Examining the links between testosterone deficiency, endothelial dysfunction, hypertension, and atherosclerosis—and what the TRAVERSE trial and TRT-associated erythrocytosis reveal about cardiovascular risk.
I. Introduction
Testosterone has historically been framed narrowly, as a reproductive hormone governing libido, spermatogenesis, and secondary sexual characteristics, or as an anabolic agent influencing muscle mass and bone density. Over the past two decades, a substantial body of epidemiological, mechanistic, and interventional literature has repositioned testosterone as a cardiometabolic hormone as well, with receptors and downstream signaling effects distributed throughout the vascular endothelium, smooth muscle, myocardium, adipose tissue, and immune cells.
This article surveys the evidence linking endogenous testosterone status to cardiovascular disease, with particular emphasis on hypertension and atherosclerosis. It covers the epidemiological associations between low testosterone and cardiovascular outcomes, the pathophysiological mechanisms proposed to explain those associations, the specific evidence implicating testosterone deficiency in blood pressure elevation and atherosclerotic plaque formation, and the clinical trial evidence — including the large TRAVERSE trial — that has reshaped this discussion. It also addresses a countervailing risk: testosterone replacement therapy (TRT) can itself induce secondary polycythemia (erythrocytosis), which raises blood viscosity and may independently contribute to hypertension and mechanical arterial wall stress. The interplay between low endogenous testosterone as a cardiovascular risk marker and supraphysiologic or poorly monitored testosterone therapy as a distinct hematologic risk is central to interpreting this literature responsibly.
This topic carries real clinical weight. Testosterone declines gradually with normal male aging, cardiovascular disease remains the leading cause of death in aging men, and testosterone prescribing has risen substantially over the past fifteen years. Clinicians and patients alike are frequently confronted with an incomplete and sometimes contradictory evidence base, spanning observational cohorts that suggest low testosterone is a marker (or possibly a cause) of vascular disease, alongside older, methodologically limited randomized trials that raised safety alarms, and now a definitive large-scale trial that has substantially — though not completely — resolved the safety question for one important population.
II. Epidemiological Associations
Testosterone, All-Cause and Cardiovascular Mortality
A large individual-participant-data meta-analysis pooling data from nine cohort studies of men found that all-cause mortality risk rose below a mass-spectrometry-measured testosterone threshold of approximately 7.4 nmol/L (213 ng/dL), and that men with testosterone below roughly 5.3 nmol/L (153 ng/dL) carried an increased risk of cardiovascular death specifically [1]. A 2025 NHANES-based cohort study of patients who already had established cardiovascular disease similarly found that low serum testosterone (defined as ≤300 ng/dL) was common — present in over 70% of male CVD patients — and was associated with markedly higher all-cause mortality during follow-up [2]. In men with chronic kidney disease, a systematic review and meta-analysis of cohort studies found that every one-standard-deviation decrease in total testosterone was associated with a 27% increase in all-cause mortality and a 100% increase in cardiovascular mortality, independent of age, BMI, diabetes, hypertension, CRP, and other confounders [4].
A review in the Journal of the American College of Cardiology summarizing roughly 70 studies found that men with cardiovascular disease had significantly lower testosterone (and higher estradiol) than men without it, a relationship that persisted after adjustment for age and BMI, and that lower baseline testosterone predicted cardiovascular mortality in longitudinal cohorts [3].
Marker Versus Mediator — The Central Unresolved Question
Not every cohort agrees. The Finnish FINRISK97 study, a large population-based cohort, found no significant association between testosterone and either incident coronary heart disease or mortality, in either men or women [6]. Reviewers have noted a pattern across this literature: studies reporting a significant association tend to be smaller with shorter follow-up and incomplete statistical adjustment, while larger, more rigorously adjusted studies more often report null findings [6]. The authors of the largest individual-participant-data meta-analysis to date were explicit that it remains unresolved whether low testosterone is a marker of poor underlying health (obesity, chronic disease, inflammation, aging) that also happens to predict cardiovascular risk, or whether it is a genuine causal contributor that would respond to correction [1]. Discrepancies between observational associations, randomized trial results, and Mendelian randomization studies (which can partially account for reverse causation and confounding) have not yet been fully reconciled [1].
This marker-versus-mediator distinction is the throughline of this entire article. Association is well established; causation, and therefore the clinical benefit of correcting testosterone levels specifically to reduce cardiovascular risk, is not.
