PubMed | Google ScholarSee all References As with sildenafil, use of nitrate or NO-donor medications is contraindicated while taking tadalafil because of the potential for marked hypotensive interactions.74x74Gresser, U and Gleiter, CH. Erectile dysfunction: comparison of efficacy and side effects of the PDE-5 inhibitors sildenafil, vardenafil and tadalafil—review of the literature. Eur J Med Res. 2002; 7: 435–446
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.
In another study from ExCEED, Penson et al.38 compared erectile function and disease-specific quality of life of men with ED and diabetes to those of men with ED without diabetes. They found that those with diabetes reported significantly worse erectile function (P = 0.004) and intercourse satisfaction (P = 0.04) than those without diabetes. Importantly, the diabetic patients also reported that ED had a significantly worse psychological impact on their overall emotional life than did their nondiabetic counterparts (P = 0.01). Interestingly, no differences were noted between the two groups in the psychological impact of ED on the sexual experience.
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
Artery size also explains the onset of ED before occurrence of CAD. Coronary arteries are 3–4 mm in diameter, while the penile artery is 1–2 mm in diameter.17 Endothelial dysfunction and plaque burden in the small arteries may cause symptoms of ED before they affect blood flow in large arteries. Also, an asymptomatic lipid-rich plaque in the coronary arteries carries the risk of rupture that leads to acute coronary syndrome or death, so ED may be predictive of these serious events without warning cardiac symptoms.17
Recent revised labeling for sildenafil states that there is a lack of controlled data for its use in patients with resting hypotension (<90/50 mm Hg) or hypertension (>170/110 mm Hg); a history of myocardial infarction, cerebrovascular accident, or life-threatening arrhythmia within the past 6 months; coronary artery disease or cardiac failure causing unstable angina; or retinitis pigmentosa and possible genetic disorders of retinal PDEs.10x10Kloner, RA and Zusman, RM. Cardiovascular effects of sildenafil citrate and recommendations for its use. Am J Cardiol. 1999; 84: 11N–17N
Other factors that “stress” the body can also increase your risk for ED. These include: substance abuse, using marijuana, smoking cigarettes, depression, anxiety and low self esteem. Cigarette smoking — or using nicotine — leads to constricted blood vessels, which has negative effects for sexual health. Other mental/emotional obstacles can cause less desire for sex and decrease testosterone. Several ways to help manage stress include:
When your blood pressure is high for an extended time, it can damage the lining of your arteries and interfere with your blood flow. This appears to affect your ability to get and maintain an erection. A 2012 study published in the journal Current Opinion in Nephrology and Hypertension found that approximately 30 percent of men with hypertension complain of ED.
A similar situation develops in the fragile penile circulation. Any disturbance in nitric oxide production lowers the capacity to dilate penile arteries, impairing penile engorgement for erection. Release of nitric oxide is readily sabotaged by many conditions, including elevated levels of cholesterol, high blood pressure, increased triglycerides, smoking, metabolic syndrome and diabetes, and excessive consumption of dietary saturated fat.9 If an artery’s inner wall can’t produce nitric oxide, an abnormal constriction of the arteries to the penis follows, effectively choking off blood flow.

