Related Experiment Video
Updated: Nov 20, 2025
A Multicenter MRI Protocol for the Evaluation and Quantification of Deep Vein Thrombosis
Published on: June 2, 2015
Testosterone replacement therapy and the risk of venous thromboembolism: A systematic review and meta-analysis of
Henok Tadesse Ayele1, Vanessa C Brunetti1, Christel Renoux2
1Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, H3T 1E2, Canada; Center for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, 3755 Cote Ste-Catherine, Montreal, Quebec, H3T 1E2, Canada.
Introduction:
The cardiovascular safety of testosterone replacement therapy (TRT) is controversial. While several studies have investigated the association between TRT and the risk of arterial thrombosis, limited information is available regarding its risk of venous thromboembolism (VTE). We aimed to compare the risk of VTE in men randomized to TRT versus placebo or active-comparator in a systematic review.
Methods:
We searched Medline, EMBASE, CINAHL, CENTRAL, and clinical trial registries to identify randomized controlled trials (RCTs) comparing TRT to placebo in men aged ≥18 years. We assessed study quality using the Cochrane Risk of Bias assessment tool and the overall quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. Data were pooled across RCTs using random-effects models.
Results:
A total of 13 RCTs (n = 5050) were included in our meta-analysis. In all, 2636 men were randomized to testosterone, and 2414 men to placebo. Sample sizes ranged from 101 to 790 men, and TRT duration from 3 to 36 months. Five studies had a high risk of bias, largely driven by unclear randomization and outcome assessment. When data were pooled across RCTs, testosterone therapy was not associated with VTE compared with placebo (RR: 1.03, 95% CI: 0.49-2.14; I2: 0%; low-quality evidence). Similar estimates were obtained for deep vein thrombosis and pulmonary embolism outcomes.
Conclusions:
Our systematic review suggests that TRT is not associated with an increased risk of VTE. However, estimates were accompanied by a wide 95% CIs, and a clinically important increased risk cannot be ruled out.
Related Concept Videos
01:29Venous Thrombosis III: Interprofessional Care
01:30Venous Thrombosis I: Introduction
01:20Venous Thrombosis II: Clinical Manifestations and Diagnostic Studies
01:30Venous Thrombosis IV: Nursing Management
01:26Testosterone: Functions and Regulation
01:23Types of Biopharmaceutical Studies: Controlled and Non-Controlled Approaches
Non-controlled studies, commonly employed for initial exploration, lack a control group, rendering them susceptible to biases and external influences. In contrast,...