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.

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.


Montorsi F,  Briganti A,  Salonia A,  Rigatti P,  Margonato A,  Macchi A,  Galli S,  Ravagnani PM,  Montorsi P. Erectile dysfunction prevalence, time of onset and association with risk factors in 300 consecutive patients with acute chest pain and angiographically documented coronary artery disease, Eur Urol , 2003, vol. 44 (pg. 360-364)https://doi.org/10.1016/S0302-2838(03)00305-1
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.
There are many alternative treatments that may be used to treat erectile dysfunction, although their effectiveness hasn't been proven. Men may benefit from acupuncture to reduce stress and help treat erectile dysfunction. Some people claim that herbal supplements such as Korean red ginseng, ginkgo, and yohimbine may be helpful for treating erectile dysfunction. Other helpful supplements for treating erectile dysfunction may include DHEA (a hormone in testosterone) and L-arginine. However, it's important to remember that these and other supplements may actually contain harmful substances, so talk with your doctor before taking supplements for treating erectile dysfunction.
Abstract | Full Text | Full Text PDF | PubMed | Scopus (66) | Google ScholarSee all References Risk of arrythmias after sexual intercourse was evaluated in 82 patients with stable coronary artery disease who were monitored with ambulatory ECG after sexual intercourse.81x81Drory, Y, Fisman, EZ, Shapira, Y, and Pines, A. Ventricular arrhythmias during sexual activity in patients with coronary artery disease. Chest. 1996; 109: 922–924
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.
Abstract | Full Text | Full Text PDF | PubMed | Scopus (58) | Google ScholarSee all References Theoretically, the risk of a cardiac event during sexual activity should be increased. Sexual activity is associated with an elevated heart rate, blood pressure level, and myocardial oxygen demand, and this increase in hemodynamic stress may result in myocardial ischemia.79x79Kimmel, SE. Sex and myocardial infarction: an epidemiologic perspective. Am J Cardiol. 2000; 86: 10F–13F
The choice is yours. You do not have to die of a heart attack, and you do not have to have erectile dysfunction. Both are the result of dietary choices, and you can make a choice right now to protect your life. Do you want to die of a heart attack or don’t you? If you don’t, then are you willing to do what it takes to reduce your risk almost 100 percent? I don’t know about you, but for me, just dropping my risk 20 to 40 percent with medical care is not enough. I want maximum protection.
The blood supply to your penis starts in your heart and flows through arteries in the belly to even smaller arteries that branch off to carry blood into the penis. With sexual stimulation, these blood vessels need to rapidly increase blood flow. If these blood vessels are blocked (atherosclerosis) by coronary artery disease, you may not be able to achieve or maintain an erection.11
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.
PDE-5 inhibitors amplify the intacavernosal production of cGMP in response to nitric oxide. This is achieved through the inhibition of cGMP's breakdown by the enzyme, PDE-5. If the predominant abnormality in the individual EDDM patient is molecular, the higher tissue levels of cGMP will overcome these inhibitory factors and the patient will regain erectile function. If the physical structure (eg, the compliance) of the cavernosal tissue has been significantly compromised by apoptosis of smooth muscle or increased collagen deposits, restoration of erectile function will not be achieved. These structural changes explain the lower efficacy rates of PDE-5 inhibitors in EDDM than in the general population.
Erectile dysfunction started to become a household term after scientists discovered a drug to treat it. Nowadays, as anyone who watches TV can attest, there are several different medications for ED. Fifty to 70 percent of men with type 1 or type 2 diabetes respond to a class of drugs—including sildenafil (Viagra), var­denafil hydrochloride (Levitra), and tadalafil (Cialis)—called phosphodiesterase-5 inhibitors.