III. Pathophysiological Mechanisms
Androgen Receptors in the Vasculature
Androgen receptors are expressed throughout the vascular endothelium and smooth muscle, and testosterone exerts both genomic effects (androgen receptor binding driving gene transcription) and rapid, non-genomic effects mediated through membrane-associated signaling [8]. This dual signaling architecture is why testosterone can produce vasoactive effects within minutes — well before any change in gene expression could occur.
Endothelial Function and Nitric Oxide
Testosterone increases the expression and activity of endothelial nitric oxide synthase (eNOS), the enzyme responsible for producing nitric oxide (NO), the principal vasodilator released by the endothelium [8]. In cultured human aortic endothelial cells, physiological concentrations of testosterone induced rapid eNOS phosphorylation and NO production through androgen-receptor-dependent activation of the PI3-kinase/Akt signaling pathway, an effect abolished by androgen receptor blockade [7]. A related study in rat aortic tissue and endothelial cell culture found that testosterone’s stimulation of NO synthesis depended on extracellular calcium influx and was mediated through protein kinase C and MAP kinase pathways [9]. Because NO also mediates smooth muscle relaxation via cGMP-dependent protein kinase, curbing NO bioavailability is one of the most direct routes by which androgen deficiency could translate into elevated vascular tone [8]. Consistent with this, a review of testosterone deficiency and endothelial dysfunction found that low testosterone is associated with reduced NO bioavailability, elevated asymmetric dimethylarginine (an endogenous eNOS inhibitor), and impaired endothelial progenitor cell function — three converging routes to impaired vascular repair capacity [10].
Inflammatory Signaling
Testosterone modulates several inflammatory pathways relevant to atherogenesis. In elderly men, low free testosterone correlates with higher levels of CRP, interleukin-6, and soluble ICAM-1, markers directly implicated in atherosclerosis progression [12]. Mechanistically, androgens regulate the expression of TNF-α, IL-1β, IL-6, and CRP, and testosterone has been shown in multiple athero-relevant cell types (monocytes, macrophages, endothelial cells, smooth muscle cells, and foam cells) to suppress pro-inflammatory cytokine production and adhesion molecule expression [11][8]. In an orchidectomized ApoE-knockout mouse model of testosterone deficiency and atherosclerosis, testosterone treatment reduced aortic lipid accumulation, reduced monocyte/macrophage infiltration into plaque, and locally reduced ICAM-1 expression at the plaque site — plausibly via downregulation of TNF-α [14]. Since monocyte adhesion to activated endothelium via ICAM-1/VCAM-1 is one of the earliest identifiable steps in atherosclerotic plaque initiation, this anti-adhesive effect is mechanistically significant for the initiation phase of atherosclerosis specifically.
Lipid Metabolism and Visceral Adiposity
Testosterone influences body composition by favoring the commitment of pluripotent stem cells toward muscle over adipocyte lineage and by inhibiting preadipocyte differentiation, which helps explain why testosterone deficiency is closely linked to expansion of visceral adipose tissue [15]. Visceral fat is not inert; it is a proinflammatory endocrine organ, and its expansion under conditions of low testosterone generates adipokines and cytokines that worsen insulin resistance and endothelial dysfunction, compounding cardiovascular risk through a second, parallel pathway [16]. Clinical trial evidence on lipids is mixed: some meta-analyses report a modest HDL-lowering effect of testosterone therapy, while other observational cohorts of obese, hypogonadal diabetic men report favorable overall lipid changes together with reduced pulse pressure and arterial stiffness during testosterone treatment [18].
Insulin Sensitivity and Metabolic Syndrome
Testosterone deficiency and insulin resistance appear to exist in a bidirectional, self-reinforcing relationship. Hypogonadism is present in up to half of men with type 2 diabetes, and low testosterone and/or low sex hormone-binding globulin (SHBG) predict the later development of metabolic syndrome and type 2 diabetes [17]. Conversely, hyperinsulinemia and obesity suppress testicular testosterone production, and reduced SHBG (itself driven by insulin resistance and inflammation) further lowers total testosterone measurements [15][17]. Because visceral adiposity, insulin resistance, dyslipidemia, and hypertension co-cluster as metabolic syndrome, and because testosterone deficiency sits at the intersection of all four components, isolating testosterone’s independent contribution to cardiovascular risk from this broader metabolic dysregulation is one of the persistent confounding challenges in this literature [15].
“Association is well established; causation, and therefore the clinical benefit of correcting testosterone levels specifically to reduce cardiovascular risk, is not.”
