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
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.
Erectile dysfunction means that a man is not able to have sex because he cannot get or keep an erection. Erectile dysfunction affects >30% of men between 40 and 70 years of age. There are several different causes of ED, including depression, low testosterone, nerve problems, and some medications, but the most common cause is a problem with the blood vessels called atherosclerosis.
Not surprisingly, they found that diabetic patients rated kidney disease and blindness as the two most important complications of their condition. Diabetic men with ED ranked ED as the third most important complication of diabetes, followed on average in order by foot ulcers, high blood pressure, high cholesterol, migraine headaches, sleeping disorders, and mild indigestion. Diabetic men without ED found ED slightly less important, ranking it behind foot ulcers and high blood pressure, although all three were grouped fairly close together (mean ranks were 4.59, 4.23, and 4.52, respectively). Interestingly, in men both with and without ED, subjects were willing to pay more per month to avoid ED than all other conditions except blindness and kidney disease (mean values for diabetic patients with ED were £50.5, £88.0, and £66.1, respectively). In summary, erectile function is important to diabetic men, and when ED is present, it has a significant negative effect on quality of life.

Penile arterial supply (top) and venous drainage (middle), longitudinal views. Bottom, Transverse and longitudinal views of venous return. From Lue TF. Physiology of penile erection and pathophysiology of erectile dysfunction and priapism. In: Walsh PC, Retik AB, Vaughan ED Jr, Wein AJ, eds. Campbell's Urology. Vol 2. 7th ed. Philadelphia, Pa: WB Saunders Co; 1998:1157-1179. With permission from Elsevier.

I have cared for hundreds of men with erectile dysfunction that have reversed their condition with a Nutritarian diet and the judicious use of dietary supplements. I have cared for hundreds of heart patients with angina and advanced heart disease, who have turned their backs on invasive cardiac procedures, recovered from angina and opened up the closed blood vessels in their diseased hearts. Out of thousands of men with advanced heart and erectile problems who have followed my nutritional advice, I have never had a patient suffer a heart attack or cardiac related death.
Abstract | Full Text | Full Text PDF | PubMed | Scopus (395) | Google ScholarSee all References Sildenafil has no effect on bleeding time or prothrombin time when used either alone or in patients taking aspirin or warfarin.61x61Nehra, A, Colreavy, F, Khandheria, BK, and Chandrasekaran, K. Sildenafil citrate, a selective phosphodiesterase type 5 inhibitor: urologic and cardiovascular implications. World J Urol. 2001; 19: 40–45

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


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.
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
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

Excess LDL cholesterol in your blood gets deposited in arteries, the blood vessels that feed the heart and brain. These deposits can join with other substances to form plaque, a thick, hard deposit in the blood vessel that leads to atherosclerosis. Plaque can narrow the passageway inside the artery and pinch off the flow of blood to the heart muscle, and to the penis.

• Medications: About 25 percent of ED cases are caused by drugs. Many medications, including common medicines prescribed for diabetes and its complications, can cause ED. The most common offenders are blood pressure drugs, antihistamines, antidepressants, tranquilizers, appetite suppressants, and cimetidine (an ulcer drug). In addition, over-the-counter medications, including certain eye drops and nose drops, have been associated with ED. That does not mean you should stop taking these medications! Rather, you should discuss them with your doctor to determine whether a different dosage, an alternate medicine, or additional treatments will resolve the ED.
Abstract | Full Text PDF | PubMed | Scopus (3562) | Google ScholarSee all References By 1996, fueled by the availability of the new oral agent sildenafil, the number of outpatient visits for ED as estimated by the National Ambulatory Medical Care Survey had increased to 1.3 million per year.5x5Feldman, HA, Johannes, CB, Derby, CA et al. Erectile dysfunction and coronary risk factors: prospective results from the Massachusetts Male Aging Study. Prev Med. 2000; 30: 328–338
Abstract | Full Text | Full Text PDF | PubMed | Scopus (95) | Google ScholarSee all References Open-label trials showed a myocardial infarction rate of only 1.0 event per 1000 person-years of treatment with sildenafil.10x10Kloner, RA and Zusman, RM. Cardiovascular effects of sildenafil citrate and recommendations for its use. Am J Cardiol. 1999; 84: 11N–17N
In a prospective human phase 1 open-label and single-arm study reported by Haahr et al. (27), 17 men with refractory post radical prostatectomy ED were given a single intracavernosal injection of autologous adipose-derived regenerative cells (ADRCs) freshly isolated after a liposuction. The procedures were well-tolerated and over a 6-month follow-up period, 8 of 17 men showed improvement of their erectile function.