Uses and risks of viagra Viagra treats erectile dysfunction and pulmonary arterial hypertension. For sexual purposes, it helps someone with erectile dysfunction achieve and maintain an erection. However, Viagra can have unpleasant side effects, and an overdose can be serious. We cover everything you need to know about Viagra in this article. Read now


Surgical implantation of a penile prosthesis, either the inflatable (2- and 3-piece) or the malleable device, is a feasible technique that offers a third-line treatment and a more permanent solution to the problem of erectile dysfunction. Interestingly, prosthesis implantation receives a significantly high satisfaction rate as evidenced by the proportionate scores in sexual satisfaction scales. Mechanical failure and infection are the two major disadvantages of those prosthetic implants however, their great efficacy, safety and satisfaction rate in general render them an attractive solution when conservative treatment fails[70-74].
In addition, when research has shown a nutrient such as zinc or niacin to improve sexual function, it's usually in people who are deficient in it. So, before you stock up on over-the-counter nutritional supplements for ED, speak with your doctor. He can test you for deficiencies and steer you toward the most effective and safest way to treat your erectile dysfunction. 
Diabetes is one of the most common causes of ED. Men who have Diabetes are three times more likely to have Erectile Dysfunction than men who do not have Diabetes. Among men with ED, those with Diabetes are likely to have experienced the problem as much as 10 to 15 years earlier than men without Diabetes. A recent study of a clinic population revealed that 5% of the men with ED also had undiagnosed Diabetes. The risk of ED increases with the number of years you have Diabetes and the severity of your Diabetes. Even though 20% to 75% of men with Diabetes have ED, it can be successfully managed in almost all men.
Crossref | PubMed | Scopus (23) | Google ScholarSee all References In some elderly men, tadalafil could be detected in the bloodstream 6 days after oral ingestion.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
Medications used in the treatment of cardiovascular disease, especially antihypertensive medications, have been implicated frequently in the development of sexual dysfunction. A study of 5485 patients in the Hypertension Detection and Follow-up Program found that, during a 5-year period, 8.3% of male hypertensive patients stopped taking their antihypertensive medications secondary to sexual adverse effects.35x35Curb, JD, Borhani, NO, Blaszkowski, TP, Zimbaldi, N, Fotiu, S, and Williams, W. Long-term surveillance for adverse effects of antihypertensive drugs. JAMA. 1985; 253: 3263–3268
PubMed | Google ScholarSee all References In comparison, a study of 132 patients evaluated by penile duplex ultrasonography after intracorporeal papaverine injection found that hypertension alone was not an independent risk factor for vasculogenic ED.34x34Shabsigh, R, Fishman, IJ, Schum, C, and Dunn, JK. Cigarette smoking and other vascular risk factors in vasculogenic impotence. Urology. 1991; 38: 227–231
If you take a diuretic, you should stay on it until high blood pressure is under control. If erection problems persist, or blood pressure goes back up, then your doctor might switch to a drug that's less likely to cause erectile dysfunction. Or, a combination of medications might work better to control high blood pressure and lower the risk of erectile dysfunction.
Your doctor may also choose to lower your dose of certain medications. Or your provider may switch the type of drug you’re taking if it’s interfering with your sex life. Some medicines used for managing blood pressure, insomnia, anxiety, depression, seizures and prostate problems increase the risk for erectile dysfunction. Beta-blockers (for high blood pressure), SSRIs (often used to treat depression) and the class of drugs called benzodiazepines (like Ativan, Xanax, Librium and Valium) are commonly tied to ED. You may want to speak to your doctor about this.
Based on this testing, EDDM patients were treated with behavioral therapy, intracavernosal (papaverine, PGE-1, or Trimix) or intraurethral PGE-1, a vacuum constriction device (VCD), or implantation of a penile prosthesis. Novel surgical procedures, ligation of incompetent cavernosal veins or penile revascularization, were seldom efficacious with EDDM and were soon abandoned. Although these nonsurgical therapies were efficacious, they were not widely requested because of their invasive or mechanical nature.
SOURCES: American Urological Association, "AUA Guideline on the Management of Erectile Dysfunction: Diagnosis and Treatment Recommendations." Barksdale, J. Pharmacotherapy, May 1999; vol 19: pp 573-581. Ferrario, C. Journal of Clinical Hypertension, November/December 2002; vol 4: pp 424-432. Fogari, R. American Journal of Hypertension, January 2001; vol. 14: pp 27-31. Grimm, R. Hypertension, January 1997; vol 29: pp 8-14. Llisteri, J. American Journal of the Medical Sciences, May 2001; vol. 321: pp 336-341. WebMD Medical Reference provided in collaboration with The Cleveland Clinic: "Hypertension: Treatment With ACE Inhibitors."

