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.
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

A limitation of the study is that the researchers did not assess the effects of untreated erectile dysfunction, or conversely, the effect of having an active sex life without taking erectile dysfunction drugs. The researchers also were unable to account for socioeconomic status; as a next step, they are planning a larger study that will include more health records and complete information on marital status, educational level and disposable income. They are also pursuing a separate analysis of outcomes from erectile dysfunction drugs in men with Type 1 and Type 2 diabetes.


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.
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
The third Princeton Consensus (Expert Panel) Conference recommends assessing cardiovascular risk in all patients with ED and CVD. This refers to estimating the risk of mortality and morbidity associated with sexual activity. The current recommendations classify patients into low-, intermediate- and high-risk, based on their New York Heart Association class.57 The consensus also recommended that all patients with ED and CVD should undergo lifestyle changes, such as exercise, smoking cessation, healthy diet and weight reduction. These measures are likely to reduce cardiovascular risk and improve erectile function.58
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.
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
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
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.
ED is a common disease affecting men with IHD. Endothelial dysfunction is the link between ED and IHD and both diseases share the same aetiology, risk factors and pathogenesis. Aggressive control of these risk factors – along with lifestyle modification – is recommended to improve symptoms of ED and reduce cardiovascular risk. PDE5 inhibitors remain the first-choice treatment for ED in IHD patients and they have been shown to be safe and effective. However, PDE5 inhibitors can potentiate the hypotensive effect of nitrates so concomitant administration of sildenafil and nitrates is contraindicated. Gene and stem cell therapy are being investigated as a future therapies for ED.

The development of PDE5-inhibitors is a clear example of how Western medicine approached the problem of ED differently from Eastern medicine. The erectogenic effect of sildenafil (Viagra®) was discovered by accident when patients undergoing heart clinical trials reported better erections as a side effect after taking sildenafil. This observation led to further elucidation of the NO/cGMP signalling pathway and development of PDE5-inhibitors as a first-line therapy in ED (5).

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.
A similar situation develops in the fragile penile circulation. Any disturbance in nitric oxide production lowers the capacity to dilate penile arteries, impairing penile engorgement for erection. Release of nitric oxide is readily sabotaged by many conditions, including elevated levels of cholesterol, high blood pressure, increased triglycerides, smoking, metabolic syndrome and diabetes, and excessive consumption of dietary saturated fat.9 If an artery’s inner wall can’t produce nitric oxide, an abnormal constriction of the arteries to the penis follows, effectively choking off blood flow.
The cardiovascular effects of sildenafil during exercise in patients with known or probable cardiovascular disease were studied in a randomized placebo-controlled trial of 105 men with a mean age of 66 years.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
Perk J,  De Backer G,  Gohlke H,  Graham I,  Reiner Z,  Verschuren WM,  Albus C,  Benlian P,  Boysen G,  Cifkova R,  Deaton C,  Ebrahim S,  Fisher M,  Germano G,  Hobbs R,  Hoes A,  Karadeniz S,  Mezzani A,  Prescott E,  Ryden L,  Scherer M,  Syvänne M,  Scholte Op Reimer WJ,  Vrints C,  Wood D,  Zamorano JL,  Zannad F. European Guidelines on cardiovascular disease prevention in clinical practice (version 2012). The Fifth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of nine societies and by invited experts). Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR), Eur Heart J , 2012, vol. 33 (pg. 1635-1701)https://doi.org/10.1093/eurheartj/ehs092

And diabetes affects more than the blood system. “Diabetes also results in nerve dysfunction and, in the penile shaft, [eventually] the muscle starts to atrophy and is replaced by scar tissue or collagen rather than smooth muscle. That’s the ultimate end result in men,” explains urologist Ajay Nehra, MD, professor of urology at the Mayo Clinic in Rochester, Minn. That scenario — damage to all the tissues that support your penis — is what could happen if you do not get and keep your diabetes under control.


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.
Experimental hyperglycemia may also affect cavernosal smooth muscle cell contractile responses. In experimental diabetes, penile smooth muscle has augmented force responses to vaconstrictors, possibly mediated by changes in expression of protein kinase C and the RhoA-Rho kinase Ca2+-sensitization pathway.32 These changes may promote flaccidity and alter the relaxation responses to nitric oxide. End-stage penile dysfunction may occur as a result of diabetes, with progressive loss of normal cavernosal endothelium and smooth muscle cells from the corpus cavernosum.33 Replacement by fibrotic tissue may lead to complete erectile failure.34
There are so many potential reasons a man might develop erectile dysfunction (ED), it's nearly impossible to generalize the best ways to treat it. What works for one man may not work for another simply because they are having problems for different reasons. That said, it may encouraging to hear that there are a variety of options that may be considered, from psychological counseling to lifestyle changes, medications to treatments and devices.
Yes, and there’s the rub. High blood pressure, especially if untreated, can lead to erectile dysfunction (ED). So can medications your doctor prescribes to bring down your high blood pressure. Fortunately, not all meds cause ED. Thiazides, diuretics or “water pills,” are common ED culprits. So are beta blockers. These effective heart meds slow your system down, and also affect blood flow where you need it -- in your penis -- at the right time. Alpha blockers, another class of medications that lower high blood pressure, are less likely to cause ED. So talk with your good doc about medication choices and side effects, so you can choose the right med for you.
If you bike a lot and have a very narrow saddle on your bicycle, consider switching to a "no-nose seat" which is wider at the back than a conventional saddle, allowing more of your weight to be distributed to the sitting bones. Make sure the seat is level or angled slightly downward and at a height that allows your knee to be just slightly bent at the bottom of the pedal cycle. Raising the handlebars on your bike so that you're sitting upright may also help.
When it comes to combating heart disease, most information sources promote drugs and surgery as the only viable options, with lip service to dietary advice that simply does not work. As a result, the demand for high-tech, expensive, but largely ineffective medical care is soaring, causing medical costs and insurance rates to skyrocket. This chase for "cures" is both financially devastating and futile. Morbidity and premature mortality from heart disease continue to rise, with no sign of abating.
Abstract | Full Text PDF | PubMed | Scopus (3562) | Google ScholarSee all References The 9-year follow-up MMAS study also found that self-reported increased cholesterol and unsaturated fat intake correlated positively with the development 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
Low testosterone represents another link between erectile dysfunction and heart disease. A man’s testosterone levels gradually diminish beginning at age 30. By the time he reaches his 70s, testosterone levels may have dropped to a tenth of youthful levels. Diminishing testosterone levels contribute to loss of muscle, increased body fat, and reduced libido. Fatigue is common, as is depression. Low testosterone levels can also result in reduced concentration, irritability, passivity, loss of interest in activities, and even hypochondria.
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
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.)
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

