Is TRT Right for You? What a Cardiologist Checks Before You Start.

He was forty-six. Two blood draws, both in the 400s. Total testosterone of 412 ng/dL on one morning and 388 on another. He had been symptomatic for two years: fatigue that did not respond to sleep, libido that had gradually become a memory, a mental fog that was making client presentations harder than they used to be. He had seen three urologists. All three had told him his numbers were “close enough to normal.”

Before I had a chance to discuss testosterone, I asked him one question.

“Has anyone ever done a CAC score on you?”

He did not know what a CAC score was.

“Has anyone checked your ApoB? Your hematocrit baseline? An echocardiogram? Your blood pressure outside of this office?”

No, no, no, and no.

He had been evaluated for whether he qualified for testosterone. He had not been evaluated for whether his cardiovascular system could safely carry the treatment if he started it.

That is the gap this article addresses. There is a $300 million telehealth testosterone industry in the United States, and it contains essentially no cardiologist oversight. Men are starting testosterone therapy without a pre-treatment cardiac evaluation. That is not a theoretical concern. It is a clinical reality with documented consequences.

The Mechanism

Testosterone does not act on the heart in one way. It acts on several systems simultaneously, and those systems interact with each other.

Erythropoiesis and blood viscosity. Testosterone stimulates the kidneys to produce erythropoietin, which drives red blood cell production. In most men, this manifests as a rise in hematocrit of three to five percentage points within the first three to six months of therapy. In some men, particularly older men, men with untreated sleep apnea, and men on injectable rather than topical formulations, the rise is steeper. As hematocrit climbs, blood viscosity increases. More viscous blood exerts higher shear stress on arterial walls, moves more slowly through small-caliber vessels, and raises the thrombotic tendency of the system. In a man whose coronary arteries already carry atherosclerotic plaque, elevated viscosity is not a trivial byproduct of treatment. It is a compounding risk factor sitting on top of existing disease.

Effects on lipids. The relationship between testosterone and lipids is not straightforward. Testosterone tends to modestly reduce total cholesterol and LDL in hypogonadal men, but it also consistently reduces HDL cholesterol, with the magnitude depending heavily on delivery method and dose. Injectable testosterone, particularly at higher doses, produces larger HDL reductions than topical gel formulations. Testosterone’s effect on ApoB, the atherogenic particle count that many cardiologists now consider more predictive than LDL-C, is less well characterized, which is exactly why a baseline ApoB measurement before starting therapy gives you a reference point when you recheck at six months and see something you do not like.

Atrial remodeling and the AF substrate. The mechanism connecting testosterone to atrial fibrillation is not fully worked out, but the biological plausibility is real. Testosterone has direct effects on cardiac ion channels, particularly potassium channels, that can shorten atrial action potential duration and increase atrial excitability. Testosterone also promotes left ventricular hypertrophy at supraphysiologic doses, and chronically elevated filling pressures from LVH produce left atrial enlargement, which is one of the most substantial structural substrates for AF. Separately, the hematocrit rise increases circulating volume and cardiac preload, which compounds atrial wall stress over time. None of these mechanisms requires a pharmacologically toxic dose. They operate at replacement doses in men with pre-existing vulnerabilities, which is exactly the population most likely to be seeking TRT.

Coagulation and venous thromboembolism. Testosterone increases platelet aggregability and alters coagulation factor activity in ways that shift the clotting balance toward thrombosis. In combination with the elevated blood viscosity from erythropoiesis, this creates a vascular environment that is less tolerant of the conditions that produce deep vein thrombosis and pulmonary embolism: prolonged sitting, dehydration, long-haul flights, perioperative states, inherited thrombophilias. A man who already carries one of these risk factors and starts TRT without that context being surfaced has an elevated PE risk that neither he nor his telehealth prescriber may be tracking.

Sleep apnea as amplifier. Untreated obstructive sleep apnea independently elevates hematocrit through intermittent nocturnal hypoxia, which stimulates erythropoietin production through the same pathway testosterone uses. A man with sleep apnea who starts TRT is stacking two erythropoietic stimuli. His hematocrit trajectory will be steeper, his blood viscosity will rise faster, and his dose thresholds for concern will be reached sooner. Additionally, testosterone worsens sleep apnea severity in some men through effects on upper airway muscle tone and respiratory drive, creating a feedback loop: testosterone raises hematocrit, worsens apnea, which raises hematocrit further.

