Should ECG (electrocardiogram) interpretations in transmen use male or female reference ranges?

ECG Interpretation in Transmen: Use Male Reference Ranges After 12 Months of Testosterone Therapy

For transmen on gender-affirming hormone therapy (GAHT) for ≥12 months, ECG parameters including QTc intervals should be interpreted using male reference ranges, as testosterone therapy causes electrocardiographic changes that trend toward the affirmed gender. 1

Evidence-Based Approach by Duration of Therapy

Transmen on Testosterone ≥12 Months

• Interpret QTc and other ECG parameters within the male reference range 1
• The 2025 Multinational Association of Supportive Care in Cancer guidelines explicitly state that QTc is influenced by GAHT, and after 12 months of therapy, values should be interpreted within the reference range for the affirmed gender 1
• Recent 2025 research demonstrates that testosterone therapy produces electrocardiographic changes that trend toward male patterns, including alterations in T-wave amplitude in precordial leads 2

Transmen on Testosterone <12 Months

• Interpret ECG values in the context of type, dose, and duration of GAHT, recognizing that values are transitioning 1
• During this period, parameters may not yet fully align with either male or female reference ranges 1

Transmen Who Stopped Testosterone ≥3 Months

• Use female (sex assigned at birth) reference ranges 1
• Hormone-related changes reverse within 3 months of discontinuation 1

Specific ECG Reference Ranges to Apply

QTc Intervals (Most Clinically Relevant)

For men (apply to transmen on testosterone ≥12 months):

• Upper limit of normal: 450 ms 1
• Gender differences in QTc appear during adolescence when testosterone shortens the rate-adjusted QT in males 1

For women (apply to transmen off testosterone ≥3 months):

• Upper limit of normal: 460 ms 1

ST-Segment Elevation Thresholds

For men (apply to transmen on testosterone ≥12 months):

• V2-V3: 0.2 mV (2 mm) if ≥40 years old; 0.25 mV (2.5 mm) if <40 years old 1
• All other leads: 0.1 mV (1 mm) 1

For women (apply to transmen off testosterone ≥3 months):

• V2-V3: 0.15 mV (1.5 mm) 1
• All other leads: 0.1 mV (1 mm) 1

Physiological Rationale

The recommendation to use male reference ranges after 12 months is based on:

• Testosterone directly influences cardiac electrophysiology, causing QRS duration changes, alterations in P-wave, R-wave, and T-wave amplitudes that shift toward male patterns 2
• Red blood cell indices, which affect cardiac parameters, stabilize within 6 months of testosterone initiation and reach male reference ranges within 3 months 1, 3
• Hemoglobin increases to male reference range within 3 months, affecting oxygen-carrying capacity and potentially cardiac electrical properties 3, 4

Critical Clinical Pitfalls to Avoid

Do Not Use Female Reference Ranges After 12 Months of Testosterone

• This could lead to false-positive diagnoses of QTc prolongation, potentially resulting in unnecessary medication changes, cardiac workup, or withholding of needed therapies 1
• Male QTc intervals are physiologically shorter than female intervals due to testosterone effects 1

Obtain Baseline and Follow-Up ECGs

• Standardized baseline ECG before initiating testosterone is recommended to track individual changes 2
• Consider repeat ECG at 12 months when values should have stabilized to male patterns 2

Special Consideration for Acute Cardiac Events

• When evaluating for acute myocardial infarction, use the appropriate gender-specific ST-elevation thresholds based on duration of testosterone therapy 1
• Misapplication of female thresholds in a transman on long-term testosterone could delay recognition of STEMI 1

Race-Specific Considerations

• Black transmen may show additional changes including increased heart rate with testosterone therapy 2
• ST-elevation normal variants are greater in Black individuals regardless of gender 1

Practical Implementation Algorithm

1. Determine testosterone therapy duration:

   • <12 months → Interpret cautiously, values transitioning
   • ≥12 months → Use male reference ranges
   • Stopped ≥3 months → Use female reference ranges

2. Apply gender-specific thresholds for:

   • QTc prolongation assessment
   • ST-elevation in acute coronary syndrome evaluation
   • Normal variant early repolarization patterns

3. Document clearly in interpretation:

   • Patient's affirmed gender
   • Duration of testosterone therapy
   • Which reference range was applied and why

This approach aligns with the most recent 2025 guidelines and emerging research demonstrating that testosterone therapy produces measurable electrocardiographic changes that necessitate interpretation using male reference standards after adequate treatment duration. 1, 2