Crossref | PubMed | Scopus (23) | Google ScholarSee all References Similar to sildenafil, vardenafil produces a slight hypotensive effect with an average maximal decrease in blood pressure level of 5 to 10 mm Hg.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
Since erectile dysfunction presents such an intimate relationship with CV parameters, it is easily deducted that it could constitute a powerful tool for detecting asymptomatic CV disease. Consequently, recognition of sexual dysfunction in a hypertensive individual should prompt further diagnostic procedures and therapeutic interventions in order to disclose its silent cardiovascular risk and improve patient’s quality of life and life expectancy.
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
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.
Taking one of these tablets will not automatically produce an erection. Sexual stimulation is needed first to cause the release of nitric oxide from your penile nerves. These medications amplify that signal, allowing some men to function normally. Oral erectile dysfunction medications are not aphrodisiacs, will not cause excitement and are not needed in men who get normal erections.
PubMed | Google ScholarSee all References Postulated mechanisms of effect on sexual function with these centrally acting medications have included increased prolactin levels and a direct effect on α2-adrenergic receptors in the central nervous system.36x36Wein, AJ and Van Arsdalen, KN. Drug-induced male sexual dysfunction. Urol Clin North Am. 1988; 15: 23–31
Co-authors Stacy Mandras, M.D., Patricia Uber, Pharm. D., and Mandeep Mehra, M.D., conducted systematic independent literature searches using the MEDLINE database and examined a broad range of medical research that focused on chronic heart failure, sexual activity and sexual dysfunction. This literature included data from patient surveys and clinical trials.

Erectile dysfunction is the persistent inability to maintain an erection that is not firm enough or lasts long enough to have sexual intercourse. This is a common problem and at least 40 % of men suffer from erectile dysfunction at least occasionally. Manipal Fertility has been instrumental in bringing Men’s Health as an independent area of focus not only for fertility but also erectile dysfunction. We are the pioneers in introducing Non Invasive Shockwave therapy for Erectile Dysfunction.
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.
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.

Treatment of ED which was previously confined to invasive procedures, cavernosal injections or to rather ineffective oral medications was revolutionized in 1999 with the introduction of the orally administered PDE5 inhibitor sildenafil. Phosphodiesterase type 5 inhibitors are the first-line therapy for ED of organic aetiology unless there is a specific contraindication to their use. This class of agents is widely used because of its effectiveness and safety.38 Interactions with cardiovascular drugs have been minimal with the exception of nitrates and other nitric oxide (NO) donors (such as nicorandil), where co-administration may result in severe vasodilation and hypotension. However, nitrates are often overused in clinical practice; therefore, the option of their discontinuation should be considered. A strong body of clinical data shows that all three agents (sildenafil, tadalafil, and vardenafil) do not increase the risk of non-fatal myocardial infarction, stroke, or cardiovascular deaths. These drugs do not exacerbate ischaemia or worsen exercise tolerance in patients with known CAD who achieve levels of exercise comparable or greater than that achieved during sexual intercourse.38,39 Phosphodiesterase type 5 is expressed throughout the human body, including the pulmonary and systemic vasculature and hypertrophied myocardium. While currently their only additional indication, beyond ED, is idiopathic pulmonary hypertension (for sildenafil and tadalafil), they show potential to be of benefit in several other conditions, such as CAD and systolic heart failure.39 Mechanisms of benefit of PDE5 inhibitors include pulmonary and systemic vasodilation, increased myocardial contractility, reduced large artery stiffness and wave reflections, improved endothelial function, and reduced apoptosis, fibrosis and hypertrophy through mechanisms involving NO, cyclic guanosine monophosphate, protein kinase G and Rho kinase.39 A very important issue is whether treatment of ED per se (and not of its risk factors and comorbidities) will have an impact on cardiovascular risk. While this applies to all therapeutic modalities of ED, it is particularly pertinent for PDE5 inhibitors, since they represent the mainstay of ED therapy. Data are limited to date. Gazzaruso et al.21 showed a trend of PDE5 inhibitors to reduce cardiovascular morbidity and mortality in diabetic patients with silent CAD and ED, while Frantzen et al.40 showed that 2 years after the introduction of sildenafil, the relative risk of the incidence of CVD among men with ED compared with healthy men significantly decreased from 1.7 to 1.1.
Guidelines recommend that phosphodiesterase type 5 (PDE5) inhibitors are the first-line drug for the treatment of ED (Table 1). Sildenafil citrate was the first oral drug approved for ED in the US.59 The newer PDE5 inhibitors include vardenafil, tadalafil and avanafil. The inhibition of PDE5 enhances cyclic guanosine monophosphate (cGMP)-NO-mediated vasodilatation by preventing PDE5 catabolism of cGMP and so delaying detumescence. PDE5 inhibitors increase the number and duration of erections, as well as the percentage of successful sexual intercourse.60

