Introduction Many athletes use short-acting inhaled beta(2)-agonists multiple times weekly during training sessions to prevent exercise-induced bronchoconstriction, but it is unclear if treatment impairs training outcomes. Herein, we investigated performance adaptations in well-trained females and males training with prior inhalation of salbutamol. Methods 19 females and 21 males with maximal oxygen uptake (V'(O2max)) of 50.5 +/- 3.3 and 57.9 +/- 4.9 mL center dot min(-1)center dot kg(-1), respectively, participated in this double-blinded, placebo-controlled, parallel-group study. We randomised participants to placebo or salbutamol inhalation (800-1600 mu g center dot training day(-1)) for 6 weeks of combined endurance (1x per week) and high-intensity interval training (2x per week). We assessed participants' body composition, V'(O2max) and muscle contractile function, and collected vastus lateralis muscle biopsies. Results Salbutamol induced a sex-specific loss of whole-body fat mass (sexxtreatment: p=0.048) where only salbutamol-treated females had a fat mass reduction compared to placebo (-0.8 kg at 6 weeks; 95% CI: -0.5 to -1.6; p=0.039). Furthermore, salbutamol-treated females exhibited a repartitioning effect, lowering fat mass while gaining lean mass ( p=0.011), which was not apparent for males (p=0.303). Salbutamol negatively impacted V'(O2max) in both sexes (treatment main effect: p=0.014) due to a blunted increase in V'(O2max) during the initial 4 weeks of the intervention. Quadriceps contractile strength was impaired in salbutamol-treated females (-39 N center dot m; 95% CI: -61 to -17; p=0.002) compared to placebo at 6 weeks. Muscle electron transport chain complex I-V abundance increased with salbutamol (treatment main effect: p=0.035), while content of SERCAI, beta(2)-adrenoceptor and desmin remained unchanged. Conclusion Inhaled salbutamol appears to be an effective repartitioning agent in females but may impair aerobic and strength-related training outcomes.
