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
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.
Crossref | PubMed | Scopus (23) | Google ScholarSee all References Only 1 published study has investigated the effect of vardenafil on cardiac function.75x75Thadani, U, Smith, W, Nash, S et al. The effect of vardenafil, a potent and highly selective phosphodiesterase-5 inhibitor for the treatment of erectile dysfunction, on the cardiovascular response to exercise in patients with coronary artery disease. J Am Coll Cardiol. 2002; 40: 2006–2012
Erectile dysfunction (ED) is highly prevalent affecting at least 50 % of men with diabetes mellitus (DM). DM may cause ED through a number of pathophysiological pathways. These include neuropathy, endothelial dysfunction, cavernosal smooth muscle structural/functional changes, and hormonal changes. Lifestyle changes, diabetes control, and treatment of hypogonadism are important as the first step in ED management since there is no curative treatment for ED. Phosphodiesterase type 5 inhibitors (PDE5i) are the first-line treatment option. Intracavernous administration of vasoactive drugs is commonly used as a second-line medical treatment when PDE5i have failed. Alprostadil is the most widely used drug in this second-line setting. The combination of papaverine, phentolamine, and alprostadil represents the most efficacious intracavernous pharmacologic treatment option that may save non-responders to alprostadil. Penile prosthesis implantation can be considered in treatment refractory cases, with excellent functional and safety results in the properly informed patients.

 Other treatment options such as penile self-injection therapy, external vacuum pumps and the medicated urethral system for erection are on rare occasions an effective long-term treatment. A very small percentage of men will continue with these treatments as evidenced by a very high drop out rate and a very low refill rate for these treatments. These procedures require extensive planning which interfere with sexual spontaneity and are really not a realistic long-term treatment for young patients with permanent ED. 
As ED has become more prevalent among the U.S. population, entrepreneurs have set out to serve this patient population by introducing a variety of non-invasive devices to help correct the condition. There’s the penis pump, which includes a plastic tube that fits over the penis and a hand or battery-powered pump attached to the tube, and a band that circles the base of the penis when it becomes erect.

