Cui Y, Zong H, Yan H, Zhang Y
Department of Urology, Beijing Tian-Tan Hospital, Capital Medical University, Beijing, China.
Prostate Cancer Prostatic Dis. 2014 Jun;17(2):132-43. doi: 10.1038/pcan.2013.60. Epub 2014 Jan 21.
Testosterone replacement therapy (TRT) is a widely accepted form of treatment worldwide for aging men with late-onset hypogonadism syndrome. Urologists have been concerned about the possibility of TRT causing prostate cancer. The aim of this study was to assess the relationship between TRT and prostate cancer.
A literature review was performed to identify all published, randomized controlled trials (RCTs) of testosterone treatment for hypogonadism. The search included the MEDLINE, Embase and the Cochrane Controlled Trials Register databases. Fixed-effect model was chosen for homogeneous studies; otherwise, a random-effect model was used. Inconsistency was quantified by using the I2 statistic, which tests the proportion of heterogeneity across studies.
Results of 22 RCTs involving a total of 2351 patients were analyzed. Eleven RCTs were short-term (<12 months) and 11 were long-term (12-36 months) comparisons of TRT with a placebo; TRT was administered transdermally, orally or by injection. Respective odds ratio (OR) and 95% confidence interval (CI) values for injection, transdermal administration and oral administration of short-term TRT were as follows: prostate cancer: 0.39 (0.06-2.45), 1.10 (0.26-4.65) and no oral; biopsy: 5.28 (0.24-113.87), 2.11 (0.32-13.73) and no oral; and prostate nodule: 1.01 (0.13-7.60), no injection and oral. Respective OR and 95% CI values for injection, transdermal administration and oral administration of long-term TRT were as follows: prostate cancer: 2.09 (0.18-24.73), 3.06 (0.12-76.70) and 0.19 (0.01-4.03); biopsy: 2.09 (0.18-24.73), 3.65 (0.88-15.20) and 0.97 (0.13-7.03); and prostate nodule: 3.13 (0.12-80.68), 1.00 (0.06-16.41) and 0.97 (0.13-7.03). Though for some routes of administration and some end points, the OR associated with testosterone administration were >1 indicating increased risk, none of these reached or even approached statistical significance (all P>0.10), which was consistent with the results of subgroup analyses and sensitivity analysis. Besides, sensitivity analysis indicated that short-term TRT was more likely to increase PSA levels than treatment with placebo (P<0.00001).
This meta-analysis shows that regardless of the administration method, TRT is the short-term safety and does not promote prostate cancer development or progression but long-term data are warranted with justifiable end points.
睾酮替代疗法（TRT）是全球范围内被广泛接受的针对迟发性性腺功能减退综合征老年男性的治疗方式。泌尿科医生一直担心TRT引发前列腺癌的可能性。本研究旨在评估TRT与前列腺癌之间的关系。
进行文献综述以识别所有已发表的关于睾酮治疗性腺功能减退的随机对照试验（RCT）。检索包括MEDLINE、Embase和Cochrane对照试验注册数据库。同质研究选择固定效应模型；否则，使用随机效应模型。通过I²统计量对不一致性进行量化，该统计量检验各研究间异质性的比例。
分析了22项RCT的结果，共涉及2351例患者。11项RCT为TRT与安慰剂的短期（<12个月）比较，11项为长期（12 - 36个月）比较；TRT通过经皮、口服或注射给药。短期TRT注射、经皮给药和口服给药的各自比值比（OR）及95%置信区间（CI）值如下：前列腺癌：0.39（0.06 - 2.45），1.10（0.26 - 4.65），口服无数据；活检：5.28（0.24 - 113.87），2.11（0.32 - 13.73），口服无数据；前列腺结节：1.01（0.13 - 7.60），注射无数据，口服。长期TRT注射、经皮给药和口服给药的各自OR及95%CI值如下：前列腺癌：2.09（0.18 - 24.73），3.06（0.12 - 76.70），0.19（0.01 - 4.03）；活检：2.09（0.18 - 24.73），3.65（0.88 - 15.20），0.97（0.13 - 7.03）；前列腺结节：3.13（0.12 - 80.68），1.00（0.06 - 16.41），0.97（0.13 - 7.03）。尽管对于某些给药途径和某些终点，与睾酮给药相关的OR>1表明风险增加，但这些均未达到甚至接近统计学显著性（所有P>0.10），这与亚组分析和敏感性分析结果一致。此外，敏感性分析表明短期TRT比安慰剂治疗更可能增加前列腺特异性抗原（PSA）水平（P<0.00001）。
该荟萃分析表明，无论给药方式如何，TRT在短期内是安全的，不会促进前列腺癌的发生或进展，但需要有合理终点的长期数据。