Abstract | PubMed | Scopus (136) | Google ScholarSee all References Attainment and maintenance of a firm erection requires good arterial inflow of blood and efficient trapping of venous outflow. Therefore, disease processes that affect the function of the arterial and venous systems would be expected to negatively affect erectile function. Unfortunately, cardiovascular disease is also prevalent in the male population and is especially evident with increasing age. The interplay of cardiovascular health and sexual function includes the risk of cardiac events precipitated by the physical exertion of sexual activity and by some medications, such as sildenafil, on the cardiovascular system. An estimated 500,000 patients survive a myocardial infarction each year in the United States, and an estimated 11 million patients have existing cardiovascular disease, making the issue of sexual function and cardiac disease relevant to many patients.8x8Muller, JE, Mittleman, A, Maclure, M, Sherwood, JB, Tofler, GH, and Determinants of Myocardial Infarction Onset Study Investigators. Triggering myocardial infarction by sexual activity: low absolute risk and prevention by regular physical exertion. JAMA. 1996; 275: 1405–1409
A number of over-the-counter herbal supplements claim to treat ED. However, according to the Mayo Clinic, you should avoid products labeled as “herbal Viagra.” These supplements can increase blood flow and cause dangerous drops in blood pressure. Risk may be particularly high for men who are using nitrates. Herbal Viagra can also interact with other prescription drugs. Herbal Viagra products may contain potentially toxic compounds that aren’t listed on the label.
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.
Most studies into the effect of beta-blockers on ED point to negative effects of first- and second-generation beta-blockers, while beta-blockers with vasodilating effects can improve erectile function. Alpha-blockers, calcium channel blockers, and angiotensin-converting enzyme inhibitors seem to have a neutral effect on erectile function. Multiple previous studies have demonstrated a beneficial effect of angiotensin receptor blockers on erectile function and they should probably be the favoured antihypertensive agents in patients with ED.29
After adjusting for cardiovascular risk factors including diabetes, heart failure and stroke, those taking PDE5 inhibitors were found to be markedly less likely to die than those taking alprostadil or no erectile dysfunction drugs. Filling more prescriptions for PDE5 inhibitors appeared to be associated with a greater benefit, although Andersson said that trend should be interpreted with caution because the study was not large enough for a definitive dose-response analysis.
Treatments might be slightly different for different people, depending on their risk factors, but in general all treatment plans have similar elements: diet, exercise, and medications, if necessary (see the Table). Diet and exercise are the cornerstones of the treatment of atherosclerosis. Every diet should include low salt (especially for high blood pressure), low fat and cholesterol (especially for high cholesterol), and limited total calories (especially for patients who are overweight). People with diabetes mellitus should limit their intake of sugars and carbohydrates. Exercise helps to limit atherosclerosis. The more exercise, the better, but every little bit helps. The general recommendation is 30 minutes a day 5 days a week. Check with your doctor to be sure that an exercise program is safe for you. Cigarettes cause a variety of health problems, including atherosclerosis, so cigarette smoking should be stopped. If diet and exercise are not enough to control your atherosclerotic risk factors, then your doctor will prescribe medications. Heart attacks are prevented by controlling atherosclerotic risk factors, which means diet, exercise, and medications if necessary.
Abstract | Full Text | Full Text PDF | PubMed | Scopus (95) | Google ScholarSee all References Vision changes are described most frequently as an increased perception of bright lights, a blue-green tinge to observed colors, or blurred vision. Sildenafil has no direct effect on platelet function but potentiates the inhibitory effect of sodium nitroprusside on adenosine diphosphate–induced platelet aggregation ex vivo.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

ED is generally associated with significant changes in established cardiovascular risk factors. Atherosclerosis is the main cause of ED development in both the general population and patients with diabetes. However, the prevalence of ED is greater in patients with diabetes than in the general population.8 ED has been shown to occur at rates as high as 50 % in patients with CAD.9 A meta-analysis of 12 prospective cohort studies has provided evidence that ED is a predictor of IHD associated with an increased risk of CVD, stroke and all-cause mortality.10


There are no studies specifically assessing the effectiveness of intraurethral suppositories of prostaglandin E1 (PGE-1) in diabetic men. A single randomized clinical trial of the effectiveness of this agent in the general population of men with ED documented that 60% of those who tried this agent were able to achieve successful sexual intercourse.53 Unfortunately, in clinical practice, this agent appears to be considerably less effective.54

Abstract | Full Text | Full Text PDF | PubMed | Scopus (30) | Google ScholarSee all References Erections result from relaxation of the corpora cavernosa, which is mediated either by increasing intracellular cyclic guanosine monophosphate (cGMP) or cyclic adenosine monophosphate or by inhibition of their degradation. Increased parasympathetic tone results in a decrease in norepinephrine release and an increase in the release of acetylcholine; subsequently, NO synthase activity increases, which releases NO from both endothelial cells and nonadrenergic, noncholinergic neurons.10x10Kloner, RA and Zusman, RM. Cardiovascular effects of sildenafil citrate and recommendations for its use. Am J Cardiol. 1999; 84: 11N–17N
Does drinking water improve erectile dysfunction? Erectile dysfunction or ED is a common concern for men. Everyday factors, such as hydration levels, may affect a person's ability to get or maintain an erection. Drinking water may, therefore, help some men with ED. In this article, learn about the link between hydration and ED, and other factors that can cause ED. Read now
Crossref | PubMed | Scopus (539) | Google ScholarSee all References Aside from the economic costs, ED can have severe psychological effects, resulting in poor self-image, decreased self-esteem, depression, and mental stress, and negative effects on personal relationships.2x2NIH Consensus Development Panel on Impotence. NIH Consensus Conference: impotence. JAMA. 1993; 270: 83–90

