Context: Several studies have demonstrated an improvement in aerobic exercise capacity with six months of GH replacement in adults with GH deficiency (GHD).

Objective: To determine whether improvements in aerobic exercise capacity with GH treatment in adults with GHD are related to changes in physical activity or affected by the GH dosing regimen.

Design: Randomized, two-arm, parallel, open-label study.

Setting: Five academic medical centers with exercise physiology laboratories.

Subjects: Adults (n=29) with GHD due to hypothalamic-pituitary disease.

Interventions: GH replacement therapy, administered either as a fixed body weight-based dosing regimen (FD) or an individualized dose titration regimen (ID) for 32 weeks.

Main outcome measures: Maximal oxygen consumption (VO₂ max), VO₂ at the lactate threshold (LT) and ventilatory threshold (VT) using a cycle ergometry protocol, and weekly energy expenditure (physical activity questionnaire), assessed at baseline and endpoint.

Results: In the group as a whole, VO₂ max increased significantly (by 9%) from baseline (19.1± 0.89 ml/kg·min) to endpoint (21.6 ± 1.23 ml/kg·min, p = 0.010). Compared to baseline, VO₂ max also changed significantly within the ID group (+2.5 ml/kg·min ± 0.98, p =0.034), but not within the FD group (+1.2 ml/kg·min ± 0.78, p = 0.15), although these changes from baseline were not significantly different between the two groups. VO₂ at LT, VO₂ at VT and weekly energy expenditure also did not change.

Conclusions: GH replacement therapy in GH-deficient adults improved VO₂ max similarly with both dosing regimens, without any influence of physical activity. There was no effect on submaximal exercise performance.