While all three forms of male sexual dysfunction can be found among diabetic men, this review will focus on the most common form, ED, because the literature is most mature in this area. Defined as the inability to achieve or maintain an erection sufficient for satisfactory sexual performance, ED is highly prevalent in diabetic men1 and is almost always organic in its etiology. Given that many patients feel that their ED is “in their heads” and that “their provider will dismiss any sexual problems they might bring up,”2 it may be a relief for patients to learn that their ED is physical, related to their diabetes, and treatable. To this end, the goal of this article is to review the epidemiology, pathophysiology, quality of life effect, and treatment of ED in men with type 2 diabetes.
A study conducted by Prince Henry’s Institute in Melbourne Australia published in the Medical Journal of Australia found that men over 20 years of age with erectile dysfunction (ED) have twice the risk of cardiovascular incidents than those of men with normal sexual health. It was also found out that 2% of men aged 55 and older experienced major stroke and cardiac arrest after the initial episode of ED, within a year; 11% experienced something within five years. Experts from Prince Henry’s Institute warned men with these failures to seek advice on erectile dysfunction and high blood pressure. This may indicate a missing vital warning sign of impending heart disease. Why is this happening? Do men with ED predispose themselves to have cardiovascular diseases and strokes or just the other way around?
Second-generation cardioselective beta-blockers (atenolol, metoprolol, bisoprolol, etc.) can also lead to ED. Atenolol was shown to cause significant reduction of sexual activity compared with placebo in a double-blind, parallel-arm study.22 The same study also showed a significant reduction in testosterone levels with atenolol versus valsartan. An open, prospective study of hypertensive men treated with atenolol, metoprolol and bisoprolol for at least 6 months showed high prevalence of ED – approaching 66 % – in these patients.23
Penile vibratory stimulator is a battery operated device with oscillating discs that can provide excitation of afferent penile nerves at various regulated frequency and amplitudes. PVS has been utilised to activate the ejaculatory reflex for patients with spinal cord injury above T10 seeking to collect retrogradely ejaculated semen in fertility treatment (10). The Viberect is a vibratory stimulation handheld device approved by FDA for treatment of ED. It is clamp-shaped with two oscillating discs facing each other near the tips, and the glans penis is placed between the two oscillating discs to receive concurrent dorsal and ventral stimulation at adjustable frequencies and amplitudes.
Erectile dysfunction (ED), or impotence, is when a man has difficulty getting or maintaining a strong enough erection for sexual intercourse or other sexual activity. It can be caused by stress, anxiety or excessive alcohol consumption. But it can also be a symptom of an underlying condition such as atherosclerosis (narrowing of the arteries), diabetes or high blood pressure. Some medications can cause erectile dysfunction, for example beta-blockers and diuretics (commonly used to treat a variety of heart-related conditions such as high blood pressure and heart failure).
ED is generally associated with significant changes in established cardiovascular risk factors. Atherosclerosis is the main cause of ED development in both the general population and patients with diabetes. However, the prevalence of ED is greater in patients with diabetes than in the general population.8 ED has been shown to occur at rates as high as 50 % in patients with CAD.9 A meta-analysis of 12 prospective cohort studies has provided evidence that ED is a predictor of IHD associated with an increased risk of CVD, stroke and all-cause mortality.10
Although ED is a common complication of diabetes, its effect on quality of life is not well understood. Recent work for the Exploratory Comprehensive Evaluation of Erectile Dysfunction (ExCEED) database demonstrates that in the general population of patients presenting to their urologist, ED negatively affects both general and disease-specific health-related quality of life (HRQOL).35 While this study provides insight into the detrimental affect of ED on quality of life, the cohort is somewhat selected, in that all of the patients were seen in sexual dysfunction clinics and therefore may have been more likely to be bothered by their condition and to report worse quality of life.
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.