IV. Testosterone and Hypertension Specifically
Mechanistic Links: RAAS and Vascular Reactivity
The relationship between testosterone and blood pressure regulation is genuinely paradoxical, and the mechanistic and observational literatures point in different directions depending on the model system. In rodent studies, testosterone has been shown to play a permissive role in angiotensin-II-induced hypertension: castrated male rats given testosterone replacement developed greater blood pressure elevation, greater vascular reactivity to vasoconstrictors, and more cardiac hypertrophy and fibrosis in response to angiotensin II infusion than castrated rats without testosterone replacement, an effect linked to a shift in the vascular AT1/AT2 receptor ratio [19]. This animal literature suggests that testosterone can potentiate one of the principal hypertensive signaling systems, the renin-angiotensin-aldosterone system (RAAS), which raises blood pressure through vasoconstriction, aldosterone-mediated sodium retention, and increased sympathetic tone [19].
Human Observational Data Point the Other Way
Human observational data, by contrast, has more often shown an inverse relationship between testosterone and blood pressure. In the Rancho Bernardo cohort of 1,132 men, both systolic and diastolic blood pressure correlated inversely with testosterone levels across the full range studied, with a stepwise decrease in blood pressure per increasing testosterone quartile [20]. A large Chinese cohort study of nearly 5,800 men, published in the Journal of the American Heart Association, found that total testosterone, free testosterone, and SHBG were all inversely associated with prevalent hypertension, an association that was strengthened in men who smoked or had a family history of hypertension [21]. A Swedish population study similarly found a strong inverse association between SHBG and both systolic and diastolic blood pressure in men, independent of BMI, insulin resistance, triglycerides, HDL, and CRP [22]. Interventional data has generally supported the observational picture rather than the rodent RAAS data: in a large observational registry of hypogonadal men, those treated with testosterone undecanoate showed significant reductions in systolic and diastolic blood pressure and pulse pressure over follow-up, while untreated men showed significant increases [23].
The likely resolution is that the RAAS-potentiation effect seen in rodent models describes testosterone’s role in exacerbating an already-activated pressor system (angiotensin II infusion), whereas the human observational and interventional data more often describe testosterone’s baseline, physiological vasodilatory contribution via nitric oxide and reduced peripheral vascular resistance in men who are not already hypertensive on that basis. Both effects may be real and simply apply to different clinical contexts — a caution that some reviewers who describe this relationship as “multifaceted and paradoxical” note explicitly.
Confounders
Age, adiposity, and obstructive sleep apnea all independently lower testosterone while independently raising blood pressure, and all three are common in the same population of aging, overweight men most often studied in this literature. Disentangling testosterone’s independent contribution from these shared upstream drivers remains difficult in observational designs, which is why interventional and mechanistic data carry disproportionate weight in this specific sub-question.
V. Testosterone and Atherosclerosis Specifically
Plaque Initiation: Endothelial Dysfunction as the First Step
Atherosclerosis begins with endothelial activation: circulating monocytes adhere to the arterial endothelium via adhesion molecules (ICAM-1, VCAM-1, P-selectin), migrate into the subendothelial space, and differentiate into macrophages that take up oxidized LDL to form foam cells, the histological hallmark of the earliest atherosclerotic lesion. As detailed above, testosterone’s suppression of adhesion molecule expression and its support of eNOS-derived nitric oxide both act directly on this initiating step, giving a mechanistic explanation for why testosterone deficiency could plausibly accelerate the earliest phase of plaque formation, independent of any effect on cholesterol.
Plaque Progression: Foam Cells and Smooth Muscle Proliferation
In the orchidectomized ApoE-/- mouse model, testosterone deficiency increased lipid accumulation and macrophage infiltration in the aortic root, while testosterone replacement reduced both, supporting a role for testosterone in slowing plaque progression once initiated, not merely in preventing initiation [14]. However, when investigators sequenced RNA from human carotid endarterectomy plaque tissue in 203 men with advanced, symptomatic atherosclerotic disease, they found no association between circulating testosterone levels and testosterone-sensitive gene expression within the plaque itself, despite testosterone being a strong predictor of secondary stroke risk in the same cohort [26]. This is an important discordance: it suggests that once advanced atherosclerotic disease is already established, testosterone’s clinical association with outcomes may operate through mechanisms other than direct transcriptional effects on the existing plaque — perhaps through systemic effects on inflammation, coagulation, or plaque-adjacent vascular tone rather than the diseased tissue itself.
