Erectile Dysfunction

The European Association of Urology defines erectile dysfunction as the persistent inability to attain and maintain an erection sufficient to permit satisfactory sexual performance. ^[1] It is a multidimensional but common male sexual dysfunction that can involve an alteration in any component of the erectile response, whether organic, relational or psychological. ^[2] Studies have repeatedly found that about 52% of men between the ages of 40 and 70 years have some degree of erectile dysfunction. ^[3] Prevalence is much higher in diabetes: it ranges from 35-90% in diabetic men and is estimated to be over 3.5 times higher than in men without diabetes. ^{[4] [5]} Erectile dysfunction can have deleterious effects on quality of life, most patients have symptoms of depression and anxiety related to sexual performance, and these symptoms also affect the partner and the couple. ^[2]

Both nonendocrine (neurogenic, vasculogenic and iatrogenic) and endocrine pathways have been proposed as causes of erectile dysfunction. ^[2] Erectile dysfunction may be one of the earliest signs of endothelial dysfunction, and in type 2 diabetes sexual dysfunction is described as a microvascular complication whose pathogenesis originates from endothelial dysfunction. ^{[3] [4]} In diabetes, the pathophysiology involves interacting pathways including endothelial dysfunction, accelerated atherosclerosis, autonomic and peripheral neuropathy, structural penile changes, hormonal imbalances and psychological factors. ^[5] A meta-analysis of 58 studies including 66,925 men with diabetes associated erectile dysfunction with HbA1C (OR: 1.44), diabetic neuropathy (OR: 3.47), cardiovascular disease (OR: 1.92), hypertension (OR: 1.74) and

A review of hypertension and reproduction describes erectile dysfunction as currently considered an early diagnostic marker of cardiovascular disease that precedes the manifestation of coronary artery disease by several years and frequently coexists with hypertension. ^[9] The Princeton IV consensus states that mounting evidence supports treating men with erectile dysfunction as being at risk for cardiac events until proven otherwise, which places the symptom within cardiovascular risk assessment. ^[10] Princeton IV integrates an algorithm based on American College of Cardiology and American Heart Association recommendations, including computed tomography coronary artery calcium scoring, into the evaluation of men presenting with erectile dysfunction. ^{[11] [10]} Owing to its strong association with metabolic syndrome and cardiovascular disease, cardiac assessment may be warranted in men with symptoms of erectile dysfunction.

The AUA guideline makes shared decision-making the cornerstone of care, with all patients informed of every treatment modality that is not contraindicated, regardless of invasiveness or irreversibility, as a potential first-line treatment. ^[15] Minimally invasive options include lifestyle modifications, oral drugs, injected vasodilator agents and vacuum erection devices, while surgery is reserved for men with contraindications to, adverse effects from or refractoriness to these treatments, or with penile fibrosis or vascular insufficiency. ^[2] Sildenafil, a selective inhibitor of phosphodiesterase type 5, improves smooth muscle relaxation in the corpus cavernosum and penile arteries in the presence of sexual stimulation, with dose-dependent side effects such as headache, flushing, indigestion and nasal congestion. ^[16] The Princeton IV consensus addresses nitrate use in an algorithm for men with erectile dysfunction and coronary artery disease, and notes that recent studies suggest potential cardiovascular benefits and cardiovascular safety of phosphodiesterase type 5 inhibitors. ^{[11] [10]} In a meta-analysis in which a total of 44 studies included 3853 men, combination therapy with a phosphodiesterase type 5 inhibitor plus another agent improved the IIEF score by 1.76 points over monotherapy without more treatment-related adverse events, although heterogeneity was high.