Sex-Related Differences in Myocardial Deformation and Systolic Function in Healthy Individuals: A Systematic Review and Meta-Analysis of Global Longitudinal Strain and Left Ventricular Ejection Fraction

Background: Left ventricular global longitudinal strain (GLS) measured by speckle-tracking echocardiography (STE) has become a key marker of myocardial systolic function, yet normal reference values remain heterogeneous, and the magnitude of physiological sex differences is not fully defined. We performed a systematic review and meta-analysis to establish pooled GLS reference estimates in healthy individuals, quantify sex-related differences, and contextualize deformation findings relative to conventional systolic function. Methods: A systematic search of PubMed, Scopus, and EMBASE identified observational studies reporting GLS in healthy adults assessed by two-dimensional or three-dimensional STE. Random-effects meta-analysis using standardized mean differences (SMD) compared GLS between women and men. Descriptive pooled reference values were derived using weighted median and interquartile range (IQR) reconstruction from study-level distributions. Meta-regression analyses explored demographic, clinical, and methodological sources of heterogeneity. A complementary analysis evaluated sex-related differences in left ventricular ejection fraction (LVEF) within the same populations. Results: Thirty-two studies, including 19,157 healthy individuals, were analyzed. The pooled population had a weighted median age of 47.5 years and 53% female participants. Overall, GLS demonstrated a weighted median of 20.3% (IQR 17.8–22.5). Women showed higher GLS values than men (20.8% 18.4–23.1 vs. 19.4% 17.0–21.6). Meta-analysis of 28 studies confirmed significantly greater GLS in females (SMD 0.487, 95% CI 0.409–0.565; p < 0.001), with consistent findings across imaging modalities and no subgroup interaction. Between-study heterogeneity was substantial (I2 = 82.7%), although effect direction was uniform. Meta-regression analyses identified no significant moderators, and sensitivity analyses confirmed stable estimates without publication bias. Segmental analysis demonstrated a physiological base-to-apex strain gradient. In contrast, LVEF was largely comparable between sexes, with no clinically meaningful difference (SMD 0.257, 95% CI 0.186–0.327; p < 0.001), indicating preserved global systolic performance despite differences in myocardial deformation. Conclusions: GLS demonstrates a consistent physiological range in healthy populations, with women exhibiting higher longitudinal deformation than men, independent of the imaging modality. These findings support the adoption of sex-specific GLS reference values and highlight the complementary roles of deformation and volumetric indices in improving the interpretation of myocardial function and reducing misclassification in clinical practice.