Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and Endocrinology, Sapienza University of Rome, Rome, Italy.
Department of Experimental and Clinical Biomedical Sciences "Mario Serio," Andrology, Women's Endocrinology and Gender Incongruence Unit, University of Florence, Florence, Italy.
Int J Impot Res. 2020 Jul;32(4):379-386. doi: 10.1038/s41443-019-0163-6. Epub 2019 Jun 24.
Despite several studies showing an inverse correlation of total testosterone with endothelial damage, the effect of testosterone replacement therapy (TTh) on endothelial function has been scarcely investigated. In order to systematically assess the relationship between endothelial dysfunction and TTh, we performed a review and meta-analysis of available prospective and cross-sectional studies. A thorough research was performed on MEDLINE for hypogonadism and endothelial dysfunction. We retrieved 28 papers, among which 23 were excluded for different reasons: five papers accounting for six studies (two crossover randomized clinical trial (RCT), three observational, one placebo controlled RCT) were therefore included in analysis. Overall, 86 patients with hypogonadism were included in analysis (mean age 49.57 ± 8.85 years). Baseline total testosterone serum levels were 8.11 ± 2.42 nmol/L and significantly increased while undergoing TTh (standard mean difference (SMD) 2.93 nmol/L, 95% confidence interval (CI) 1.89:3.97, p < 0.001). Due to the paucity of studies available, flow-mediated dilation (FMD) was chosen as the best surrogate marker of endothelial dysfunction. FMD did not significantly change after testosterone administration (SMD -0.22, 95% CI -1.29:0.84, I = 90%); acute testosterone administration was associated with an increase in FMD, whereas a reduction in FMD emerged following chronic treatment, but statistical significance was not reached for both effects. This is the first meta-analysis study assessing the influence of TTh on endothelial function; however, results are far from conclusive, as proven by the high heterogeneity.
尽管有几项研究表明总睾酮与内皮损伤呈负相关，但睾酮替代疗法（TTh）对内皮功能的影响却鲜有研究。为了系统评估内皮功能障碍与 TTh 之间的关系，我们对现有的前瞻性和横断面研究进行了综述和荟萃分析。我们在 MEDLINE 上对性腺功能减退和内皮功能障碍进行了彻底的研究。我们检索到 28 篇论文，但由于各种原因排除了 23 篇：因此，有 5 篇论文（涉及 6 项研究，其中 2 项为交叉随机临床试验（RCT），3 项为观察性研究，1 项安慰剂对照 RCT）被纳入分析。总的来说，有 86 名性腺功能减退患者被纳入分析（平均年龄 49.57±8.85 岁）。基线总睾酮血清水平为 8.11±2.42nmol/L，在接受 TTh 治疗时显著升高（标准均数差（SMD）为 2.93nmol/L，95%置信区间（CI）为 1.89:3.97，p<0.001）。由于可用的研究较少，血流介导的扩张（FMD）被选为内皮功能障碍的最佳替代标志物。睾酮给药后 FMD 无显著变化（SMD-0.22，95%CI-1.29:0.84，I=90%）；急性睾酮给药与 FMD 增加相关，而慢性治疗后 FMD 减少，但两种作用均未达到统计学意义。这是第一项评估 TTh 对内皮功能影响的荟萃分析研究；然而，正如高度异质性所证明的那样，结果远非定论。