Crossref | PubMed | Scopus (25) | Google ScholarSee all References In comparison, a randomized placebo-controlled trial of 65 patients given either placebo or 95 mg/d of sustained-release metoprolol for 4 months after percutaneous coronary angioplasty found no significant difference in sexual function between the 2 groups.44x44Franzen, D, Metha, A, Seifert, N, Braun, M, and Hopp, HW. Effects of beta-blockers on sexual performance in men with coronary heart disease: a prospective, randomized and double blinded study. Int J Impot Res. 2001; 13: 348–351

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.

Crossref | PubMed | Scopus (539) | Google ScholarSee all References Sleep studies in 175 patients with hypertension and erectile problems showed significantly lower penile rigidity measured by strain gauge plethysmography compared with 110 normotensive male controls with similar subjective erectile problems.33x33Hirshkowitz, M, Karacan, I, Gurakar, A, and Williams, RL. Hypertension, erectile dysfunction, and occult sleep apnea. Sleep. 1989; 12: 223–232
Faced with concern about ED pills and the heart, the FDA has urged caution in patients who have suffered heart attacks, strokes, or serious disturbances of the heart's pumping rhythm in the previous six months, in men with a history of congestive heart failure or unstable angina, and in men with low blood pressure or uncontrolled high blood pressure (above 170/110 mm Hg). Because certain medications can boost the blood levels of these drugs, men taking erythromycin or certain antifungal or anti-HIV medications should use only low-dose PDE-5 inhibitors. Reduced dosage is also important for men with advanced age and for those with significant kidney or liver disease.

Abstract | Full Text | Full Text PDF | PubMed | Scopus (95) | Google ScholarSee all References Phase 2 and 3 trials reported minimal associated cardiac adverse effects, which occurred in 3% of patients taking sildenafil and in 3.5% of patients receiving placebos.10x10Kloner, RA and Zusman, RM. Cardiovascular effects of sildenafil citrate and recommendations for its use. Am J Cardiol. 1999; 84: 11N–17N
"If you have an active sex life after a heart attack, it is probably safe to use PDE5 inhibitors," said Daniel Peter Andersson, MD, PhD, a postdoctoral researcher at Karolinska Institutet in Stockholm and the study's lead author. "This type of erectile dysfunction treatment is beneficial in terms of prognosis, and having an active sex life seems to be a marker for a decreased risk of death."
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If you have symptoms of ED, it’s important to check with your doctor before trying any treatments on your own. This is because ED can be a sign of other health problems. For instance, heart disease or high cholesterol could cause ED symptoms. With a diagnosis, your doctor could recommend a number of steps that would likely improve both your heart health and your ED. These steps include lowering your cholesterol, reducing your weight, or taking medications to unclog your blood vessels.
The use of penile support device such as penile cast worn externally during intercourse has been tried to provide length and rigidity to the penile shaft (24). Each device can be customised to the patient’s penile size and provided an option for patients who are seeking non-pharmaceutical/non-invasive treatment, or have end-organ failure who may not be candidates for, or unable to afford, penile prosthesis implant.
Diaclina (also known as Panzer’s Darkling Beetle), Korean bug are used as aphrodisiacs in China, Korea and Southeast Asia. These are consumed either whole or as compounds within capsules. It is felt that the aphrodisiac properties come by stimulating the urogenital structures. Flies have been studied for their aphrodisiac effects, including Spanish fly, Chinese cantharide, and Eastern-Indian cantharide (32). The active compound found in the dried and mashed up bodies of these flies is cantharidin, which is a pheromone produced in the accessory glands of the male flies’ genitals. Cantharidin, stimulates the urogenital tract, causing pelvic hyperemia and possibly erections. As cantharidin is toxic and its safety dose not well determined, its use cannot be recommended. Cantharidin is lethal at high doses and exposure can lead to gastrointestinal and urogenital hemorrhage as well as acute renal failure.
Many products contain undocumented “fillers” that can cause allergic reactions.  In recent years, the FDA has found over 300 herbal products that contain hidden, deceptively labeled, or dangerous ingredients4. And since 2015, the FDA has released public warnings on more than 160 ED supplements and “male enhancement” products found to contain dangerous ingredients and contaminants5 .   An independent study of FDA data, conducted in 2018, found almost 800 herbal supplements that contained unlisted ingredients6.

