Cavallini, G., Modenini, F., Vitali, G., & Koverech, A. (2005, November). Acetyl-L-carnitine plus propionyl-L-carnitine improve efficacy of sildenafil in treatment of erectile dysfunction after bilateral nerve-sparing radical retropubic prostatectomy. Urology, 66(5), 1080-5. Retrieved from http://www.sciencedirect.com/science/article/pii/S0090429505006515
Smoking is an independent risk factor for ED. Tobacco smoking causes direct toxicity to endothelial cells, including decreased eNOS activity, increased adhesion expression and impaired regulation of thrombotic factors.6 A meta-analysis of 19 studies by Tengs and Osgood suggested that 40 % of the impotent men studied were current smokers compared with 28 % who had never smoked.49
Erectile dysfunction (ED) is highly prevalent affecting at least 50 % of men with diabetes mellitus (DM). DM may cause ED through a number of pathophysiological pathways. These include neuropathy, endothelial dysfunction, cavernosal smooth muscle structural/functional changes, and hormonal changes. Lifestyle changes, diabetes control, and treatment of hypogonadism are important as the first step in ED management since there is no curative treatment for ED. Phosphodiesterase type 5 inhibitors (PDE5i) are the first-line treatment option. Intracavernous administration of vasoactive drugs is commonly used as a second-line medical treatment when PDE5i have failed. Alprostadil is the most widely used drug in this second-line setting. The combination of papaverine, phentolamine, and alprostadil represents the most efficacious intracavernous pharmacologic treatment option that may save non-responders to alprostadil. Penile prosthesis implantation can be considered in treatment refractory cases, with excellent functional and safety results in the properly informed patients.
Erection is a neurovascular event that involves spinal and supra spinal pathways. The final common pathway involves the release of nitric oxide (NO) from both endothelial cells and neurons, which acts as a vasodilator causing penile engorgement and erection. NO is degraded by the enzyme phosphodiesterase (PDE) type 5 in the penis. Erectile dysfunction (ED), defined as the persistent inability to achieve and/or maintain an erection sufficient for satisfactory sexual performance, results when the neurovascular pathway is interrupted by medical conditions or drugs. A 15-item self-administered questionnaire, the International Index of Erectile Function (IIEF), is one of the most useful tools to evaluate erectile function (EF) in clinical trials, although of much less use in routine clinical practice. The MMAS (Massachusetts Male Aging Study) was the first major epidemiological investigation to study the prevalence of ED. The study found that ED was three times more common in patients with diabetes mellitus. The aetiopathogenesis of ED in diabetes is multifactorial, with vascular and neural factors being equally implicated. Hyperglycaemia is believed to give rise to biochemical perturbations that lead to these microvascular changes. In the MMAS, ED in diabetes was strongly correlated with glycaemic control, duration of disease and diabetic complications. The incidence increased with increasing age, duration of diabetes and deteriorating metabolic control, and was higher in individuals with type 2 diabetes than those with type 1.ED in men with diabetes often affects their quality of life and, as patients are often reluctant to come forward with their symptoms, a carefully taken history is one of the most useful approaches in identifying affected individuals. The PDE inhibitors have revolutionised the management of ED and oral drug therapy is currently first-line therapy for the condition. These agents act by potentiating the action of intracavernosal NO, thereby leading to a more sustained erection. Sildenafil was the first PDE5 inhibitor to undergo evaluation and has been studied extensively. More recently two other agents, vardenafil and tadalafil, have been introduced. All the drugs have been shown to be effective across a wide range of aetiologies of ED, including diabetes. The drugs have been shown to improve EF domain scores, penetration and maintenance of erection, resulting in more successful intercourse. Their effects are greater at higher doses. Sildenafil and vardenafil are shorter-acting agents, while tadalafil has a longer half-life allowing the user more flexibility in sexual activity. Common adverse effects include headache, nasal congestion and dyspepsia, all actions related to inhibition of PDE5. The drugs are generally well tolerated and withdrawal from the clinical studies as a result of drug-related adverse effects were rare. The use of PDE5 inhibitors in the presence of oral nitrates is absolutely contraindicated. The clinical studies to date have not evaluated the use of one drug in the case of treatment failure with another agent. Sublingual apomorphine, which stimulates central neurogenic pathways, is a new agent and may be a suitable alternative in those patients in whom PDE5 inhibitors are ineffective or contraindicated. In clinical trials, all IIEF domains except sexual desire were found to have improved after apomorphine. The median times to erection in these studies were 18.9 and 18.8 minutes for the 2 and 3mg doses, respectively. Intraurethral and intracavernosal alprostadil may be a useful alternative when oral drug therapy is ineffective or contraindicated. The management of ED in the diabetic patient may often involve a multidisciplinary approach where psychosexual counselling and specialist urologist advice is required in addition to the skills and expertise of the diabetologist. Finally, the introduction of the new oral agents have completely revolutionised the management of ED and allowed more individuals to come forward for treatment.
Abstract | Full Text | Full Text PDF | PubMed | Scopus (272) | Google ScholarSee all References Most adverse effects are mild and are related primarily to vasodilation (headache, flushing, nasal congestion), gastrointestinal disturbances (dyspepsia), or retinal effects such as vision changes.10x10Kloner, RA and Zusman, RM. Cardiovascular effects of sildenafil citrate and recommendations for its use. Am J Cardiol. 1999; 84: 11N–17N
Cigarette smoking is an established risk factor in the development of atherosclerotic vascular changes and thus would be expected to play a role in the development of vasculogenic ED. The MMAS 9-year follow-up study found that the risk of developing moderate or complete ED in smokers was nearly doubled (odds ratio, 1.97) compared with that in matched nonsmokers.5x5Feldman, HA, Johannes, CB, Derby, CA et al. Erectile dysfunction and coronary risk factors: prospective results from the Massachusetts Male Aging Study. Prev Med. 2000; 30: 328–338
Although ED is a common complication of diabetes, its effect on quality of life is not well understood. Recent work for the Exploratory Comprehensive Evaluation of Erectile Dysfunction (ExCEED) database demonstrates that in the general population of patients presenting to their urologist, ED negatively affects both general and disease-specific health-related quality of life (HRQOL).35 While this study provides insight into the detrimental affect of ED on quality of life, the cohort is somewhat selected, in that all of the patients were seen in sexual dysfunction clinics and therefore may have been more likely to be bothered by their condition and to report worse quality of life.
There are a number of reasons a man may not achieve the desired result from an oral erectile dysfunction drug. In some cases, a man may experience drug side effects severe enough to outweigh any potential benefit of taking the drug. Possible side effects of these drugs include headache, facial flushing, nasal congestion, and transient abnormal vision. (In October 2007, the FDA added a warning about sudden hearing loss to the package labels of oral erectile dysfunction drugs. While it’s not absolutely clear that the drugs can cause sudden hearing loss, a number of cases have been reported in men within hours or days of taking one of the drugs.)
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