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


METHODS
This was a double-blind, cross-over trial.


METHODS
Participants included nine healthy male athletes.


METHODS
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).


CONCLUSIONS
Tadalafil administration amplified the salivary cortisol and testosterone responses to a maximal exercise-related stress in healthy trained humans.
Unit of Endocrinology, Department of Health Sciences, University of Rome Foro Italico, Piazza Lauro de Bosis, 15, 00194 Rome, Italy. luigi.diluigi@iusm.it
Luigi
L
Di Luigi
Carlo
C
Baldari
Paolo
P
Sgrò
Gian Pietro
GP
Emerenziani
Maria Chiara
MC
Gallotta
Serena
S
Bianchini
Francesco
F
Romanelli
Fabio
F
Pigozzi
Andrea
A
Lenzi
Laura
L
Guidetti
D000328:Adult; D002243:Carbolines / Q000494:pharmacology*; D018592:Cross-Over Studies; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood* / Q000378:metabolism; D004311:Double-Blind Method; D015444:Exercise / Q000502:physiology*; D006262:Health; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D008297:Male; D058986:Phosphodiesterase 5 Inhibitors; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010919:Placebos; D012463:Saliva / Q000187:drug effects* / Q000378:metabolism; D013312:Stress, Physiological / Q000378:metabolism; D000068581:Tadalafil; D013739:Testosterone / Q000097:blood* / Q000378:metabolism
D002243:Carbolines; D058986:Phosphodiesterase 5 Inhibitors; D010726:Phosphodiesterase Inhibitors; D010919:Placebos; D013739:Testosterone; D019314:Dehydroepiandrosterone Sulfate; D000068581:Tadalafil; D006854:Hydrocortisone