Slater S, Oliver R T
Department of Medical Oncology, St Bartholomew's and The Royal London Hospital School of Medicine, West Smithfield, England.
Drugs Aging. 2000 Dec;17(6):431-9. doi: 10.2165/00002512-200017060-00001.
Evidence from studies in patients with prostate cancer of intermittent hormone therapy combined with results from rechallenge of hormone resistant patients with testosterone demonstrate that the majority of prostate cancers retain a similar degree of dependence on male sex hormone milieu as normal prostate cells. Yet there has so far been no conclusive evidence, despite 34 studies, that levels of circulating testosterone in individuals developing prostate cancer are higher than in controls. The aim of this article was to critically evaluate this evidence and seek clues to other mechanisms whereby sex hormones could influence the development of prostate cancer. Additionally, epidemiological data were examined to investigate the interplay between sex hormone levels and environmental factors to help understand the development of prostate cancer and identify a safe way to provide hormone replacement therapy (HRT). Three overviews provide similar evidence that there is no significant difference in mean testosterone levels between patients and controls. However in the most recent review of studies, though there was no difference in means between cases and controls, there was a significant risk (adjusted odds ratio 2.34) for individuals identified by comparing incidence of prostate cancer in men in the upper and lower quartile of testosterone level. This report, taken with epidemiological data demonstrating that prostate cancer risk is increased by early age of onset of sexual activity and multiple nonspecific sexually transmitted diseases (STDs), has led to the hypothesis that the link between sex hormones and prostate cancer is indirect. Those individuals with high testosterone levels were more at risk of acquisition of multiple nonspecific STDs. This promotes transformation of prostate cells and damage to Leydig cells in the testis leading to there being no difference in testosterone compared with controls by the time the tumour is diagnosed. Because of the observed relationship between testosterone and prostate cancer development there has been anxiety about marketing HRT for men. Two observations support the view that the prostate cancer risks from use of testosterone hormone replacement may not be as great as first feared. Firstly, prostate cancers arising in men with low serum testosterone levels are more malignant and frequently nonresponsive to hormones. Secondly, breast cancers diagnosed in women on HRT though increased in number are less malignant possibly because of enhanced sensitivity to hormone therapy, and the situation may prove to be analogous with prostate cancer and testosterone replacement.
前列腺癌患者间歇性激素治疗的研究证据，以及对激素抵抗患者进行睾酮再激发的结果表明，大多数前列腺癌与正常前列腺细胞一样，对男性性激素环境保持相似程度的依赖。然而，尽管有34项研究，但迄今为止，尚无确凿证据表明患前列腺癌个体的循环睾酮水平高于对照组。本文的目的是严格评估这一证据，并寻找性激素可能影响前列腺癌发生的其他机制的线索。此外，还研究了流行病学数据，以调查性激素水平与环境因素之间的相互作用，以帮助理解前列腺癌的发生，并确定提供激素替代疗法（HRT）的安全方法。三项综述提供了类似的证据，表明患者和对照组之间的平均睾酮水平没有显著差异。然而，在最近的研究综述中，尽管病例组和对照组的均值没有差异，但通过比较睾酮水平处于上四分位数和下四分位数的男性前列腺癌发病率来确定的个体存在显著风险（调整后的优势比为2.34）。这份报告，结合流行病学数据表明前列腺癌风险会因性活动开始年龄早和多种非特异性性传播疾病（STD）而增加，导致了这样一种假设，即性激素与前列腺癌之间的联系是间接的。那些睾酮水平高的个体更易感染多种非特异性STD。这促进了前列腺细胞的转化和睾丸中Leydig细胞的损伤，导致在肿瘤被诊断时，与对照组相比睾酮水平没有差异。由于观察到睾酮与前列腺癌发生之间的关系，人们对男性激素替代疗法的推广感到担忧。两项观察结果支持这样一种观点，即使用睾酮激素替代疗法带来的前列腺癌风险可能不像最初担心的那么大。首先，血清睾酮水平低的男性所患的前列腺癌更具恶性，且通常对激素无反应。其次，接受HRT的女性中诊断出的乳腺癌，尽管数量增加，但恶性程度较低，这可能是因为对激素治疗的敏感性增强，而且这种情况可能与前列腺癌和睾酮替代疗法类似。
