Italy.
Erectile dysfunction (ED) is a multidimensional disorder characterized by the inability to have successful intercourse with negative consequences in personal self-esteem and in couple relationship. Organic, relational and intrapsychic problems always concur in determining the erectile problem, although in different combination according to the patient characteristics, including age. Fifteen years ago, we have developed and validated a structured interview to identify and quantify the weight of each ED determinant. The organic determinant contributes significantly to ED in all age bands. In young and middle-age patients, intrapsychic disturbances are also important, while they result no longer statistically significant in aged individuals. Relational problems show a major contribution in younger subjects. Recognizing and treating ED is important in all age bands, because they often represent a harbinger of forthcoming cardiovascular (CV) problems. This is particularly relevant in young individuals, where having ED strongly increase CV risk. Several endocrine disorders are underlying the organic component of ED. Among them are metabolic disturbances, such as diabetes mellitus (T2DM) and obesity, hypogonadism, hyperprolactinemia and, to a lower extent, thyroid diseases. Recognizing the underlying endocrine disorder is of capital relevance because treating it could restore a normal erectile function and improve overall health. For example, treating hypogonadism significantly improve erectile function, as demonstrated by a recent meta-analysis considering RCTs having International Index of Erectile Function (IIEF) as end-point. However, the improvement in IIEF score was modest upon testosterone replacement therapy (TRT), i.e. 23 points, and apparent only in trials involving overt hypogonadism. Hence, there is often the need to associate other types of intervention to fully restore erectile function. Considering that T2DM, obesity and metabolic syndrome (MetS) are the major cause of ED-associated hypogonadism, their treatment is mandatory for sexual health. In fact, lifestyle intervention, including physical activity, improves erectile function and often reverts hypogonadism. In an experimental model of MetS we demonstrated that in the hypothalamus there is clear inflammation associated to a decrease in GnRH expression, secondary hypogonadism and ED. In MetS rabbits, regular physical activity (treadmill) reverted hypothalamic alterations, doubling GnRH expression, restoring normal testosterone levels and erectile function, including cGMP signaling within the penis. Several medications blocking cGMP catabolism in the penis, through the inhibition of phosphodiesterase type 5 (PDE5 inhibitors), are available as a symptomatic aid for improving ED. Although PDE5 inhibitors result very efficient in improving ED (more than 5 IIEF points) they do not resolve the underlying problems.