Research · PMID 26205547 · Landmark study
Reviewed by Neal Rouzier, MD, Preventive Medicine · Sep 2026
Risk of Venous Thromboembolism in Men Receiving Testosterone Therapy.
Mayo Clinic proceedings · August 2015 · Jacques Baillargeon, Randall J Urban, Abraham Morgentaler, Charles J Glueck, Gwen Baillargeon, et al.
What this study found
Having filled a prescription for testosterone therapy was not associated with an increased risk of VTE in commercially insured middle-aged and older men. These findings may provide clinically relevant information about the benefit-risk assessment for men with testosterone deficiency considering treatment.
Why this trial matters
Baillargeon testosterone VTE cohort
How RAGMD uses this study
Clinical questions this paper informs
Synthesis lives on the evidence question — this page shows where the study sits in that analysis.
Primary study
Does testosterone therapy increase venous thromboembolism risk?
Large observational cohorts suggest a modest increase in venous thromboembolism risk with testosterone therapy, particularly early after initiation. Absolute risk remains low in most populations but warrants attention in predisposed patients.
Open evidence analysisSupporting literature
Does testosterone replacement increase cardiovascular risk?
Large randomized data (including TRAVERSE) do not show a significant increase in major adverse cardiovascular events with testosterone therapy in hypogonadal men over median follow-up of roughly three years. Older observational studies conflict, and absolute risk depends on baseline cardiovascular disease, formulation, and monitoring.
Open evidence analysisSupporting literature
Does testosterone therapy increase prostate cancer risk?
Current systematic reviews and trial secondary analyses do not show a convincing increase in prostate cancer incidence among hypogonadal men treated with testosterone, though surveillance remains standard practice.
Open evidence analysisSupporting literature
Does testosterone therapy increase hematocrit and polycythemia risk?
Testosterone therapy commonly raises hematocrit; polycythemia is a recognized adverse effect requiring dose adjustment, formulation changes, or phlebotomy when thresholds are exceeded.
Open evidence analysisSupporting literature
Does testosterone therapy suppress fertility in men?
Exogenous testosterone suppresses the hypothalamic-pituitary-gonadal axis and reliably reduces spermatogenesis. Recovery after discontinuation is variable and may be incomplete in some men.
Open evidence analysisSupporting literature
Does testosterone therapy reduce cardiovascular events?
TRAVERSE found no significant difference in major adverse cardiovascular events between testosterone and placebo over trial follow-up. Meta-analyses of earlier trials are mixed; testosterone should not be prescribed primarily for cardiovascular protection.
Open evidence analysisSupporting literature
Does estradiol level affect symptoms and bone health in men on testosterone therapy?
Estradiol in men derives largely from aromatization of testosterone and contributes to bone density and possibly symptom control. Over-suppression with aromatase inhibitors may impair bone health; optimal targets in clinical practice remain debated.
Open evidence analysisSupporting literature
Do aromatase inhibitors in men increase bone loss risk?
Aromatase inhibitors lower estradiol and can reduce bone mineral density in men. Routine use to suppress estradiol during testosterone therapy is not supported by outcome evidence and may carry skeletal risk.
Open evidence analysisSupporting literature
Does testosterone therapy worsen obstructive sleep apnea?
Testosterone may worsen sleep apnea in predisposed men. Screening and monitoring for OSA is recommended before and during therapy, especially when symptoms emerge or hematocrit rises.
Open evidence analysisSupporting literature
How should low testosterone be diagnosed in symptomatic men?
Diagnosis requires consistent symptoms plus repeatedly low morning total testosterone on valid assays, with secondary causes excluded. A single borderline value should prompt repeat testing before initiating therapy.
Open evidence analysisSupporting literature
Do transdermal and injectable testosterone differ in safety or efficacy?
All FDA-approved formulations can restore testosterone when dosed appropriately. Transdermal routes may have less erythrocytosis than injectable esters in some comparisons, but transfer, adherence, and peak-trough patterns differ by formulation.
Open evidence analysisSupporting literature
Does testosterone therapy affect blood pressure?
Testosterone effects on blood pressure are modest and inconsistent across trials. Monitoring blood pressure remains part of routine TRT follow-up, especially with fluid retention or erythrocytosis.
Open evidence analysis