You're on TRT. Here Is What Your Cardiologist Should Be Checking.

He called the office on a Thursday afternoon. He had been on testosterone cypionate injections for fourteen months, prescribed through a telehealth men’s health clinic. His last hematocrit had been 51 percent. The clinic had flagged it and told him to stay hydrated. He had read somewhere that hematocrit above 50 could increase stroke risk. He wanted to know if he was in danger.

The question he was asking was reasonable. The conversation he had never been offered was the one I needed to have with him. Not just about hematocrit. About what his cardiovascular system was actually experiencing, and what needed to be checked that the telehealth platform’s standard dashboard had not included.

That conversation is this article.

What the TRAVERSE Trial Actually Found

The TRAVERSE trial enrolled 5,246 men with hypogonadism and cardiovascular risk, randomized to testosterone gel versus placebo for a mean of 33 months. Primary result: TRT was non-inferior to placebo for major cardiovascular events (heart attack, stroke, cardiovascular death). This is reassuring and represents the most definitive evidence to date.

The secondary findings require clinical attention:

Atrial fibrillation: 3.5 percent in the testosterone group versus 2.4 percent in placebo, a 16 percent higher rate. 4 / Promising

Pulmonary embolism: 0.9 percent versus 0.5 percent in placebo, a 2.3-fold higher rate. 4 / Promising

Acute kidney injury: Small but statistically significant excess in the testosterone group. The AKI signal likely reflects hemodynamic stress from increased red cell mass: as hematocrit rises and blood viscosity increases, renal perfusion pressure changes in ways that can unmask borderline kidney function in men who already carry early chronic kidney disease. This is worth knowing because men on TRT who also use NSAIDs, contrast agents, or experience dehydration are operating with less physiological reserve than they may assume. A baseline creatinine and eGFR before starting TRT, and annual rechecks, belong in the monitoring protocol for this reason.

These signals do not mean TRT should be avoided. They mean TRT should be monitored. The man on testosterone who has never had his cardiac rhythm assessed, who has never had his home blood pressure tracked, who has never had his ApoB measured, is not receiving the monitoring the evidence indicates he needs.

The Hematocrit Story in Full

Testosterone stimulates erythropoiesis through erythropoietin upregulation and direct effects on bone marrow progenitor cells. The hematocrit rise on TRT is predictable, present across all delivery methods, and dose-dependent. In a man with a baseline hematocrit of 44 percent, expect a rise to 46 to 52 percent in most cases within 6 months. In some men, particularly older men, men with sleep apnea, or men on higher doses, the rise reaches 54 percent or above.

The cardiovascular mechanism of concern: elevated hematocrit increases blood viscosity. More viscous blood produces greater shear stress on arterial walls and raises the risk of platelet aggregation and thrombosis. In a man with subclinical coronary artery disease or an irregular cardiac rhythm, elevated blood viscosity is not a trivial finding.

The clinical threshold: hematocrit above 54 percent is the standard trigger for intervention in most guidelines. Options include dose reduction, switching delivery method (transdermal patches typically produce smaller hematocrit elevations than injections), and therapeutic phlebotomy (blood donation or medical venesection).

Hematocrit should be checked at 3 months, 6 months, 12 months, and annually thereafter if stable. A single result of 52 percent without prior documentation of the trajectory is not a complete picture. The trend matters as much as the value.

The Pulmonary Embolism Signal

The 2.3-fold higher rate of pulmonary embolism in the TRAVERSE testosterone group is the finding that receives the least attention in men’s health content and the most clinical weight in hospital medicine. Understanding why requires understanding how testosterone promotes clot formation.

Testosterone increases erythropoiesis, which raises red cell mass and blood viscosity. But it also has direct effects on coagulation factors independent of hematocrit. Research published in the journal Thrombosis and Haemostasis has documented that supraphysiologic and high-normal testosterone levels are associated with increased platelet aggregability and reduced fibrinolytic activity. In plain terms: the blood clots more readily and breaks down clots more slowly. The combination of elevated viscosity from higher hematocrit and a procoagulant shift in the clotting cascade creates conditions favorable for venous thromboembolism, which includes both deep vein thrombosis and pulmonary embolism.

The men most at risk for a PE event on TRT are not always the men who look highest-risk in the clinic. A man with a Factor V Leiden mutation, an antiphospholipid antibody, a protein S or protein C deficiency, or a prior history of DVT carries baseline thrombophilic risk that testosterone can amplify substantially. If you have a personal or family history of blood clots and are on TRT, and no one has discussed the TRAVERSE PE signal with you, that conversation is overdue.

Symptoms of pulmonary embolism include sudden onset shortness of breath, chest pain that worsens with breathing, coughing up blood, rapid heart rate, and lightheadedness. Symptoms of DVT include leg swelling, warmth, redness, and tenderness, usually in one calf. Neither symptom set should be attributed to workout soreness or fatigue without evaluation. If you experience them on TRT, call your physician the same day or go to the emergency department. The TRAVERSE PE signal puts these symptoms into a different clinical category than they occupy for the average man not on testosterone.