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.”
Abstract | Full Text | Full Text PDF | PubMed | Scopus (95) | Google ScholarSee all References Rates of severe cardiovascular adverse effects were also similar at 1.7 per 1000 person-years of treatment with sildenafil compared with 1.0 events per 1000 personyears with placebo treatment.10x10Kloner, RA and Zusman, RM. Cardiovascular effects of sildenafil citrate and recommendations for its use. Am J Cardiol. 1999; 84: 11N–17N
Counselling or sex therapy (58% of people find this works for them) –mind-related causes of erectile dysfunction can affect anyone. They are more likely if you experience erectile dysfunction at a younger age. Talking to a counsellor or therapist can help some people overcome erectile dysfunction related to these problems, possibly for good. They can also help you if your erectile dysfunction is causing you stress, as this can make matters worse.
Abstract | Full Text | Full Text PDF | PubMed | Scopus (395) | Google ScholarSee all References Phosphodiesterase type 5 is primarily responsible for the breakdown of cGMP in cavernosal tissues. The inhibition of PDE-5 by sildenafil therefore causes continued activation of the NO-cGMP pathway in the cavernosal tissue, thereby improving erectile function.10x10Kloner, RA and Zusman, RM. Cardiovascular effects of sildenafil citrate and recommendations for its use. Am J Cardiol. 1999; 84: 11N–17N
Ginkgo Biloba is promoted to treat conditions ranging from hypertension to Alzheimer’s dementia. There is evidence that shows improvement of memory enhancements in the geriatric population (47), improvement in terms of cognitive function via effect on cerebral vasculature (48), improvement of claudication distance and cutaneous ulcers in patients with peripheral vascular disease (49). Ginkgo Biloba extract is proposed to induce NO in endothelial cells and thus causing relaxation of vascular smooth muscles. Animal studies have reported relaxation of rabbit corpus cavernosal smooth muscle cells with the use of Ginkgo Biloba (50). Adverse effects include headaches, major bleeding (in patient who are taking warfarin concurrently) and seizures with reported fatality (36).
The vascular endothelium has an important role in angiogenesis and vascular repair by producing regulatory substances, including NO, prostaglandin, endothelins, prostacyclin and angiotensin II. These regulatory factors regulate the blood flow to the penis by controlling smooth muscle contractility and subsequent vasoconstriction and vasodilatation. Generally, in erectile tissue, increased blood flow through the cavernosal artery increases shear stress and produces NO, which further relaxes the vascular smooth muscles and increases blood flow in the corpora cavernosa.54 These events cause penile erection. However, in ED, endothelial NO synthesis is reduced and there is increased endothelial cell death (Figure 2).55
Ginkgo Biloba is promoted to treat conditions ranging from hypertension to Alzheimer’s dementia. There is evidence that shows improvement of memory enhancements in the geriatric population (47), improvement in terms of cognitive function via effect on cerebral vasculature (48), improvement of claudication distance and cutaneous ulcers in patients with peripheral vascular disease (49). Ginkgo Biloba extract is proposed to induce NO in endothelial cells and thus causing relaxation of vascular smooth muscles. Animal studies have reported relaxation of rabbit corpus cavernosal smooth muscle cells with the use of Ginkgo Biloba (50). Adverse effects include headaches, major bleeding (in patient who are taking warfarin concurrently) and seizures with reported fatality (36).
Nehra A,  Jackson G,  Miner M,  Billups KL,  Burnett AL,  Buvat J,  Carson CC,  Cunningham GR,  Ganz P,  Goldstein I,  Guay AT,  Hackett G,  Kloner RA,  Kostis J,  Montorsi P,  Ramsey M,  Rosen R,  Sadovsky R,  Seftel AD,  Shabsigh R,  Vlachopoulos C,  Wu FC. The Princeton III Consensus recommendations for the management of erectile dysfunction and cardiovascular disease, Mayo Clin Proc , 2012, vol. 87 (pg. 766-778)https://doi.org/10.1016/j.mayocp.2012.06.015
Yohimbe A number of clinical trials have shown that the primary component of this bark from an African tree can improve sexual dysfunction associated with selective-serotonin reuptake inhibitors (SSRIs) used to treat depression. This herb has been linked to a number of side effects, including increased blood pressure, fast or irregular heartbeat, and anxiety. Yohimbe shouldn't be used without a doctor's supervision.
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.
Abstract | Full Text | Full Text PDF | PubMed | Scopus (207) | Google ScholarSee all References Adverse-effect profiles of headaches, flushing, rhinitis, and dyspepsia, without visual changes, mimic those of vardenafil.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
In the vessels that supply the heart, healthy arteries enlarge in diameter up to 50% during exercise when sufficient nitric oxide is present. Because of its brief half-life, a continual supply of nitric oxide is required for optimal effect. If the supply of nitric oxide is inadequate, endothelial dysfunction—a core factor in heart disease—is made worse. Endothelial dysfunction can trigger the growth of coronary plaque.8
To reduce the risk of side effects from these medications, including sexual problems, take medications exactly as prescribed. If you still have side effects, talk to your doctor about other possible medications that may have fewer side effects. On the other hand, you should not take any medication that promotes and erection while on medication to lower blood pressure.
Deer velvet is a covering found on the growing bone and cartilage of deer’s antlers. In Eastern medicine, deer velvet is sought after for its Chinese medicinal properties which include boosting one’s endurance and improving one’s immunity. People have also used deer velvet as an aphrodisiac or to treat ED. The randomized double-blind placebo-controlled study on deer velvet by Conaglen et al. (31), no benefit but this study was underpowered involving healthy participants with no sexual dysfunction.