However, sildenafil should be used carefully with nitrates because their combination can result in severe hypotension and death.68 Both short- and long-acting nitrates are commonly prescribed to treat angina, but they have no prognostic benefit. In addition, there are numerous alternatives to treat angina, such as ranolazine and ivabradine, which do not interact with PDE5 inhibitors. As a result, patients with ED wishing to take PDE5 inhibitors can safely discontinue their nitrates and replace this treatment with the other anti-anginal agents.68
Erectile dysfunction is frequent in patients with established CAD with prevalence rates ranging between 47 and 75% in studies.2,4,14 The AssoCiatiOn Between eRectile dysfunction and coronary Artery disease (COBRA) trial tested the hypothesis that the ED rate differs in CAD patients according to the clinical presentation (acute vs. chronic coronary syndromes) and the extent of vessel involvement (one vs. two to three vessel disease)15 (Figure 3). The overall ED prevalence in CAD patients was 47%, whereas in the normal coronary angiography group the ED rate was 24%. When separately considered, the ED rate was 22% in patients with acute coronary syndromes (ACS) and one-vessel disease and 55 and 65% in patients with ACS and multi-vessel disease and with chronic coronary syndrome, respectively. The study also showed that both severity (IIEF <10) and duration (>24 months) of ED were predictive of severe coronary involvement at angiography. This study offers pathophysiological and mechanistic explanations related to the clinical setting. In patients with multi-vessel disease, regardless of the clinical presentation, the advanced coronary and systemic atherosclerosis is the reason for the high rate of ED. However, in the setting of acute myocardial infarction with one-vessel disease, ED is far less frequent because the atherosclerotic burden is modest (i.e. abrupt occlusion of a single non-obstructing plaque in the absence of extensive atherosclerosis) in both the coronary and penile circulations.15,16
Crossref | PubMed | Google ScholarSee all References Risk factors for cardiovascular disease include diabetes mellitus, obesity, physical inactivity, hyperlipidemia, tobacco use, and hypertension. Often, the relative risk of each of these factors in the development of ED is difficult to assess because many patients with ED and cardiovascular disease have more than 1 risk factor. Another important consideration is the effect of cardiac disease itself on erectile function. A history of a prior myocardial infarction was not found to be a significant independent risk factor for ED in a study comparing sexual function in 50 patients who had a prior myocardial infarction with a control group of 50 patients.14x14Dhabuwala, CB, Kumar, A, and Pierce, JM. Myocardial infarction and its influence on male sexual function. Arch Sex Behav. 1986; 15: 499–504
Diaclina (also known as Panzer’s Darkling Beetle), Korean bug are used as aphrodisiacs in China, Korea and Southeast Asia. These are consumed either whole or as compounds within capsules. It is felt that the aphrodisiac properties come by stimulating the urogenital structures. Flies have been studied for their aphrodisiac effects, including Spanish fly, Chinese cantharide, and Eastern-Indian cantharide (32). The active compound found in the dried and mashed up bodies of these flies is cantharidin, which is a pheromone produced in the accessory glands of the male flies’ genitals. Cantharidin, stimulates the urogenital tract, causing pelvic hyperemia and possibly erections. As cantharidin is toxic and its safety dose not well determined, its use cannot be recommended. Cantharidin is lethal at high doses and exposure can lead to gastrointestinal and urogenital hemorrhage as well as acute renal failure.
Inflatable prostheses are complex mechanical devices that imitate the natural process of erection. Parts are inserted surgically into the penis and scrotum, and activated by squeezing. When erection is no longer desired, a valve on the pump is pressed, and the penis becomes flaccid. Self-contained single-unit prostheses are similar to the inflatable types, but more compact. The entire device is implanted into the penis. When erection is desired, the unit is activated by either squeezing or bending, depending on which of the two types of self-contained prostheses is used.