Human Imaging Evidence: Carotid IMT and Coronary Calcium
The Tromsø study, a large Norwegian population cohort, found in cross-section that total testosterone and SHBG were inversely associated with age-adjusted carotid intima-media thickness (IMT), independent of smoking, physical activity, blood pressure, and lipids, though not independent of BMI [25]. A prospective follow-up of the same cohort over seven years found an inverse association between testosterone and carotid plaque area in the cross-sectional analysis, again reinforcing a protective association for normal endogenous testosterone [24]. A separate cohort study of middle-aged men with symptoms of late-onset hypogonadism likewise found endogenous testosterone inversely associated with common carotid IMT [24].
Interventional imaging data tells a more sobering story about causality. In the Testosterone’s Effects on Atherosclerosis in Aging Men (TEAAM) trial, 306 older men with low or low-normal testosterone were randomized to three years of testosterone gel or placebo, with cIMT progression and coronary artery calcium (CAC) as primary endpoints. The trial found no significant difference in the rate of cIMT progression between groups (0.010 mm/year placebo versus 0.012 mm/year testosterone) and no significant difference in CAC progression [27]. This is one of the more important pieces of evidence in the entire literature: it directly tested whether correcting testosterone slows the anatomic progression of atherosclerosis, and found a neutral result — supporting the interpretation that low testosterone is more likely a marker correlated with atherosclerosis risk than a modifiable causal driver of plaque progression, at least over a three-year interventional window in older men.
VI. Clinical Trial Evidence and Controversies
The Pre-TRAVERSE Era: Conflicting Signals
Concern about testosterone’s cardiovascular safety dates to a 2010 New England Journal of Medicine report by Basaria and colleagues, which found significantly more cardiovascular events in older, mobility-limited men randomized to testosterone versus placebo, leading the trial to be stopped early [3]. Subsequent observational studies compounded the concern: the Vigen study reported increased mortality and cardiovascular events associated with testosterone therapy, and a separate analysis by Finkle and colleagues found a higher rate of non-fatal myocardial infarction in the 90 days following a new testosterone prescription [30]. Both studies drew substantial methodological criticism (for confounding by indication and inadequate control groups) but were influential enough to contribute to a 2015 FDA-mandated black-box warning and a requirement that manufacturers conduct a dedicated cardiovascular safety trial [30][29]. Earlier meta-analyses spanning 2005–2010 had, by contrast, found generally neutral effects of testosterone on major cardiovascular events, with the main consistent findings being an increase in hematocrit/hemoglobin and small effects on lipids [3]. A 2022 individual-patient-data meta-analysis pooling 17 randomized trials (3,431 participants) found no cardiovascular event subtype significantly more common with testosterone than placebo, though the analysis was underpowered for mortality given the low absolute number of deaths recorded [5].
TRAVERSE: The Definitive Trial
The Testosterone Replacement Therapy for Assessment of Long-term Vascular Events and Efficacy Response in Hypogonadal Men (TRAVERSE) trial was the FDA-mandated response to this uncertainty: a randomized, double-blind, placebo-controlled, event-driven, non-inferiority trial enrolling 5,246 men aged 45–80 with confirmed hypogonadism (two fasting testosterone levels below 10.4 nmol/L) and either pre-existing cardiovascular disease or elevated cardiovascular risk [28]. Participants received daily transdermal testosterone gel or placebo for a mean of 27.1 months. The trial’s primary finding was that testosterone therapy was non-inferior to placebo for the composite of major adverse cardiovascular events (MACE), with a hazard ratio of 0.96 (95% CI 0.78–1.17) [29]. This result held consistently across pre-specified subgroups [29].
TRAVERSE was reassuring but not unqualified. Secondary safety signals emerged: the testosterone group had significantly more non-fatal arrhythmias requiring intervention, atrial fibrillation, acute kidney injury, and venous thromboembolic events, as well as more fractures, compared to placebo [28]. These findings led the investigators to explicitly recommend caution in using testosterone in men with a prior history of thromboembolic events [28]. A subsequent position statement from the European Expert Panel for Testosterone Research characterized TRAVERSE as “groundbreaking but limited in scope,” noting it does not resolve practical questions such as optimal hematocrit monitoring protocols, management in men with functional (as opposed to organic) hypogonadism, or applicability to populations with different baseline comorbidity profiles than the trial cohort [30].
