THE IMPACT OF TESTOSTERONE REPLACEMENT THERAPY ON METABOLIC HOMEOSTASIS, VASCULAR RESILIENCE, AND CARDIOVASCULAR SAFETY IN HYPOGONADAL MEN: A COMPREHENSIVE ANALYSIS OF THE METABOLIC-VASCULAR AXIS AND PRECISION ENDOCRINE REHABILITATION (2018–2026)

Kinga Karczewska; Małgorzata Ziółek; Kornelia Domagała; Magdalena Maroszek; Kamil Szymczak; Bartosz Janik; Ariadna Bakier; Jagoda Kuniewicz; Michał Tokarczyk; Julia Kuczkowska; Milena  Wątek; Maria Skorupa; Małgorzata Kurowska; Tomasz Piszczek; Andrzej Samujilik

doi:10.31435/ijitss.2(50).2026.5457

Authors

Kinga Karczewska MD, 7th Naval Hospital in Gdańsk, Gdańsk, Poland https://orcid.org/0009-0002-4773-3044
Małgorzata Ziółek MD, 7th Naval Hospital in Gdańsk, Gdańsk, Poland https://orcid.org/0009-0006-4162-7899
Kornelia Domagała MD, 7th Naval Hospital in Gdańsk, Gdańsk, Poland https://orcid.org/0009-0008-4148-9320
Magdalena Maroszek MD, 7th Naval Hospital in Gdańsk, Gdańsk, Poland https://orcid.org/0009-0005-3826-1788
Kamil Szymczak MD, 7th Naval Hospital in Gdańsk, Gdańsk, Poland https://orcid.org/0009-0002-7719-7625
Bartosz Janik MD, 7th Naval Hospital in Gdańsk, Gdańsk, Poland https://orcid.org/0009-0003-2112-1477
Ariadna Bakier MD, 7th Naval Hospital in Gdańsk, Gdańsk, Poland https://orcid.org/0009-0008-3812-5403
Jagoda Kuniewicz MD, 7th Naval Hospital in Gdańsk, Gdańsk, Poland https://orcid.org/0009-0007-4848-4306
Michał Tokarczyk MD, 7th Naval Hospital in Gdańsk, Gdańsk, Poland https://orcid.org/0009-0005-5122-7365
Julia Kuczkowska MD, 7th Naval Hospital in Gdańsk, Gdańsk, Poland https://orcid.org/0009-0004-8320-876X
Milena Wątek MD, 7th Naval Hospital in Gdańsk, Gdańsk, Poland https://orcid.org/0009-0006-9223-7591
Maria Skorupa MD, 7th Naval Hospital in Gdańsk, Gdańsk, Poland https://orcid.org/0009-0007-8486-1607
Małgorzata Kurowska MD, 7th Naval Hospital in Gdańsk, Gdańsk, Poland https://orcid.org/0000-0001-8442-4510
Tomasz Piszczek MD, 7th Naval Hospital in Gdańsk, Gdańsk, Poland https://orcid.org/0009-0002-6486-6746
Andrzej Samujilik MD, 7th Naval Hospital in Gdańsk, Gdańsk, Poland https://orcid.org/0009-0008-8901-3719

DOI:

https://doi.org/10.31435/ijitss.2(50).2026.5457

Keywords:

Testosterone Replacement Therapy, Metabolic Syndrome, Cardiovascular Safety, Hypogonadism, Endothelial Function, T4DM, TRAVERSE Trial

Abstract

The clinical management of hypogonadism in aging males has shifted toward a multimodal strategy centered on metabolic stabilization and vascular protection. This review evaluates the impact of testosterone replacement therapy on metabolic homeostasis, vascular resilience, and cardiovascular safety, incorporating evidence available through 2026. Data from landmark clinical trials, including the Testosterone for Diabetes Mellitus (T4DM) and the Testosterone Replacement Therapy for Assessment of Long-term Vascular Events and Efficacy Response (TRAVERSE) studies, indicate that testosterone replacement therapy improves glycemic control and reduces visceral adiposity. Reductions in glycated hemoglobin typically range from 0.6% to 1.2%, accompanied by a decrease in insulin resistance as measured by the HOMA-IR index. Testosterone replacement therapy enhances vascular resilience by improving flow-mediated dilation and promoting nitric oxide bioavailability. These changes contribute to systemic reductions in systolic blood pressure. The TRAVERSE trial provides evidence that testosterone replacement therapy is non-inferior to placebo regarding major adverse cardiovascular events in high-risk populations, which addresses historical safety concerns. However, the results emphasize the necessity of rigorous clinical monitoring, particularly concerning hematocrit levels and prostate-specific antigen to mitigate risks of erythrocytosis. Monitored testosterone replacement therapy is an effective modality for disrupting the cycle of obesity and insulin resistance while reinforcing the cardiovascular system in hypogonadal men. A precision medicine approach to dosing and delivery systems is essential for optimizing long-term health outcomes.

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