Since their introduction in the therapeutic field, more than a decade ago, PDE-5 inhibitors have revolutionized the treatment of sexual dysfunction. By blocking the activity of PDE-5 isoenzyme, localized throughout the smooth muscle cells of the vasculature (genital vessels included), PDE-5 inhibitors increase the levels of cyclic guanosine monophosphate thus exerting vasodilating properties and facilitating penile erection[40-42]. Due to these properties, sildenafil was the first drug of its class to receive wide acceptance. Its short half-life, food interactions and the associated visual disturbances however, paved the way for the development of newer PDE-5 inhibitors. As such vardenafil with its more rapid onset of action, and tadalafil with its longer half-life and the lack of food interactions or side effects, have offered significant alternatives to sildenafil[43-50].
PubMed | Google ScholarSee all References The risk of ED was 1.83 times higher in men with a total cholesterol level greater than 240 mg/dL as opposed to less than 180 mg/dL. Also, an HDL cholesterol level greater than 60 mg/dL was found to be protective against the development of ED. In the MMAS, HDL cholesterol levels were noted to have an inverse relationship with the presence of ED.4x4Feldman, HA, Goldstein, I, Hatzichristou, DG, Krane, RJ, and McKinlay, JB. Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study. J Urol. 1994; 151: 54–61

A collection of risk factors that strongly predict heart disease—termed the metabolic syndrome—is also associated with erectile dysfunction. An increasingly prevalent condition, this syndrome includes low HDL, increased triglycerides, high blood sugar, and heightened inflammation and causes a three-fold or greater risk of heart attack, stroke, and diabetes. It is largely attributable to excess weight, poor diet, and inactivity and afflicts at least 47 million Americans, signaling that an epidemic of erectile dysfunction is sure to follow. Indeed, a survey of 2,400 men participating in a health screening revealed that metabolic syndrome increases the likelihood of erectile dysfunction by 48%.10
Abstract | Full Text | Full Text PDF | PubMed | Scopus (53) | Google ScholarSee all References Coital position has not been shown to play a role in increased cardiovascular risk; similar peak heart rates and blood pressure levels are evident with either the man or the woman in the superior position during intercourse.90x90Nemec, ED, Mansfield, L, and Kennedy, JW. Heart rate and blood pressure responses during sexual activity in normal males. Am Heart J. 1976; 92: 274–277
Diabetes doubles or even triples the chance that you’ll have erectile dysfunction (ED) and that you could develop it a decade earlier than other men. In fact, the two conditions are so closely linked that some experts believe that for men younger than 45, impotence, or ED, could be an early warning sign of diabetes. The good news is that diabetes treatment, especially if you identify type 2 diabetes early, can also ease ED.
Oral medications (Viagra™, Cialis™, Levitra™ and Stendra™) are a common first step to treat ED, but they don’t work for everyone – especially men with heart disease. Men taking nitrates for heart disease or those taking alpha blocking agents for blood pressure are generally not candidates for oral ED medication.13 In addition, some medications simply do not work for certain men. When ED medication is not the answer, there are other options.

Abstract | Full Text | Full Text PDF | PubMed | Scopus (272) | Google ScholarSee all References No data suggested adverse interactions between sildenafil and other drugs commonly used in the treatment of coronary artery disease, such as aspirin, heparin, or narcotics.10x10Kloner, RA and Zusman, RM. Cardiovascular effects of sildenafil citrate and recommendations for its use. Am J Cardiol. 1999; 84: 11N–17N


Erectile dysfunction is common in the patient with cardiovascular disease. It is an important component of the quality of life and it also confers an independent risk for future cardiovascular events. The usual 3-year time period between the onset of erectile dysfunction symptoms and a cardiovascular event offers an opportunity for risk mitigation. Thus, sexual function should be incorporated into cardiovascular disease risk assessment for all men. A comprehensive approach to cardiovascular risk reduction (comprising of both lifestyle changes and pharmacological treatment) improves overall vascular health, including sexual function. Proper sexual counselling improves the quality of life and increases adherence to medication. This review explores the critical connection between erectile dysfunction and cardiovascular disease and evaluates how this relationship may influence clinical practice. Algorithms for the management of patient with erectile dysfunction according to the risk for sexual activity and future cardiovascular events are proposed.

