Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu, China.
Department of Geriatrics and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.
Front Endocrinol (Lausanne). 2024 Nov 13;15:1448394. doi: 10.3389/fendo.2024.1448394. eCollection 2024.
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been widely used for type 2 diabetes (T2D) and weight management. However, the causal relationship of GLP-1RAs with erectile dysfunction (ED) was still unclear.
Mendelian randomization (MR) analysis was conducted to reveal the association of genetically proxied GLP-1RAs with ED. The proportion of potential mediators mediating GLP-1RAs to ED was also assessed by two-step MR. Finally, a series of sensitivity analyses and Two-Sep cis-MR (TSCMR) were performed to evaluate the robustness of the results.
MR evidence suggested that genetically proxied GLP-1RAs reduced the risk of ED [odds ratio (OR): 0.493; 95% confidence interval (95% CI): 0.430 to 0.565; <0.001]. Further mediation analysis via two-step MR showed that this effect was partly mediated through reduced T2D, obesity, hypertension and cardiovascular disease (CVD), with mediated proportions of 2.89% (95% CI: 1.28% to 4.49%), 6.83% (95% CI: 2.25% to 11.41%), 3.22% (95% CI: 1.21% to 5.23%), and 3.06% (95% CI: 0.51% to 5.62%), respectively.
GLP-1RAs were associated with a reduced risk of ED, and to a lesser extent, T2D, obesity, hypertension and CVD mediated this effect. Nevertheless, the potential implications of our results for ED prevention policies required validation in further clinical randomized controlled trials.
胰高血糖素样肽-1 受体激动剂（GLP-1RAs）已广泛用于 2 型糖尿病（T2D）和体重管理。然而，GLP-1RAs 与勃起功能障碍（ED）之间的因果关系仍不清楚。
采用孟德尔随机化（MR）分析揭示遗传上接近的 GLP-1RAs 与 ED 之间的关联。还通过两步 MR 评估潜在介导物介导 GLP-1RAs 至 ED 的比例。最后，进行了一系列敏感性分析和双 cis-MR（TSCMR）分析，以评估结果的稳健性。
MR 证据表明，遗传上接近的 GLP-1RAs 降低了 ED 的风险[比值比（OR）：0.493；95%置信区间（95%CI）：0.430 至 0.565；<0.001]。通过两步 MR 进行的进一步中介分析表明，这种效应部分是通过降低 2 型糖尿病、肥胖、高血压和心血管疾病（CVD）介导的，介导比例分别为 2.89%（95%CI：1.28%至 4.49%）、6.83%（95%CI：2.25%至 11.41%）、3.22%（95%CI：1.21%至 5.23%）和 3.06%（95%CI：0.51%至 5.62%）。
GLP-1RAs 与 ED 风险降低相关，在较小程度上，2 型糖尿病、肥胖、高血压和 CVD 介导了这种效应。然而，我们的结果对 ED 预防政策的潜在影响需要在进一步的临床随机对照试验中验证。
