Salvio Gianmaria, Ciarloni Alessandro, Ambo Nicola, Bordoni Monia, Perrone Michele, Rossi Silvia, Balercia Giancarlo
Endocrinology Clinic, Department of Clinical and Molecular Sciences, Polytechnic University of Marche, Ancona, Italy.
Andrology. 2025 Mar 19. doi: 10.1111/andr.70022.
Hypogonadism and infertility are two conditions that are heavily affected by overweight and obesity in the male patient. Glucagon-like peptide 1 agonists (GLP-1RAs) are a recently introduced class of antidiabetic drugs with powerful weight-loss effect; this may induce an indirect positive effect on the testicular function. Nevertheless, recent evidence also suggests a potential direct influence of these molecules on the gonadal function.
Our study aims at evaluating the effects of GLP-1RAs on hormone secretion in male patients and comparing their impact on the testicular function with other antidiabetic agents or weight-lowering drugs.
A literature search was conducted using PubMed, EMBASE, and Scopus database to assess the effects of GLP-1RAs on hormone levels, sperm parameters, and erectile function in overweight and obese men. Before-after analysis and comparison between therapy with GLP-1RAs and other treatment regimens were performed.
Seven studies (n = 680) were included in the quantitative analysis. Treatment with GLP-1RAs produced a significant increase in total serum testosterone (TT), with a standardized mean difference of 1.39 ng/mL (95% confidence interval: 0.70, 2.09; p < 0.0001). Free serum testosterone (FT), sex hormone-binding globulin (SHBG), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) showed similar increase, while weight, body mass index (BMI), waist circumference (WC), and glycated hemoglobin (HbA1c) decreased. Meta-regression showed a significant negative correlation between standardized mean difference in TT levels before-after treatment and percentage change in weight and BMI. When compared with other treatment options, GLP-1RAs showed a comparable effect on serum androgens, but greater BMI reduction and increase in serum gonadotropins and indexes of the erectile function.
Our systematic review and meta-analysis suggest a possible role for GLP-1RAs in the therapy of functional hypogonadism related to overweight and obesity, while also promoting weight loss. The limitations of the current literature do not allow to demonstrate a direct action of GLP-1RAs on the testicular function.
性腺功能减退和不育是男性患者中受超重和肥胖严重影响的两种病症。胰高血糖素样肽1激动剂（GLP-1RAs）是最近引入的一类具有强大减肥效果的抗糖尿病药物；这可能对睾丸功能产生间接的积极影响。然而，最近的证据也表明这些分子对性腺功能有潜在的直接影响。
我们的研究旨在评估GLP-1RAs对男性患者激素分泌的影响，并将其对睾丸功能的影响与其他抗糖尿病药物或减肥药物进行比较。
使用PubMed、EMBASE和Scopus数据库进行文献检索，以评估GLP-1RAs对超重和肥胖男性激素水平、精子参数和勃起功能的影响。对GLP-1RAs治疗前后以及与其他治疗方案之间进行分析和比较。
七项研究（n = 680）纳入定量分析。GLP-1RAs治疗使血清总睾酮（TT）显著升高，标准化平均差为1.39 ng/mL（95%置信区间：0.70，2.09；p < 0.0001）。游离血清睾酮（FT）、性激素结合球蛋白（SHBG）、促黄体生成素（LH）和促卵泡生成素（FSH）也有类似升高，而体重、体重指数（BMI）、腰围（WC）和糖化血红蛋白（HbA1c）下降。Meta回归显示治疗前后TT水平的标准化平均差与体重和BMI的百分比变化之间存在显著负相关。与其他治疗选择相比，GLP-1RAs对血清雄激素的影响相当，但在降低BMI以及增加血清促性腺激素和勃起功能指标方面效果更显著。
我们的系统评价和荟萃分析表明，GLP-1RAs在与超重和肥胖相关的功能性性腺功能减退治疗中可能发挥作用，同时还能促进体重减轻。当前文献的局限性不允许证明GLP-1RAs对睾丸功能有直接作用。
