Role and Clinical Relevance of Nerve Growth Factor (NGF) and Its Receptors (TrKA and p75NTR) in Patients With Erectile Dysfunction and Diabetes With or Wothout Metabolic Syndrome

Penile erection is a complex phenomenon which implies a delicate and co-ordinated equilibrium among the neurological, vascular and the smooth muscle compartment. It includes arterial dilation, trabecular smooth muscle relaxation and activation of the corporeal veno-occlusive mechanism. Erectile Dysfunction (ED) is defined as the persistent inability to attain and maintain an erection sufficient to permit satisfactory sexual performance. Erectile Dysfunction may affect physical and psychosocial health and may have a significant impact on the quality of life (QoL) of sufferers and their partner's . There is increasing evidence that ED can be an early manifestation of coronary artery and peripheral vascular disease. Erectile Dysfunction should not be regarded only as a QoL issue, but also as a potential warning sign of cardiovascular disease (CVD) .The most important organic causes of ED are vascular, metabolic, neurogenic, hormonal and pharmacological. 35-90% of diabetic patients suffer from ED In the latter metabolic disease, Dai et al. have identified as a possible etiology of ED a lack of interaction between nerve growth factor (NGF) and its TrKA receptor, resulting in a noticeable increase in NGF levels in the corpora cavernosa11. Furthermore, Hou et al. have shown that the activation of the NGF / TrKA system in the corpora cavernosa (increased expression of NGF and TrKA mRNA and upregulation of c-raf, ERK1 / 2 and CREB1) improves erectile function in mice with ED and diabetes mellitus.

The objectives of this study are:

• The primary outcome is to evaluate the systemic plasma concentration and the concentration in cavernous bodies of penis of NGF in patients with ED and diabetes with or without metabolic syndrome (a); (b) the expression of its TrKA and p75NTR receptors in the mononuclear cells taken from peripheral blood and in cavernous bodies of penis.
• The secondary outcome is to evaluate whether the levels of NGF and its receptors in the mononuclear cells can correlate with the clinical staging of ED.

Prospective pilot study. 12 patients diagnosed with ED with diabetes with or without metabolic syndrome( Mets )aged between 18 and 65 will be recruited. Each patient will undergo an initial evaluation that includes: the pathological and pharmacological anamnesis, the local objective examination and the compilation of the validated questionnaire International Index of Erectile Function Questionnaire short form (IIEF5).

Based on the IIEF5 score, patients will be divided into 4 groups (each of 10 patients):