When counseling diabetic men who are considering a PDE-5 inhibitor for ED, it is important to set realistic expectations and explain that studies document that all three agents are less effective in diabetic patients than in the general population of men with ED.45–49 For additional information, readers are referred to the excellent review of the use of PDE-5 inhibitors in diabetic men by Vickers and Satyanarayana.50

Abstract | Full Text | Full Text PDF | PubMed | Scopus (95) | Google ScholarSee all References When used in combination with NO-donor medications such as nitroglycerin, the modest blood pressure effects of sildenafil are potentiated, resulting in a significant decrease in systolic (21-55 mm Hg) and diastolic (up to 26 mm Hg) blood pressure levels, as well as vasodilatory symptoms such as headache, light-headedness, and nausea.10x10Kloner, RA and Zusman, RM. Cardiovascular effects of sildenafil citrate and recommendations for its use. Am J Cardiol. 1999; 84: 11N–17N


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
Alprostadil is an ED drug that comes in two forms. One form (Caverject, Caverject Impulse, or Edex) is injected into the side of the penis to increase blood flow and cause an erection within 5 to 20 minutes. Its effects last 1 hour or less. The most common side effect is pain. Other side effects include bruising, redness, numbness, bleeding, and irritation.

There are few data specifically relating to the effectiveness of vacuum erection devices (VEDs) in diabetic men with ED. In a single-center study of 44 men with diabetes who choose VED for the treatment of ED in the early 1990s, 75% reported that they were able to achieve erections satisfactory for intercourse with the use of the device.51 However, the manner in which patients were accrued to this study probably biased its findings, resulting in substantially higher effectiveness rates than are normally observed in clinical practice. A recent review of the use of VEDs in the general treatment of ED notes that satisfaction rates with this therapy are much lower, varying between 20 and 50%.52


This may seem like a lot to manage at a glance, however, just focus on one step at a time. If it is more exercise you want to start with, park your car further away from the front door at work so you have to walk a little more every day. Or go out on a walk to make your phone calls.  If you need to eat better,  try low-fat meat and chicken for lunch. Just keep it simple and don’t try to do it all at once.
If you can't take one of these oral medications, your physician may have you try Caverject (alprostadil for injection), a hormone that you inject into your penis using a fine needle, or Muse (alprostadil urogenital), a tiny suppository that you insert into the tip of the penis. Both of these will bring on an erection within five to 15 minutes without sexual stimulation.

Other effective Diabetic Erectile Dysfunction Treatment therapies available include (a) an intraurethral suppository of the vasodilator drug alprostadil (prostaglandin E1), (b) intracavernosal self injection (penile self injection) of the non-specific PDE drug papaverine, the non-selective alpha-adrenergic antagonist phentolamine, and the vasodilator prostaglandin E1, used alone or in combination, or (c) penile prostheses (penile implants).
With atherosclerosis, the blood vessels are not able to dilate properly, which is called endothelial dysfunction (see the Figure). Cholesterol builds up in the blood vessel walls and forms plaques, which make the vessels narrow and slow down blood flow. When a plaque becomes very advanced, it can completely stop blood from passing through, which is what happens in a heart attack. Atherosclerosis affects not only the blood vessels supplying the heart (coronary arteries), but also blood vessels throughout the entire body. Atherosclerosis causes angina (chest pain that is often exertional), heart attacks, strokes, claudication (pain in the legs with walking), and ED. Atherosclerosis affects different people in different places, but it often affects the penis first, then the heart and brain, and the legs last. Because the first stage of atherosclerosis, endothelial dysfunction, usually affects the penis first, ED can be a warning sign that a heart attack or a stroke may follow, often in the next 3 to 5 years. This warning sign can be a good thing if it alerts you and your doctor that you have atherosclerosis, because then you can take steps to treat the atherosclerosis and prevent a heart attack or stroke.
Crossref | PubMed | Scopus (539) | Google ScholarSee all References After adjusting for age, vascular disease, psychiatric disease, hormonal factors, and marital status, a study of 4462 US Army veterans aged 31 to 49 years found an odds ratio of 1.8 for the risk of developing ED in men who smoked.26x26Mannino, DM, Klevens, RM, and Flanders, WD. Cigarette smoking: an independent risk factor for impotence?. Am J Epidemiol. 1994; 140: 1003–1008

