Cardiovascular Effects of Testosterone Replacement Therapy in Hypogonadal Men: A Systematic Review of Lipid Profiles, Inflammatory Markers, and Vascular Function

TL;DR

This review examines how testosterone replacement therapy affects heart health in men with low testosterone, finding some benefits in cholesterol and inflammation.

Contribution

The study provides a systematic review of TRT's cardiovascular effects, emphasizing physiological dosing and long-term safety.

Findings

TRT reduces total and LDL cholesterol while modestly increasing or stabilizing HDL cholesterol.

Testosterone therapy decreases pro-inflammatory cytokines like IL-6 and TNF-α.

TRT improves endothelial function and shows generally reassuring long-term cardiovascular safety.

Abstract

Testosterone replacement therapy (TRT) is commonly used to treat men with hypogonadism in order to replace the physiological levels of testosterone, although the cardiovascular safety and metabolic advantages of this treatment are still controversial. This article is a systematic review of the existing literature on the cardiovascular impact of TRT on lipid levels, inflammatory parameters, as well as endothelial activity in hypogonadal men. This systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Search was conducted in PubMed, Scopus, Embase, Web of Science, and Google Scholar of peer-reviewed studies that were published between 2005 and 2025. The Revised Assessment of Multiple Systematic Reviews (R-AMSTAR) tool was used to evaluate methodological quality, and the data were synthesized narratively due to substantial heterogeneity across study designs, including differences in TRT formulations, dosing regimens, treatment duration, and the clinical characteristics of hypogonadal populations. Quality ratings were considered when interpreting the evidence, with higher-quality studies providing stronger support for the cardiovascular effects of TRT. In this review, 25 studies were included as they met the inclusion criteria. The included studies comprised randomized controlled trials and observational research designs (systematic reviews, meta-analyses, and cohort studies). Overall, TRT was associated with reductions in total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), while high-density lipoprotein cholesterol (HDL-C) showed modest increases or remained stable across studies. Anti-inflammatory effects of testosterone therapy were demonstrated by the decrease in pro-inflammatory cytokines (interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α)) and the enhancement of endothelial-dependent vasodilation.

In hypogonadal men, TRT shows some improvements in endothelial function and reduced systemic inflammation, with benefits most evident under physiological dosing, while its lipid effects may be generally neutral to mildly favorable (decrease in TC/LDL, HDL often somewhat decreased depending on formulation). Long-term cardiovascular safety appears generally reassuring with respect to major adverse cardiac events in appropriately selected patients, though some adverse events may warrant monitoring. High-quality, longer-duration trials remain needed to strengthen these conclusions.

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