Pathophysiology and treatment of diabetic erectile dysfunction.
The pathophysiology of diabetes is multifactorial and no single etiology is at the forefront. The proposed mechanisms of erectile dysfunction (ED) in diabetic patients includes elevated advanced glycation end-products (AGEs) and increased levels of oxygen free radicals, impaired nitric oxide (NO) synthesis, increased endothelin B receptor binding sites and ultrastructural changes, upregulated RhoA/Rho-kinase pathway, NO-dependent selective nitrergic nerve degeneration and impaired cyclic guanosine monophosphate (cGMP)-dependent kinase-1 (PKG-1). The treatment of diabetic ED is multimodal. Treatment of the underlying hyperglycemia and comorbidities is of utmost importance to prevent or halt the progression of the disease. The peripherally acting oral phosphodiesterase type 5 (PDE5) inhibitors are the mainstay of oral medical treatment of ED in diabetics. Vacuum erection devices are an additional treatment as a non-invasive treatment option. Local administration of vasoactive medication via urethral suppository or intracorporal injection can be effective with minimal side-effects. Patients with irreversible damage of the erectile mechanism are candidates for penile implantation. Future strategies in the evolution of the treatment of ED are aimed at correcting or treating the underlying mechanisms of ED. With an appropriate vector, researchers have been able to transfect diabetic animals with agents such as neurotrophic factors and nitric oxide synthase (NOS). Further studies in gene therapy are needed to fully ascertain its safety and utility in humans.
Moore
Charles R
CR
Department of Urology, University of Texas Health Science Center and MD Anderson Cancer Center, 6431 Fannin Street, Suite 6.018, Houston, Texas 77030, USA.
Wang
Run
R
D000527:Alprostadil / Q000008:administration & dosage / Q000627:therapeutic use; D017869:Cyclic GMP-Dependent Protein Kinases / Q000502:physiology; D048909:Diabetes Complications / Q000503:physiopathology*; D003929:Diabetic Neuropathies / Q000503:physiopathology; D007172:Erectile Dysfunction / Q000209:etiology* / Q000503:physiopathology / Q000628:therapy*; D017127:Glycation End Products, Advanced / Q000502:physiology; D006801:Humans; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D010410:Penile Erection; D015917:Penile Prosthesis; D010413:Penis / Q000098:blood supply; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use; D044023:Receptor, Endothelin B / Q000502:physiology; D013488:Suppositories; D014618:Vacuum
D017127:Glycation End Products, Advanced; D010726:Phosphodiesterase Inhibitors; D044023:Receptor, Endothelin B; D013488:Suppositories; D009569:Nitric Oxide; D017869:Cyclic GMP-Dependent Protein Kinases; D000527:Alprostadil