Research · PMID 37326322 · Landmark study
Reviewed by Neal Rouzier, MD, Preventive Medicine · Sep 2026
Cardiovascular Safety of Testosterone-Replacement Therapy.
The New England journal of medicine · July 2023 · A Michael Lincoff, Shalender Bhasin, Panagiotis Flevaris, Lisa M Mitchell, Shehzad Basaria, et al.
What this study found
In men with hypogonadism and preexisting or a high risk of cardiovascular disease, testosterone-replacement therapy was noninferior to placebo with respect to the incidence of major adverse cardiac events. (Funded by AbbVie and others; TRAVERSE ClinicalTrials.gov number, NCT03518034.).
Why this trial matters
TRAVERSE primary cardiovascular safety
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 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 analysisCore study
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 analysisPrimary study
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 analysisCore 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 analysisPrimary study
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 analysisCore study
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 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
Can hormone therapy help insulin resistance in peri- and postmenopausal women?
Some studies show improved insulin sensitivity with estrogen-based therapy in early postmenopause, but results are not uniform across regimens. HRT should not replace evidence-based diabetes prevention or treatment.
Open evidence analysisSupporting literature
Do omega-3 supplements prevent cardiovascular disease in the general population?
High-dose EPA (icosapent ethyl) reduced events in selected high-risk statin-treated patients in REDUCE-IT. General over-the-counter omega-3 supplements show inconsistent or null benefit in primary prevention populations.
Open evidence analysisSupporting literature
Should aspirin be used for primary cardiovascular prevention?
Current guidelines generally discourage routine aspirin for primary prevention in low-to-moderate-risk adults because bleeding harm offsets modest benefit. Select high-risk individuals may still be considered with shared decision-making.
Open evidence analysis