Is it appropriate to prescribe testosterone for a transgender patient with a history of ischemic stroke on aspirin (acetylsalicylic acid)?

Testosterone Therapy in Transgender Patients with Prior Ischemic Stroke

Yes, it is appropriate to prescribe testosterone for transgender-affirming care in a patient with a history of ischemic stroke on aspirin, provided that all modifiable cardiovascular risk factors are optimized and intensive monitoring is implemented. 1, 2

Evidence Supporting Testosterone Safety in Transmasculine Individuals

The most recent and highest-quality evidence demonstrates that testosterone therapy does not increase stroke risk in transgender men:

• The 2024 American Heart Association/American Stroke Association guidelines found no difference in stroke incidence for transgender men (median age 23 years) compared to cisgender populations. 1

• A 2025 large-scale study comparing 6,251 trans men treated with testosterone to matched controls found no significant increase in cardiovascular outcomes, including stroke, myocardial infarction, or mortality when compared to both untreated trans men and cisgender men. 3

• The Netherlands cohort study similarly demonstrated no elevated stroke risk in transgender men receiving testosterone therapy. 1

This contrasts sharply with transfeminine individuals on estrogen therapy, who show a 1.9-fold increased risk of ischemic stroke. 2

Critical Pre-Treatment Risk Assessment

Before initiating testosterone, you must thoroughly evaluate and aggressively manage all modifiable stroke risk factors: 2

• Complete stroke workup to determine mechanism (ensure it was noncardioembolic, as your patient is appropriately on aspirin per guidelines) 1
• Blood pressure control (target <130/80 mmHg) 2
• Lipid profile optimization 2
• Mandatory tobacco cessation if applicable 1, 2
• Baseline hematocrit/hemoglobin measurement 2
• Assessment for sleep apnea 2

Testosterone Initiation Protocol

If cardiovascular risk factors are optimized and no contraindications exist: 2

• Start testosterone cypionate or enanthate 50-100 mg intramuscularly every 1-2 weeks 2, 4
• Target trough testosterone levels of 300-1,000 ng/dL 2
• Alternative: Transdermal testosterone gel (40.5 mg daily) carries lower erythrocytosis risk and may be preferable given stroke history 2

The FDA label confirms testosterone cypionate can be administered every 2-4 weeks for hypogonadal males, with dosing adjusted based on patient response. 4

Intensive Monitoring Requirements

Given the prior stroke history, monitoring must exceed standard protocols: 2

• Hematocrit every 3 months initially, then every 6 months (testosterone increases erythrocyte production) 2, 4
• Blood pressure at every visit 2
• Lipid profile every 6 months for the first year 2
• Testosterone levels at 2-3 months, then every 6-12 months once stable 2
• Clinical assessment of stroke symptoms and neurological examination at each visit 2

Testosterone-Specific Risks and Mitigation

The primary testosterone-related cardiovascular concerns are: 2, 4

• Erythrocytosis/polycythemia: If this develops, switch from injectable to transdermal formulation 2
• Potential lipid changes (though recent evidence suggests minimal cardiovascular impact) 3
• Sleep apnea exacerbation 2

If erythrocytosis occurs, do not discontinue testosterone—switch to transdermal gel instead. 2

Continuation of Aspirin Therapy

Your patient should remain on aspirin 75-100 mg daily as recommended for noncardioembolic ischemic stroke. 1 There is no indication to add anticoagulation or additional antiplatelet agents unless atrial fibrillation or another cardioembolic source is identified. 1

Quality of Life Considerations

Gender-affirming hormone therapy with testosterone is medically necessary for many transgender individuals, with strong evidence showing improvements in quality of life and relief of psychological distress associated with gender dysphoria. 2 The 2025 study demonstrated a 52% reduction in suicide attempts for trans men treated with testosterone compared to untreated trans men (HR 0.52,95% CI 0.35-0.78). 3

The mental health benefits of testosterone therapy must be weighed against theoretical cardiovascular risks—and current evidence shows no increased stroke risk. 1, 2, 3

Important Caveats

The observational studies have limitations including young participant age, limited follow-up time, and lack of detailed information on hormone regimens and lifestyle factors. 1, 2 However, the most recent 2025 data with 5-year follow-up provides reassuring evidence of cardiovascular safety. 3

Interventions on known vascular risk factors such as tobacco use and hypertension are effective at reducing stroke risk in transgender populations. 1, 2