Basaria S, Coviello AD, Travison TG, Storer TW, Farwell WR, Jette AM, Eder R, Tennstedt S, Ulloor J, Zhang A, Choong K, Lakshman KM, Mazer NA, Miciek R, Krasnoff J, Elmi A, Knapp PE, Brooks B, Appleman E, Aggarwal S, Bhasin G, Hede-Brierley L, Bhatia A, Collins L, LeBrasseur N, Fiore LD, Bhasin S. Adverse events associated with testosterone administration, N Engl J Med , 2010, vol. 36 (pg. 109-122)https://doi.org/10.1056/NEJMoa1000485
The diagnosis of ED in a patient may affect its management in two ways.30 The first relates to the fact that the ED patient, irrespective of whether he has or has not established CVD, is ‘reclassified’ into a higher risk category for future CV events. Management in this case is altered in the sense that more aggressive treatment of risk factors, as well as a close follow-up, is warranted. Implementation of biomarkers in this setting is desirable.
Third, men with Diabetes need to control their blood sugar levels. When your blood sugar is not under control, your body does not produce enough Nitric Oxide (NO) and vascular tissues don’t respond as effectively to NO. When enough blood flows into the penis, penile veins close off and block the blood from flowing out. This process results in an erection. If your body does not produce enough NO or if your penile tissues do not respond to NO, the pressure of the blood flowing into your penis is not sufficient to trap the blood, you penis will not get hard.
A considerable number of patients with ED can have psychogenic factors as the only cause, or in combination with organic causes of ED. Depression, low self-esteem and social stresses are among the psychogenic factors that can lead to ED. Depression is an independent risk factor for both ED and IHD; these three disease conditions are interlinked.51 Psychogenic ED can be managed by multiple psychological interventions such as cognitive behavioural therapy, couples counselling and guided sexual stimulation techniques.52
Crossref | PubMed | Scopus (539) | Google ScholarSee all References After adjusting for age, vascular disease, psychiatric disease, hormonal factors, and marital status, a study of 4462 US Army veterans aged 31 to 49 years found an odds ratio of 1.8 for the risk of developing ED in men who smoked.26x26Mannino, DM, Klevens, RM, and Flanders, WD. Cigarette smoking: an independent risk factor for impotence?. Am J Epidemiol. 1994; 140: 1003–1008
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 obvious risks are the same that accompany any surgery: infection, pain, bleeding, and scarring. If for some reason the prosthesis or parts become damaged or dislocated, surgical removal may be necessary. With a general success rate of about 90 percent, any of the devices will restore erections, but they will not affect sexual desire, ejaculation, or orgasm.
Table 3 is a suggested algorithm for the assessment of patients and their further categorization and handling. There are parts of investigation that are common for patients both with and without CVD, while additional elements of investigation are helpful in categorizing the patient without CVD to the appropriate risk category. Determination of exercise ability and stress testing is crucial to the assessment (see also below ‘Exercise ability: the risk of sexual activity’). Patients without established CVD or diabetes should be evaluated for their risk of future events according to risk scores (SCORE or Framingham). Patients with established CVD or diabetes are by default considered at increased risk. Patients with adequate exercise ability or a negative stress test can initiate or resume sexual activity and begin treatment for ED. In patients with a positive stress test or in high-risk patients, sexual activity should be deferred until the cardiac condition has been treated and stabilized. In all cases, patient follow-up and reassessment is recommended.
David F. Penson, MD, MPH, is an associate professor of urology and preventive medicine in the Keck School of Medicine at the University of Southern California, in Los Angeles. Hunter Wessells, MD, is an associate professor of urology at the University of Washington School of Medicine and chief of urology at Harborview Medical Center in Seattle, Wash.
In the early years of my cardiology practice, I was surprised by the number of men with heart disease who also suffered from impotence. In fact, being incapable of having an erection was the norm rather than the exception after heart attack. In those days, impotence was widely attributed to the psychological depression that often followed heart attack.