Penile implants - are generally used if physical damage (like an accident) makes the anatomical parts needed for an erection not work. These are inserted by surgery and can provide a permanent treatment choice if others fail to work. The implants can be semi-rigid or inflatable. They can be pretty expensive and are not usually available on the NHS.
Three FDA-approved oral medications, sildenafil, tadalafil, and vardenafil are available. These drugs are phosphodiesterase type 5 (PDE-5) inhibitors that can prolong levels of cGMP in tissue allowing improved smooth muscle relaxation, thus facilitating an erection. PDE-5 inhibitor drugs are effective in 56-63% of diabetic men with ED. More stringent glycemic control can improve these results. Men with testosterone deficiency may benefit from a combination of oral ED medication and testosterone supplementation.
The medications used to treat high blood pressure do not take into account the symptoms of erectile dysfunction, as their intention is to lower the blood pressure to a more manageable state, reducing the stress put on blood vessels. High blood pressure and ED are seen as separate entities, with the former taking priority for pharmaceutical treatment. This means that the medications used might do nothing to cure erectile dysfunction and may, in fact, prolong it. Medications that lower blood pressure might actually cause a low blood pressure state in the groin area and the arteries supplying the penis, making it near impossible to achieve an erection. The following are examples of such medications:
"Just because there is evidence doesn't mean it's good evidence," says Andrew McCullough, MD, associate professor of clinical urology at New York University Langone Medical Center in New York City, and one of the original clinical investigators for the ED drug Viagra (sildenafil). "And before men with ED start down the naturopathic route, it's smart to make sure that there isn't some underlying medical condition that needs to be corrected." Moreover, it is estimated that 30 million American men have erectile dysfunction, and 70% of cases are a result of a potentially deadly condition like atherosclerosis, kidney disease, vascular disease, neurological disease, or diabetes. Additionally, ED can also be caused by certain medications, surgical injury, and psychological problems.
As a primary care doctor, my most important job is to tailor treatment for my patients while still making decisions based on the medical literature. So when patients tell me their treatment is causing undesired side effects—like ED—I work with them to create a plan to treat the condition while also finding a way to relieve those side effects. Fortunately, there are ways to deal with medically induced ED.
Abstract | Full Text | Full Text PDF | PubMed | Scopus (95) | Google ScholarSee all References Sildenafil is absorbed rapidly, and peak plasma levels of 127 to 560 ng/mL are seen in a fasting state approximately 1 hour (range, 0.5-2 hours) after ingestion.3x3Zusman, RM, Morales, A, Glasser, DB, and Osterloh, IH. Overall cardiovascular profile of sildenafil citrate. Am J Cardiol. 1999; 83: 35C–44C
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
Erectile dysfunction (ED) is commonly called impotence. It’s a condition in which a man can’t achieve or maintain an erection during sexual performance. Symptoms may also include reduced sexual desire or libido. Your doctor is likely to diagnose you with ED if the condition lasts for more than a few weeks or months. ED affects as many as 30 million men in the United States.
The cardiovascular adverse effects of sildenafil use have been studied extensively. Phosphodiesterase type 5, although located primarily in the genitalia, also can be found throughout the systemic vasculature, although other PDEs predominate there10x10Kloner, RA and Zusman, RM. Cardiovascular effects of sildenafil citrate and recommendations for its use. Am J Cardiol. 1999; 84: 11N–17N
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

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.

