Artificial Intelligence-Augmented Electrocardiogram in Determining Sex: Correlation with Sex Hormone Levels

Objective: To study the relationship between the sex probability derived from the artificial intelligence (AI)-augmented electrocardiogram (ECG) and sex hormone levels. Patients and Methods: Adult patients with total testosterone (TT; ng/dL) or estradiol (E2; pg/mL) levels (January 1, 2000, to December 31, 2020) with ECGs obtained within 6 months of the blood sample were identified. The closest ECG to the blood test was used. The AI-ECG model output ranges from 0.0 to 1.0, with higher numbers indicating high probability of being male. Low male probability was defined as ≤0.3, intermediate as 0.31 to 0.69, and high as ≥0.7. Continuous variables are expressed as median (interquartile range). Results: Paired TT-ECGs were available in 58,084 male subjects and 11,190 female subjects. Paired E2-ECGs were available in 2835 male patients and 18,228 female patients. TT levels had moderate positive correlation with AI-ECG male sex probability (r=0.46, P<.001). Male subjects with low AI-ECG male sex probability had lower TT and higher E2 levels compared with men with high probability (TT: 303 [129-474] vs 381 [264-523], P <.001; E2: 35 [21-49] vs 32 [22-38], P=.05). Female subjects with high AI-ECG male sex probability had higher TT and lower E2 levels compared with those who had low male probability (TT: ≤50 years of age: 31 [18-55] vs 26 [16-39], P<.001; >50 years of age: 27 [12-68] vs 20 [12-34], P<.001; E2: ≤50 years of age: 58 [30-124] vs 47 [25-87], P=.001; >50 years of age: 30 [10-55] vs 21 [10-41], P=.006). Conclusion: In this study, TT levels were lower and E2 levels higher with decreasing AI-ECG male probability in both sexes. Male and female patients with discordant AI-ECG sex probability had significantly different TT or E2 levels. This suggests that the ECG could be used as a biomarker of hormone status.