The authors observe that multiple factors may be involved. In addition to decreased exercise capacity, patients with chronic heart failure have blood vessel and circulation abnormalities that can reduce blood flow into the penis and interfere with the ability to maintain an erection. And erectile dysfunction can be caused or worsened by many of the medications that are commonly prescribed to treat chronic heart failure.
This form of therapy has a response rate of well over 70%. The sympathetic nervous system normally maintains the penis in a flaccid or non-erect state. All of the vasoactive drugs, when injected into the corpora cavernosae, inhibit or override sympathetic inhibition to encourage relaxation of the smooth muscle trabeculae. The rush of blood engorges the penile corpora cavernosae sinusoidal spaces and creates an erection.
Melissa Conrad Stöppler, MD, is a U.S. board-certified Anatomic Pathologist with subspecialty training in the fields of Experimental and Molecular Pathology. Dr. Stöppler's educational background includes a BA with Highest Distinction from the University of Virginia and an MD from the University of North Carolina. She completed residency training in Anatomic Pathology at Georgetown University followed by subspecialty fellowship training in molecular diagnostics and experimental pathology.
The development of PDE5-inhibitors is a clear example of how Western medicine approached the problem of ED differently from Eastern medicine. The erectogenic effect of sildenafil (Viagra®) was discovered by accident when patients undergoing heart clinical trials reported better erections as a side effect after taking sildenafil. This observation led to further elucidation of the NO/cGMP signalling pathway and development of PDE5-inhibitors as a first-line therapy in ED (5).
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.
Crossref | PubMed | Google ScholarSee all References The risk of myocardial infarction with sexual activity has been estimated to be less than 3% in high-risk patients with prior cardiovascular disease if they can exercise to more than 7 METs without symptoms.89x89Moss, AJ and Benhorin, J. Prognosis and management after a first myocardial infarction. N Engl J Med. 1990; 322: 743–753
Following the breakthrough in ED treatment using PDE5-inhibitors, Western medicine has now moved on to a new frontier of regenerative medicine, with stem cell and gene therapy leading the way (25). There is a practical need for novel therapy as a significant portion of diabetic or post-prostatectomy ED patients do not respond to oral pharmacotherapy. To date, stem cells derived from different sites including adipose tissue-derived stem cells, bone marrow mesenchymal stem cells and muscle-derived stem cells have been investigated using animal models for ED, to study their effects on neural, vascular, endothelial or smooth muscle regeneration (25,26).
There’s some evidence that bark from the yohimbe tree can help with ED. The bark contains a substance called yohimbine. It’s been traditionally used in Africa as an aphrodisiac. Today, a pharmaceutical form of yohimbine (called yohimbine hydrochloride) is being studied to treat erectile dysfunction in men. However, it can cause severe side effects, including high blood pressure, tremors, and anxiety.
The cardiovascular effects of sildenafil during exercise in patients with known or probable cardiovascular disease were studied in a randomized placebo-controlled trial of 105 men with a mean age of 66 years.63x63Arruda-Olson, AM, Mahoney, DW, Nehra, A, Leckel, M, and Pellikka, PA. Cardiovascular effects of sildenafil during exercise in men with known or probable coronary artery disease: a randomized crossover trial. JAMA. 2002; 287: 719–725
Crossref | PubMed | Scopus (71) | Google ScholarSee all References However, a double-blind, placebo-controlled study of 22 middle-aged men with hypercholesterolemia treated for 6 weeks with pravastatin or lovastatin showed improved erectile function with both medications.54x54Kostis, JB, Rosen, RC, and Wilson, AC. Central nervous system effects of HMG CoA reductase inhibitors: lovastatin and pravastatin on sleep and cognitive performance in patients with hypercholesterolemia. J Clin Pharmacol. 1994; 34: 989–996
Poor sleep patterns can be a contributing factor for erectile dysfunction, Mucher says. One review published in the journal Brain Research emphasized the intricate relationship between the level of sex hormones like testosterone, sexual function, and sleep, noting that testosterone levels increase with improved sleep, and lower levels are associated with sexual dysfunction. Hormone secretion is controlled by the body’s internal clock, and sleep patterns likely help the body determine when to release certain hormones.
