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Since 1998, when sildenafil (brand name Viagra) first came on the market, oral therapy has been successfully used to treat erectile dysfunction in many men with diabetes. (Sildenafil was followed in 2003 by the drugs tadalafil [Cialis], vardenafil [Levitra] and avanafil [Stendra], which work in much the same way.) Some 50% of men with Type 1 diabetes who try the drugs report improved erections, and some 60% men with Type 2 diabetes do, too. However, that leaves a large percentage of men with diabetes and erectile dysfunction who do not respond to therapy with one of these pills. This article takes a look at what can be done to treat those men who do not respond to oral therapy.

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
Neurological (nerve and brain) diseases: The nervous system plays a vital part in achieving and maintaining an erection. It is common for men with conditions such as stroke, multiple sclerosis (MS), Alzheimer’s disease, Parkinson’s disease, and spinal cord injuries to experience ED. This is due to an interruption in the transmission of nerve impulses between the brain and the penis.

A nutrient-dense, plant-rich (Nutritarian) diet is a huge defense. When men eat for optimal health, they protect their heart, prostate, brain, and, in effect, the entire body. A nutrient-dense, plant-rich (Nutritarian) diet floods the body with protective nutrients, and supports a healthy weight. It not only normalizes risk factors for heart disease and diabetes, but also offers a substantial level of protection against common cancers.
Current American College of Cardiology/American Heart Association guidelines quote an absolute contraindication to sildenafil use in the setting of chronic nitrate treatment or the use of short-acting nitrate medications.10x10Kloner, RA and Zusman, RM. Cardiovascular effects of sildenafil citrate and recommendations for its use. Am J Cardiol. 1999; 84: 11N–17N
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.
Does drinking water improve erectile dysfunction? Erectile dysfunction or ED is a common concern for men. Everyday factors, such as hydration levels, may affect a person's ability to get or maintain an erection. Drinking water may, therefore, help some men with ED. In this article, learn about the link between hydration and ED, and other factors that can cause ED. Read now
To date, there are no studies directly comparing the effectiveness of these three agents among diabetic men with ED, so it is impossible to state that one agent is superior to another in terms of effectiveness in diabetic patients. However, there are an number of studies that compare the individual agents to placebo in diabetic men with ED. For example, Boulton et al.41 completed a 12-week double-blind, placebo-controlled randomized clinical trial of the effectiveness of sildenafil in 219 men with ED and type 2 diabetes. They found that sildenafil resulted in a significant improvement in the ability to both achieve and maintain an erection adequate for sexual intercourse in men with type 2 diabetes. In a similar study, Rendell et al.42 randomized 268 diabetic men with ED to receive either sildenafil in a dose-escalation manner or placebo. At the conclusion of the 12-week study, 56% of the patients in the sildenafil arm reported improved erections, compared to 10% in the placebo arm (P < 0.001). Additionally, 61% of patients in the diabetic arm reported at least one successful attempt at sexual intercourse in the final month of the study, compared to 22% in the control arm (P < 0.001). Similar randomized studies have documented the effectiveness of both tadalafil43 and vardenafil44 in the treatment of diabetes-related ED.
• Medications: About 25 percent of ED cases are caused by drugs. Many medications, including common medicines prescribed for diabetes and its complications, can cause ED. The most common offenders are blood pressure drugs, antihistamines, antidepressants, tranquilizers, appetite suppressants, and cimetidine (an ulcer drug). In addition, over-the-counter medications, including certain eye drops and nose drops, have been associated with ED. That does not mean you should stop taking these medications! Rather, you should discuss them with your doctor to determine whether a different dosage, an alternate medicine, or additional treatments will resolve the ED.
A significant proportion (ranging from ∼60 to 90%) of heart failure patients report ED and marked decrease in sexual interest, with ultimately one-quarter reporting cessation of sexual activity altogether.48 Erectile dysfunction contributes further to the poor quality of life and aggravates depression. Of interest, many heart failure patients place a greater importance on improving the quality of life (including sexual activity) than on improving survival. Sexual function correlates with the symptomatic status (i.e. NYHA functional class and 6-minute walk test).48 In the Evaluation of Role of Sexual Dysfunction in the Saarland (EROSS) Program, left ventricular dysfunction was a risk factor for ED independent of heart failure symptoms. While heart failure and ED share common pre-disposing risk factors, heart failure by itself can cause ED or affect engagement to sexual activity. Neurohumoral activation, medication (thiazides), limited exercise capacity, and depression are responsible.49

Three longitudinal studies have estimated incidence rates of ED in men with diabetes. Unfortunately, none of these studies specifically examined men with type 2 disease. In a cohort of 278 diabetic men with type 1 or type 2 diabetes potent at study entry, the proportion of patients reporting ED at 5-year follow-up was 28%.7 A follow-up analysis of the Massachusetts Male Aging Study, a community-based cohort of men between 40 and 70 years of age, found that the incidence of ED in the diabetic men was 51/1,000 population-years.8 This figure was similar to the 68/1,000 person-years crude incidence rate of ED reported in a study of 1,010 men with diabetes.5 However, new studies need to be carried out in well-characterized populations of men with diabetes in order to better determine the incidence of ED and potential effects of interventions to reduce complications.


