Evidence map›Paper›PMID 42364061›Full record

ReviewJournal of endocrinological investigation2026

Testosterone replacement therapy and cardiovascular safety in older men: lessons from TRAVERSE and beyond.

Daniele Tienforti, Giovanni Terrana, Riccardo Di Geronimo, Elisabetta Perfetto, Luca Spagnolo, Marco Giorgio Baroni, Arcangelo Barbonetti

Abstract readReview
PubMed Publisher
In one paragraph

Review in Journal of endocrinological investigation, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Daniele TienfortiAndrology Unit, Department of Clinical Medicine, Life, Health and Environmental Sciences, University of L'Aquila, Via Vetoio, L'Aquila, 67100, Italy. daniele.tienforti@graduate.univaq.it.ORCID http://orcid.org/0000-0002-9359-7955
Giovanni TerranaAndrology Unit, Department of Clinical Medicine, Life, Health and Environmental Sciences, University of L'Aquila, Via Vetoio, L'Aquila, 67100, Italy.
Riccardo Di GeronimoAndrology Unit, Department of Clinical Medicine, Life, Health and Environmental Sciences, University of L'Aquila, Via Vetoio, L'Aquila, 67100, Italy.
Elisabetta PerfettoAndrology Unit, Department of Clinical Medicine, Life, Health and Environmental Sciences, University of L'Aquila, Via Vetoio, L'Aquila, 67100, Italy.
Luca SpagnoloAndrology Unit, Department of Clinical Medicine, Life, Health and Environmental Sciences, University of L'Aquila, Via Vetoio, L'Aquila, 67100, Italy.
Marco Giorgio BaroniAndrology Unit, Department of Clinical Medicine, Life, Health and Environmental Sciences, University of L'Aquila, Via Vetoio, L'Aquila, 67100, Italy.
Arcangelo BarbonettiAndrology Unit, Department of Clinical Medicine, Life, Health and Environmental Sciences, University of L'Aquila, Via Vetoio, L'Aquila, 67100, Italy.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe cardiovascular safety of testosterone replacement therapy (TRT) in older men with hypogonadism has been debated for over a decade, largely on the basis of underpowered trials and conflicting observational data. The TRAVERSE trial, published in 2023, provided the first adequately powered, placebo-controlled evidence on this question.

objectivesThis review synthesises current evidence on the cardiovascular safety of TRT in older men, with particular attention to the interpretation of TRAVERSE findings, the clinical significance of non-MACE safety signals, and the practical management of organic versus functional hypogonadism.

methodsA systematic search of PubMed/MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) was conducted through March 2026. Approximately 450 articles were identified; 64 met the inclusion criteria and were selected for review. Evidence was appraised according to study design, with RCTs and meta-analyses weighted above observational data.

resultsTRAVERSE demonstrated non-inferiority of TRT versus placebo for major adverse cardiovascular events (MACE) in men with confirmed hypogonadism and elevated cardiovascular risk (HR 0.96, 95% CI 0.78-1.17) [5]. Non-MACE signals - including atrial fibrillation (3.1% vs. 2.4%), pulmonary embolism (2.0% vs. 1.5%), and acute kidney injury (2.3% vs. 1.5%) - were numerically higher in the TRT arm but did not reach statistical significance within the trial. In contrast, large observational cohorts consistently report statistically significant associations between TRT and AF and VTE. Erythrocytosis was the most reproducible adverse effect (17.0% vs. 3.3%, p < 0.001). Functional hypogonadism secondary to obesity or metabolic syndrome responds to lifestyle intervention and GLP-1/GIP agonists, with testosterone normalisation in 81.4% at 6 months and 89.5% at 24 months after bariatric surgery [45].

conclusionsTRT does not increase MACE risk in men with confirmed organic hypogonadism when titrated to physiological levels. Non-MACE signals warrant vigilance rather than contraindication. Metabolic optimisation should precede TRT in functional hypogonadism. Individualised monitoring and careful patient selection remain essential.

Indexed as

Atrial fibrillationCardiovascular safetyErythrocytosisFunctional hypogonadismHypogonadismTestosterone replacement therapyTRAVERSEVenous thromboembolism

Identifiers

PMID42364061

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.