Vis André N, Schröder Fritz H
Department of Urology, VU Medical Centre, Amsterdam, the Netherlands.
BJU Int. 2009 Nov;104(9):1191-7. doi: 10.1111/j.1464-410X.2009.08743.x. Epub 2009 Jul 14.
The inhibition of 5alpha-reductase (5AR) blocks the synthesis of the most powerful intracellular androgen, dihydrotestosterone (DHT). The prostate has two 5AR isoenzymes (5AR1 and 5AR2) that change in expression and cellular location during the development of prostate cancer and tumour progression. The objective of this review is to provide an understanding of the pharmacological properties and the potential clinical benefits of 5AR inhibition.
We searched Pubmed for data obtained from pharmacological, preclinical and clinical studies.
5AR1 expression increases with increasing aggressiveness and extension of malignant prostatic disease. Conversely, 5AR2 expression decreases from benign prostatic tissue to localized prostate cancer. The efficacy of 5AR2 monotherapy with finasteride alone or in combination with an androgen receptor antagonist on more final outcome measures seems to be limited. Combining an androgen receptor antagonist with a 5AR inhibitor in patients with asymptomatic, locally advanced or recurrent prostate cancer might be a reasonable first therapeutic hormonal approach. As plasma testosterone levels are maintained, beneficial effects on quality of life, potency and sexual function are expected. From studies on the dual 5AR inhibitor dutasteride, the drug produces a biochemical response in some men who progressed under androgen-deprivation therapy, and is generally well tolerated.
Achieving more potent suppression of intracellular DHT synthesis by 5AR inhibition is expected to provide clinical benefit to patients. Previous studies have shown that 5AR inhibition, by dutasteride in particular, halts/delays the progression of disease, and might even cause regression of disease in patients with advanced prostate cancer.
抑制5α-还原酶（5AR）可阻断最强效的细胞内雄激素双氢睾酮（DHT）的合成。前列腺有两种5AR同工酶（5AR1和5AR2），在前列腺癌发生发展及肿瘤进展过程中，其表达和细胞定位会发生变化。本综述的目的是让人们了解5AR抑制的药理特性及潜在临床益处。
我们在PubMed上搜索了从药理学、临床前和临床研究中获得的数据。
5AR1的表达随着前列腺恶性疾病侵袭性和范围的增加而升高。相反，从良性前列腺组织到局限性前列腺癌，5AR2的表达降低。单用非那雄胺或与雄激素受体拮抗剂联合使用5AR2单一疗法对更多最终结局指标的疗效似乎有限。对于无症状、局部晚期或复发性前列腺癌患者，将雄激素受体拮抗剂与5AR抑制剂联合使用可能是一种合理的初始激素治疗方法。由于血浆睾酮水平得以维持，预期对生活质量、性功能和勃起功能有益。从对双重5AR抑制剂度他雄胺的研究来看，该药物在一些接受雄激素剥夺治疗病情进展的男性中产生了生化反应，且总体耐受性良好。
通过抑制5AR更有效地抑制细胞内DHT合成有望为患者带来临床益处。既往研究表明，5AR抑制，尤其是度他雄胺，可阻止/延缓疾病进展，甚至可能使晚期前列腺癌患者的病情出现消退。
