When counseling diabetic men who are considering a PDE-5 inhibitor for ED, it is important to set realistic expectations and explain that studies document that all three agents are less effective in diabetic patients than in the general population of men with ED.45–49 For additional information, readers are referred to the excellent review of the use of PDE-5 inhibitors in diabetic men by Vickers and Satyanarayana.50
Erections are extremely complicated and surprisingly fragile. Erections involve chemical signals, nerve impulses, complicated blood pressure changes, and overall fitness in systems ranging from your heart and hormones to your mood. When medication changes how one of these factors works—like blood pressure drops or depression medication—ED is a common side effect. The problem with these completely predictable medically induced side effects is how people react.

Crossref | PubMed | Google ScholarSee all References After controlling for age, trauma, hypertension, and diabetes mellitus, a study of 97 young patients with ED who underwent selective pudendal angiography showed a significant relationship between lifetime cigarette smoking and the degree of internal pudendal and common penile arterial atherosclerosis.28x28Rosen, MP, Greenfield, AJ, Walker, TG et al. Cigarette smoking: an independent risk factor for atherosclerosis in the hypogastric-cavernous arterial bed of men with arteriogenic impotence. J Urol. 1991; 145: 759–763
After getting a diagnosis of ED, most patients can begin treatment right away, but treatment may be delayed for some patients until the health of the heart is more fully assessed or improved. The most common treatment for ED is a pill (phosphodiesterase-5 inhibitor; PDE5-I): Viagra (sildenafil), Cialis (tadalafil), or Levitra (vardenafil). Each of these pills improves erections when taken before sexual activity; alternatively, a low dose of Cialis can be taken once a day. These medicines work by allowing the blood vessels that supply blood to the penis to dilate better during sexual stimulation. The PDE5-Is decrease blood pressure a little bit, but they are safe with most other medications and with other blood pressure pills. The PDE5-Is are not safe with nitrate medications like nitroglycerin, Nitrostat, Nitro Paste, Imdur, isosorbide mononitrate, and Isordil. Mixing a PDE5-I with a nitrate medication could result in severely low blood pressure and even death. Inform all medical professionals (including the ambulance or emergency department) about your most recent ED pill ingestion so that nitrates can be avoided. If you have high blood pressure or benign prostatic hypertrophy (enlarged prostate) and take medicines called α-blockers, your doctor may need to start you on the lowest dose of the PDE5-I.

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.
After getting a diagnosis of ED, most patients can begin treatment right away, but treatment may be delayed for some patients until the health of the heart is more fully assessed or improved. The most common treatment for ED is a pill (phosphodiesterase-5 inhibitor; PDE5-I): Viagra (sildenafil), Cialis (tadalafil), or Levitra (vardenafil). Each of these pills improves erections when taken before sexual activity; alternatively, a low dose of Cialis can be taken once a day. These medicines work by allowing the blood vessels that supply blood to the penis to dilate better during sexual stimulation. The PDE5-Is decrease blood pressure a little bit, but they are safe with most other medications and with other blood pressure pills. The PDE5-Is are not safe with nitrate medications like nitroglycerin, Nitrostat, Nitro Paste, Imdur, isosorbide mononitrate, and Isordil. Mixing a PDE5-I with a nitrate medication could result in severely low blood pressure and even death. Inform all medical professionals (including the ambulance or emergency department) about your most recent ED pill ingestion so that nitrates can be avoided. If you have high blood pressure or benign prostatic hypertrophy (enlarged prostate) and take medicines called α-blockers, your doctor may need to start you on the lowest dose of the PDE5-I.
It is recommended that testosterone be measured in patients with ED because low levels are a reliable measure of hypogonadism. Hypogonadism is not only a treatable cause of ED, but can also lead to reduced or lack of response to PDE5 inhibitors.73 Testosterone deficiency is also associated with increased cardiovascular and all-cause mortality.74 Levels >350 ng/dl do not usually require replacement, but in patients with testosterone <230 ng/dl, replacement can usually be beneficial.57 In patients with congestive heart failure, testosterone replacement can lead to fluid retention, so caution is advised. In these patients, the aim should be to keep testosterone levels in the middle range, i.e. 350–600 ng/dl.57
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
Abstract | Full Text | Full Text PDF | PubMed | Scopus (95) | Google ScholarSee all References Originally evaluated as a mild preload reducer and antianginal agent in its early phases of development, sildenafil's effect on male and female genitalia became quickly apparent.10x10Kloner, RA and Zusman, RM. Cardiovascular effects of sildenafil citrate and recommendations for its use. Am J Cardiol. 1999; 84: 11N–17N
Ischaemic heart disease (IHD), also known as coronary artery disease (CAD), is a predominant manifestation of cardiovascular disease (CVD). CVD is the leading cause of morbidity and mortality, accounting for 17.3 million deaths globally every year; this figure is expected to grow to 23.6 million by the year 2030. Eighty per cent of these deaths occur in lower- and middle-income countries.5 ED and IHD are highly prevalent and occur concomitantly because they share the same risk factors, including diabetes, hypertension, hyperlipidaemia, obesity and smoking.
Dr. Shiel received a Bachelor of Science degree with honors from the University of Notre Dame. There he was involved in research in radiation biology and received the Huisking Scholarship. After graduating from St. Louis University School of Medicine, he completed his Internal Medicine residency and Rheumatology fellowship at the University of California, Irvine. He is board-certified in Internal Medicine and Rheumatology.

