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

Centrally active compounds such as apomorphine have been used in men with ED whose cardiovascular comorbidity may prohibit PDE5i use, or in men who have concurrent apomorphine use for its anti-parkinsonian properties. Unfortunately, its side effect profile and poor effectiveness compared to other ED treatments have impaired its mainstream utilization (118). It is suspected that the side effects of apomorphine relate to its D2 receptor affinity. D4 receptor agonists, such as ABT-724 and azulenylmethylpiperazines, may not have the same associated side effects and show potent pro-erectile effects in animal models compared to apomorphine (32,119).
Associated morbidity may include various other male sexual dysfunctions, such as premature (early) ejaculation and male hypoactive sexual desire disorder. The NHSLS found that 28.5% of men aged 18-59 years reported premature ejaculation, and 15.8% lacked sexual interest during the past year. An additional 17% reported anxiety about sexual performance, and 8.1% had a lack of pleasure in sex. [51]
Palmer MR, Holt SK, Sarma AV, Dunn RL, Hotaling JM, Cleary PA, Braffett BH, Martin C, Herman WH, Jacobson AM, Wessells H; Diabetes Control and Complications Trial and Epidemiology of Diabetes Interventions and Complications Research Group. Longitudinal Patterns of Occurrence and Remission of Erectile Dysfunction in Men With Type 1 Diabetes. J Sex Med. 2017 Oct;14(10):1187-1194. Doi: 10.1016/j.jsxm.2017.07.012. Epub 2017 Aug 26.
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.
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"The good news is, our study also found that a large proportion of men were naturally overcoming erectile dysfunction issues. The remission rate of those with erectile dysfunction was 29%, which is very high. This shows that many of these factors affecting men are modifiable, offering them an opportunity to do something about their condition," Professor Wittert says.
For best results, men with ED take these pills about an hour or two before having sex. The drugs require normal nerve function to the penis. PDE5 inhibitors improve on normal erectile responses helping blood flow into the penis. Use these drugs as directed. About 7 out of 10 men do well and have better erections. Response rates are lower for Diabetics and cancer patients.
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