PubMed | Google ScholarSee all References A dose-related phenomenon with propranolol use was suggested by another study, which showed that patients receiving propranolol dosages exceeding 120 mg/d developed ED at a higher rate than patients who received lower dosages of the same medication.43x43Warren, SC and Warren, SG. Propranolol and sexual impotence [letter]. Ann Intern Med. 1977; 86: 112

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.
Montorsi P,  Ravagnani PM,  Galli S,  Rotatori F,  Veglia F,  Briganti A,  Salonia A,  Dehò F,  Rigatti P,  Montorsi F,  Fiorentini C. Association between erectile dysfunction and coronary artery disease. Role of coronary clinical presentation and extent of coronary vessels involvement: the COBRA trial, Eur Heart J , 2006, vol. 27 (pg. 2632-2639)https://doi.org/10.1093/eurheartj/ehl142
While a widely held perception is that CVD drugs cause ED, data attest towards the contrary and some agents may be even beneficial.41 Only thiazide diuretics lead clearly to ED, while some older beta-blockers also do so, but the side-effect of ED was very low (∼3%) when the patient was blinded for the drug administration.42 In fact, the vasodilating nebivolol may even improve erectile function.35,43 ACE-inhibitors, angiotensin-receptor blockers, and calcium-channel blockers are reported to have neutral or even a positive effect on erectile function35,41,43 but more evidence is needed. Regarding statins, the largest body of evidence point towards a beneficial effect.44 A negative effect has been reported in high statin doses, possibly related to a potential reduction in serum testosterone levels, but this dose dependency warrants further investigation. In terms of patient management, when ED onset and therapy initiation are linked and a cause-and-effect association is presumed, a short period of drug withdrawal with monitoring for ED resolution for verification may be an option. In patients who developed ED long after the initiation of CV drug treatment, sexual dysfunction is less likely to be drug associated and PDE5 inhibition therapy may be initiated.
Abstract | Full Text | Full Text PDF | PubMed | Scopus (46) | Google ScholarSee all References Sedentary patients with a history of cardiac disease and patients with unstable angina or advanced congestive heart failure should undergo a full medical evaluation before resuming sexual activity.80x80Muller, JE. Triggering of cardiac events by sexual activity: findings from a case-crossover analysis. Am J Cardiol. 2000; 86: 14F–18F
The number of men reporting improvement was at 88% during the study. The number of men involved in the study who reported impotence dropped from 75.3 % to 11.8%. The results of this study raise hope for men who have quit taking other blood pressure medications because they interfered with sexual function. Sexual dysfunction was defined for the study as decreased libido, impotence and poor sexual satisfaction.
In the past 6 years, the FDA has approved three oral agents for the treatment of ED: sildenafil, vardenafil, and tadalafil. All three are phosphodiesterase type 5 (PDE-5) inhibitors and work by potentiating the effect of nitric oxide in the penis. In particular, they block the hydrolysis of cyclic guanosine monophosphate to guanosine 5'-monophosphate, thus enhancing nitric oxide–mediated smooth muscle relaxation, increasing blood flow to the penis and facilitating erection.
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 (66) | Google ScholarSee all References However, α-blockers are a well-known cause of retrograde ejaculation secondary to a reversible relaxation of bladder neck smooth muscle.50x50Meinhardt, W, Kropman, RF, Vermeij, P, Nijeholt, AA, and Zwartendijk, J. The influence of medication on erectile function. Int J Impot Res. 1997; 9: 17–26
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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