Impotence, or erectile dysfunction (ED), is the inability for a man to sustain an erection long enough for normal, satisfying sexual intercourse.  To understand the underlying causes of impotence, it helps to know the basics about how an erection develops, along with potential problems that get in the way. Erections begin in the brain with a thought related to sexual desire. Then a chemical message travels from the brain to the penis. Blood flow to the penis increases as blood vessels leading to the reproductive system relax and allow for increased circulation.
Abstract | Full Text | Full Text PDF | PubMed | Scopus (95) | Google ScholarSee all References Since then, several other oral PDE-5 inhibitors have been developed, including vardenafil and tadalafil, which generated considerable interest in both the scientific and lay communities. There was also much concern about their safety, especially in men with cardiovascular disease. Compared with the 2 newer PDE-5 inhibitors vardenafil and tadalafil, sildenafil has been available for a much longer time; therefore, the vast majority of published cardiovascular safety studies have been performed on this medication. Recommended starting and maximum doses of oral PDE-5 inhibitors are shown in Table 1.
The obvious risks are the same that accompany any surgery: infection, pain, bleeding, and scarring. If for some reason the prosthesis or parts become damaged or dislocated, surgical removal may be necessary. With a general success rate of about 90 percent, any of the devices will restore erections, but they will not affect sexual desire, ejaculation, or orgasm.
Crossref | PubMed | Scopus (539) | Google ScholarSee all References Possible etiologies for ED secondary to hypertension include vascular damage due to hypertensive changes as well as hormonal abnormalities such as elevated prolactin levels.30x30Jaffe, A, Chen, Y, Kisch, ES, Fischel, B, Alon, M, and Stern, N. Erectile dysfunction in hypertensive subjects: assessment of potential determinants. Hypertension. 1996; 28: 859–862
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Abstract | Full Text | Full Text PDF | PubMed | Scopus (46) | Google ScholarSee all References The Princeton Consensus Panel provided guidelines (Table 4) for physicians regarding patients who are being evaluated for their level of risk in resuming sexual activity.51x51DeBusk, R, Drory, Y, Goldstein, I et al. Management of sexual dysfunction in patients with cardiovascular disease: recommendations of the Princeton Consensus Panel. Am J Cardiol. 2000; 86: 62F–68F
Abnormalities in the vascular, neural, endocrine, muscular, or psychiatric systems can result in ED.2,3 EDDM is due to multisystemic disease. Atrophy or apoptosis of cavernosal smooth muscle can occur due to loss of Bcl-2 expression in cavernosal smooth muscle and lead to ED. Abnormal amounts of advanced glycation end products is a common occurrence. These chemicals may have an effect on potassium channels that facilitate intracellular calcium release and subsequent cavernosal smooth muscle relaxation. Connective tissue synthesis is increased due to transforming growth factor-beta. The decrease in smooth muscle and the increase in collagen decreases the compliance of the erectile tissue. Neuropathic damage to both the somatic and autonomic nerves has been clearly defined in DM. Partial occlusion of the pelvic or intracavernosal arteries, hypogonadotropic hypogonadism, and depression associated with a chronic illness (DM) can all play a primary or secondary role in the development of EDDM. On a molecular level, studies have demonstrated decreased levels of endothelial and neuronal nitric acid synthase (NS) and decreased cavernosal artery and sinusoidal response to nitric oxide. Abnormalities in nitric oxide rapidly render the functional syncytium of the corpora cavernosa unable to synchronously relax. As the patient with diabetes ages, the concentration of constrictors, including endothelin, prostanoids, and possibly angiotensin, increases as the production of the relaxants, including nitric oxide, vasointestinal peptide, and prostacyclin, decreases.

