Sex differences in fitness and cardiac function during exercise in adolescents with chronic fatigue

Females demonstrate less robust Frank-Starling mechanism with respect to cardiac preload than males at rest. We asked whether this phenomenon would also affect cardiac performance during exercise. We hypothesized that stroke volume (SV) response to exercise would be more limited in deconditioned females such that cardiac output would be mainly rate dependent, compared with males. We conducted a chart audit of clinical exercise tests performed by adolescents with chronic fatigue. Oxygen uptake VO₂ was measured breath-by-breath at rest and during cycle ergometry, while cardiac output was measured by acetylene rebreathing at rest plus 2-3 subthreshold workloads. SV response was analyzed in two ways: after normalization for body surface area (SV index, SVI) and as percentage change from resting values. Among 304 adolescents (78% females) with chronic fatigue, 189 (80%) of 236 females and 52 (76%) of 68 males were deconditioned (peak VO₂ <90% predicted). Heart rate trajectory during exercise was steeper for unfit than fit females, 70 vs 61 beat·min⁻¹ per L·min⁻¹ VO₂, (P=.003); but not for males, 47 vs 42 beat·min⁻¹ per L·min⁻¹ VO₂ (P=.23). The highest measured SVI did not differ between unfit vs fit females (42.8 vs 41.5 mL·m⁻², P=.39) while fit males showed larger SV during exercise than their unfit peers (highest SVI 55.9 vs 48.0 mL·m⁻², P=.014). Both qualitative and quantitative sex differences exist in SV responses to exercise among chronically fatigued adolescents, suggesting volume loading may be more efficacious in girls.