Taking one of these tablets will not automatically produce an erection. Sexual stimulation is needed first to cause the release of nitric oxide from your penile nerves. These medications amplify that signal, allowing some men to function normally. Oral erectile dysfunction medications are not aphrodisiacs, will not cause excitement and are not needed in men who get normal erections.

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

Diabetes mellitus is associated with both decreased erectile function and increased cardiovascular risk. The MMAS found that the age-adjusted probability of complete impotence was 3 times higher in patients with diabetes mellitus than in those without the disease.6x6Kloner, RA. Erectile dysfunction and cardiovascular risk factors. Hosp Pract (Off Ed). 2001; 36: 41–44 (49-51.)


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.
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

Gutiérrez-González, Enrique; Castelló, Adela; Fernández-Navarro, Pablo; Castaño-Vinyals, Gemma; Llorca, Javier; Salas-Trejo, Dolores; Salcedo-Bellido, Inmaculada; Aragonés, Nuria; Fernández-Tardón, Guillermo; Alguacil, Juan; Gracia-Lavedan, Esther; García-Esquinas, Esther; Gómez-Acebo, Inés; Amiano, Pilar; Romaguera, Dora; Kogevinas, Manolis; Pollán, Marina; Pérez-Gómez, Beatriz. “Dietary Zinc and Risk of Prostate Cancer in Spain: MCC-Spain Study.” Nutrients. Jan 2019, 11(1).


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
The recommended dosage of sildenafil is 50 mg/day, usually taken 1 hour before sexual activity. This dose may be increased to 100 mg or decreased to 25 mg based on side effects.6 PDE5 inhibitors also have a beneficial effect in the treatment of heart failure with reduced ejection fraction as well as pre- and post-capillary pulmonary hypertension. The use of PDE5 inhibitors in the treatment of right heart failure and left ventricular failure associated with combined pre- and post-capillary pulmonary hypertension has been well studied.71,72
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
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

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 (ED) can be treated by urologists or other specialists or even by your general practitioner. Your doctor may recommend medication that works by relaxing penis muscles and increasing blood flow into the penis. Other treatments include therapy, implants, surgery and lifestyle changes, like exercising regularly, losing weight and eating right.
Intraurethral alprostadil (Muse) provides a less invasive alternative to intrapenile injection. It is a pellet that is inserted 5–10 min before intercourse, and its effects last for 1 h. The response rate is ∼50–60%. It can be used twice daily but is not recommended for use with pregnant partners. Complications of priapism and penile fibrosis are less common than after alprostadil given by penile injection. The cost is ∼$18–24 per treatment.
Diuretics: Diuretics are also referred to as water pills. They can make the flow of blood to your penis less intense. This makes getting an erection difficult. Diuretics are also known to lower zinc levels, which can decrease the amount of testosterone your body makes. In turn, this can decrease your sex drive. It may also affect your muscle contraction.
In Eastern medicine, animal products are commonly used for their perceived health benefits. The philosophy “like nourishes like”, suggests that consuming the organ of an animal will bring benefits to the corresponding organ in one’s body is a common belief. Men seeking greater potency have turned to eating penises from goats, bull, deer, horses, seals and other mammals in the form of cooked dishes or herbal preparations. While there is no scientific evidence supporting this practice, the cultural beliefs remain strong and supplements containing extracts from animal penises are readily available in the form of capsules, often mixed with herbal compounds pitching similar erectogenic properties. A significant proportion of these potency-inducing supplements in Asia have been found to contain PDE5-inhibitors substrates such as tadalafil and sildenafil (30). However uncontrolled use of illicit PDE5-inhibitors under the guise of natural supplements remains a health threat to the general public.

