The phosphodiesterases type 5 inhibitor tadalafil reduces the activation of the hypothalamus-pituitary-adrenal axis in men during cycle ergometric exercise

Objective: Phosphodiesterase type 5 (PDE5) inhibitors may influence human physiology, health and performance by also modulating endocrine pathways. We evaluated the effects of a two-days tadalafil administration on adenohypophyseal and adrenal hormones adaptation to exercise in humans. Methods: fourteen healthy males were included in a double blind crossover trial. Each volunteer randomly received two tablets of placebo or tadalafil (20 mg/die with 36 h of interval) before a maximal exercise was performed. After a two-week washout, the volunteers were crossed over. Blood samples were collected -30, -15 min and immediately before exercise, immediately after, and during recovery (+15, +30, +60 and +90 min) for adrenocorticotropin (ACTH), β-endorphin, growth hormone (GH), prolactin (PRL), cortisol (C), corticosterone, dehydroepiandrosterone-sulfate (DHEAS) and cortisol binding globulin (CBG) assays. C/CBG (free cortisol index, FCI) and DHEAS/C ratios were calculated. Exercise intensity, perceived exertion rate, O(2) consumption, CO(2) and blood lactate concentration were evaluated. Results: ACTH, GH, C, corticosterone and CBG absolute concentrations and/or areas under curve (AUC) increased after exercise after both placebo and tadalafil. Exercise increased DHEAS only after placebo. Compared to placebo, tadalafil administration reduced the ACTH, C, corticosterone and FCI responses to exercise and was associated to higher β-endorphin AUC and DHEAS/C ratio during recovery, without influencing cardio-respiratory and performance parameters. Conclusion: Tadalafil reduced the activation of the hypothalamus-pituitary-adrenal axis during exercise by probably influencing brain's nitric oxide-cyclic guanosine monophosphate mediated pathways. Further studies are necessary to confirm our results and to identify the involved mechanisms, possible health risks and potential clinical uses.