In another scientific article published in 2015 in the American Journal of Lifestyle Medicine, respondents who were not taking cholesterol-lowering medication experienced an average 42 mg/dl decrease in LDL cholesterol and an average decrease in triglycerides of 79.5 mg/dl about one year after switching to a Nutritarian diet. Furthermore, case histories presented in that publication documented atherosclerosis reversal.7
In diabetic patients who fail medical management of ED, penile implantation surgery remains a viable therapeutic option. In a recent review of 372 men who underwent implantation of a three-piece inflatable penile implant, 86% reported that the device was still functional 5 years after implantation, and 79% reported that they used the device at least twice monthly.59
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.
Abstract | Full Text | Full Text PDF | PubMed | Scopus (95) | Google ScholarSee all References Another contraindication is the use of recreational drugs (“poppers”) that contain amyl nitrate. The guidelines also caution use in patients who have a high risk of cardiovascular effects, including patients with active coronary artery disease who are not taking nitrates, patients with congestive heart failure with a borderline low blood pressure level and low blood volume, or those with complicated multidrug antihypertensive regimens.
Abstract | Full Text | Full Text PDF | PubMed | Scopus (66) | Google ScholarSee all References However, α-blockers are a well-known cause of retrograde ejaculation secondary to a reversible relaxation of bladder neck smooth muscle.50x50Meinhardt, W, Kropman, RF, Vermeij, P, Nijeholt, AA, and Zwartendijk, J. The influence of medication on erectile function. Int J Impot Res. 1997; 9: 17–26
"If you have an active sex life after a heart attack, it is probably safe to use PDE5 inhibitors," said Daniel Peter Andersson, MD, PhD, a postdoctoral researcher at Karolinska Institutet in Stockholm and the study's lead author. "This type of erectile dysfunction treatment is beneficial in terms of prognosis, and having an active sex life seems to be a marker for a decreased risk of death."
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.
Abstract | Full Text | Full Text PDF | PubMed | Scopus (259) | Google ScholarSee all References Sildenafil should be used with caution in patients with liver dysfunction or renal impairment, as well as in patients taking any medications that inhibit the P-450 pathway such as cimetidine or erythromycin.3x3Zusman, RM, Morales, A, Glasser, DB, and Osterloh, IH. Overall cardiovascular profile of sildenafil citrate. Am J Cardiol. 1999; 83: 35C–44C
Crossref | PubMed | Scopus (528) | Google ScholarSee all References Sildenafil also has good efficacy in patients with ischemic heart disease, as shown by a retrospective subanalysis of data from 11 double-blind, placebo-controlled studies involving 3672 patients with ED and ischemic heart disease who were not taking nitrates.59x59Kloner, RA. Cardiovascular risk and sildenafil. Am J Cardiol. 2000; 86: 57F–61F
Crossref | PubMed | Scopus (42) | Google ScholarSee all References Apomorphine does not appear to have any notable cardiovascular adverse effects and has been used successfully in Europe. However, apomorphine use has been associated with other unpleasant adverse effects such as nausea and emesis, and the drug has not been approved by the US Food and Drug Administration (FDA) for use in the United States.
Erectile dysfunction can occur as a side effect of medication taken for another health condition. Common culprits are high blood pressure meds, antidepressants, some diuretics, beta-blockers, heart medication, cholesterol meds, antipsychotic drugs, hormone drugs, corticosteroids, chemotherapy, and medication for male pattern baldness, among others.
Abstract | Full Text | Full Text PDF | PubMed | Scopus (24) | Google ScholarSee all References Erectile function relies on the arterial blood supply from the internal pudendal arteries, which are branches of the hypogastric arterial system (Figure 1). Substantial increases in internal pudendal arterial flow result in pressures within the penis that are comparable to systemic arterial levels.12x12Rampin, O and Giuliano, F. Central control of the cardiovascular and erection systems: possible mechanisms and interactions. Am J Cardiol. 2000; 86: 19F–22F
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 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.