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.
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
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.
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.
Abstract | Full Text | Full Text PDF | PubMed | Scopus (58) | Google ScholarSee all References However, if optimally treated with β-blockers, lipid-lowering agents, and aspirin, these patients have no significantly increased cardiovascular risk associated with sexual activity, although they should receive appropriate risk information.88x88Jackson, G. The use of sildenafil in heart disease [editorial]. Hosp Med. 2000; 61: 526–527
How common is impotence? According to findings from several studies, including “The Massachusetts Male Aging Study,” overall prevalence for men between 40–70 years old is around 52 percent (or around 30 percent of all men between 18–60 years old). That’s right — nearly half of all men over 40 experience erectile dysfunction symptoms at some point. Not surprisingly, research demonstrates that impotence is increasingly prevalent with age. Around 40 percent of men in their 40s experience sexual dysfunction. Up to 70 percent of men in their 70s experience ED. (1) Every year more than 617,000 new cases of impotence occur in the United States alone.

The Epimedium plant is a flowering perennial found throughout Asia and parts of the Mediterranean. Horny Goat Weed’s active ingredient is icariin, a falvonol glycoside and reputed to improve cardiovascular function, hormone regulation, modulation of immunological function and antitumor activity (44). Icariin has also been shown to have a PDE5i effect. Animal studies have been carried out showing improvements in penile hemodynamic parameters. There is one report of tachyarrhythmia and hypomania with the use of this herb (45).

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.
DHEA. Testosterone is essential for a healthy libido and normal sexual function, and erectile dysfunction sufferers known to have low testosterone improve when placed on prescription testosterone replacement therapy. Similarly, studies have shown that taking over-the-counter supplements containing DHEA, a hormone that the body converts to testosterone and estrogen, can help alleviate some cases of ED. But DHEA can cause problems, including suppression of pituitary function, acne, hair loss and its long-term safety is unknown, says McCullough. For this reason, many experts discourage use of the supplements.
Despite the existing controversies, available data so far imply the old generation b-blockers (e.g., propranolol) as the major culprits for sexual dysfunction with the newer ones (carvedilol, celiprolol) to exert a less pronounced negative effect[21-24]. A luminous exception to the rule, nebivolol, is a newer agent of its class which significantly ameliorates erectile dysfunction through increased nitric oxide generation, an effect consistently demonstrated in recent studies[25,26]. Diuretics, even on adjunct therapy, constitute another antihypertensive agent negatively associated with sexual function[27-29]. On the other hand, calcium antagonists and angiotensin converting enzyme inhibitors seem to demonstrate a neutral effect[30-32]. Interestingly, angiotensin receptor blockers (ARBs) by blocking the vasoconstrictive action of angiotensin II seem to positively affect erectile function and are thus regarded as a first-line treatment in hypertensive patients with erectile dysfunction[22,25,33-35].
Abstract | Full Text | Full Text PDF | PubMed | Scopus (328) | Google ScholarSee all References Their mean resting systolic and diastolic blood pressure levels decreased by 6% and 11%, respectively, compared with baseline. These patients also experienced a mild decrease in mean resting right atrial pressure, pulmonary artery pressure, pulmonary artery occlusion pressure, and cardiac output. However, the hemodynamic response to exercise was preserved. Phase 2 and 3 trials showed no difference in the rate of adverse events between sildenafil and placebo in patients being treated with antihypertensive medications. The effects of sildenafil on blood pressure level were similar in patients who were taking antihypertensive medications compared with those who were not. In healthy volunteers, no consistent or significant doserelated electrocardiographic (ECG) changes were noted at 1 and 2 hours after doses of sildenafil ranging from 1.25 to 200 mg.3x3Zusman, RM, Morales, A, Glasser, DB, and Osterloh, IH. Overall cardiovascular profile of sildenafil citrate. Am J Cardiol. 1999; 83: 35C–44C
Diabetes mellitus (DM) is strongly associated with an increased risk of erectile dysfunction (ED), the persistent inability to achieve or maintain an erection sufficient for satisfactory sexual performance, but this condition can be successfully treated in the majority of diabetes patients. ED is present in 32% of type 1 and 46% of type 2 DM patients. Several population- based studies of ED prevalence calculated the odds ratios for the association between ED and various chronic diseases. An odds ratio must be sufficiently greater than 1.0 to identify an increased risk. Diabetes has an odds ratio, ED risk multiplier of 4.1, compared with 1.7 for hyperlipidemia and 1.6 for hypertension. Erectile dysfunction in diabetes mellitus (EDDM) patients has been considered to have an organic etiology. Healthcare providers have long realized that ED can be the first symptom of DM.
According to the Cleveland Clinic, “because erectile dysfunction is caused by a complex set of psychosocial, neurologic, and vascular factors, a specific cause in a patient may remain ambiguous.” The root causes are often related to a blockage or dysfunction of blood vessels. For example, ED can be due to conditions like atherosclerosis or diabetes, hormonal imbalances or problems related to mental health. It’s been found that common causes typically include one or more of the following factors: (2)
A medical history focused on risk factors, such as cigarette smoking, hypertension, alcoholism, drug abuse, trauma, and endocrine problems including hypothyroidism, low testosterone levels, and hyperprolactinemia, is very important. Commonly used drugs that disrupt male sexual function are spironolactone (Aldactone), sympathetic blockers such as clonidine (Catapres), guanethidine (Islemin), methyldopa (Aldomet), thiazide diuretics, most antidepressants, ketoconazole (Nizoral), cimetidine (Tagamet), alcohol, methadone, heroin, and cocaine. Finally, assessment of psychiatric history will help identify emotional issues such as interpersonal conflict, performance anxiety, depression, or anxiety.
Beta-blockers: A popular blood pressure medication that affects part of the nervous system in an attempt to slow and regulate heartbeats, helping reduce blood pressure. Unfortunately, this same part of the nervous system is also responsible for causing erections, and when beta blockers are used, it indirectly reduces the amount of blood flow to the penis.