Abstract | Full Text | Full Text PDF | PubMed | Scopus (58) | Google ScholarSee all References Avoiding sexual activity between 6 AM and noon may be recommended to higher-risk patients because this is the time of peak incidence of most arrhythmias, myocardial ischemia, sudden cardiac death, and cerebrovascular accidents.1x1Muller, JE. Sexual activity as a trigger for cardiovascular events: what is the risk?. Am J Cardiol. 1999; 84: 2N–5N
Olsson et al. conducted a randomised, double-blind, placebo-controlled, parallel group, and flexible dose study in 224 men with ED and one CVD, including IHD (20 %) and hypertension (80 %). This study reported that the sildenafil-treated group showed 71 % improvement in ED compared with the placebo-controlled group (24 %).64 Furthermore, no treatment-related cardiovascular adverse events were reported.65 Conti et al. showed in an early study that sildenafil is an effective treatment for ED in patients with IHD; the majority of patients reported improvement in penile erection with it.66 Another double-blind, placebo-controlled study of patients with ED and stable CAD showed statistically significant improvement with sildenafil versus placebo in both the frequency of penetration and frequency of maintained erections after penetration.67
Until recently, erectile dysfunction (ED) was one of the most neglected complications of diabetes. In the past, physicians and patients were led to believe that declining sexual function was an inevitable consequence of advancing age or was brought on by emotional problems. This misconception, combined with men’s natural reluctance to discuss their sexual problems and physicians’ inexperience and unease with sexual issues, resulted in failure to directly address this problem with the majority of patients experiencing it.
Some commonly prescribed cardiovascular drugs (beta-blockers, diuretics, angiotensin-converting enzyme inhibitors, etc.) contribute to ED.18 Previous studies have shown a strong association between ED and diuretics in patients treated with hydrochlorothiazide or chlorthalidone.19,20 It has also been shown that patients treated with first-generation non-selective beta-blockers, such as propranolol, had more frequent ED than those treated with a placebo.21
While all three forms of male sexual dysfunction can be found among diabetic men, this review will focus on the most common form, ED, because the literature is most mature in this area. Defined as the inability to achieve or maintain an erection sufficient for satisfactory sexual performance, ED is highly prevalent in diabetic men1 and is almost always organic in its etiology. Given that many patients feel that their ED is “in their heads” and that “their provider will dismiss any sexual problems they might bring up,”2 it may be a relief for patients to learn that their ED is physical, related to their diabetes, and treatable. To this end, the goal of this article is to review the epidemiology, pathophysiology, quality of life effect, and treatment of ED in men with type 2 diabetes.
Most of the time, ED is the first symptom of poor cardiovascular health. Hypertension oftentimes doesn’t manifest outward symptoms of heart disease. Some men go undiagnosed with high blood pressure for a long time. It can be troublesome for many men who feel uncomfortable discussing ED with their health providers. Many fail to seek medical advice and suffer from progressive worsening of their cardiovascular problems before deciding to undergo treatment.
Prescription drugs called “oral phosphodiesterase-5 (PDE5) inhibitors” are considered the “first-line non-invasive treatment” options for patients with ED. These include the drugs that go by brand names: Sildenafil, Vardenafil or Tadalafil. They work by helping the smooth muscle cells lining the blood vessels that supply the penis with blood to work properly. This allows a man to maintain an erection more easily.
Erectile dysfunction and heart disease are very serious medical conditions that requires prompt treatment. In addition to being a symptom of heart disease; ED is linked to many other physical and psychological problems. Men with ED can be withdrawn from their partner and even avoid romantic relationships. It may be difficult for men with erectile dysfunction to reproduce and can lead to low self-esteem, depression and poor work performance. Frequent medical check ups for patients with erectile dysfunction and high blood pressure is recommended.
Age is a critical risk factor for the development of ED and endothelial dysfunction.4,5 ED is the most common condition occurring in middle-aged and older men.5 Kinsey et al. reported that 25 % of 65-year-old men and 75 % of ≥80-year-old men have ED.39 Moreover, ageing also decreases endothelial function, which is responsible for IHD.5 The incidence and severity of ED increases with age (a man aged 70 years is three-times more likely to have ED than a man aged 40 years).40
Table 3 is a suggested algorithm for the assessment of patients and their further categorization and handling. There are parts of investigation that are common for patients both with and without CVD, while additional elements of investigation are helpful in categorizing the patient without CVD to the appropriate risk category. Determination of exercise ability and stress testing is crucial to the assessment (see also below ‘Exercise ability: the risk of sexual activity’). Patients without established CVD or diabetes should be evaluated for their risk of future events according to risk scores (SCORE or Framingham). Patients with established CVD or diabetes are by default considered at increased risk. Patients with adequate exercise ability or a negative stress test can initiate or resume sexual activity and begin treatment for ED. In patients with a positive stress test or in high-risk patients, sexual activity should be deferred until the cardiac condition has been treated and stabilized. In all cases, patient follow-up and reassessment is recommended.
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.
ED is a common complication of diabetes and people with diabetes are also prone to developing cardiovascular complications.48 The risk of ED is relatively high in patients with known CVD. This was supported by a study of men with known CVD, in which ED was substantially predictive of all-cause mortality and the composite of CVD death, admission for heart failure, MI and stroke.17 Macroangiopathy, microangiopathy and endothelial dysfunction are among the mechanisms by which diabetes causes ED.
In some cases, however, these drugs may be unsuitable for patients with heart disease. If you are considering one of these drugs and you have heart disease, as many diabetics do, be sure to tell your doctor. In rare cases, the pills may create “priapism,” a prolonged and painful erection lasting six hours or more (although reversible with prompt medical attention).