Because ED has several causes, sorting out exactly what is causing your problem may take some time. First, make sure your doctor knows about all the medicines you are using, including over-the-counter or herbal products. Drugs frequently used to treat high blood pressure, anxiety, depression, and peptic ulcers can all cause ED. But don’t stop taking any of your medications without first talking to your doctor.
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.
This form of therapy has a response rate of well over 70%. The sympathetic nervous system normally maintains the penis in a flaccid or non-erect state. All of the vasoactive drugs, when injected into the corpora cavernosae, inhibit or override sympathetic inhibition to encourage relaxation of the smooth muscle trabeculae. The rush of blood engorges the penile corpora cavernosae sinusoidal spaces and creates an erection.
Logically, ED secondary to testosterone deficiency should be treated by testosterone replacement. Testosterone levels in men decrease with age.4 Both epidemiological and observational studies have demonstrated that reduced testosterone is associated with increased cardiovascular risk. One meta-analysis showed lower testosterone and higher 17β oestradiol as significant risk predictors despite adjustment for age and body mass index.4 Patients with coronary artery disease (CAD) have been found to have lower testosterone levels than controls, and there is inverse correlation between testosterone and the incidence of major cardiovascular disease (CVD).4 A significant negative correlation has been reported between total testosterone levels and Framingham risk score.4 However, it has been pointed out that ‘It is unclear if this is a causal association or due to low testosterone being a biomarker of poor health’.4 Testosterone replacement as a treatment for …
In a study by Segal et al. (11), 4 out of 5 healthy individuals were able to achieve tumescence beyond 60% maximum rigidity when subjected to PVS using the Viberect® alone, with no other external visual sexual stimulation. In a randomized controlled study by Fode et al. (12) involving 68 men who underwent nerve-sparing radical prostatectomy, 30 men who received PVS to the frenulum daily for 6 weeks, using the Ferticare® vibrator, showed a trend towards better erections. After 1 year, 53% in the PVS group had an IIEF score ≥18 compared with 32% in the control group, although no statistical achievement was achieved. The role of PVS in penile rehabilitation is based on the postulation that PVS provides early activation of the parasympathetic erectile spinal centres at S2–S4 level, which result in early recovery of the neuropraxic cavernosal nerves.
Penile Injection Medication: This is just what it sounds like. Injected at home directly into the penis, the medication alprostadil produces erection by relaxing certain muscles, increasing blood flow into the penis and restricting outflow. Although some sources report an 80 percent success rate, the therapy has disadvantages, such as risks of infection, pain, and scarring—fibrosis—in the penis, and it may also cause priapism. A popular version of this medication is Upjohn Corporation’s Caverject. The MUSE System, by VIVUS, involves the same medicine (a pellet of alprostadil) applied with an eye-dropper-like applicator, directly into the urethra.
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
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)
The 12-week study of 164 men, all with hypertension, was divided into 2 groups of 82, one group with sexual dysfunction, the other group reported normal sexual functioning. Both groups took losartan in dosages of 50 to 100 milligrams daily for the 12 weeks of the study. In the group of men with sexual dysfunction, 88 percent reported improvement in at least one area of sexual function and 73.7% reported an improved quality of life.

