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link between diabetes, cardiovascular disease (CVD) and ED

by Janet Casperson, BS, MSN, ANP-C

Erectile dysfunction and some forms of female sexual dysfunction are a common complication of diabetes. In fact, sometimes sexual dysfunction is the symptom that causes the patient to seek healthcare and leads to the diagnosis of the diabetes.

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Prevalence of Erectile Dysfunction in Men with Diabetes

The prevalence of erectile dysfunction in men with diabetes is 5% to 75%; at age 60 that number is reported to be anywhere from 55% to 95%. Decreased desire and orgasmic function, as well as the inability to achieve and maintain an erection may mark the onset of sexual dysfunction for men. In men with diabetes, this occurs within 5 to 10 years from the onset of the disease and increases with age.

Men with Type I diabetes have an earlier onset and a more severe degree of sexual dysfunction and they are generally less responsive to conservative medical treatment. Additionally, most of the men who develop Type I diabetes usually do so in their early teens well before they are sexual active and by the time they begin to have sexual activity the disease is typically more advanced.

Almost 100% of men who develop diabetic neuropathy as a complication of their diabetes will have some form and degree of erectile dysfunction. Often we see a more significant degree of erectile dysfunction in men with diabetes because many men with Type II diabetes probably have had the disease for a least a decade and did not know it. Women with diabetes have repeatedly reported decreased lubrication and decreased sexual arousal.

What is the link between diabetes and sexual dysfunction?

As clinicians we frequently ask why this particular symptom is repeatedly showing up in both men and women with sexual dysfunction. Why is sexual dysfunction earlier, more severe and more challenging to treat in our patients who have diabetes? Recently more resources are being given to study this phenomenon and the results are both astounding and complex. Sexual dysfunction, in particular erectile dysfunction, is multi-factorial but the simplest explanation is that endothelial dysfunction is the underlying cause in both men and women. This is the same underlying risk factor as cardiovascular disease. Given that diabetes accelerates atherosclerosis or the hardening of the arteries, we see that endothelial dysfunction is the common link between erectile dysfunction, cardiovascular disease and diabetes.

Unfortunately, in patients with diabetes, endothelial dysfunction is manifested in many different ways which can cause not only erectile dysfunction but multiple comorbidities in many patients. Other mechanisms that cause sexual dysfunction in patients with diabetes include atherosclerosis of the large vessels, neuropathy, obesity, hormonal imbalances, poor glycemic control, stress, hypertension, dyslipidemia, medications, gonadal function, depression, age, microvascular disease, tobacco use and sedentary life style. Any of these factors can be the cause of erectile dysfunction by themselves but when presenting together they are often synergistic. When the symptoms finally present clinically, the effects are often profound and even irreversible.

Diagnostic Work-up for Men with Diabetes and Erectile Dysfunction 

The diagnostic work-up for men with diabetes and erectile dysfunction is similar to that for any man with erectile dysfunction. It must include an evaluation of the severity of the problem with the International Index of Erectile Dysfunction (IIEF), a detailed medical, social and sexual history, a physical examination including a careful examination of the genitalia, an assessment of testicular volume and sensation to the genitals as well. Blood testing is a very important component of the work-up of diabetes and erectile dysfunction.

Blood testing should include a complete blood count, electrolytes (the minerals in the blood stream), a fasting glucose, urea, creatinine, prostate specific antigen (PSA), prolactin, a total testosterone level and hemoglobin A1C. We frequently will add detailed lipid profiles, C-reactive protein, homocystine levels and urinalysis. The urinalysis is important to look for microalbuminuria. This is a relatively new diagnostic marker that is very specific for early endothelial dysfunction and is also seen in people with diabetes and hypertension. It's an additional independent risk factor for cardiovascular disease. What this means is that people who do not have microalbuminuria are at much less risk for silent cardiovascular disease.

When a man has a long history of diabetes, uncontrolled diabetes or is unresponsive to conservative medical treatment for his erectile dysfunction, we always perform a duplex penile Doppler ultrasound. This ultrasound will better enable us to identify the precise cause for the erectile dysfunction and aid in determining the best course of treatment for the couple.

It's important to mention that primary prevention, if aggressively maintained, will stop the progression of erectile dysfunction. If men do not modify the primary cause of erectile dysfunction such as diabetes or uncontrolled hypertension, the medications to help with erectile dysfunction will cease to work with time.

Treatment for Erectile Dysfunction with Diabetes

Treatment for sexual dysfunction and diabetes is dependent on the severity of the disease and how far the couple is willing to go to restore their love making ability. Primary treatment is aimed at preventing and controlling the diabetes with both life style modifications and medications for erections. This centers around maintaining tight glycemic control and control of any other comorbid factors such as the dyslipidemia and hypertension. Tight glycemic control means that the patient will carefully manage his diabetes so his blood sugars are maintained in a relatively tight range and do not go up dramatically two hours after a meal. The degree of control is very easily measured in a serum blood test called the hemoglobin A1C which measures the rate of red blood cells and how much sugar they are exposed to. This test gives the clinician a snapshot of the last three months of glycemic control.