Men with a known thrombophilia, a prior VTE, or significant immobility risk should be assessed specifically for whether TRT is appropriate at all before starting, and re-evaluated regularly if already on it. 4 / Promising

The Atrial Fibrillation Assessment Most Men Have Not Had

The TRAVERSE AF signal warrants a specific clinical response: every man who has been on TRT for more than 6 months should have had an ECG to assess for atrial fibrillation if they have not had one recently. Men with the AF risk factors present in TRAVERSE (hypertension, sleep apnea, obesity, elevated BMI, left atrial enlargement) should have this conversation explicitly with their cardiologist.

Atrial fibrillation risk factors that compound the TRAVERSE signal:

Sleep apnea. OSA produces nocturnal atrial stretch through hypoxia-driven pulmonary hypertension and sympathetic surges that produce left atrial size increase over time. OSA is both an AF risk factor and an independent hematocrit elevator on TRT. Men on TRT with sleep apnea require more frequent hematocrit monitoring and a formal AF risk assessment.

Hypertension. Left ventricular hypertrophy from uncontrolled hypertension produces left atrial enlargement, the most consistent anatomical predictor of AF. A man on TRT whose blood pressure is not well controlled is compounding his AF risk.

Elevated BMI. Obesity independently predicts AF through epicardial fat deposition and left atrial enlargement. Men on TRT who are overweight require explicit AF risk discussion.

The ApoB and Lipid Effect of TRT

Testosterone has variable effects on the lipid profile depending on the delivery method and dose. Injectable testosterone tends to reduce HDL more substantially than transdermal formulations. LDL changes are variable. The more relevant measure is ApoB.

ApoB counts the number of atherogenic lipoprotein particles directly. A man with an LDL of 110 mg/dL can have a high or low ApoB depending on particle size and number: small, dense LDL particles are more atherogenic per unit of measured LDL, and men with the metabolic syndrome phenotype often carry exactly this pattern. LDL-cholesterol is a mass measurement, not a particle count. ApoB is the particle count. In a man with the metabolic syndrome phenotype (elevated triglycerides, low HDL, abdominal obesity, insulin resistance), testosterone therapy tends to improve insulin sensitivity and reduce visceral fat over 12 to 18 months, which can lower ApoB even when raw LDL does not change dramatically. This has been documented in trials including the TEAAM study (JAMA Internal Medicine, 2015), which followed older men with low testosterone through two years of treatment and found that metabolic parameters improved in men with baseline metabolic syndrome more reliably than in men without it.

In contrast, men on high-dose injectable testosterone who are not in a metabolic syndrome phenotype may see HDL reduction without meaningful ApoB benefit. The HDL reduction with injectable testosterone, particularly with cypionate and enanthate at weekly or twice-weekly injection schedules, can be 10 to 15 percent below baseline in some men. Whether this translates to increased cardiovascular event risk over the long term is not settled, but it makes ApoB tracking essential: if ApoB is rising on TRT, that finding warrants either dose adjustment, delivery method change, or initiation of statin therapy in men not already on one.

Establishing a baseline ApoB before starting TRT and rechecking at 6 months and annually provides the most complete picture of atherogenic risk trajectory on treatment.

The Delivery Method Variable

Not all TRT is the same from a cardiovascular risk profile standpoint. The delivery method affects peak testosterone levels, hematocrit response, HDL impact, and, likely, the magnitude of some TRAVERSE-identified risks. This matters because most of the men currently on TRT through telehealth platforms are receiving weekly or twice-weekly intramuscular or subcutaneous injections of testosterone cypionate or enanthate. These are the formulations that produce the most pronounced peaks and troughs in serum testosterone, and they are associated with the largest hematocrit elevations and the greatest HDL reduction.

Intramuscular and subcutaneous injections (cypionate, enanthate): Peak serum testosterone occurs 24 to 48 hours after injection and can reach well above the normal physiologic range before declining over 5 to 7 days to trough levels. This peak-to-trough swing is the driver of the hematocrit elevation: the erythropoiesis signal is strongest at peak testosterone. Men on weekly injections of 100 to 200 mg typically show the largest hematocrit rises in the TRT population. Splitting the same weekly dose into two smaller twice-weekly injections reduces peak concentrations and typically produces a 2 to 4 percentage point lower hematocrit than weekly dosing, all else being equal.

Topical gels and creams: Testosterone delivered transdermally produces a more stable daily serum level without pronounced peaks. The hematocrit elevation with gels is real but smaller on average than with injections, as documented in the TRAVERSE trial itself, which used a gel formulation and still showed AF and PE signals. HDL reduction with topical testosterone is also generally smaller than with injectable forms. The tradeoff: absorption varies significantly between men, and dosing adjustment is less precise. Skin transfer to a partner or child is a real safety consideration requiring careful hygiene.

