New achievement and novel therapeutic applications of PDE5 inhibithors in older males.
Erectile dysfunction (ED) increases in prevalence and severity because of aging processes and related organic, iatrogenic and social problems. Decline of testosterone (T) levels is observed with age and also in illnesses with a common basis of endothelial damage. The T deficiency may lead to decreased energy, mood depression, reduction of sexual desire, but no correlation has been reported between T level and severity of ED, which is mainly a neurovascular disease. In facts, inhibition of phosphodiesterase type 5 (PDE5) isoenzyme with sildenafil, tadalafil and vardenafil enhances vasodilatation in the corpus cavernosum and subsequent penile erection. Absolute pharmacological potency of PDE5 inhibitors is similar and non-selectivity defines the side-effects profile, while their elimination half-life explains not only the different duration of action, but also short and long-term tolerability. Efficacy of PDE5 inhibitors in younger patients is greater in respect to older subjects because of associated pathologies and the decline in hypothalamic-pituitary-gonadal function. T is essential in erectile function, controlling the expression and activity of PDE5 and therefore, androgen supplementation improves therapeutic response to PDE5 inhibitors in hypogonadal subjects. Since sexual behavior is a complex interplay of physical, psychological, and social factors, the possible effect of these drugs on androgen levels and brain function need to be deeply investigated. The ubiquitarious distribution of PDE5 and the availability of selective inhibitory molecules foster newer studies in the treatment of heart failure, pulmonary hypertension, inflammation, and depression. This new progress is certainly contributing to a better medical approach to sexuality and quality of life in aging people.
Frajese
G V
GV
Department of Internal Medicine and Endocrinology, University of Roma Tor Vergata, Roma, Italy gaetano.frajese@uniroma2.it
Pozzi
F
F
D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000368:Aged; D000375:Aging; D000818:Animals; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D007172:Erectile Dysfunction / Q000188:drug therapy*; D020249:Hormone Replacement Therapy; D006801:Humans; D007031:Hypothalamus / Q000502:physiology; D008297:Male; D010413:Penis / Q000098:blood supply; D010902:Pituitary Gland / Q000502:physiology; D013737:Testis / Q000502:physiology; D013739:Testosterone / Q000172:deficiency; D014664:Vasodilation
D004791:Enzyme Inhibitors; D013739:Testosterone; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; C517381:PDE5A protein, human