Second-generation cardioselective beta-blockers (atenolol, metoprolol, bisoprolol, etc.) can also lead to ED. Atenolol was shown to cause significant reduction of sexual activity compared with placebo in a double-blind, parallel-arm study.22 The same study also showed a significant reduction in testosterone levels with atenolol versus valsartan. An open, prospective study of hypertensive men treated with atenolol, metoprolol and bisoprolol for at least 6 months showed high prevalence of ED – approaching 66 % – in these patients.23
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
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.
The medicine causes blood vessels to expand, increasing blood flow in the body and to the penis, thus helping patients to get an erection. Invasive surgeries that involve rods and balloons are also available to patients suffering from ED. While these treatments often come with potential side effects, discomfort and a financial burden, some ED patients may see success with them.
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.
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 (37) | Google ScholarSee all References One MET is equal to a resting state, or 3.5 mL/kg per minute. The relative MET values of sexual activity compared with other forms of activity are shown in Table 3. In general, sexual activity is similar to mild or moderate activity for most patients either with or without coronary artery disease.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
Previous studies reported that there is a strong chance of future cardiac events when ED occurs in younger men compared with older men.11 Another study suggested that there is consistent association across age groups.12 A study of men with diabetes found that ED acts as an indicator of cardiovascular events after adjusting for other illnesses, psychological aspects and the usual cardiovascular risk factors.13 Another large-scale study comprising 25,650 men with pre-existing ED suggested that these men had a 75 % increased risk of peripheral vascular disease.14 Moreover, some studies demonstrated a relationship between ED score and number of diseased coronary arteries and plaque burden in coronary arteries.2,15
This may seem like a lot to manage at a glance, however, just focus on one step at a time. If it is more exercise you want to start with, park your car further away from the front door at work so you have to walk a little more every day. Or go out on a walk to make your phone calls.  If you need to eat better,  try low-fat meat and chicken for lunch. Just keep it simple and don’t try to do it all at once.
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
Undoubtedly, heart disease is and will continue to be one of the major health problems of modern society. Approximately one death every forty seconds occurs due to cardiovascular (CV) disease in the United States alone and arterial hypertension is one of the greatest culprits for it[1]. Considering the fact that around 25% of the global population suffer from arterial hypertension, predicted to reach 1.5 billion people in the foreseeable future, it is easily deducted that a respectful part of the general population is under major and constant CV risk[2,3].
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
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.
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.
A considerable number of patients with ED can have psychogenic factors as the only cause, or in combination with organic causes of ED. Depression, low self-esteem and social stresses are among the psychogenic factors that can lead to ED. Depression is an independent risk factor for both ED and IHD; these three disease conditions are interlinked.51 Psychogenic ED can be managed by multiple psychological interventions such as cognitive behavioural therapy, couples counselling and guided sexual stimulation techniques.52
When antihypertensive medication comes to the fore, certain issues need to be carefully addressed. This is due to the fact that medically induced erectile dysfunction is one of the major reasons for non-adherence and treatment discontinuation, a reality that could have deleterious consequences on patient’s cardiovascular profile and health quality in the long term[38,39].
Combination therapy has proven effective for some men who don’t respond adequately to oral medicines. The idea is to use two drugs with different mechanisms of action for better results. Commonly, sildenafil is used in combination with pellets of alprostadil (synthetic prostaglandin E1) that are inserted into the urethra (the tube in the penis that carries urine from the bladder to the outside of the body). Alprostadil also increases the blood supply to the penis, but by different means.
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