Abstract | Full Text | Full Text PDF | PubMed | Scopus (95) | Google ScholarSee all References Phosphodiesterase type 5 is found predominantly in the smooth muscle of the corpora cavernosa but can be found in smaller quantities in platelets and other vascular smooth muscle.56x56Wallis, RM, Corbin, JD, Francis, SH, and Ellis, P. Tissue distribution of phosphodiesterase families and the effects of sildenafil on tissue cyclic nucleotides, platelet function, and the contractile responses of trabeculae carneae and aortic rings in vitro. Am J Cardiol. 1999; 83: 3C–12C
Abstract | Full Text | Full Text PDF | PubMed | Scopus (164) | Google ScholarSee all References Several double-blind, placebo-controlled studies have shown vardenafil to be more effective than placebo in the treatment of ED secondary to a wide range of other etiologies as well.71x71Hellstrom, WJ, Gittelman, M, Karlin, G..., and Vardenafil Study Group. Sustained efficacy and tolerability of vardenafil, a highly potent selective phosphodiesterase type 5 inhibitor, in men with erectile dysfunction: results of a randomized, double-blind, 26-week placebo-controlled pivotal trial. Urology. 2003; 61: 8–14
A variety of personal habits and lifestyle choices have been linked to ED. In some ways, this is a good thing, since habits can be broken and choices reconsidered. What's more, many of the lifestyle factors that contribute to sexual problems are ones that affect overall health and well-being, both physical and mental. Addressing these factors, therefore, can have benefits beyond improving erectile dysfunction.
The body’s source for nitric oxide production is the amino acid L-arginine, which is naturally found in many foods. The average American ingests about 3,000–5,000 mg of L-arginine per day, as it is an amino acid naturally contained in many foods. Meats of all varieties, nuts, and dairy products are rich in L-arginine, so the body is accustomed to intake levels of several thousand milligrams every day.
Oral medicines: The best known ED medications are the Big Three: Viagra (sildenafil citrate, made by Pfizer, Inc.), Levitra (vardenafil HCl, made by Bayer and GlaxoSmithKline), and Cialis (tadalafil, made by Eli Lilly). The three are chemically very similar, and all have proven very effective. Because they are effective, convenient, and relatively inexpensive (about nine dollars per pill), these medicines have become the treatment of choice for most men experiencing ED.
Abstract | Full Text | Full Text PDF | PubMed | Scopus (95) | Google ScholarSee all References Open-label trials showed a myocardial infarction rate of only 1.0 event per 1000 person-years of treatment with sildenafil.10x10Kloner, RA and Zusman, RM. Cardiovascular effects of sildenafil citrate and recommendations for its use. Am J Cardiol. 1999; 84: 11N–17N
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.
The bad news: Men with diabetes are three times more likely to report having problems with sex than non-diabetic men. The most common sexual problem is Erectile Dysfunction, or ED, sometimes called impotence. Even worse, because ED is such a private issue, many men feel embarrassed to discuss the problem with their doctor, or even their partner, so the problem is never addressed.
Diabetic damage doesn’t stop with these small vessels, he said. “You really have two parallel situations: You need blood flow that feeds the muscle of the penis, and you need an artery dedicated to bringing blood rapidly when a man becomes aroused and wants to be sexually active,” he said. “That artery is also affected by diabetes. They’ll say ‘I can get a partial erection, but I can’t maintain it.’ ”
Like all diabetic complications, ED can occur even when you have followed your doctor’s advice and carefully managed your diabetes. Also like all diabetes complications, ED is less likely to occur with good blood sugar control. Poorly controlled diabetes and high cholesterol increase the chances of vascular complications, which may lead to ED or other circulatory problems. In addition, regular smoking and alcohol use can contribute to ED.