Subcutaneous pellets: Pellets implanted under the skin every 3 to 6 months produce very stable testosterone levels over time, avoiding injection peaks and troughs. Hematocrit response is lower than with injections but requires monitoring. The limitation is that dose adjustment mid-cycle is not possible: if a man’s hematocrit rises to 55 after pellet insertion, dose reduction requires waiting for the pellets to metabolize over weeks to months. This inflexibility makes pellets a poor choice for men with borderline hematocrit at baseline or significant erythrocytosis risk.

Nasal gel and buccal troches: These deliver testosterone locally through the nasal mucosa or buccal absorption and produce very short pharmacokinetic half-lives. Systemic testosterone exposure is lower, hematocrit elevation is minimal, and HDL impact is small. They are not appropriate for every man, but for the man whose primary concern is the cardiovascular risk profile of TRT, the nasal or buccal route may provide symptom benefit with a more favorable monitoring burden.

When a man’s hematocrit is trending toward the upper range on injectable TRT, delivery method switch is often the first intervention worth considering before therapeutic phlebotomy. This conversation requires a prescriber who knows the pharmacokinetics of each delivery form, which is not always the case at a telehealth clinic primarily offering cypionate injections.

The Full Monitoring Protocol

Hematocrit and CBC: Baseline, then at 3, 6, and 12 months, then annually if stable. Threshold for intervention: above 54 percent.

Blood pressure home average: Monthly during the first year. Seven morning readings twice daily using a validated upper-arm cuff. TRT does not consistently raise blood pressure, but individual variation exists and the AF signal makes blood pressure control more important, not less.

ApoB and lipid panel: Baseline and at 6 months, then annually. Note which delivery method was used (injection vs topical) as HDL response varies.

ECG: Baseline (should have been done before starting), then annually, specifically noting rhythm. If any palpitations, irregular heartbeat, or symptoms of AF (racing heart, unusual fatigue, shortness of breath), ECG immediately.

Echocardiogram: Not required for every man on TRT, but should be considered in men with hypertension, sleep apnea, or obesity, given the left atrial enlargement risk that compounds AF susceptibility.

Sleep apnea evaluation or re-evaluation: If not previously evaluated or if symptoms have changed. OSA and TRT interact in ways that require both conditions to be managed explicitly.

Creatinine and eGFR: Baseline and annually. Relevant in the context of the TRAVERSE AKI signal and in any man who uses NSAIDs regularly or has known chronic kidney disease risk factors.

DVT and PE symptom awareness: Not a laboratory test, but a clinical education point. Every man on TRT should know the symptoms of deep vein thrombosis and pulmonary embolism and understand that these symptoms warrant same-day evaluation, not watchful waiting.

What to Do This Week

1. Pull your most recent hematocrit result. If it was above 50 percent and was not followed by a clinical discussion about the TRAVERSE AF signal, schedule that conversation. Bring the TRAVERSE trial citation to your appointment.

2. Check whether you have had an ECG in the past year. If not, and if you have been on TRT for more than 6 months, request one. Ask specifically about your cardiac rhythm.

3. Track your home blood pressure for two weeks using the validated protocol: morning readings, twice, before coffee, after 5 minutes of rest. Average the readings. If your average is above 135/85, your blood pressure management becomes more important in the context of TRT, not less.

4. If you have sleep apnea and are on TRT and have not been compliant with CPAP or alternative OSA treatment, address OSA directly. The combination of untreated sleep apnea and TRT creates an AF and hematocrit risk profile that neither condition alone produces.

5. If you are over 40 and have not had a PSA checked since starting TRT, request one. Testosterone does not cause prostate cancer, but it can accelerate the growth of existing prostate cancer that was subclinical before treatment began. The Endocrine Society recommends PSA at baseline, at 3 to 6 months after initiating TRT, and annually thereafter in men over 40. A PSA that doubles in the first year of TRT, or that rises above 1.4 ng/mL above baseline within any 12-month period, warrants urology referral regardless of absolute value. This is a standard-of-care item that a surprising number of telehealth TRT prescribers do not include in their monitoring panels.

6. If you are already on an anticoagulant (warfarin, apixaban, rivaroxaban, or similar) for any reason, the TRAVERSE PE signal is directly relevant to your situation. Testosterone therapy while anticoagulated requires coordination between the prescriber managing your TRT and the provider managing your anticoagulation. The procoagulant effects of testosterone are not fully neutralized by anticoagulation, and the combination of high hematocrit and anticoagulant therapy creates its own risk calculus that needs to be explicitly managed. If the two prescribers are not talking to each other, that is the first problem to fix.

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.