Endogenous and exogenous testosterone and prostate cancer: decreased-, increased- or null-risk?
Endogenous and exogenous testosterone and prostate cancer: decreased-, increased- or null-risk?
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内源性和外源睾丸激素和前列腺癌：减少，增加或无效风险？
DOI：
10.21037/tau.2017.05.35
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发表时间：
2017-06
影响因子：
2
通讯作者：
Canfield S
中科院分区：
文献类型：
--
作者：
Lopez DS;Advani S;Tsilidis KK;Wang R;Canfield S
70多年来，认为高睾酮水平或使用睾酮治疗(TTH)会增加前列腺癌(PCa)的发生和进展的观点已经被广泛接受和实践。然而，越来越多和不断涌现的关于睾丸素研究的证据似乎挑战了这一论点。回顾内源性和外源性睾酮与前列腺癌风险降低、增加或无效之间的关系的文献，并仅进一步评估那些报道多变量建模相关性大小的研究，因为它将混杂影响降至最低。我们进行了文献检索，以确定研究内源性总睾酮[连续(每单位增加1个单位，增加5nmol/L)和分类(高与低)]以及TTH的使用与PCa事件的相关性的研究[1990年至2016年]。重点是多变量分析中报告的关联度[优势比(OR)、相对风险(RR)和风险比(HR)]的研究/分析，以确定前列腺癌的风险及其统计学意义。大多数已确定的研究/分析包括观察性和随机安慰剂对照试验。该综述分为三个部分：(I)内源性总睾酮(每单位增量和5nmol/L增量)与前列腺癌的关系；(Ii)内源性总睾酮(绝对高与低)与前列腺癌的关系；(Iii)在随机安慰剂对照试验的荟萃分析中，TTH的使用与前列腺癌的关系。第一部分包括31项观察性研究[20项前瞻性研究(每5nmol/L增量)和11项前瞻性和回顾性队列研究(每单位增量)]。在20项前瞻性研究中，没有一项发现总睾酮(5nmol/L增量)与前列腺癌风险增加或降低之间存在显著关联。11项研究/分析中有两项表明，每增加1个单位的总睾酮，前列腺癌的风险显著降低，但另外两项研究显示，前列腺癌的风险显著增加。其余研究报告的风险值为零。第二部分：25项研究中有8项报告，睾酮水平高的男性与低水平的男性相比，前列腺癌的风险增加，但只有4项研究有统计学意义。然而，17项研究表明，在比较高水平和低水平的睾酮后，前列腺癌的风险降低，但有11项研究/分析具有统计学意义。第三部分：对随机安慰剂对照试验(n=8和n=11)进行的两项荟萃分析(n=8和n=11)，研究了TTH和PCA的使用情况，报告了PCA的风险没有显著降低。高睾酮水平或使用TTH会增加前列腺癌风险的论点似乎没有得到文献的支持。然而，我们仍然需要有足够的力量、随访数据、流行病学、病理学和临床数据来支持在前列腺癌的自然历史和男性健康中使用高水平的内源性睾酮或TTH的安全性和益处。
For more than 70 years, the contention that high levels of testosterone or that the use of testosterone therapy (TTh) increases the development and progression of prostate cancer (PCa) has been widely accepted and practiced. Yet, the increasing and emerging evidence on testosterone research seems to challenge that contention. To review literature on the associations of endogenous and exogenous testosterone with decreased-, increased-, or null-risk of PCa, and to further evaluate only those studies that reported magnitude of associations from multivariable modeling as it minimizes confounding effects. We conducted a literature search to identify studies that investigated the association of endogenous total testosterone [continuous (per 1 unit increment and 5 nmol/L increment) and categorical (high vs. low)] and use of TTh with PCa events [1990–2016]. Emphasis was given to studies/analyses that reported magnitude of associations [odds ratio (OR), relative risk (RR) and hazard ratios (HRs)] from multivariable analyses to determine risk of PCa and their statistical significance. Most identified studies/analyses included observational and randomized placebo-controlled trials. This review was organized in three parts: (I) association of endogenous total testosterone (per 1 unit increment and 5 nmol/L increment) with PCa; (II) relationship of endogenous total testosterone (categorical high vs. low) with PCa; and (III) association of use of TTh with PCa in meta-analyses of randomized placebo-controlled trials. The first part included 31 observational studies [20 prospective (per 5 nmol/L increment) and 11 prospective and retrospective cohort studies (per 1 unit increment)]. None of the 20 prospective studies found a significant association between total testosterone (5 nmol/L increment) and increased- or decreased-risk of PCa. Two out of the 11 studies/analyses showed a significant decreased-risk of PCa for total testosterone per 1 unit increment, but also two other studies showed a significant increased-risk of PCa. Remaining studies reported null-risks values. Second part: eight of out of 25 studies reported an increased-risk of PCa for men with high levels of testosterone compared to low, but only four were statistically significant. However, 17 studies showed a decreased-risk of PCa after comparing high vs. low levels of testosterone, but 11 studies/analyses were statistically significant. Third part: two meta-analyses of randomized placebo-controlled trials (n=8 and n=11, each) that investigated use of TTh with PCa reported not significant decreased-risks of PCa. The contention that high levels of testosterone or that the use of TTh increases the risk of PCa doesn’t seem to be supported from the literature. Yet, we still need a study with the adequate power, follow-up data, epidemiological, pathological and clinical data that can support the safety and beneficial effects of high levels of endogenous testosterone or use of TTh in the natural history of PCa and in men’s health.
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影响因子：
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