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
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
Nebivolol seems to have an advantage over other beta-blockers when used to treat men with hypertension and ED. It has additional vasodilating effects because it stimulates endothelial release of nitric oxide (NO), resulting in relaxation of smooth muscle in the corpus cavernosum, allowing penile erection.25 Despite limited studies, nebivolol does not seem to worsen erectile function and some studies have demonstrated significant improvement in erectile function with nebivolol compared with second-generation cardioselective beta-blockers.23,26–28
Abstract | Full Text | Full Text PDF | PubMed | Scopus (24) | Google ScholarSee all References Withdrawal of sexual stimulation causes a return of sympathetic tone and degradation of cGMP, predominantly by phosphodiesterase type 5 (PDE-5) within the trabecular smooth muscle.11x11Nehra, A. Intracavernosal therapy: when oral agents fail. Curr Urol Rep. 2001; 2: 468–472
Towards this direction, several sufficiently powered studies have demonstrated a higher incidence of erectile dysfunction in patients with coronary artery disease, either asymptomatic or overt. At the same time, patients with erectile dysfunction are more prone to have established coronary artery stenosis of more than 50% and consequently evident CV disease[75]. This is in conformity with the “artery size hypothesis” according to which smaller arteries (e.g., penile arteries) are the first to undergo a vascular lesion prior to the larger ones (e.g., coronary arteries). Moreover, in such patients erectile dysfunction is connected to the number of occluded vessels and more interestingly occurs over three years before coronary artery disease becomes apparent[76-80].
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
For centuries, men have tried all sorts of natural remedies for erectile dysfunction (ED) -- the repeated inability to get or maintain an erection firm enough for sexual intercourse. But do they really work? It is simply not scientifically known at this point. Furthermore, you take these remedies at your own risk, because their safety profiles have not been established. What follows are commentaries by experts and reviews in the field of alternative treatments that are available over the counter for erectile dysfunction and impotence.
Crossref | PubMed | Scopus (174) | Google ScholarSee all References This study concluded that patients who have stable coronary artery disease who can exercise to 4.5 metabolic equivalents (METs) with a negative or mildly positive stress test and without angina or hypotension can safely take sildenafil. Physicians who prescribe sildenafil should counsel their patients that, if they have chest pain or other cardiac symptoms with sexual intercourse, they should not take nitrates and should immediately call their physician.66x66Jackson, G. Sexual intercourse and stable angina pectoris. Am J Cardiol. 2000; 86: 35F–37F

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


Figure. Progression of atherosclerosis. Endothelial dysfunction occurs early in atherosclerosis and prevents blood vessels from dilating properly. When the blood vessels that supply the penis are not able to dilate during sexual stimulation because of endothelial dysfunction, the penis cannot fill with blood, and the man develops erectile dysfunction. As atherosclerosis progresses, plaques build up in blood vessels and blood flow is slowed, further worsening erectile function. A heart attack occurs when an atherosclerotic plaque in a coronary artery ruptures, a blood clot forms over the plaque, and blood flow to the heart muscle is completely blocked. Atherosclerotic risk factors (black arrows) worsen cardiovascular health; modification of these risk factors (red arrows) improves cardiovascular health.
To understand what happens in ED, it's helpful to know some anatomical basics. When aroused by either sensory or mental stimuli, the brain sends a signal through the nerves to the penis, causing the muscles there to relax. This opens up space for blood to flow in and engorge the penis. A membrane within the penis traps blood inside to help maintain the erection, which subsides when the penile muscles contract, forcing blood back into the rest of the body. Any number of things can go wrong in this process, leading to erectile dysfunction.
A cold slice of watermelon can do more than just satisfy thirst and hunger during the warm summer months; it can help with bedroom satisfaction. Citrulline, the amino acid found in high concentrations of watermelon, is found to improve blood flow to the penis. A 2011 study revealed men who suffered from mild to moderate ED and took L-citrulline supplementation showed an improvement with their erectile function and were very satisfied. Natural watermelon juice, or “nature’s Viagra,” can also be easier on the stomach, since taking pills like Viagra can cause nausea and diarrhea.
Crossref | PubMed | Scopus (35) | Google ScholarSee all References Also, if lower blood pressure level was the primary etiology of ED, all classes of antihypertensive agents should be expected to have relatively similar effects on erectile function because of their efficacy in lowering pressure, which has not been seen.6x6Kloner, RA. Erectile dysfunction and cardiovascular risk factors. Hosp Pract (Off Ed). 2001; 36: 41–44 (49-51.)
Abstract | Full Text | Full Text PDF | PubMed | Scopus (66) | Google ScholarSee all References However, patients with hypertrophic obstructive cardiomyopathy and idiopathic hypertrophic subaortic stenosis are at increased risk of syncope and sudden death after exercise.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
Another oral treatment that has been used with very little success is yohimbine (Yocon, Yohimex). This is an alpha 2 adrenergic receptor blocker that increases cholinergic and decreases adrenergic tone. It stimulates the mid-brain and increases libido. Optimal results occur when used in men with psychogenic ED. Side effects include anxiety and insomnia.
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