Hypertension can affect endothelial function in many ways. It can reduce endothelium-dependent vasodilatation by increasing the vasoconstrictor tone as a result of increased peripheral sympathetic activity.41–43 Another mechanism is hypertension-induced increase in cyclooxygenase activity that leads to an increase in reactive oxygen species; these in turn damage endothelial cells and disrupt their function.44–46 In some cases, endothelial NO synthase (eNOS) gene variations may relate to hypertension-associated endothelial dysfunction.6
Chlamydia and erectile dysfunction: What's the link? Some people who have chlamydia also experience erectile dysfunction (ED), which involves problems getting or maintaining an erection. Chlamydia can infect the prostate gland, leading to prostatitis, pain, and ED. In this article, learn more about the link between this common infection and ED, and treatments for both. Read now
A sexually competent male must have a series of events occur and multiple mechanisms intact for normal erectile function. He must 1) have desire for his sexual partner (libido), 2) be able to divert blood from the iliac artery into the corpora cavernosae to achieve penile tumescence and rigidity (erection) adequate for penetration, 3) discharge sperm and prostatic/seminal fluid through his urethra (ejaculation), and 4) experience a sense of pleasure (orgasm). A man is considered to have ED if he cannot achieve or sustain an erection of sufficient rigidity for sexual intercourse. Most men, at one time or another during their life, experience periodic or isolated sexual failures. However, the term “impotent” is reserved for those men who experience erectile failure during attempted intercourse more than 75% of the time.
Abstract | Full Text | Full Text PDF | PubMed | Scopus (95) | Google ScholarSee all References Sildenafil has a 4000-fold increased selectivity for PDE-5 over PDE-3, has negligible effects on heart rate, and has only a modest effect on blood pressure level in healthy persons, with an average systolic pressure decrease of 10 mm Hg with a single dose of 100 mg.3x3Zusman, RM, Morales, A, Glasser, DB, and Osterloh, IH. Overall cardiovascular profile of sildenafil citrate. Am J Cardiol. 1999; 83: 35C–44C
The mechanisms of action by which antihypertensive medications cause ED are currently unknown. Some investigators have theorized that antihypertensive medications affect erectile function by decreasing blood pressure, which reduces the perfusion pressure needed to maintain sufficient blood flow for erections through atherosclerotic penile arteries.37x37Benet, AE and Melman, A. The epidemiology of erectile dysfunction. Urol Clin North Am. 1995; 22: 699–709
Diabetes mellitus (DM) is strongly associated with an increased risk of erectile dysfunction (ED), the persistent inability to achieve or maintain an erection sufficient for satisfactory sexual performance, but this condition can be successfully treated in the majority of diabetes patients. ED is present in 32% of type 1 and 46% of type 2 DM patients. Several population- based studies of ED prevalence calculated the odds ratios for the association between ED and various chronic diseases. An odds ratio must be sufficiently greater than 1.0 to identify an increased risk. Diabetes has an odds ratio, ED risk multiplier of 4.1, compared with 1.7 for hyperlipidemia and 1.6 for hypertension. Erectile dysfunction in diabetes mellitus (EDDM) patients has been considered to have an organic etiology. Healthcare providers have long realized that ED can be the first symptom of DM.
Dr. Eid also urges these patients to treat their diabetes in order to avoid developing ED for life. “They need to manage their diabetes and make sure they control it so the ED will not progress and will stabilize, as a result,” he said. “If the diabetes is controlled after the patient is first diagnosed, then the erections will come back. But if the patient has diabetes for many years, and suddenly decides it’s time to control it, they cannot prevent the damage that’s already been done.”
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).