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

Abstract | Full Text | Full Text PDF | PubMed | Scopus (95) | Google ScholarSee all References Phase 2 and 3 trials reported minimal associated cardiac adverse effects, which occurred in 3% of patients taking sildenafil and in 3.5% of patients receiving placebos.10x10Kloner, RA and Zusman, RM. Cardiovascular effects of sildenafil citrate and recommendations for its use. Am J Cardiol. 1999; 84: 11N–17N
• Medications: About 25 percent of ED cases are caused by drugs. Many medications, including common medicines prescribed for diabetes and its complications, can cause ED. The most common offenders are blood pressure drugs, antihistamines, antidepressants, tranquilizers, appetite suppressants, and cimetidine (an ulcer drug). In addition, over-the-counter medications, including certain eye drops and nose drops, have been associated with ED. That does not mean you should stop taking these medications! Rather, you should discuss them with your doctor to determine whether a different dosage, an alternate medicine, or additional treatments will resolve the ED.

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.
Erectile dysfunction (ED) is a common sexual problem affecting many men irrespective of cultures, beliefs and nationalities. While medical therapy for ED has been revolutionized by the advent of oral phosphodiesterase type 5 inhibitors and intracavernosal injection of vasoactive agents, recent technological advances such stem cell therapy, low intensity shock wave and newer generation of penile prosthesis implant offer hope to men who do not respond to conventional medical therapy. In contrast, traditional and complementary medicine (TCM) focuses on the restoration and better overall bodily regulation with the use of various herbal and animal products as well as exercises to invigorate qi (energy) in vital organs. Western medicine involves an analysis of ED symptom and underlying causes that contribute to ED, while TCM emphases the concept of holism and harmonization of body organs to achieve natural sexual life. The following article reviews our current understanding regarding the philosophical approach, and evaluates the evidence surrounding various ED therapies between mainstream Western Medicine and TCM.
Abstract | Full Text | Full Text PDF | PubMed | Scopus (164) | Google ScholarSee all References Several double-blind, placebo-controlled studies have shown vardenafil to be more effective than placebo in the treatment of ED secondary to a wide range of other etiologies as well.71x71Hellstrom, WJ, Gittelman, M, Karlin, G..., and Vardenafil Study Group. Sustained efficacy and tolerability of vardenafil, a highly potent selective phosphodiesterase type 5 inhibitor, in men with erectile dysfunction: results of a randomized, double-blind, 26-week placebo-controlled pivotal trial. Urology. 2003; 61: 8–14
Prescription drugs called “oral phosphodiesterase-5 (PDE5) inhibitors” are considered the “first-line non-invasive treatment” options for patients with ED. These include the drugs that go by brand names: Sildenafil, Vardenafil or Tadalafil. They work by helping the smooth muscle cells lining the blood vessels that supply the penis with blood to work properly. This allows a man to maintain an erection more easily.
* Low-risk patients include those with complete revascularization (eg, via coronary artery bypass grafting, stenting, or angioplasty), patients with asymptomatic controlled hypertension, those with mild valvular disease, and patients with left ventricular dysfunction/heart failure (NYHA classes I and II) who achieved 5 metabolic equivalents of the task METS without ischemia on recent exercise testing.
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
The initial step in evaluating ED is a thorough sexual history and physical exam. The history can help in distinguishing between the primary and psychogenic causes. It is important to explore the onset, progression, and duration of the problem. If a man gives a history of “no sexual problems until one night,” the problem is most likely related to performance anxiety, disaffection, or an emotional problem. Aside from these causes, only radical prostatectomy or other overt genital tract trauma causes a sudden loss of male sexual function.
Abstract | Full Text | Full Text PDF | PubMed | Scopus (207) | Google ScholarSee all References Adverse-effect profiles of headaches, flushing, rhinitis, and dyspepsia, without visual changes, mimic those of vardenafil.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
Crossref | Google ScholarSee all References Other investigators have suggested these medications may exert a hormonal effect. β-Blockers have been associated with decreased free and total testosterone levels in placebo-controlled trials.39x39Rosen, RC and Weiner, DN. Cardiovascular disease and sleep-related erections. J Psychosom Res. 1997; 42: 517–530
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

Abstract | Full Text PDF | PubMed | Scopus (19) | Google ScholarSee all References However, there has been disagreement regarding the effects of diuretics on erectile function; many studies found that only rarely have these medications been implicated convincingly as the cause of a patient's ED.36x36Wein, AJ and Van Arsdalen, KN. Drug-induced male sexual dysfunction. Urol Clin North Am. 1988; 15: 23–31


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 bottom line is that nearly all men with diabetes who wish to have an erection adequate for sexual intercourse can do so with the therapies currently available. And with commitment and communication, the experience of erectile dysfunction can be changed from a potential personal tragedy to an opportunity for greater emotional intimacy in a couple.
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