Abstract | Full Text PDF | PubMed | Scopus (3562) | Google ScholarSee all References The 9-year follow-up MMAS study also found that self-reported increased cholesterol and unsaturated fat intake correlated positively with the development of ED.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
Crossref | PubMed | Scopus (1) | Google ScholarSee all References Angiotensin-converting enzyme inhibitors also have low rates of secondary ED associated with their use in both animal and human studies.45x45Srilatha, B, Adaikan, PG, Arulkumaran, S, and Ng, SC. Sexual dysfunction related to antihypertensive agents: results from the animal model. Int J Impot Res. 1999; 11: 107–113
The cardiovascular adverse effects of sildenafil use have been studied extensively. Phosphodiesterase type 5, although located primarily in the genitalia, also can be found throughout the systemic vasculature, although other PDEs predominate there10x10Kloner, RA and Zusman, RM. Cardiovascular effects of sildenafil citrate and recommendations for its use. Am J Cardiol. 1999; 84: 11N–17N
Erectile dysfunction is common in the patient with cardiovascular disease. It is an important component of the quality of life and it also confers an independent risk for future cardiovascular events. The usual 3-year time period between the onset of erectile dysfunction symptoms and a cardiovascular event offers an opportunity for risk mitigation. Thus, sexual function should be incorporated into cardiovascular disease risk assessment for all men. A comprehensive approach to cardiovascular risk reduction (comprising of both lifestyle changes and pharmacological treatment) improves overall vascular health, including sexual function. Proper sexual counselling improves the quality of life and increases adherence to medication. This review explores the critical connection between erectile dysfunction and cardiovascular disease and evaluates how this relationship may influence clinical practice. Algorithms for the management of patient with erectile dysfunction according to the risk for sexual activity and future cardiovascular events are proposed.
I have cared for hundreds of men with erectile dysfunction that have reversed their condition with a Nutritarian diet and the judicious use of dietary supplements. I have cared for hundreds of heart patients with angina and advanced heart disease, who have turned their backs on invasive cardiac procedures, recovered from angina and opened up the closed blood vessels in their diseased hearts. Out of thousands of men with advanced heart and erectile problems who have followed my nutritional advice, I have never had a patient suffer a heart attack or cardiac related death.
Both erectile dysfunction and heart disease have been linked with impaired activity of nitric oxide, the body’s most powerful vasodilator. An endogenous (produced by the body) compound called asymmetric dimethylarginine is an L-arginine analog, which interferes with the production of nitric oxide and may increase the risk for erectile dysfunction and heart disease.
The term “heart disease” is often used interchangeably with the term “cardiovascular disease.” Cardiovascular disease generally refers to conditions that involve narrowed or blocked blood vessels that can lead to a heart attack, chest pain (angina) or stroke. Other heart conditions, such as those that affect your heart’s muscle, valves or rhythm, also are considered forms of heart disease.
Abstract | Full Text | Full Text PDF | PubMed | Scopus (328) | Google ScholarSee all References Their mean resting systolic and diastolic blood pressure levels decreased by 6% and 11%, respectively, compared with baseline. These patients also experienced a mild decrease in mean resting right atrial pressure, pulmonary artery pressure, pulmonary artery occlusion pressure, and cardiac output. However, the hemodynamic response to exercise was preserved. Phase 2 and 3 trials showed no difference in the rate of adverse events between sildenafil and placebo in patients being treated with antihypertensive medications. The effects of sildenafil on blood pressure level were similar in patients who were taking antihypertensive medications compared with those who were not. In healthy volunteers, no consistent or significant doserelated electrocardiographic (ECG) changes were noted at 1 and 2 hours after doses of sildenafil ranging from 1.25 to 200 mg.3x3Zusman, RM, Morales, A, Glasser, DB, and Osterloh, IH. Overall cardiovascular profile of sildenafil citrate. Am J Cardiol. 1999; 83: 35C–44C
Abstract | Full Text | Full Text PDF | PubMed | Scopus (66) | Google ScholarSee all References Although some case studies have reported a relationship between calcium channel blockers and ED, most studies suggest that this effect is minimal and that any relationship is likely secondary to a decrease in blood pressure with consequent reflex sympathetic activation.42x42Weiss, RJ. Effects of antihypertensive agents on sexual function. Am Fam Physician. 1991; 44: 2075–2082
Abstract | Full Text | Full Text PDF | PubMed | Scopus (124) | Google ScholarSee all References This was a doubleblind, single-dose crossover study involving 41 men with stable coronary artery disease characterized by reproducible stable exertional angina. After taking either 10 mg of vardenafil or placebo, these men underwent treadmill exercise tolerance testing to 5 to 10 METs. Compared with placebo, vardenafil use did not result in a change in exercise treadmill time or time to first awareness of angina but significantly increased the time to ischemic threshold. At peak exercise levels, vardenafil did not cause a change in either heart rate or blood pressure level. This study concluded that 10 mg of vardenafil did not impair the ability of men with stable coronary artery disease to exercise at levels consistent with the exertion associated with sexual intercourse.
A man needs to try the medicine at least four times before he concludes that it doesn’t work for him. It is unlikely that a man with diabetes who has other medical problems such as high blood pressure, is taking multiple medicines, and has not had sexual intercourse for several years will be able to have an erection adequate for intercourse the first time he takes a pill. Most men need to try the medicine several times before they have the desired results.