Can testosterone replacement therapy increase blood viscosity and risk of thrombotic events in patients with a history of cardiovascular disease?

Can Testosterone Make Your Blood Thicker?

Yes, testosterone therapy can increase blood thickness by causing erythrocytosis (elevated red blood cell production), which occurs in 3-44% of patients depending on the formulation used, with injectable forms carrying the highest risk. 1, 2

Mechanism and Incidence of Blood Thickening

Testosterone increases blood viscosity through stimulation of red blood cell production, affecting hemoglobin and hematocrit levels rather than through direct vascular effects. 3, 4 The risk varies dramatically by formulation:

• Intramuscular injections: 43.8% risk of elevated hematocrit (>52%) 1, 2
• Transdermal preparations: 3-18% risk depending on dose 2
• Transdermal patches (5 mg/day): 2.8% incidence 1
• Gel preparations (10 mg/day): 17.9% incidence 1

Men receiving testosterone replacement therapy have a 315% greater risk of developing erythrocytosis compared to controls. 4

Clinical Significance and Thrombotic Risk

The relationship between testosterone-induced blood thickening and actual thrombotic events remains controversial. The 2018 AUA guidelines note that observational studies since the 2014 FDA warning have not shown an association between testosterone therapy and increased risk of venous thromboembolic events (VTE), despite the FDA requiring warning labels based on anecdotal post-marketing reports. 1

However, important nuances exist:

• No testosterone-associated thromboembolic events had been reported in controlled studies as of 2004 1
• A 2024 meta-analysis of randomized controlled trials found no increased risk of VTE, stroke, myocardial infarction, or mortality in men with testosterone <12 nmol/L 5
• A 2021 large cohort study of 204,857 US veterans found no increased cardiovascular risk with either transdermal or intramuscular testosterone 6
• Isolated case reports exist of testosterone-induced arterial thrombosis, including dermal and epidermal arteries, even without elevated hemoglobin 7

Monitoring Requirements

Hematocrit must be monitored at 2-3 months after initiation, then every 6-12 months thereafter. 2 Most hemoglobin and hematocrit changes occur within the first three months of therapy. 1

If erythrocytosis develops, appropriate measures include:

• Dosage reduction 1
• Withholding testosterone temporarily 1
• Therapeutic phlebotomy 1
• Blood donation 1

Formulation-Specific Recommendations

For patients with cardiovascular disease or risk factors, strongly prefer transdermal testosterone gel over injections or pellets. 2, 8 Injectable and implantable formulations carry substantially higher cardiovascular risk due to fluctuating testosterone levels and increased polycythemia risk. 8

The FDA specifically contraindicated oral testosterone undecanoate for age-related hypogonadism due to demonstrated blood pressure increases. 3, 2

Key Clinical Pitfalls

• Supraphysiologic dosing increases risk: Target testosterone levels in the middle tertile of normal range (450-600 ng/dL) to minimize erythrocytosis 1
• Pre-existing conditions amplify risk: Patients with chronic obstructive pulmonary disease or baseline hematocrit >50% face higher risk of clinically significant erythrocytosis 1, 2
• Route matters more than suspected: The difference between 2.8% and 43.8% erythrocytosis rates between formulations is clinically substantial 1