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.
Apostolo A,  Vignati C,  Brusoni D,  Cattadori G,  Contini M,  Veglia F,  Magrì D,  Palermo P,  Tedesco C,  Doria E,  Fiorentini C,  Montorsi P,  Agostoni P. Erectile dysfunction in heart failure: correlation with severity, exercise performance, comorbidities, and heart failure treatment, J Sex Med , 2009, vol. 6 (pg. 2795-2805)https://doi.org/10.1111/j.1743-6109.2009.01416.x

Abstract | Full Text PDF | PubMed | Scopus (49) | Google ScholarSee all References Also, cigar smoking and passive exposure to cigarette smoke have been shown to significantly predict onset of ED.5x5Feldman, HA, Johannes, CB, Derby, CA et al. Erectile dysfunction and coronary risk factors: prospective results from the Massachusetts Male Aging Study. Prev Med. 2000; 30: 328–338
Abstract | Full Text | Full Text PDF | PubMed | Scopus (95) | Google ScholarSee all References Originally evaluated as a mild preload reducer and antianginal agent in its early phases of development, sildenafil's effect on male and female genitalia became quickly apparent.10x10Kloner, RA and Zusman, RM. Cardiovascular effects of sildenafil citrate and recommendations for its use. Am J Cardiol. 1999; 84: 11N–17N
Whereas lifestyle modification is a reasonable initial step when approaching a hypertensive patient with sexual dysfunction, finding the appropriate antihypertensive treatment is usually the next “complicated” move to care for. Several observational and clinical studieshave consistently associated antihypertensive medication with sexual dysfunction[20]. Whether one class of antihypertensive agents is associated exclusively or more with erectile dysfunction compared to another, however, is a difficult puzzle to solve as there are many other factors (comorbid conditions, concomitant medications, personal characteristics) to be taken into account at the same time. In addition, erectile dysfunction has never been studied as the primary end-point before and as a result a definite causative relationship between antihypertensive medication and sexual dysfunction has never been proven.
Side effects of sildenafil are similar to those from taking niacin or any vasodilator, namely, headaches, lightheadedness, dizziness, and flushing. Some individuals experience a bluish tinge of their cornea, which makes them feel as if they are wearing light blue–tinted sunglasses. This effect can last for several hours. Syncope and myocardial infarction, the most serious side effects, are seen in men who are also taking nitrates for coronary heart disease. Sildenafil also has adverse effects in people with hypertrophic cardiomyopathy because a decrease in preload and after load in the cardiac output can increase the outflow obstruction, culminating in an unstable hemodynamic state.

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


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
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.
A component of the increased risk conferred by ED could be testosterone deficiency.24 Low testosterone leads to increased levels of total and LDL cholesterol, as well as to increased production of pro-inflammatory markers and mediators.25 Endothelial dysfunction and increased arterial wall thickness, stiffening, and calcification also ensue. On this basis it has been hypothesized that chronically lowered testosterone may increase CVD risk. Indeed, androgen deficiency has emerged as a predictor of CV events, as well as of all-cause and CV mortality, both in the general population and in patients with CV risk factors, with hypertension, with established CVD, and with ED.26 Viewed from the opposite angle, higher serum testosterone showed a protective role for CV events in elderly men.27 A 2010 meta-analysis limited to studies in middle-aged men found no association between total testosterone (TT) levels and CVD risk.28 However, a more recent meta-analysis involving a larger number of studies identified significant associations between androgen deficiency and increased risk of CVD and CVD mortality.29 It should be stressed, however, that the nature of these studies cannot prove causality. The possibility that low testosterone may be an epiphenomenon, marking poor general health rather than modulating CVD risk per se has to be explored.

Yet another common erectile dysfunction treatment that can be used in combination with oral drugs is a vacuum pump. This device consists of a plastic cylinder, a pump, a set of constriction bands, and a water-soluble lubricant. The lubricant is applied to the base of the penis to help form an airtight seal. The cylinder is placed over the flaccid penis and held tight against the pelvis. The pump is used to create a vacuum within the cylinder, drawing blood into the penis. Once the penis is engorged with blood, a constriction band is rolled off the cylinder to near the base of the penis. The constriction band is helpful for men with venous leakage, in which blood flows out of the penis as fast as it flows in. However, it should be left on for no more than 30 minutes at a time.
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