The pathogenesis of organic ED is related to dysfunction of the endothelium. Endothelial cells can become injured through a variety of mechanisms, most of which cause oxidative stress on the tissues. Many of these causes of oxidative stress are related to lifestyle issues which lead to hypertension, diabetes and dyslipidaemia (figure 1). Endothelial cell dysfunction results in reduction of endothelium-dependent vasorelaxation as well as increased adhesion of leukocytes to the endothelium. Endothelial cell injury then leads to a variety of sequelae, including ED, other types of vasoconstriction, atherosclerosis and thrombus formation.18
PDE5 inhibitors, the primary second-line therapy, have been the mainstay of ED treatment since the release of sildenafil (Viagra) in 1998, with the subsequent development of many others, and still more in the development stage. These medications do improve erectile quality for the majority of men, and they work by enhancing blood flow in the corpora cavernosa. These medications are generally used on demand and need to be taken about an hour before sexual intimacy. Tadalafil (Cialis) is longer acting and does come in a daily preparation potentially eliminating the ‘on-demand’ need. The daily dosing of tadalafil, 2.5–5 mg\day, has also been approved by the FDA for treatment of symptoms of BPH.41 PDE5 inhibitors are contraindicated in men taking nitrates, but otherwise PDE5 inhibitors are very safe and effective. When PDE5 inhibitors are coadministered with nitrates, pronounced systemic vasodilation and severe hypotension are possible. Many patients with ED are elderly and have the same risk factors as patients with CAD, so these drug combinations are commonly considered or encountered in clinical practice.42

However, a review of a United Kingdom medical record database found no evidence that the use of 5-alpha reductase inhibitors independently increase the risk for ED. In 71,849 men with benign prostatic hyperplasia (BPH), the risk of ED was not increased with the use of finasteride or dutasteride only (odds ratio [OR] 0.94), or a 5-alpha reductase inhibitor plus an alpha blocker (OR 0.92) compared with an alpha blocker only. In addition, the risk of ED was not increase in 12 346 men prescribed finasteride 1 mg for alopecia, compared with unexposed men with alopecia (OR 0.95). The risk of ED did increase with longer duration of BPH, regardless of drug exposure. [48]


An analysis of 14 studies involving more than 90,000 patients with ED confirmed the relation between ED and an increased risk of cardiovascular events and mortality. [56] Compared with patients without ED, those with ED had a 44% increased risk of cardiovascular events, a 25% increased risk of all-cause mortality, a 62% increased risk of MI, and a 39% increased risk of cerebrovascular events. Treatment of ED, either through lifestyle interventions or by pharmacologic means, may improve prognosis and reduce risk.

Conditions associated with reduced nerve and endothelium function (eg, aging, hypertension, smoking, hypercholesterolemia, and diabetes) alter the balance between contraction and relaxation factors (see Pathophysiology). These conditions cause circulatory and structural changes in penile tissues, resulting in arterial insufficiency and defective smooth muscle relaxation. In some patients, sexual dysfunction may be the presenting symptom of these disorders.
Diabetes mellitus: Erectile dysfunction tends to develop 10 to 15 years earlier in diabetic men than among nondiabetic men. The increased risk of erectile dysfunction among men with diabetes mellitus may be due to the earlier onset and greater severity of atherosclerosis (hardening of the arteries) that narrows the arteries and thereby reduces the delivery of blood to the penis. Atherosclerosis can affect the arteries in the penis, as well as the arteries in the pelvis that supply the penile arteries. Diabetes mellitus also causes erectile dysfunction by damaging nerves that go to the penis, much like the effect of diabetes on nerves in other areas of the body (diabetic neuropathy). Diabetes can also affect the muscles in the penis, leading to troubles with erections. Smoking cigarettes, obesity, poor control of blood glucose levels, and having diabetes mellitus for a long time further increase the risk of erectile dysfunction in people with diabetes.

En español | If you watch TV or read magazines, you could easily conclude that men seeking treatment for erectile dysfunction (ED) have but one option: pills. The three dominant brands — Cialis, Levitra and Viagra — are locked in an expensive battle for men’s allegiances, and have, through their suggestive advertising, triggered both satire and controversy in the 14 years since the Food and Drug Administration approved Viagra.

