The type 5 phosphodiesterase inhibitor tadalafil influences salivary cortisol, testosterone, and dehydroepiandrosterone sulphate responses to maximal exercise in healthy men

CONTEXT: Physical exercise-related stress activates hypothalamus-pituitary-adrenal (HPA) axis; nitric oxide is one of the mediators of the HPA axis response to stress, and phosphodiesterase type 5 inhibitors influences nitric oxide-linked biological activities. OBJECTIVE: The objective of the study was to investigate whether a single oral long half-life phosphodiesterase type 5 inhibitor (tadalafil) administration influences the HPA axis response to exercise-related stress. DESIGN: This was a double-blind, cross-over trial. PARTICIPANTS: Participants included nine healthy male athletes. INTERVENTIONS: All subjects performed a maximal exercise test in normoxia, after which they received a single oral administration of tadalafil or placebo. Then after a 2-wk washout period, they were crossed over and repeated the exercise test. Each subject was his own control. Salivary collections, for steroid evaluations [cortisol, dehydroepiandrosterone sulphate (DHEAS), testosterone] and respective ratio calculation (DHEAS to cortisol, testosterone to cortisol, testosterone to DHEAS), were performed before each exercise (Pre-Ex), immediately after (Post-Ex), and at 30 min during recovery. RESULTS: As expected, mean salivary cortisol concentration increased immediately after exercise after both 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 to cortisol and testosterone to 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.