What the Evidence Shows

The history of testosterone and cardiac safety research is a story of small, methodologically compromised studies followed by one definitive trial that answered the primary question and opened two new ones.

The alarm studies. In 2013, Vigen et al. published an observational analysis in JAMA of 8,709 men in the VA system with low testosterone who underwent coronary angiography. Men who received testosterone after catheterization had a higher rate of death, heart attack, and stroke than men who did not. The study had significant methodological problems, including a crude correction for baseline cardiovascular risk and a comparison group that had no clinical reason to receive testosterone, but it generated headlines that still circulate in primary care offices. In 2014, Finkle et al. published a case-control study in PLOS One suggesting that the rate of non-fatal heart attack was higher in the 90 days following a testosterone prescription in men over 65. Again, observational, again with confounding issues, but again widely cited. These studies raised the alarm. They did not settle the question.

The TRAVERSE trial. The TRAVERSE trial (Lincoff et al., NEJM 2023) was designed to settle the MACE question definitively. It enrolled 5,246 men aged 45 to 80 with confirmed hypogonadism (total testosterone below 300 ng/dL on two separate morning measurements) and pre-existing cardiovascular disease or elevated cardiovascular risk. They were randomized to 1.62 percent testosterone gel versus placebo and followed for a mean of 33 months. This was a pre-specified non-inferiority trial with a primary composite endpoint of death from cardiovascular causes, non-fatal myocardial infarction, or non-fatal stroke.

Primary result: testosterone was non-inferior to placebo for MACE. 5 / Solid The event rates were 7.0 percent in the testosterone group and 7.3 percent in the placebo group. The upper bound of the confidence interval fell below the non-inferiority margin. The Vigen and Finkle signals, at least for hard cardiac events in men with monitored therapy, did not replicate in a properly powered prospective trial.

But the TRAVERSE trial also reported pre-specified secondary outcomes that received less attention in the consumer press.

The AF signal. Atrial fibrillation occurred in 3.5 percent of men in the testosterone group versus 2.4 percent in the placebo group, representing a 16 percent higher relative rate in the testosterone arm. 4 / Promising This was a pre-specified secondary outcome, not a post-hoc finding. It was statistically significant. It has direct clinical implications for any man with pre-existing AF risk factors: obesity, hypertension, sleep apnea, a dilated left atrium on echo, a history of palpitations, or simply being over 60 with multiple comorbidities.

The PE signal. Pulmonary embolism occurred in 0.9 percent of men in the testosterone group versus 0.5 percent in the placebo group, a 2.3-fold higher rate in the testosterone arm. 4 / Promising This too was a pre-specified secondary outcome. An absolute difference of 0.4 percentage points may sound small, but at the population level, in a country where millions of men are receiving or considering TRT, 0.4 percent of a large exposed population is a number that warrants systematic pre-treatment VTE risk assessment. It also represents a clinically serious event: pulmonary embolism carries a mortality rate of approximately 2 to 3 percent in unselected populations, and higher in men with underlying cardiopulmonary disease.

What TRAVERSE settled and what it did not. TRAVERSE is the definitive answer to the question “does TRT cause heart attacks and strokes in hypogonadal men?” It does not, when prescribed appropriately with monitoring. TRAVERSE is not the end of the story on atrial fibrillation and pulmonary embolism. Those signals are real, they are from a high-quality randomized trial, and they have not been incorporated into the intake process of most telehealth TRT platforms.

The Polycythemia Protocol: Hematocrit Monitoring on TRT

The erythropoietic effect of testosterone is the mechanism most reliably observable in clinical practice. For most men on standard therapeutic doses, hematocrit rises three to five percentage points within the first three to six months, from a pre-treatment value near 44 to 46 percent toward a value in the 47 to 51 percent range. This is usually the expected and manageable trajectory. The clinical concern begins when it does not stop there.

