Nishiyama Tsutomu
Division of Urology, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Urol Oncol. 2014 Jan;32(1):38.e17-28. doi: 10.1016/j.urolonc.2013.03.007. Epub 2013 Jun 13.
Androgens and the androgen receptor play a role in the progression of prostate cancer. Androgen deprivation therapy (ADT) is a mainstay in the treatment of metastatic prostate cancer. ADT is expected to reduce serum testosterone levels from a normal level of about 500 to 600 ng/dl (17.3-20.8 nmol) down to castration levels. Traditionally, castration was considered to be achieved if testosterone levels were lowered to a threshold of 50 ng/dl (1.73 nmol/l), a definition determined more by measurement methods derived from the use of old assay methods than by evidence. Serum testosterone levels in three-quarter patients after surgical castration drop to less than 20 ng/dl (0.69 nmol/l). Ineffective suppression of testosterone is currently poorly recognized and may possibly have an effect of prostate cancer mortality. Persistent levels of serum testosterone after castration are mainly derived from adrenal androgens. Furthermore, the arrival of new therapies targeting androgen synthesis and androgen receptor activity has renewed interest on serum testosterone. This review discusses the biosynthetic pathway for androgen synthesis in humans and provides a comprehensive review of serum testosterone levels after surgical or medical castration. This review assesses serum testosterone levels after surgical castration and different pharmacologic castration in patients with prostate cancer under ADT, and ineffective testosterone suppression. The author proposes methods to better lower serum testosterone levels during ADT.
雄激素和雄激素受体在前列腺癌进展中发挥作用。雄激素剥夺疗法(ADT)是转移性前列腺癌治疗的主要手段。ADT预期将血清睾酮水平从正常的约500至600 ng/dl(17.3 - 20.8 nmol)降至去势水平。传统上,如果睾酮水平降至50 ng/dl(1.73 nmol/l)的阈值,则认为实现了去势,这一定义更多是由源自旧检测方法的测量方法决定,而非基于证据。手术去势后四分之三患者的血清睾酮水平降至低于20 ng/dl(0.69 nmol/l)。目前对睾酮抑制无效的认识不足,其可能对前列腺癌死亡率产生影响。去势后血清睾酮的持续水平主要源自肾上腺雄激素。此外,针对雄激素合成和雄激素受体活性的新疗法的出现,重新引发了对血清睾酮的关注。本综述讨论了人类雄激素合成的生物合成途径,并全面回顾了手术或药物去势后的血清睾酮水平。本综述评估了接受ADT的前列腺癌患者手术去势和不同药物去势后的血清睾酮水平,以及睾酮抑制无效的情况。作者提出了在ADT期间更好地降低血清睾酮水平的方法。