Intracavernosal and intraurethral injections are second-line therapy for patients with ED. Alprostadil is the agent most commonly used for intracavernosal injections. The main adverse effects of intracavernosal injections are painful erection, priapism and development of scarring at the injection site.73 Alprostadil is also available as a topical cream in patients who cannot tolerate injections.75
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.
Crossref | PubMed | Scopus (528) | Google ScholarSee all References Sildenafil also has good efficacy in patients with ischemic heart disease, as shown by a retrospective subanalysis of data from 11 double-blind, placebo-controlled studies involving 3672 patients with ED and ischemic heart disease who were not taking nitrates.59x59Kloner, RA. Cardiovascular risk and sildenafil. Am J Cardiol. 2000; 86: 57F–61F
In another scientific article published in 2015 in the American Journal of Lifestyle Medicine, respondents who were not taking cholesterol-lowering medication experienced an average 42 mg/dl decrease in LDL cholesterol and an average decrease in triglycerides of 79.5 mg/dl about one year after switching to a Nutritarian diet. Furthermore, case histories presented in that publication documented atherosclerosis reversal.7

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


Experts feel that treating erectile dysfunction on your own, without consulting a doctor, is unsafe. "If you have ED, the first thing you need is a diagnosis," says impotence expert Steven Lamm, MD, a New York City internist and the author of The Hardness Factor (Harper Collins) and other books on male sexual health. He says men with severe erectile dysfunction probably need one of the prescription ED drugs, which include Levitra (vardenafil) and Cialis (tadalafil) as well as Viagra. But, he says, mild ED -- including the feeling that "you're not as hard as you could be" -- often responds to natural remedies.
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."

The following products are considered to be alternative treatments or natural remedies for Erectile Dysfunction. Their efficacy may not have been scientifically tested to the same degree as the drugs listed in the table above. However there may be historical, cultural or anecdotal evidence linking their use to the treatment of Erectile Dysfunction.

Abstract | PubMed | Scopus (136) | Google ScholarSee all References Other candidate mechanisms linking ED and cigarette smoking include hypercoagulability and increased platelet aggregation, increased release of free fatty acids and catecholamines, changes in NO synthetic pathways, and a possible direct toxic effect on vascular endothelium.13x13Chung, WS, Shim, BS, and Park, YY. Hemodynamic insult by vascular risk factors and pharmacologic erection in men with erectile dysfunction: Doppler sonography study. World J Urol. 2000; 18: 427–430
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].
Abstract | Full Text | Full Text PDF | PubMed | Scopus (56) | Google ScholarSee all References Of 1774 patients with a history of myocardial infarction, only 2 who had experienced a myocardial infarction after sexual intercourse were able to exercise to at least 6 METs without symptoms.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
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.
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