Context: Physical exercise-related stress activate hypothalamus-pituitary-adrenal (HPA) axis, nitric oxide (NO) is one of the mediators of the HPA axis response to stress, and phosphodiesterase's type 5 inhibitors (PDE5i) influences NO-linked biological activities.

Objective: To investigate whether a single oral long half-life PDE5i (tadalafil) administration influences the HPA axis response to exercise-related stress.

Design: Double blind crossover trial

Participants: Nine healthy male athletes

Interventions: All subjects performed a maximal exercise test in normoxia, after received a single oral administration of tadalafil or placebo. Then, after a 2-weeks washout period, they were crossed over and repeated the exercise test. Each subject was is own control. Salivary collections, for steroids evaluations [cortisol, dehydroepiandrosterone sulphate (DHEAS), testosterone] and respective ratios calculation (DHEAS/cortisol, testosterone/cortisol, testosterone/DHEAS), were performed before each exercise (Pre-Ex), immediately after (Post-Ex), and at thirty minutes during recovery.

Results: As expected mean salivary cortisol concentration increased immediately after exercise both after tadalafil and placebo (p = 0.014, and p =0.036 vs Pre-Ex, respectively), however, the cortisol increase was significantly higher after tadalafil administration (p = 0.034 vs placebo). Furthermore, an increased salivary testosterone after exercise was observed only after tadalafil administration (p = 0.029 vs Pre-Ex). No effects of either exercise and/or tadalafil administration on salivary DHEAS concentrations were observed. DHEAS/cortisol and testosterone/cortisol ratios significantly decreased after exercise after tadalafil administration (p = 0.037, and p = 0.02 vs placebo, respectively).

Conclusion: Tadalafil administration amplified the salivary cortisol and testosterone responses to a maximal exercise-related stress in healthy trained humans.