A New Era of Testosterone and Prostate Cancer: From Physiology to Clinical Implications

Context

Decades-old beliefs regarding androgens and prostate cancer (PCa) have undergone dramatic shifts in light of modern evidence and new theoretical constructs, but considerable confusion remains on this topic, particularly with regard to the use of testosterone therapy in men with any history of PCa.

Objective

To review current literature regarding the relationship of serum testosterone on PCa and in particular the effect of testosterone therapy on PCa progression and recurrence.

Evidence acquisition

A Medline search was conducted to identify all original and review articles assessing the effect of androgens on the prostate and the use of testosterone in men with a history of treated and untreated PCa.

Evidence synthesis

Contrary to traditional teaching, high endogenous serum testosterone does not increase the risk of developing PCa, and low serum testosterone does not protect against PCa. Although limited in size and duration, current studies similarly fail to indicate any increased risk of PCa in men receiving testosterone therapy. These results indicate a finite ability of androgens to stimulate PCa growth (the saturation model). A majority of studies demonstrate an association between low serum testosterone and poor prognostic features of PCa, including high-grade disease, advanced pathologic stage, and increased risk of biochemical recurrence following radical prostatectomy. The prostate-specific antigen-to-testosterone ratio predicted PCa risk in several biopsy studies. Multiple reports of testosterone therapy in men after treatment for localized PCa have shown low or absent recurrence rates. Some men with untreated PCa have received testosterone therapy without evidence for PCa progression.

Conclusions

The long-held belief that PCa risk is related to high serum androgen concentrations can no longer be supported. Current evidence indicates that maximal androgen-stimulated PCa growth is achieved at relatively low serum testosterone concentrations. It may therefore be reasonable to consider testosterone therapy in selected men with PCa and symptomatic hypogonadism.     

反义核酸对放疗诱导前列腺癌细胞VEGF高表达的抑制作用

目的 :探讨放疗过程中病人血清血管内皮生长因子 (VEGF)升高的机制 ,以及VEGF反义硫代寡核苷酸(AS ODN)对前列腺癌细胞VEGF表达分泌的抑制作用。　方法 :动态观察前列腺癌病人放疗期间血清VEGF变化 ;体外照射培养的前列腺癌PC3M细胞 ,观察放疗对肿瘤细胞VEGF表达分泌的诱导作用及AS ODN的抑制效应。　结果 :前列腺癌病人血清VEGF浓度在放疗开始后逐渐升高 ,15d左右达到峰值后开始下降 ,到 6 0d时基本恢复到正常。前列腺癌细胞受X线照射后VEGF的分泌较对照组明显升高 ,AS ODN加照射组癌细胞VEGF分泌量较单纯照射组显著下降 (P <0 .0 1)。　结论 :放疗可刺激前列腺癌细胞中VEGF的表达分泌 ,VEGFAS ODN对放疗诱导的VEGF高表达有较好的抑制作用