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


Abstract | Full Text | Full Text PDF | PubMed | Scopus (30) | Google ScholarSee all References Increased cGMP levels cause intracellular calcium levels to decrease, resulting in relaxation of the corporeal smooth muscle, active dilatation of the penile arteries, arterioles, and sinusoids, and finally, increased arterial inflow and passive compression of penile venous outflow.10x10Kloner, RA and Zusman, RM. Cardiovascular effects of sildenafil citrate and recommendations for its use. Am J Cardiol. 1999; 84: 11N–17N
There have been some studies to suggest that a placebo effect that improves ED may work for some men. One study found that men taking an oral placebo pill showed as much improvement in ED symptoms as men who took actual medication to improve ED. Conversely, men who were given therapeutic suggestions to improve ED did not see signs of symptom improvement.

Crossref | PubMed | Scopus (47) | Google ScholarSee all References Because of this perceived increase in risk, many couples are concerned about resuming sexual activity in the setting of cardiac disease. A study that monitored male patients after coronary artery bypass grafting found that 17% of patients and 35% of their partners were afraid of resuming sexual activity.1x1Muller, JE. Sexual activity as a trigger for cardiovascular events: what is the risk?. Am J Cardiol. 1999; 84: 2N–5N
Several other facts support the close relationship between sexual dysfunction and CV disease. Endothelial dysfunction mediated by decreased nitric-oxide bioavailability as well as atherosclerotic lesions constitute a common pathophysiologic substrate affecting both CV disease and erectile dysfunction, a disease considered to be primarily of vascular origin[76,80-82]. Several traditional CV risk factors (diabetes mellitus, hypertension, dyslipidemia, and smoking) are frequently found in individuals with erectile dysfunction, conferring a detrimental cardiovascular burden to them. More interestingly, the increased cardiovascular risk observed in those patients is independent of the aforementioned CV risk factors[81-88].
What comes after an ED diagnosis in diabetic patients? Often, Dr. Eid will instantly refer these men to a cardiologist. “If a patient has diabetes and is newly diagnosed, a significant portion of these men are going to develop coronary artery disease in the next 2-3 years,” he said. “One of the things we do is recommend is that they see a cardiologist and perhaps have a stress test or some sort of evaluation.”
At the same time, people with diabetes are susceptible to a type of blood vessel damage known as endothelial dysfunction. A recent study found that men with ED are at a greater risk of heart disease, which is also associated with endothelial dysfunction. If blood vessels aren't in good working order, the penis may not get enough blood for an erection.

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


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medicines called alpha-blockers such as Hytrin (terazosin
HCl), Flomax (tamsulosin HCl), Cardura (doxazosin
mesylate), Minipress (prazosin HCl), Uroxatral (alfuzosin HCl),
 Jalyn (dutasteride and tamsulosin HCl), or Rapaflo (silodosin).
Alpha-blockers are sometimes prescribed for prostate
problems or high blood pressure. In some patients, the use
of Sildenafil with alpha-blockers can lead to a drop in blood pressure or to fainting

airdone/ShutterstockErectile dysfunction (ED) is a serious issue for men, which helps explain all the prescription drugs, over-the-counter treatments, and herbal concoctions that claim to cure ED. (In fact, it’s one of the top nine health risks men need to watch out for.) But before any guy decides to take matters into his own hands, he should talk to his doctor about a heart checkup: A new study published in the journal Vascular Medicine suggests ED can signal cardiovascular concerns.
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).
Hyperlipidemia has been implicated in the development of ED by several different mechanisms. Hyperlipidemia is associated with development of atherosclerotic blood vessel disease, thus contributing to vasculogenic impotence. Penile vascular changes have been noted in impotent patients with elevated serum lipids.7x7Virag, R, Bouilly, P, and Frydman, D. Is impotence an arterial disorder? a study of arterial risk factors in 440 impotent men. Lancet. 1985; 1: 181–184
Penile prosthesis implant remains the most effective and permanent treatment for ED. Penile prosthesis implants can be broadly divided into malleable and inflatable prostheses (20). Malleable penile prosthesis, also known as semi-rigid prosthesis, does not allow for (physiological) flaccid state of the penis. The patient can bend the prosthesis upwards for sexual intercourse and downwards for concealment. Although the angle of prosthesis concealment has improved with recent devices, however due to the constant rigid state of the penis, they are still less comfortable compared to their inflatable counterparts, are more likely to cause social embarrassment and associated with higher risk of implant erosions (21). However, malleable prosthesis still has its place for the treatment of ED as these implants are easier to handle, easier to place and would benefit patients with impaired manual dexterity.
Cigarette smoking is an established risk factor in the development of atherosclerotic vascular changes and thus would be expected to play a role in the development of vasculogenic ED. The MMAS 9-year follow-up study found that the risk of developing moderate or complete ED in smokers was nearly doubled (odds ratio, 1.97) compared with that in matched nonsmokers.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
Abstract | Full Text | Full Text PDF | PubMed | Scopus (95) | Google ScholarSee all References Sildenafil is taken orally 1 hour before anticipated sexual intercourse and enhances the normal response to sexual stimulation; however, it has no effect on erections in the absence of stimulation.10x10Kloner, RA and Zusman, RM. Cardiovascular effects of sildenafil citrate and recommendations for its use. Am J Cardiol. 1999; 84: 11N–17N
Relation between erectile dysfunction prevalence and type of coronary syndrome (A). Time interval (months) between erectile dysfunction and coronary artery disease symptom onset in chronic coronary syndrome according to the number of vessels involved (B). ACS, acute coronary syndrome; CCS, chronic coronary syndrome, G1: ACS and 1-VD; G2: ACS and 2-,3-VD; G3: CCS. VD, vessel disease; C: the control group with normal coronary angiography. With permission from Montorsi et al.15