Most cases of sexual dysfunction are related to a physical cause. The most common causes are diabetes, heart disease, neurological trauma or disease, and side effects of medications. Stress and anxiety can also contribute to impotence. While most of the focus has been on men with erectile dysfunction, a number of women also suffer from this disorder.


There are many alternative treatments that may be used to treat erectile dysfunction, although their effectiveness hasn't been proven. Men may benefit from acupuncture to reduce stress and help treat erectile dysfunction. Some people claim that herbal supplements such as Korean red ginseng, ginkgo, and yohimbine may be helpful for treating erectile dysfunction. Other helpful supplements for treating erectile dysfunction may include DHEA (a hormone in testosterone) and L-arginine. However, it's important to remember that these and other supplements may actually contain harmful substances, so talk with your doctor before taking supplements for treating erectile dysfunction.
Your choice of blood pressure medications could make a difference in the bedroom (or wherever you like to have sex). Thiazides (diuretics or “water pills”) and beta blockers are the most likely to cause erectile dysfunction (ED), while alpha blockers the least likely. Alpha blockers work by reducing nerve impulses to blood vessels, allowing blood to pass more easily. Ask your doctor whether these or other blood pressure medications are best for you.

Another study showed a forty percent increase of blood flow to the heart within one year of starting a dietary program designed similar to the one described in my book, The End of Heart Disease. Of pertinent note is that, in the same study, the patients following a high-protein Atkins’ diet decreased blood flow to the heart by forty percent in one year.8 These dangerous high-protein diets are a certain path to erectile impotence and a premature cardiac death.
While additional investigation is usually necessary, the medical and sexual history is essential and frequently the most revealing aspect of the ED assessment process. Questionnaires are an integral part of the history. The International Index of Erectile Function (IIEF), a 15-item, self-evaluation questionnaire is a validated instrument for assessing erectile function, orgasmic function, desire and satisfaction after sexual relations.8 An abridged version of the IIEF is a 5-item questionnaire the Sexual Health Inventory for Men (SHIM) or IIEF-5 (Table 2). Responses to the five questions range from 1 (worst) to 5 (best). Questions 2 to 4 may be graded 0 (if there is no sexual activity, or no sexual intercourse attempt) and the final score ranges from 1 to 25 points; a descending score indicates worsening of erectile function, with values ≤21 being diagnostic of ED.8 Importantly, validated questionnaires correlate with the extend of CAD9 and improve the predictive value of ED for total cardiovascular events compared with a single-question ED diagnosis.5 It cannot be overemphasized that the SHIM can be effectively used not only by andrologists and urologists but by a wide array of medical specialists, such as cardiologists, diabetologists, primary care physicians, etc.
Intracavernosal and intraurethral injections are second-line therapy for patients with ED. Alprostadil is the agent most commonly used for intracavernosal injections. The main adverse effects of intracavernosal injections are painful erection, priapism and development of scarring at the injection site.73 Alprostadil is also available as a topical cream in patients who cannot tolerate injections.75
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And yes, this may all seem easier said than done, when it comes to a condition that is more often than not the subject of jokes—or the cause of embarrassment. Talking to your doctor is the first step in dealing with this complication, which can wreak havoc on your quality of life. Keeping diabetes in check and enjoying a healthy lifestyle can make a huge difference in reducing ED risk, but if that isn't enough, there are successful treatments. Sex brings a range of physical and psychological benefits, whether you have diabetes or not. Preventing or reversing ED isn't just about sex—it's a step toward better health and a more satisfying life.
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.

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Oral medicines: The best known ED medications are the Big Three: Viagra (sildenafil citrate, made by Pfizer, Inc.), Levitra (vardenafil HCl, made by Bayer and GlaxoSmithKline), and Cialis (tadalafil, made by Eli Lilly). The three are chemically very similar, and all have proven very effective. Because they are effective, convenient, and relatively inexpensive (about nine dollars per pill), these medicines have become the treatment of choice for most men experiencing ED.
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