发毒性较小的ADT形式。解决这个问题的一种新方法是使用雌激素来诱导雄激素抑制。虽然口服雌激素疗法已知与血栓栓塞并发症有关，但对前列腺癌男性患者使用胃肠外雌激素的研究表明，与传统ADT相比，使用胃肠外雌激素可实现目标雄激素抑制，不会对促血栓形成蛋白水平产生不利影响，也不会与不良的代谢、骨骼和身体成分变化相关。在此，我们综述了前列腺癌中使用胃肠外雌激素的数据、雌激素在前列腺癌中的抗肿瘤作用机制、与传统ADT相比胃肠外雌激素的潜在优势，以及前列腺癌中使用胃肠外雌激素尚存的障碍。