But closer questioning often revealed a very different story—men would admit that struggles to achieve an erection usually preceded a heart attack or other cardiac event by one, two, or three years. Back then, the pattern of erectile dysfunction and cardiac disease was so widespread, that most in the medical profession attributed it to simple “aging,” as common as wrinkles and constipation.
Qigong is a form of breathing exercises commonly practised in Asia to maintain health (53). In a cross-sectional population-based comparison study in Taiwan, individuals practising Qigong demonstrate higher SF-36 scores in the domains of physical functioning, role limitations due to physical problems, bodily pain, general health and vitality (54). Techniques to concentrate the energy or qi in the pelvis or genitals are regularly practised, but the effects of Qigong on ED have not been studied.
Crossref | PubMed | Scopus (335) | Google ScholarSee all References Glycemia, as measured by glycosylated hemoglobin, also has been associated with the risk of developing ED in diabetic patients.21x21Klein, R, Klein, BE, Lee, KE, Moss, SE, and Cruickshanks, KJ. Prevalence of self-reported erectile dysfunction in people with long-term IDDM. Diabetes Care. 1996; 19: 135–141
Lindau ST,  Abramsohn E,  Gosch K,  Wroblewski K,  Spatz ES,  Chan PS,  Spertus J,  Krumholz HM. Patterns and loss of sexual activity in the year following hospitalization for acute myocardial infarction (a United States National Multisite Observational Study), Am J Cardiol , 2012, vol. 109 (pg. 1439-1444)https://doi.org/10.1016/j.amjcard.2012.01.355
Some commonly prescribed cardiovascular drugs (beta-blockers, diuretics, angiotensin-converting enzyme inhibitors, etc.) contribute to ED.18 Previous studies have shown a strong association between ED and diuretics in patients treated with hydrochlorothiazide or chlorthalidone.19,20 It has also been shown that patients treated with first-generation non-selective beta-blockers, such as propranolol, had more frequent ED than those treated with a placebo.21
Yohimbine is an indole alkaloid derived from the bark of the African yohimbe tree (33). Yohimbine has been noted to treat fatigue, depression, diabetes, and sexual dysfunction. A meta-analysis of seven placebo-controlled trials (34) deemed yohimbine superior to placebo for the treatment of ED with rare adverse events. The proposed mechanism of action (35) is via the inhibition of central alpha-2-adrenergic receptors, decreasing central inhibition of arousal, and increasing penile nerve stimulation resulting in increased NO. Common side effects include headache, sweating, agitation, hypertension and insomnia. Contraindications include patients on tricyclic antidepressants, anti-hypertensives and central nervous system stimulants.
Dey J. “Evaluation and treatment of erectile dysfunction in men with diabetes mellitus.” Mayo Clinic Proceedings 77. 2002. 276-282. Shabsigh R. “Erectile Dysfunction in Men with Diabetes Mellitus.” Men’s Sexual Health Consult Collection. 2006 Nov. Moore C, Wang R. “Pathophysiology and treatment of diabetic erectile dysfunction.” Asian J Andrology. 2006 Nov. 8: 67-684. Penson D, Latini D, Lubeck D, Wallace K, Henning J, Lue T. “Do impotent men with diabetes have more severe erectile dysfunction and worse quality of life than general population of impotent patients?” Diabetes Care 26. 2003. 1093-1099. Sun P, Cameron A, Seftel A, Shabsigh R, Niederberger C, Guay A. “Erectile dysfunction – an observable marker of diabetes mellitus? A large national epidemiological study.” Journal of Urology 176. 2006. 1081-1085.
Crossref | PubMed | Google ScholarSee all References After controlling for age, trauma, hypertension, and diabetes mellitus, a study of 97 young patients with ED who underwent selective pudendal angiography showed a significant relationship between lifetime cigarette smoking and the degree of internal pudendal and common penile arterial atherosclerosis.28x28Rosen, MP, Greenfield, AJ, Walker, TG et al. Cigarette smoking: an independent risk factor for atherosclerosis in the hypogastric-cavernous arterial bed of men with arteriogenic impotence. J Urol. 1991; 145: 759–763
Crossref | PubMed | Scopus (174) | Google ScholarSee all References All these men had ED and twice underwent symptom-limited supine bicycle exercise echocardiography 1 hour after taking either sildenafil (50 mg or 100 mg) or placebo. This study found no significant changes in resting heart rate, diastolic blood pressure level, or wall motion score index, and the exercise capacity of the 2 groups was similar. Both groups had similar numbers of patients who experienced dyspnea and/or chest pain, had a positive exercise echocardiographic test, and had exercise-induced wall motion abnormalities. Sildenafil caused a mean decrease of 7 mm Hg in the resting systolic blood pressure level compared with the placebo group. In conclusion, this study showed that in patients with stable coronary artery disease, sildenafil caused no change in symptoms, exercise endurance, or presence/extent of exercise-induced ischemia as measured by exercise echocardiography.
Crossref | PubMed | Scopus (53) | Google ScholarSee all References A study of 24 patients with ED and untreated essential hypertension showed decreased levels of free and total serum testosterone compared with normal controls.31x31Hughes, GS, Mathur, RS, and Margolius, HS. Sex steroid hormones are altered in essential hypertension. J Hypertens. 1989; 7: 181–187

A number of nonprescription products claim to be herbal forms of Viagra. Some of these products contain unknown amounts of ingredients similar to those in prescription medications, which can cause dangerous side effects. Some actually contain the real drug, which should be given by prescription only. Although the Food and Drug Administration has banned many of these products, some potentially dangerous erectile dysfunction remedies remain on the market.
A component of the increased risk conferred by ED could be testosterone deficiency.24 Low testosterone leads to increased levels of total and LDL cholesterol, as well as to increased production of pro-inflammatory markers and mediators.25 Endothelial dysfunction and increased arterial wall thickness, stiffening, and calcification also ensue. On this basis it has been hypothesized that chronically lowered testosterone may increase CVD risk. Indeed, androgen deficiency has emerged as a predictor of CV events, as well as of all-cause and CV mortality, both in the general population and in patients with CV risk factors, with hypertension, with established CVD, and with ED.26 Viewed from the opposite angle, higher serum testosterone showed a protective role for CV events in elderly men.27 A 2010 meta-analysis limited to studies in middle-aged men found no association between total testosterone (TT) levels and CVD risk.28 However, a more recent meta-analysis involving a larger number of studies identified significant associations between androgen deficiency and increased risk of CVD and CVD mortality.29 It should be stressed, however, that the nature of these studies cannot prove causality. The possibility that low testosterone may be an epiphenomenon, marking poor general health rather than modulating CVD risk per se has to be explored.
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.
×