DataSheet_1_The effect of different administrations of testosterone therapy on adverse prostate events: A Bayesian network meta-analysis.docx

BackgroundHypogonadism has become a major cause endangering men’s health and quality of life all over the world. Testosterone Therapy (TT) is a widely accepted treatment for relieving hypogonadal symptoms. However, the effect of different administrations of TT on prostate safety is still unclear.
MethodsWe did a thorough search of PubMed, Embase and Cochrane Library to identify eligible studies up to January 2022. Randomized controlled trials (RCTs) and Cohort studies evaluating the impacts of using different formulations of TT on prostate parameters were included. Changes of prostate-specific antigen (PSA) level and prostate cancer (Pca) cases were used as the primary outcomes. Quality of individual studies was estimated by RoB2 (Cochrane tool for assessing the risk of bias in randomized trials) and the Newcastle-Ottawa scale (Tool for assessing non-RCTs). Certainty of evidence for each study was evaluated according to the evidence assessment criteria of the Oxford Evidence-based Medicine Center. Random-effect network meta-analysis(NMA)was performed based on the Bayesian model.
ResultsThirty-five studies (30 RCTs and 5 Cohort studies) with 7,740 participants were included. TT administration led to fewer Pca patients (RR=0.62, 95%CI [0.39,0.99], I2=0%), while little decreasing in PSA level (MD=-0.05, 95%CI [-0.08, -0.02], I2=0%). The NMA revealed that compared with other formulations, the intramuscular injection was the most likely to rank first in decreasing Pca cases. The TT also resulted in more biopsy cases (RR=2.38, 95%CI [1.01,5.60], I2=0%). As for NMA, intramuscular injection also performed relatively better in fewer prostate biopsy cases compared with transdermal group.
ConclusionTT does not lead to abnormal PSA changes and increased risk of Pca in patients with hypogonadism or low testosterone level. Compared with other preparations of TT, intramuscular injection proved better in minimizing Pca cases and was more likely to result in fewer prostate biopsy cases.

背景 性腺功能减退症已成为全球范围内危害男性健康与生活质量的主要病因之一。睾酮治疗（Testosterone Therapy，TT）是目前公认的缓解性腺功能减退症状的常用手段，但不同给药方式的TT对前列腺安全性的影响仍不明确。
方法 本研究系统性检索了PubMed、Embase及Cochrane Library数据库，纳入截至2022年1月发表的符合标准的相关研究。纳入评估不同剂型TT对前列腺参数影响的随机对照试验（Randomized controlled trials，RCTs）与队列研究。以前列腺特异性抗原（prostate-specific antigen，PSA）水平变化及前列腺癌（prostate cancer，Pca）发病例数作为主要结局指标。采用RoB2工具（Cochrane随机试验偏倚风险评估工具）与纽卡斯尔-渥太华量表分别评估RCTs与非随机对照试验的研究质量，并依据牛津循证医学中心的证据评价标准对各项研究的证据确定性进行评级。基于贝叶斯模型开展随机效应网络Meta分析（network meta-analysis，NMA）。
结果 本研究共纳入35项研究，其中30项RCTs与5项队列研究，涉及7740名受试者。结果显示，TT给药可降低Pca发病例数（相对风险RR=0.62，95%置信区间CI[0.39, 0.99]，I²=0%），但仅引起PSA水平小幅下降（均数差MD=-0.05，95%CI[-0.08, -0.02]，I²=0%）。网络Meta分析结果表明，相较于其他给药剂型，肌内注射在降低Pca发病例数方面排名首位。此外，TT可增加前列腺活检例数（RR=2.38，95%CI[1.01, 5.60]，I²=0%）；相较于经皮给药组，肌内注射在减少前列腺活检例数方面同样表现更优。
结论 对于性腺功能减退症或睾酮水平低下的患者，TT不会引起PSA水平异常变化及前列腺癌发病风险升高。相较于其他TT剂型，肌内注射在降低Pca发病例数方面效果更优，且更有助于减少前列腺活检例数。