Unlike intraurethral suppositories, intracavernosal injection (IC) injection of vasoactive agents such as PGE-1 has consistently been shown to be effective in the treatment of ED in men with diabetes. In a study of 336 men with diabetes-related ED, 83% of patients reported erections satisfactory for intercourse after IC injection of PGE-1.55 Unfortunately, 24% of these patients also reported penile pain, one of the most common side effects of IC injection therapy. Other studies have noted similar effectiveness rates.56,57
Pomegranate juice. Drinking antioxidant-rich pomegranate juice has been shown to have numerous health benefits, including a reduced risk for heart disease and high blood pressure. Does pomegranate juice also protect against ED? No proof exists, but results of a study published in 2007 were promising. The authors of this small-scale pilot study called for additional research, saying that larger-scale studies might prove pomegranate juice's effectiveness against erectile dysfunction. "I tell my patients to drink it," says Espinosa. "It could help ED, and even if it doesn't, it has other health benefits."
The initial event for normal erectile function is sexual stimulation. Subsequent to processing in the central nervous system neural impulses are conveyed along the spinal cord, exiting through the pelvic parasympathetic preganglionic nerves. These pelvic nerves form the pelvic plexus and send their message through first messenger, acetyl choline, to the cavernosal nerves. The cavernosal nerves enter erectile bodies (corpora cavernosa) (Figure 1). Here, their nerve endings release a second messenger, nitric oxide. Nitric oxide activates the enzyme guanylyl cyclase, which lyses guanosine triphosphate (GTP) to produce a third messenger, the intracellular cyclic guanosine monophosphate (cGMP). Ultimately, the result is a decrease of intracellular calcium and an opening of potassium channels with the resultant relaxation of vascular smooth muscle in the arteries, aterioles, and sinusoids of the corpora cavernosa. The sinusoids open and rapidly fill with blood. Finally, the distended sinusoids compress their drainage pathways (venules) against the fibroelastic covering of the cavernosal bodies (tunica albuginea) and trap the blood in cavernosal bodies. The combination of an increased inflow of blood into the penis and coincident markedly diminished outflow results in rapidly increasing intracavernosal pressure that ultimately approximates systolic pressure. At this pressure the penis has sufficient axial rigidity to permit vaginal penetration.

If you have been diagnosed with heart disease or have already had a heart attack and are experiencing erectile dysfunction, it is critical that you discuss erectile dysfunction medication with your physician before considering taking it. Popular erectile dysfunction medications such as Viagra (sildenafil), Cialis (tadalafil) and Levitra (vardenafil) can interact with a range of cardiovascular disease medications. Interactions are possible with blood pressure medications; blood thinners such as Coumadin (warfarin), nitrates for the treatment of chest pain, and antiarrhythmia medication for the treatment of irregular heart rhythms.
Before Viagra hit the market in 1998, there was no proven treatment for erectile dysfunction that men could take in pill form. Doctors were interested in yohimbe, an herb that increases heart rate and blood pressure. Some doctors prescribed it to their patients in combination with other treatments for erectile dysfunction. Even then it was not a recommended treatment and is still not today. Studies have not proven that it works.

Ginseng. Korean red ginseng has long been used to stimulate male sexual function, but few studies have tried systematically to confirm its benefits. In one 2002 study involving 45 men with significant ED, the herb helped alleviate symptoms of erectile dysfunction and brought "enhanced penile tip rigidity." Experts aren't sure how ginseng might work, though it's thought to promote nitric oxide synthesis. "I would recommend ginseng [for men with ED]," says Espinosa. Discuss with your doctor before taking it since ginseng can interact with drugs you may already be taking and cause allergic reactions.
A follow-up study from the ExCEED database compared men with ED and prostate cancer to men with ED without prostate cancer and found that the prostate cancer survivors had worse erectile function but reported better quality of life than those without prostate cancer.37 The authors hypothesized that the prostate cancer survivors were able to “rationalize” away their sexual dysfunction with the knowledge that they may have been “cured” of their prostate cancer. Clearly, diabetic men could not use the same rationale.
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.
• Blood Vessels: Diabetes damages blood vessels, especially the smallest blood vessels such as those in the penis. Diabetes can also cause heart disease and other circulatory problems. Proper blood flow is absolutely crucial to achieving erection. “Erection is a hydraulic phenomenon that occurs involuntarily,” says Arturo Rolla, MD, of Harvard University School of Medicine. “Nobody can will an erection!” Anything that limits or impairs blood flow can interfere with the ability to achieve an erection, no matter how strong one’s sexual desire.
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