Gender-Affirming Testosterone Therapy in a 22-Year-Old with Prior Ischemic Stroke
Testosterone therapy for gender affirmation can be considered in this 22-year-old transgender male with a history of ischemic stroke, as current evidence shows no increased stroke risk in transmasculine individuals receiving testosterone, unlike the elevated risk seen in transfeminine individuals on estrogen therapy. However, this requires aggressive cardiovascular risk factor management and careful monitoring given the prior stroke history.
Evidence Supporting Testosterone Safety in Transmasculine Individuals
The 2024 American Heart Association/American Stroke Association guidelines provide the most relevant guidance for this clinical scenario. Stroke incidence in transmasculine individuals receiving testosterone was similar to cisgender populations, with no difference found for transgender men (median age 23 years) compared to cisgender reference groups 1. This contrasts sharply with transfeminine individuals on estrogen therapy, who show a 1.9-fold increased risk of ischemic stroke compared to cisgender women 1.
A large Kaiser Permanente cohort study of 2,118 transmasculine people found that testosterone use did not increase stroke incidence compared to cisgender populations, though the evidence was insufficient to allow definitive conclusions due to the young age of participants 1. A Netherlands study similarly found no difference in stroke risk for transgender men 1.
Critical Risk Factor Assessment and Management
Before initiating testosterone, you must thoroughly evaluate and aggressively manage all modifiable stroke risk factors 1. The AHA/ASA guidelines emphasize that interventions on known vascular risk factors such as tobacco use and hypertension would be effective at reducing stroke risk in transgender populations 1.
Mandatory Pre-Treatment Evaluation:
- Complete stroke workup to identify the etiology of the prior ischemic stroke (thrombophilia screening, cardiac evaluation, vascular imaging) 1
- Blood pressure monitoring and aggressive hypertension management (testosterone may increase blood pressure) 1, 2
- Lipid profile assessment (testosterone may increase triglycerides and LDL while decreasing HDL) 1, 2
- Tobacco cessation if applicable (critical given prior stroke) 1
- Baseline hematocrit/hemoglobin (testosterone causes erythrocytosis, which increases stroke risk) 1, 2
- Fasting glucose and diabetes screening 2
Testosterone Therapy Protocol
If cardiovascular risk factors are optimized and no contraindications exist, initiate testosterone cypionate or enanthate 50-100 mg intramuscularly every 1-2 weeks, targeting trough testosterone levels of 300-1,000 ng/dL 2. Transdermal testosterone gel (40.5 mg daily) is an alternative with lower erythrocytosis risk 2.
Expected Physical Changes:
- Voice deepening within 3-12 months 2
- Facial and body hair growth 2
- Menstrual suppression in most patients 2
- Increased muscle mass and decreased fat mass 2, 3
- Clitoral growth and increased libido 2
Intensive Monitoring Requirements
Given the prior stroke history, monitoring must be more frequent than standard protocols:
- Hematocrit every 3 months initially, then every 6 months (withhold testosterone if >54% and consider phlebotomy) 1, 2
- Blood pressure at every visit 1, 2
- Lipid profile every 6 months for the first year 1, 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 1
Critical Monitoring Thresholds:
- Hematocrit >54%: Temporarily withhold therapy, reduce dose, or perform phlebotomy 2
- Blood pressure >130/80 mmHg: Intensify antihypertensive therapy 1
- Significant lipid abnormalities: Consider statin therapy 1
Important Caveats and Risk Mitigation
The observational studies have major limitations: young age of participants, limited follow-up time, and lack of detailed information on hormone regimens, lifestyle factors, and minority stress 1. The median age in existing studies was 23 years, and few individuals >50 years (when strokes are more likely) have been studied 1.
Testosterone-specific risks to monitor:
- Erythrocytosis/polycythemia (particularly common with injectable formulations—consider switching to transdermal if this develops) 1, 2
- Potential increased cardiovascular risk through lipid changes 1, 2
- Sleep apnea (which independently increases stroke risk) 1
If erythrocytosis develops, switch to transdermal testosterone gel, which has lower risk of erythrocytosis compared to injectable formulations 2.
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 mental health benefits of testosterone therapy must be weighed against the theoretical cardiovascular risks in this patient with prior stroke.
The decision to proceed should involve shared decision-making with the patient, clearly explaining that while current evidence does not show increased stroke risk in transmasculine individuals on testosterone, the data are limited and the patient's prior stroke history requires exceptional vigilance 1.