Erectile Dysfunction

Erectile dysfunction (ED) is “the inability to achieve or sustain an erection that is sufficient for satisfactory sexual performance.”^[1] The prevalence of ED among adult males aged 40–79 has been estimated to be between 30% and 50%.^[2][3]

Sexual stimulation normally causes the release of nitric oxide (NO) and acetylcholine (ACh) from nerve fibers in the penis, initiating a molecular signaling cascade that ultimately results in the relaxation of penile smooth muscle tissue, an elevation in blood flow, and tumescence (an erection). These processes are disrupted in ED. ED can be categorized as psychogenic ED or organic ED; the latter can be broadly characterized as neurogenic ED, vasculogenic ED, or iatrogenic (medication- or surgery-induced) ED.^[1]

Men with ED are unable to achieve an erection when they want to, or can achieve an erection but are not able to sustain the erection long enough for sexual intercourse.

Signs of ED may include the presence of lower urinary tract symptoms (LUTS) in men with benign prostatic hyperplasia (BPH) — both of which are associated with ED. Other signs of ED may include penile deformities, prostate disease, or hypogonadism (i.e., small testes or alterations in secondary sex characteristics).

Symptoms of organic ED include the consistent inability to achieve or sustain an erection; in organic ED, this inability is often gradual in onset, yet progressive in nature. Symptoms of psychogenic ED include ED that is more intermittent, variable, or situational. Psychogenic ED often has a sudden onset, and men with psychogenic ED tend to have more difficulty sustaining than achieving an erection.^[1]

The diagnosis of ED begins with a comprehensive evaluation including medical, sexual, and psychosocial history, a physical examination of genitourinary anatomy, and laboratory testing to rule out other conditions. Diagnosis and assessment of ED are also conducted using validated questionnaires such as the International Index of Erectile Function (IIEF), which assesses a patient’s response to various treatment strategies. The IIEF classifies ED into five categories: no ED (score of 22–25), mild ED (score of 17–21), mild-moderate ED (score of 12–16), moderate ED (score of 8–11), and severe ED (score of 1–7).^[4]

In certain cases, specialized diagnostic testing, including vascular testing using ultrasound, nocturnal penile tumescence (NPT), erection rigidity testing, and neuropsychological testing, may be performed.^[5]

The first-line therapy for ED is the use of a phosphodiesterase-5 inhibitor (PDE5I), of which sildenafil (Viagra), tadalafil, vardenafil, and avanafil are the most commonly prescribed. PDE5I in combination with prescription testosterone therapy has also been effective in improving ED symptoms.^[6]

Other treatments for ED include the application of vasodilators like alprostadil (topical, intraurethral, or intracavernosal), low-intensity extracorporeal shockwave therapy (Li-ESWT), vacuum erection devices, testosterone therapy (intramuscular or transdermal), psychosexual counseling,cognitive behavioral therapy (CBT), vascular surgery, and the use of penile prostheses (inflatable or semirigid devices). Among these, the strongest evidence supports CBT (often in combination with PDE5Is), intracavernous alprostadil injections, and penile prosthesis implantation.^[7]

Ginseng appears to have trivial effects on erectile function, but may improve men’s self-reported ability to have intercourse and their satisfaction with intercourse.^[11] Saffron (Crocus sativus),^[12] Tribulus terrestris,^[13] Pycnogenol (Pinus pinaster),^[14] Maca (Lepidium meyenii),^[15] and Tongkat Ali (Eurycoma longifolia)^[16] also appear to improve ED symptoms, though there are only a few studies to support each of these herbs.^[17]

Supplementing with L-Arginine (alone or combined with L-Citrulline, Pycnogenol, ornithine, or yohimbine) improves erectile function.^[18] Yohimbine, especially when combined with L-Arginine, also improves ED symptoms, but doesn’t seem to increase sexual function.^[19] L-Citrulline (a precursor to L-Arginine) has also been shown in one study to improve erection hardness in men with ED.^[20]

The Mediterranean diet, plant-based diets, and diets containing high amounts of fruits and vegetables, nuts, legumes, fish, whole grains, antioxidants, and omega-3 fatty acids and lower amounts of red and processed meat, trans fat, dairy, sugar, sodium, and alcohol are associated with a lower risk of ED.^{[21][22][23][24][25][26][27]}

However, some studies suggest that any association between the type of diet one follows (i.e., Mediterranean, low-fat, low-carbohydrate, ketogenic, vegetarian/vegan, pescatarian) and ED disappears when controlling for age, BMI, and other risk factors.^[28][29] Weight loss achieved through a low-fat, low-calorie diet;^[30][31], a high-protein, low-carbohydrate diet;^[32] a high-protein, low-fat diet; or a high-carbohydrate, low-fat diet^[33] improves erectile function in men with diabetes and/or overweight/obesity.

Weight loss, whether achieved through diet and/or physical activity^[34][35][36] or through bariatric surgery,^[37] improves ED in men with overweight or obesity.

Physical inactivity increases the risk for ED,^[38][39] while exercise — particularly moderate- to vigorous-intensity aerobic exercise — improves erectile function in men with ED and comorbidities including obesity, metabolic syndrome, and cardiovascular disease.^[40][41] In fact, a 2019 review indicated that among all ED treatments, physical activity interventions caused the largest improvement in ED,  with effectiveness similar to pharmacological therapy.^[42]

Other emerging yet experimental ED treatments include gene therapy, stem cell therapy,^[43][44] Li-ESWT,^[45][46][45] platelet-rich plasma (PRP), low-intensity pulsed ultrasound (LIPUS), hyperbaric oxygen therapy, penile vibratory stimulation,^[47][48] and pelvic floor muscle training.^[49].

At its core, ED is caused by a deficit in NO release, cyclic GMP (cGMP) and calcium signaling, or smooth muscle relaxation. However, many overlapping mechanisms can interrupt this signaling cascade.

Psychogenic or sympathetic-mediated ED is caused by stress, depression, or anxiety about sexual performance. Neurogenic ED is caused by a deficit in nerve signaling to the penis, which may be secondary to spinal cord injury, traumatic brain injury, or surgery. Vasculogenic ED — the most common form of ED — is caused by underlying vascular disease, endothelial dysfunction, and structural changes to the arterial walls. Iatrogenic ED is most often the result of pelvic surgery or the use of medications. Finally, endocrine causes of ED include low levels of androgens (e.g., testosterone) and other hormones.

A number of medications have been linked to ED, including antihypertensives (blood pressure medications); 5𝛼-reductase inhibitors, anti-androgens, luteinizing hormone-releasing agonists and antagonists (used to treat prostate cancer), antidepressant medications, and opiates.^[1]