Aetiology
Erectile dysfunction is an alteration in any of the components of the erectile response, including organic, relational, and psychological causes.[15][16]
Organic causes are categorised as neurogenic, hormonal, arterial, cavernosal, or drug induced.[17] Impaired local-regional blood flow is a common characteristic, and arteriogenic is the most common cause:[15][18]
Vascular/arteriogenic - 40%
Diabetes - 30%
Medicine - 15%
Pelvic surgery/radiation/trauma - 6%
Neurogenic - 5%
Endocrine - 3%
Other - 1%.
Atherosclerosis is an important factor in diabetic ED and other vascular conditions (hypertension, hypercholesterolaemia).[15][17] Diabetic ED is multifactorial and involves endothelial dysfunction as well as arteriogenic and neurogenic mechanisms, and correlates inversely with the degree of glycaemic control.[15][19] Nerve injury commonly occurs after radical pelvic surgery (e.g., radical retropubic prostatectomy, abdominoperineal resection) and direct injury to the spinal cord or pelvic nerve fibres and/or vasculature.[15] Disorders of the central nervous system, such as stroke, multiple sclerosis, Alzheimer's disease, and Parkinson's disease, are also associated with ED.[15][17] Endocrine causes include hypogonadism, hypo/hyperthyroidism, pituitary tumour, and hyperprolactinaemia, secondary to alterations in circulating androgens, which are pro-erectogenic.[15][17][20][21]
Prostate cancer and the resultant treatments of surgery or radiotherapy have been a major source of ED over the past several decades. Current guidelines have lessened the number of potential candidates for prostate cancer surgery by increasing active surveillance, so globally one may expect the number of men who undergo radical prostate surgery for cancer to decrease as active surveillance increases.[22] However, how this alters the prevalence of ED is unknown.
Pathophysiology
Penile erection depends on a complex intracellular cascade that results in cavernosal smooth muscle relaxation, increased sinusoidal blood flow, and occlusion of venous outflow, followed by rigidity.[15] Nitric oxide is liberated in the presynaptic cavernous nerve fibres and endothelial cells, and is responsible for initiating and maintaining vascular smooth muscle cell relaxation.[15] Diffusion of nitric oxide across the synaptic cleft activates guanylate cyclase. Guanosine triphosphate is converted to cyclic guanosine monophosphate (cGMP), triggering intracellular Ca²+ sequestration in the endoplasmic reticulum. Smooth muscle relaxation occurs as cytosolic Ca²+ levels decrease. Phosphodiesterase-5 (PDE5) converts cGMP to 5'-guanosine monophosphate, allowing Ca²+ levels to normalise. Drugs that competitively inhibit PDE5 (e.g., sildenafil, vardenafil) result in a build-up of cGMP, smooth muscle relaxation, and promotion of an erection.[15] Adrenergic stimulation results in vasoconstriction and detumescence.[17]
The penile erection cascade can be initiated in three ways:[23]
Psychogenic erections occur in response to afferent sensory stimulation (T11-L2 and S2-S4) to trigger central dopaminergic erection from the pre-optic area.
Reflexogenic erections, which are often preserved in men with spinal cord injury above the sacral level, occur following genital stimulation, and are mediated in the spinal cord and autonomic nuclei.
Nocturnal erections that occur during rapid eye movement sleep probably result from suppression of inhibitory sympathetic outflow by the pontine reticular formation and amygdala.
Interference with any of the factors can result in ED. In general, ED occurs when the response to neurovascular stimulation is impaired and is believed to be related to endothelial dysfunction. Atherosclerosis is a common pathway for several aetiologies and is thought to act through impaired smooth muscle relaxation and venous occlusion as a result of diminished cavernosal artery flow and sequelae of diminished cavernous oxygen tension.[23]
Classification
International Society of Impotence Research[2]
Organic
Vasculogenic
Arteriogenic
Cavernosal
Mixed
Neurogenic
Anatomical
Endocrine
Psychogenic, generalised
Generalised unresponsiveness
Primary lack of sexual arousal
Ageing-related decline in sexual arousal or libido
Generalised inhibition
Chronic disorder of sexual intimacy
Psychogenic, situational
Partner-related
Lack of arousability in specific relationship
Lack of arousability owing to sexual object preference
High central inhibition owing to partner conflict or threat
Performance-related
Associated with other sexual dysfunction/s (e.g., rapid ejaculation)
Situational performance anxiety (e.g., fear of failure)
Psychological distress- or adjustment-related
Associated with negative mood state (e.g., depression) or major life stress (e.g., death of partner)
Clinical classification[3]
Ageing
Psychological disorders (e.g., depression, anxiety)
Neurological disorders (e.g., cerebral diseases, spinal cord injury, spinal disease, peripheral neuropathy, pudendal nerve injury)
Hormonal disorders (e.g., hypogonadism, hyperprolactinoma, thyroid disease, Cushing's syndrome, Addison's disease)
Vascular disorders (atherosclerosis, ischaemic heart disease, peripheral vascular disease, venous incompetence, cavernosal disorders)
Medicines (e.g., antihypertensives, antidepressants, oestrogens, anti-androgens, digoxin)
Habits (e.g., marijuana, alcohol abuse, narcotic use, cigarette smoking)
Other (e.g., diabetes mellitus, renal failure, hyperlipidaemia, hypertension, COPD)
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