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
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
When the diagnosis of vasculogenic sexual dysfunction has been carefully reached, physicians will have to come up with an effective treatment. Appropriate lifestyle measures and adoption of a healthier attitude could represent an initial, efficient and cost-effective treatment option[14]. This is due to the fact that traditional CV risk factors such as hypertension, physical inactivity-obesity, smoking and dyslipidemia have been consistently linked with endothelial and consequently sexual dysfunction[15].In this context, it has been demonstrated that moderate physical activity can reduce up to 30% the risk of erectile dysfunction contrary to sedentary life, which exerts a deleterious effect[16]. Interestingly, the beneficial effect of physical exercise on sexual dysfunction seems to be independent of its favorable impact on the general cardiovascular profile[17]. In terms of caloric reduction, Mediterranean diet exerts a positive effect on sexual function parameters of patients with metabolic syndrome[18]. Moreover, combined physical exercise and caloric restriction can result in weight reduction which in succession can reduce up to 30% the risk of obesity-associated erectile dysfunctio[19].
Erections are extremely complicated and surprisingly fragile. Erections involve chemical signals, nerve impulses, complicated blood pressure changes, and overall fitness in systems ranging from your heart and hormones to your mood. When medication changes how one of these factors works—like blood pressure drops or depression medication—ED is a common side effect. The problem with these completely predictable medically induced side effects is how people react.
Owing to its delicate nature, discussion about the sexual life of the patient is effective not on a circumstantial visit to the doctor, but on the basis of confidence between the patient and the physician, as is usually the case with the cardiologist. Thus, the cardiologist is given a unique opportunity to identify ED and thus ‘recharacterize’ the risk of the patient. In addition, since normal sexual activity is important to most men with CVD, irrespective of age, the cardiologist can clarify issues that relate to such activity after a cardiac event or to a specific cardiac condition (e.g. heart failure). Often, such issues are hampered by misconceptions from the side of the patient. Therefore, while less than half of the patients receive information about resuming sexual activity after a cardiac event, proper counselling increases their likelihood to resume their previous level of sexual activity by 50%.50 Furthermore, the cardiologist can increase adherence to the medication by clarifying that it is uncommonly the true cause of ED. Finally, proper counselling is required to ensure safety of concomitant PDE5 inhibitors medication, the use of which has the additional advantage to increase compliance to CVD mediation, especially in hypertension. It should be noted that while patients are often reluctant to bring up the issue of sexual health, they are relieved and respond positively when their cardiologist has done so. It should also be emphasized that, frequently, sexual counselling is more effective when done together with their partner.
Erectile dysfunction carries an independent risk for cardiovascular events. A considerable number of studies have examined the ability of ED to predict the risk of future fatal and non-fatal cardiovascular events (myocardial infarction, stroke, revascularization) and total mortality in the general population and in high CV risk patients, in diabetics and in heart failure patients.5,19–22 In a meta-analysis of 14 prospective cohort studies involving 92 757 men followed for a mean period of 6.1 years (Figure 4), ED increased significantly and independently of traditional risk factors the risk of CV events, CV mortality, myocardial infarction, cerebrovascular events, and all-cause mortality by 44, 19, 62, 39, and 25% respectively.5 This predictive ability also extends in men with known CVD: ED increased the risk of all-cause mortality by 90%.5 Of importance, the predictive ability of ED is higher in younger ED patients5 despite the fact that probability of ED increases with age, most likely identifying a group of patients with early and aggressive vascular disease.23 Clinical implementation of ED as a biomarker relies on whether its addition on classical risk scores such as the Systematic COronary Risk Evaluation (SCORE) or the Framingham correctly reclassifies a meaningful percentage of patients into a higher or lower risk category. To this end, data are limited. Yet, in a population-based study of men 40–70 years of age, the addition of the ED status to the Framingham risk score resulted in a reclassification of 6.4% of low-risk patients to intermediate risk.19
Since 1998, when sildenafil (brand name Viagra) first came on the market, oral therapy has been successfully used to treat erectile dysfunction in many men with diabetes. (Sildenafil was followed in 2003 by the drugs tadalafil [Cialis], vardenafil [Levitra] and avanafil [Stendra], which work in much the same way.) Some 50% of men with Type 1 diabetes who try the drugs report improved erections, and some 60% men with Type 2 diabetes do, too. However, that leaves a large percentage of men with diabetes and erectile dysfunction who do not respond to therapy with one of these pills. This article takes a look at what can be done to treat those men who do not respond to oral therapy.
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