Whenever I am prescribing a medication to a patient, I’m always asking myself, what can the patient do before requiring the medication? What changes do they have to make in order to reduce the amount of medication or preclude their even needing it? So a good candidate is somebody who has an understanding of a healthy lifestyle, about physical activity, about sleep, about nutrition, alcohol, smoking. So patients, individuals, have to do their share before they’re a candidate for anything. All right?
In some cases, ED can be a warning sign of more serious disease. One study suggests ED is a strong predictor of heart attack, stroke, and death from cardiovascular disease. The researchers say all men diagnosed with ED should be evaluated for cardiovascular disease. This does not mean every man with ED will develop heart disease, or that every man with heart disease has ED, but patients should be aware of the link.
PDE5i use in PD has not been well studied; however its benefits have been shown. Raffaele performed an open label, prospective study evaluating the efficacy of sildenafil 50 mg on demand and depressive symptoms experienced by the PD patient (73). Erections were improved in approximately 85% of men and 75% noted improvements in their depressive symptoms as well. Sildenafil was well tolerated without significant side effects. Zesiewicz et al., performed a shorter study showing improvements in erectile function but no change in depression and parkinsonisms after ED treatment (74).
There are two kinds of surgery for ED: one involves implantation of a penile prosthesis; the other attempts vascular reconstruction. Expert opinion about surgical implants has changed during recent years; today, surgery is no longer so widely recommended. There are many less-invasive and less-expensive options, and surgery should be considered only as a last resort.
Phosphodiesterase type V inhibitors (PDE-5 inhibitors) are the most commonly used therapy for erectile dysfunction. These medications work by preventing the breakdown of chemicals that stimulate increased blood flow into the penis. Several different PDE-5 inhibitors are available, which differ slightly in how to use them and their side effects. They appear to be equally effective in the treatment of erectile dysfunction in general, but some individuals may respond to one of these medications more effectively than another.
Since endothelial dysfunction, CVD and ED are closely associated in epidemiological studies, the question for clinicians is whether to recommend the man presenting with ED undergo a cardiovascular (CV) evaluation. Clearly, based on numerous studies, ED can be considered at least a ‘marker’ for possible further vascular disease or CVD.15 In their report, Vlachopoulos and coworkers make the point that the man presenting with ED, the clinician, is offered an opportunity to attempt to improve the health of the man by addressing lifestyle modification, and consider further vascular evaluation owing to the clear relationship between endothelial dysfunction, ED and CVD.19
Research is mixed on the effectiveness of acupuncture as an erectile dysfunction cure, but one study published in November 2013 in the Journal of Alternative and Complementary Medicine found that acupuncture can be beneficial for men experiencing erectile dysfunction as a side effect of antidepressants, including selective serotonin reuptake inhibitors (SSRIs) and serotonin noradrenaline reuptake inhibitors (SNRIs).
Injections: Injections are a reliable way to restore testosterone levels, but this therapy requires periodic injections (usually every two weeks) to sustain an effective level. It also causes high hormone levels right after the injection and low hormone levels just before the next shot. This is thought to be slightly more risky than other methods that maintain a moderate hormone level throughout the treatment period.
Alprostadil is a potent vasodilator and smooth muscle relaxant identical to the naturally occurring PGE1. PGE1 binds with specific receptors on smooth muscle cells and activates intracellular adenylate cyclase to produce cAMP, which in turn induces tissue relaxation through a second messenger system (96). PGE1 is the only FDA approved form of intracavernosal therapy and is available commercailly as EDEX, or Caverject. Its efficacy was demonstrated in several clinical trials where the rate of responders ranged from 40% to 80% (97,98). The most common adverse event is penile pain, which is not related to the injection of the medication itself. In men with prolonged use the pain is usually self-limited (99).
Ultrasound with Doppler imaging (ultrasound plus evaluation of blood flow in the arteries and veins) can provide additional information about blood flow of the penis and may help in the evaluation of patients prior to surgical intervention. This study is typically performed after the injection of a chemical that causes the arteries to open up, a vasodilator (prostaglandin E1), into the corpora cavernosa in order to cause dilation of blood vessels and promote blood flow into the penis. The rate of blood flow into the penis can be measured along with an evaluation of problems with compression of the veins.
The neurovascular events that ultimately occur result in the inhibition of adrenergic tone and the release of the nonadrenergic, noncholinergic neurotransmitter, nitric oxide. Nitric oxide is believed to be released from nonadrenergic, noncholinergic nerves and endothelial cells. It subsequently stimulates the guanylate cyclase enzyme system in penile smooth muscle. This results in increased levels of cyclic guanosine monophosphate (cGMP) and ultimately in smooth muscle relaxation, enhancement of arterial inflow, and veno-occlusion, producing adequate firmness for sexual activity.
ED can also occur as a side effect of some medications, for example some high blood pressure medications such as certain diuretics and beta blockers. If you think that a medication you are taking has a negative effect on your sex life, you should discuss this with your prescribing doctor. Your doctor may be able to recommend an alternative treatment.
In some cases, ED can be a warning sign of more serious disease. One study suggests ED is a strong predictor of heart attack, stroke, and death from cardiovascular disease. The researchers say all men diagnosed with ED should be evaluated for cardiovascular disease. This does not mean every man with ED will develop heart disease, or that every man with heart disease has ED, but patients should be aware of the link.
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