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.
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.
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).

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 natural history of ED in people with diabetes is normally gradual and does not occur overnight. Both vascular and neurological mechanisms are most commonly involved in people with diabetes. Atherosclerosis in the penile and pudendal arteries limits the blood flow into the corpus cavernosum. Because of the loss of compliance in the cavernous trabeculae, the venous flow is also lost. This loss of flow results in the inability of the corpora cavernosae to expand and compress the outflow vessels.
If you’re taking medication to treat blood pressure, depression, pain, allergies, inflammation, seizures, or heart conditions, you’re one of the tens of millions of people at risk for medically induced erectile dysfunction. It’s just the nature of drug side effects. Yet erectile dysfunction is one of the least talked about side effects of prescription medication.
Abstract | Full Text PDF | PubMed | Scopus (16) | Google ScholarSee all References These medications cause intracavernosal pressure changes in animal models, and human studies have noted deleterious effects on erectile function, decreased libido, and ejaculatory problems.42x42Weiss, RJ. Effects of antihypertensive agents on sexual function. Am Fam Physician. 1991; 44: 2075–2082
Sexual problems might mean you have a broken heart, literally. The most common sexual problem in men is erectile dysfunction (ED). ED affects up to 30 million men in the United States. Surprisingly, ED might be a sign of heart problems. It is important to discuss sexual health with your doctor. Not only can your doctor prescribe medications to improve sexual function, but together you may be able to prevent a major heart problem like a heart attack. This article outlines the steps that you should take if you think you have ED.

The drugs come in several strengths. Most men should start with a low to moderate dose. The dose can be adjusted depending on the results. Men with potential problems should always start with the lowest dose. Every man should avoid consuming alcohol before taking these drugs. Men who do not respond to a full dose on two or three different occasions should try other treatments.


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
PubMed | Google ScholarSee all References However, other studies have noted that, when blood pressure levels are monitored after initiation of antihypertensive therapy, changes in blood pressure level are not correlated with sexual function.38x38Rosen, RC, Kostis, JB, Jekelis, A, and Taska, LS. Sexual sequelae of antihypertensive drugs: treatment effects on self-report and physiological measures in middle-aged male hypertensives. Arch Sex Behav. 1994; 23: 135–152

88. Böhm M, Baumhäkel M, Teo K, Sleight P, Probstfield J, Gao P, Mann JF, Diaz R, Dagenais GR, Jennings GL, et al. Erectile dysfunction predicts cardiovascular events in high-risk patients receiving telmisartan, ramipril, or both: The ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial/Telmisartan Randomized AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease (ONTARGET/TRANSCEND) Trials. Circulation. 2010;121:1439–1446. [PubMed]
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 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.
Abstract | Full Text | Full Text PDF | PubMed | Scopus (95) | Google ScholarSee all References In conclusion, sildenafil, when used alone, seems to produce minimal decreases in blood pressure level, which are well tolerated in healthy patients and in those with stable ischemic coronary disease.3x3Zusman, RM, Morales, A, Glasser, DB, and Osterloh, IH. Overall cardiovascular profile of sildenafil citrate. Am J Cardiol. 1999; 83: 35C–44C
Testosterone therapy (TTh) should be reserved for patients who (i) are symptomatic (ED or reduced libido) of testosterone deficiency45 and (ii) they have biochemical evidence of low testosterone (TT <8 nmol/L or 2.3 ng/mL). In men with borderline TT (8–12 nmol/L or 2.3–3.5 ng/mL), a TTh trial (for 3–6 months and continuation if effective) may be envisaged. While adding a PDE5 inhibitor can be considered in men who have not improved with TTh, the usual clinical scenario is to add TTh in patients who have not responded to PDE5 inhibitors. Improvement is dependent on the testosterone levels with better results being obtained at lower levels of TT.45 Despite evidence of benefit in patients with pre-existing cardiovascular conditions (angina or heart failure), it should be emphasized that TTh is not a medication with cardiovascular indications.
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).
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
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

Some doctors prefer to start a man on the lowest dose of an oral medicine and increase the dose until an effective one is found. Others prefer to start with the highest dose and go to a lower dose only if a man complains of side effects. In either case, it’s important for a man to communicate with his doctor to let him know how the dose he’s using is working.
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