The U-Shaped Curve Hypothesis
Several observational cohorts studying the full physiological range of testosterone (rather than just deficient versus normal) have found evidence for a U-shaped or J-shaped risk curve, in which both low and supraphysiologically high testosterone levels are associated with elevated cardiovascular risk relative to mid-range, physiological levels [21]. If correct, this would imply that the therapeutic target for testosterone replacement is not simply “higher is better” but rather restoration to a specific physiological range, and that supraphysiologic dosing (a recognized risk in poorly monitored, self-directed, or performance-oriented TRT use) may carry its own distinct hazards, plausibly compounded by the erythrocytosis mechanism discussed in Section VII.
VII. A Countervailing Mechanism: TRT-Induced Polycythemia, Blood Viscosity, and Arterial Wall Strain
The sections above describe evidence that low endogenous testosterone is associated with, and may mechanistically contribute to, hypertension and atherosclerosis. Testosterone replacement therapy, however, introduces a distinct and mechanistically opposite cardiovascular risk: secondary erythrocytosis (polycythemia), which can raise blood pressure and impose direct mechanical strain on arterial walls through an entirely separate pathway — elevated blood viscosity — rather than through androgen receptor signaling.
Mechanism: How TRT Raises Hematocrit
Testosterone stimulates erythropoiesis through several converging mechanisms: it raises the erythropoietin set-point (the hemoglobin level at which erythropoietin production is suppressed), increases iron bioavailability by suppressing hepcidin and ferritin, and directly stimulates bone marrow erythroid progenitors [31][32]. All formulations of TRT raise hemoglobin and hematocrit to some degree, but injectable formulations (testosterone cypionate/enanthate) produce the largest effect, followed by oral undecanoate, with transdermal patches and intranasal gels producing more modest increases [35]. Clinically meaningful erythrocytosis — hematocrit above roughly 52–54% — is common enough with injectable TRT that professional society guidelines (AUA, EAU, Endocrine Society) recommend baseline and periodic hematocrit monitoring, dose adjustment or formulation switching when thresholds are exceeded, and consideration of therapeutic phlebotomy in refractory cases [32][33].
From High Hematocrit to High Blood Viscosity
Hematocrit is the dominant determinant of whole blood viscosity: as red cell mass rises, blood becomes measurably more viscous, and this relationship is nonlinear, with viscosity rising steeply once hematocrit exceeds the mid-50s percentile range [35]. Because viscosity is one of the core determinants of resistance to flow, elevated blood viscosity directly increases total peripheral vascular resistance, one of the two hemodynamic determinants of blood pressure alongside cardiac output [36]. A study of hemorheological (blood-flow) profiles in patients with prehypertension found that elevated blood viscosity was independently associated with higher blood pressure, and proposed that in states of high viscosity, systemic blood pressure must rise to overcome the increased frictional resistance and maintain adequate tissue perfusion [34]. A dedicated review of blood viscosity in the pathogenesis of arterial hypertension similarly concludes that elevated viscosity is a contributing hemodynamic factor in some hypertensive states, operating through increased vascular resistance [35].
Mechanical Strain on the Arterial Wall
Beyond its effect on systemic blood pressure, elevated blood viscosity changes the local mechanical forces the arterial wall experiences at the endothelial surface. Wall shear stress — the frictional force exerted by flowing blood parallel to the vessel wall — is a direct function of blood viscosity, flow velocity, and vessel geometry [36]. Acute changes in hematocrit produce acute changes in wall shear stress, and abnormal (either excessively high or excessively low, or abnormally pulsatile) shear stress patterns are implicated in adverse vascular remodeling, endothelial activation, and atherogenic changes at the vessel wall [36]. Separately, elevated hematocrit and the accompanying rise in blood volume and viscosity increase circumferential (tensile) wall stress by raising the pressure the vessel wall must withstand — a form of mechanical loading distinct from, but additive to, shear stress. Chronically elevated wall stress of either kind is a recognized driver of vascular remodeling, arterial stiffening, and end-organ damage in sustained hypertension of any cause [36], meaning TRT-induced polycythemia can plausibly contribute to arterial wall injury through purely biomechanical, non-inflammatory, non-androgen-receptor-mediated pathways layered on top of the hormonal mechanisms discussed elsewhere in this article.