Erectile dysfunction is defined as the inability to attain or maintain a penile erection sufficient for satisfactory sexual performance. Cases of ED may be classified as predominantly organic in nature, predominantly psychogenic, or mixed. Usual organic aetiologies are vasculogenic, hormonal, and neurogenic. Owing to the relationship of vasculogenic ED with CVD, it is important to distinguish men with predominantly vasculogenic ED from those with predominantly psychogenic ED or non-vasculogenic organic ED.
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

This category of treatments includes external vacuum therapies: devices that go around the penis and produce erections by increasing the flow of blood in, while constricting the flow out. Such devices imitate a natural erection, and do not interfere with orgasm. External vacuum therapy mechanisms are approximately 95 percent successful in causing and sustaining an erection. All are portable, and costs range between $200-$500, covered under most insurance plans and Medicare Part B.
Crossref | PubMed | Google ScholarSee all References In the general population, the estimated relative risk of experiencing a myocardial infarction within 2 hours after sexual intercourse is approximately 2.5 times higher than the baseline infarction risk of that individual, which itself is extremely low8x8Muller, 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
PubMed | Google ScholarSee all References Diabetes was found to play a major role in vasculogenic impotence in a study of 265 patients with ED who underwent color duplex ultrasonography of the cavernosal arteries after intracavernosal injection of prostaglandin E1.13x13Chung, 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
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.
PubMed | Google ScholarSee all References As with sildenafil, use of nitrate or NO-donor medications is contraindicated while taking tadalafil because of the potential for marked hypotensive interactions.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
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
A number of over-the-counter herbal supplements claim to treat ED. However, according to the Mayo Clinic, you should avoid products labeled as “herbal Viagra.” These supplements can increase blood flow and cause dangerous drops in blood pressure. Risk may be particularly high for men who are using nitrates. Herbal Viagra can also interact with other prescription drugs. Herbal Viagra products may contain potentially toxic compounds that aren’t listed on the label.
A recent systematic review and meta-analysis of relevant studies in this field confirmed that erectile dysfunction is associated with increased risk of CV events and all-cause mortality[89]. The pooled relative risks were 1.44 (95%CI: 1.27-1.63) for total CV events, 1.19 (95%CI: 0.97-1.46) for CV mortality, 1.62 (95%CI: 1.34-1.96) for myocardial infarction, 1.39 (95%CI: 1.23-1.57) for cerebrovascular events, and 1.25 (95%CI: 1.12-1.39) for all-cause mortality, for men with vs without erectile dysfunction. Of note, the relative risk was higher in intermediate-compared with high- or low-CV-risk populations and with younger age, with obvious clinical implications. Interestingly, the relative risks were higher when erectile dysfunction was diagnosed with the use of a questionnaire compared with a single question (RR = 1.61; 95%CI: 1.38-1.86 vs RR = 1.27; 95%CI: 1.18-1.37, respectively; P = 0.006).
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.

A man needs to try the medicine at least four times before he concludes that it doesn’t work for him. It is unlikely that a man with diabetes who has other medical problems such as high blood pressure, is taking multiple medicines, and has not had sexual intercourse for several years will be able to have an erection adequate for intercourse the first time he takes a pill. Most men need to try the medicine several times before they have the desired results.
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