TRAVERSE provided the most precise data on polycythemia rates in a randomized setting. Hematocrit at or above 54 percent occurred in 5.7 percent of men in the testosterone group versus 1.4 percent in the placebo group, a statistically significant fourfold higher rate with active treatment. Importantly, this finding came from men on a 1.62 percent topical testosterone gel, which produces steadier pharmacokinetic exposure than injectable formulations. Injectable testosterone, whether intramuscular or subcutaneous, produces higher peak concentrations in the days following injection before falling to trough levels before the next dose. Peak-driven erythropoiesis exceeds steady-state erythropoiesis, meaning injectable protocols are associated with greater hematocrit elevation than topical protocols at equivalent monthly testosterone doses. The TRAVERSE polycythemia rate of 5.7 percent should be understood as a floor, not a ceiling, for men on injectable regimens.

The standard clinical response thresholds, based on current Endocrine Society and American Urological Association guidance, are: hematocrit at or above 54 percent warrants dose reduction, formulation switch from injectable to topical, or therapeutic phlebotomy; hematocrit between 50 and 54 percent requires more frequent monitoring and clinical consideration of dose adjustment, particularly in men with other thrombotic risk factors. A single therapeutic phlebotomy, removing approximately 450 to 500 mL of whole blood, reduces hematocrit by three to four percentage points and is the most rapid non-pharmacological intervention available.

Men at highest risk for clinically significant polycythemia on TRT share a recognizable pattern: injectable rather than topical delivery, untreated obstructive sleep apnea stacking its own erythropoietic stimulus alongside testosterone’s, older age, pre-treatment hematocrit already in the upper-normal range (46 to 49 percent), and residence at altitude where baseline hematocrit is physiologically elevated. Identifying this profile before initiation, not six months into therapy, allows for informed formulation selection, pre-treatment sleep apnea evaluation, and individualized monitoring intervals proportionate to the actual polycythemia risk. 4 / Promising

What to Do This Week

1. Before starting TRT, request a pre-treatment evaluation that includes at minimum: baseline hematocrit and complete blood count, ApoB and full lipid panel, a home blood pressure average (seven mornings, two readings each, validated cuff device, not a clinic reading), and an ECG. If you have symptoms of sleep apnea, including snoring, witnessed breathing pauses, or non-restorative sleep, add a sleep study or at minimum a validated home sleep apnea screening tool before starting.

2. If you are already on TRT from a telehealth platform and have never had a cardiac evaluation, schedule one this month. Bring your current dose, delivery method, frequency, and your most recent hematocrit result. If your hematocrit has been measured and is above 50 percent, that conversation is more urgent.

3. If your total testosterone is between 300 and 500 ng/dL and you have not yet started exogenous testosterone, ask your physician about clomiphene or enclomiphene before committing to a regimen that suppresses your HPG axis. These agents block estrogen receptors at the hypothalamus and pituitary, increase GnRH and LH, and stimulate the Leydig cells to produce more endogenous testosterone. The testes remain active, fertility is preserved or enhanced, and you avoid the HPG suppression that makes stopping exogenous testosterone later more complicated. The telehealth TRT industry has limited financial incentive to offer this conversation. A cardiologist or reproductive endocrinologist does.

4. If you have diagnosed atrial fibrillation, or if you have been told you have an “irregular heartbeat,” or if you have experienced unexplained palpitations, this is a mandatory cardiologist consultation before starting TRT. The TRAVERSE AF signal applies directly to your risk profile. Your cardiologist needs to assess your CHA2DS2-VASc score in the context of added testosterone before you start.

5. If you are currently on TRT and your hematocrit is rising, understand the threshold. Most guidelines recommend dose reduction, switching from injectable to topical formulation, or therapeutic phlebotomy when hematocrit exceeds 54 percent. A single phlebotomy is not a crisis intervention. It is a routine clinical response. What is not routine is a hematocrit of 56 percent in a man with a CAC score of 300 and untreated sleep apnea, who has never been told that these numbers are in conversation with each other.

The gap between “qualified for testosterone” and “cardiovascular system evaluated for testosterone” is not a gap that telehealth platforms are designed to close. It is a gap that requires a physician who looks at the cardiovascular system as a whole, who knows what hematocrit and ApoB and sleep apnea do to each other under an erythropoietic stimulus, and who has read the secondary outcomes tables of TRAVERSE rather than only its headline. That physician is worth finding before you start.

The Signal Check is fifteen questions mapping the male cardiovascular risk pattern, including the physiological domains most commonly missed in standard screenings. It produces a specific starting point for your next clinical conversation.