Conversely, and of significant clinical importance, is how often patients with ED as their first and sole clinical manifestation suffer from subclinical CAD.17 Previous studies reported a rate of inducible ischaemia by exercise stress testing (EST) in 22% (with a wide range of 5–56%) of ED patients reflecting differences in patient population, risk factors and criteria used for ED and CAD diagnosis. Interestingly, those patients further assessed with coronary angiography had obstructive atherosclerosis in >90% of cases.4,18 In a prospective angiographic study, we documented that 19% of ED patients suffer from clinically silent obstructive CAD.18


Overall, sildenafil appears to be relatively safe and effective for treatment of ED in men with stable cardiovascular disease who are not taking NO-donor medications. In a study of 105 men with ED and known or likely coronary artery disease, patients underwent symptom-limited supine bicycle echocardiography 2 times after receiving either sildenafil or placebo.63x63Arruda-Olson, AM, Mahoney, DW, Nehra, A, Leckel, M, and Pellikka, PA. Cardiovascular effects of sildenafil during exercise in men with known or probable coronary artery disease: a randomized crossover trial. JAMA. 2002; 287: 719–725
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).
Contraindications for TTh include (for detailed listing, please refer to Buvat et al.45) patients with breast or prostate cancer, while patients with a palpable prostate nodule or induration, or prostate-specific antigen >4 ng/mL (or >3 ng/mL in men at high risk for prostate cancer, such as African-Americans or men with first-degree relatives with prostate cancer), should first undergo urological evaluation. Testosterone therapy is contraindicated also in patients with haematocrit >50% (TTh increases haematocrit) and uncontrolled congestive heart failure (risk of fluid retention). Risk for adverse CVD events may be increased in patients and with the mode of treatment epitomized in the study of Basaria et al.46 (see earlier).
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
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.)

The blood supply to your penis starts in your heart and flows through arteries in the belly to even smaller arteries that branch off to carry blood into the penis. With sexual stimulation, these blood vessels need to rapidly increase blood flow. If these blood vessels are blocked (atherosclerosis) by coronary artery disease, you may not be able to achieve or maintain an erection.11

In an open-label study, 8 patients monitored with a Swan-Ganz catheter were given a total of 40 mg of sildenafil in 4 intravenous transfusions (the equivalent of 1 to 3 times the plasma concentration after an oral dose of 100 mg).62x62Jackson, G, Benjamin, N, Jackson, N, and Allen, MJ. Effects of sildenafil citrate on human hemodynamics. Am J Cardiol. 1999; 83: 13C–20C

Patients who use this therapy should be trained under the guidance of a urologist, and sterile technique must be used. The drugs must be injected into the shaft of the penis and into one of the penile erectile bodies (corpus cavernosum) 10–15 min before intercourse. Most patients do not complain of pain upon injection. Sexual stimulation is not required, and resulting erections may last for hours. Side effects include penile pain and priapism. The cost is about $12–20 per injection.
medicines called alpha-blockers such as Hytrin (terazosin
HCl), Flomax (tamsulosin HCl), Cardura (doxazosin
mesylate), Minipress (prazosin HCl), Uroxatral (alfuzosin HCl),
 Jalyn (dutasteride and tamsulosin HCl), or Rapaflo (silodosin).
Alpha-blockers are sometimes prescribed for prostate
problems or high blood pressure. In some patients, the use
of Sildenafil with alpha-blockers can lead to a drop in blood pressure or to fainting
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.

Having your current medication checked – if you are taking medication already, it could be that your erection problems are a side effect. Have a doctor check whether this is the cause of your problems and if it is, you might be able to switch medications and then find that your erectile dysfunction goes away completely – or at least improves. Medications that can cause erection problems include:
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
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
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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