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The Type 5 Phosphodiesterase Inhibitor Tadalafil Influences Salivary Cortisol, Testosterone, and Dehydroepiandrosterone Sulphate Responses to Maximal Exercise in Healthy Men

Units of Endocrinology (L.D.L., P.S., S.B.), Sport Sciences (C.B., G.P.E.), Exercise Sciences (M.C.G., L.G.), and Sport Medicine (F.P.), Department of Health Sciences, University of Rome "Foro Italico," 00194 Rome, Italy; and Department of Medical Physiopathology (F.R., A.L.), University of Rome "La Sapienza," 00161 Rome, Italy

Address all correspondence and requests for reprints to: Professor Luigi Di Luigi, M.D., Unit of Endocrinology, Department of Health Sciences, University of Rome "Foro Italico," Piazza Lauro de Bosis, 15, 00194 Rome, Italy. E-mail: luigi.diluigi{at}iusm.it.

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.