Clinical and Thrombotic Significance
The clinical relevance of TRT-induced erythrocytosis is reinforced by outcome data: a large cohort study found that men who developed secondary polycythemia during testosterone therapy had a significantly increased risk of major adverse cardiovascular events and venous thromboembolism specifically within the first year of therapy, and the authors proposed elevated blood viscosity as the plausible mediating mechanism, drawing an analogy to the well-documented thrombotic risk seen in idiopathic (primary) erythrocytosis and polycythemia vera [31]. Notably, this thrombotic and hypertensive risk from erythrocytosis is mechanistically and temporally distinct from the low-testosterone-associated cardiovascular risk discussed in Sections II–V: one arises from androgen deficiency acting on the endothelium and metabolism over years, while the other arises from androgen excess (relative to what the bone marrow was calibrated for) acting on blood rheology within months. Both can plausibly raise blood pressure and injure the arterial wall, but through opposite hormonal directions and different physical mechanisms — underscoring why cardiovascular risk assessment in testosterone therapy requires monitoring hematocrit as a distinct variable from testosterone level itself, and why correcting testosterone is not risk-free simply because deficiency itself carries risk.
VIII. Synthesis and Clinical Implications
Where the Evidence is Strong
The association between low endogenous testosterone and adverse cardiovascular outcomes — all-cause mortality, cardiovascular mortality, prevalent hypertension, and carotid atherosclerosis burden — is consistently observed across multiple large, independent cohorts and is not easily attributable to a single confounder. The cellular and molecular mechanisms by which testosterone plausibly protects the endothelium (nitric oxide signaling, suppression of adhesion molecules and pro-inflammatory cytokines, favorable body composition effects) are well characterized in vitro and in animal models and are biologically coherent with the epidemiology.
Where the Evidence is Weaker or Contradicted
The causal question — whether restoring testosterone in deficient men actually slows or reverses cardiovascular disease — is not well supported. The TEAAM trial found testosterone therapy had no effect on the anatomic progression of subclinical atherosclerosis (carotid IMT or coronary calcium) over three years. Plaque tissue from men with advanced atherosclerotic disease showed no relationship between circulating testosterone and testosterone-responsive gene expression within the plaque itself. Rodent RAAS data suggest testosterone can be permissive for angiotensin-II-driven hypertension rather than uniformly protective. And the largest and most rigorous cohort studies, with the longest follow-up and most complete adjustment, are the ones most likely to find null or attenuated associations — a pattern that should raise, rather than lower, suspicion of residual confounding in the positive studies.
TRAVERSE Resolved Safety for its Studied Population, Not the Whole Causal Question
TRAVERSE demonstrates convincingly that testosterone therapy, appropriately dosed and monitored, does not increase major adverse cardiovascular events in men with confirmed hypogonadism and elevated baseline cardiovascular risk — an important and clinically actionable safety finding. It does not demonstrate that testosterone therapy reduces cardiovascular risk, and it identified real secondary hazards (arrhythmia, venous thromboembolism, acute kidney injury) that clinicians should weigh, particularly alongside the erythrocytosis-driven viscosity and wall-stress mechanism detailed in Section VII.
Open Questions
Several questions remain genuinely unresolved: whether the U-shaped risk curve is real and where its inflection points lie; whether functional hypogonadism (low testosterone secondary to obesity or illness, without primary testicular or pituitary pathology) behaves differently from organic hypogonadism with respect to cardiovascular risk and treatment response; what hematocrit thresholds and monitoring intervals best balance the benefits of testosterone correction against erythrocytosis-related thrombotic and hypertensive risk; and whether longer-duration or higher-risk subgroups (younger men, men on supraphysiologic or self-directed dosing regimens, or men with pre-existing erythrocytosis risk factors such as obstructive sleep apnea) face a materially different risk-benefit calculus than the TRAVERSE trial population.
Conclusion
Testosterone is now well established as a cardiometabolic hormone with genuine, biologically plausible effects on endothelial function, vascular inflammation, lipid and glucose metabolism, and — with less consistency — blood pressure regulation. Low endogenous testosterone tracks reliably with worse cardiovascular outcomes across large observational cohorts. What remains unproven is that testosterone deficiency is a primary causal driver of hypertension and atherosclerosis, rather than a downstream marker of the same aging, adiposity, and inflammatory processes that independently drive vascular disease. The TRAVERSE trial provides real reassurance about the short-to-medium-term cardiovascular safety of testosterone therapy in a well-defined population but does not establish a cardioprotective benefit, and it surfaced secondary risks — arrhythmia, thromboembolism, and, mechanistically, erythrocytosis-driven increases in blood viscosity and arterial wall stress — that argue for careful patient selection and ongoing hematologic monitoring rather than an unqualified verdict of safety.
