Cavernous smooth muscles: innovative potential therapies are promising for an unrevealed clinical diagnosis.

While erectile dysfunction (ED) is highly prevalent worldwide, unrevealed cavernous smooth muscles (CSM) defects can confound the diagnosis of vascular ED and lead to failure of treatments. Currently, the first-line oral treatment for ED is phosphodiesterase type 5 inhibitors (PDE5Is). Patients with diabetes mellitus (DM), those who have undergone a radical prostatectomy (RP), and the elderly population are difficult to treat by the PDE5Is; unrevealed CSM defects can result in corporo veno-occlusive dysfunction (CVOD); and penile veno-ligation surgeries are currently abandoned due to high failure rates. It has been found that gene and stem cell therapies, among others, reduce cavernous tissue apoptosis and fibrosis and can specifically target CSM defects such as the nitric oxide (NO)-mediated signaling pathway, Rho-ROCK system, and transformation growth factor (TGF)-β1/angiotensin II (Ang II) pathway, in several laboratory animals. Current data clarify the need of diagnostic techniques that can provide an initial assessment of CSM. This assessment should be essential before giving a diagnosis of vascular ED and before applying several tests searching for a specific CSM defect to guide the specific therapy. Moreover, while patients with corporal fibrosis would fail the current medical therapies, these patients can benefit from the stem cell-based therapies that induce the internal mechanisms of tissue repair. However, penile elastography can determine the stiffness of tissues and corpus cavernosum electromyography (CC-EMG) can assess the integrated activity of CSM bulk, further refinements are required for these techniques before being considered in the evaluation of patients with ED. In conclusion, on the basis of the current scientific research, it may be possible to formulate new therapies and achieve the appropriate selection of patients who can benefit from these therapies.