Phosphodiesterase Type 5 Inhibitors, Sport and Doping

Abstract

Phosphodiesterase type 5 inhibitors (PDE5i) (e.g., sildenafil, tadalafil, vardenafil, and avanafil) are drugs commonly used to treat erectile dysfunction, pulmonary arterial hypertension, and benign prostatic hyperplasia. PDE5i are not prohibited by the World Anti-Doping Agency (WADA) but are alleged to be frequently misused by healthy athletes to improve sporting performance. In vitro and in vivo studies have reported various effects of PDE5i on cardiovascular, muscular, metabolic, and neuroendocrine systems and the potential, therefore, to enhance performance of healthy athletes during training and competition. This suggests well-controlled research studies to examine the ergogenic effects of PDE5i on performance during activities that simulate real sporting situations are warranted to determine if PDE5i should be included on the prohibited WADA list. In the meantime, there is concern that some otherwise healthy athletes will continue to misuse PDE5i to gain an unfair competitive advantage over their competitors.

Effect of Tadalafil Administration on Redox Homeostasis and Polyamine Levels in Healthy Men with High Level of Physical Activity

“…Finally, plasma's total antioxidant capacity, which expressed the reactivity of plasmatic antioxidant compounds in counteracting radicals, also remained unchanged. In vitro analysis of the scavenger capacity of tadalafil showed modest activity (Table 7) and, therefore, although the molecule may act for longer than other PDE5 inhibitors [6], its contribution to the plasma total antioxidant capacity may be not significant. There are few studies evaluating the effects of tadalafil on healthy athletes [27,[53][54][55].…”

“…Phosphodiesterase type 5 inhibitors (PDE5Is) (e.g., avanafil, sildenafil, vardenafil, tadalafil), represent a class of drugs routinely consumed worldwide, because of their great therapeutic role for the treatment of erectile dysfunction (ED) (avanafil, sildenafil, vardenafil, tadalafil), and pulmonary arterial hypertension (sildenafil and tadalafil), and for the management, in men, of moderate to severe lower urinary tract symptoms (LUTS) secondary to benign prostatic obstruction with or without ED (tadalafil) acting mainly via the nitric oxide (NO) and cyclic guanosine monophosphate (NO–cGMP) pathways [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 ].…”

Annual banned‐substance review: Analytical approaches in human sports drug testing

“…Phosphodiesterase type 5 (PDE5) inhibitors have not been the subject of WADA's monitoring program so far. Anecdotal evidence exists that PDE5 inhibitors have been misused in sports for performance‐enhancing purposes and several studies exist that suggest some potential to affect athletic performance as recently summarized by di Luigi et al Yet, studies simulating conditions of elite level sport are missing and more information will be required.…”

Roflumilast, a type of phosphodiesterase 4 inhibitor, can reduce intestinal injury caused by sepsis

“…In recent years, PDEs have been attracting increased attention as new therapeutic targets and have become a new research hotspot. The clinical research of selective PDE4 and PDE5 inhibitors has also received significant attention ( 9 , 10 ). PDE4 has multiple isozymes, which are divided into four subtypes: PDE4A, B, C and D ( 11 ).…”