Because of the nature of diabetes and comorbidities, we often use a combination of therapies to treat erectile dysfunction. This is because the diabetes has generally progressed to the point that the tissues are unresponsive to lower doses of medications. Treatment for erectile dysfunction with diabetes includes oral medications, testosterone replacement, vacuum erection devices, constriction rings, intraurethral medications, penile injections and penile implant surgery or a combination of these treatments. We explain these treatments in more detail in other articles at this Center.

Drug Treatments for Erectile Dysfunction with Diabetes

Patients are usually started on Viagra®, Levitra® and Cialis®, usually at higher doses, unless they have contraindications to PDE-5 inhibitors such as concomitant administration of nitroglycerin or alpha blockers. We give patients meticulous dosing instructions when they start taking PDE-5 inhibitors. Several studies have shown that patients respond better when they are given tailored instructions rather than just handed sample packages of medication. We too find the success rate of PDE-5 inhibitors is dramatically improved with tailored instructions especially for patients with diabetes. If the spouse or partner is not present for the visit, we encourage the man to talk to them about starting this medication. We also teach our patients that these medications are not going to cure erectile dysfunction, increase arousal, serve as a form of birth control or protect the man or his partner against sexually transmitted diseases.

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The different PDE-5 inhibitors require slightly different patient education and instruction. The PDE-5 inhibitors all inhibit the same enzyme but there are several nuances that make each one unique in clinical situations. Viagra® should be taken on an empty stomach without alcohol with the onset being approximately 1 hour and a half-life of about 4 hours. The half-life means the amount of time the drug is active in the body. If a man tells us he has not had a successful response to Viagra®, for example, we recommend that he dose it daily for several days before attempting intercourse again. This can frequently lead to success for a substantial number of these patients.

Levitra® can be taken with or without food and with or without alcohol with the onset at approximately 1 hour and a half-life of approximately 4 to 5 hours. Cialis® is unique in that it's taken with or without food with a slower onset of about 1 ½ hours to 2 hours but a half-life of 17 hours; it can remain in the body with good activity for up to 36 hours. This 36 hour number, however, is dependent on the specific patient, how the patient metabolizes the medication and, more importantly, the degree of sexual dysfunction.

These medications all have similar side effects including headache, indigestion, flushing and stuffy nose. Cialis® has a unique but infrequent side effect of muscle aches and back pain seen in a few patients. Viagra® has the unique side effect of blue vision which is seen only at very high doses and typically is without morbidity. If chest pain occurs, you must tell the emergency room doctor that you have used these medications because they can interact with the nitrates commonly used to treat patients with chest pain, causing life threatening hypotension or low blood pressure. Additionally, there has been coverage in the press linking these drugs to incidence of vision loss called NAION. However, research data has not justified this and it is probably not of concern clinically. We often tell patients that if they notice a sudden change in their vision with these medications, they should stop immediately and tell their doctor. We do not feel, however, that these medications are unsafe in this situation.

These medications have ushered in a new sexual revolution and have been a dramatic change in our approach in the management and treatment of erectile dysfunction. Probably more importantly than treating the erection, they've allowed us to understand why men get erectile dysfunction and understand the fact that these treatments are treating only symptoms. Modifying risk factors and lifestyle is still the mainstay of treatment for erectile dysfunction.

Since the advent of these medications in 1998, it's not uncommon to see men who come to the office because these medications have stopped working over the last several years. They may have started the medication in 1998 at low doses and slowly over the years have progressed to the highest dose but it's become ineffective. This is because the primary risk factors have not been changed. We can not emphasize this enough.

Hypogonadism (Low Testosterone) with Diabetes

For several reasons, hypogonadism (low testosterone) is an extremely common condition in men with diabetes. Probably the biggest reason is the increased weight and increased levels of a protein in the blood stream called sex hormone binding globulin (SHBG). The SHBG binds up the body's available testosterone so the available levels are lower in hypogonadal men, which leads to a cycle that prevents the man from losing the weight so weight increases, the SHBG binds up more of the testosterone and the weight continues to increase. Several recent studies have demonstrated that erectile dysfunction is much more successfully treated when the testosterone level is at the optimal level. This is particularly true for a patient with diabetes. It is not uncommon for us to see men who have a poor response to PDE-5 inhibitors whose response dramatically improves when they are treated with testosterone. There is a very specific reason for this: the enzyme needed for PDE-5 inhibitors to work is called nitric oxide (NO). This substance depends on the presence of testosterone for production. When there is no nitric oxide synthase, there is no nitric oxide and these drugs do not work. When the testosterone level is normal to high normal in men with diabetes, the oral medications are more effective.

Interestingly, several studies have addressed the optimal testosterone level to maximize erectile improvement; these levels typically range toward the higher end. In our clinical practice we frequently use higher doses of testosterone and PDE-5 inhibitors in men with diabetes in order to achieve patient and partner satisfaction. Morning erections are directly correlated with testosterone levels; when the testosterone replacement is sufficient, the morning erections return. This is a nice clinical guide. This is further discussed in the article on testosterone replacement.

Other Treatments for ED with Diabetes

Vacuum erection devices, commonly called VEDs, are effective but not particularly popular in the treatment of erectile dysfunction in men with diabetes. With a VED, the constriction ring can decrease sensation in the penis. Coupled with the decreased sensation within the penis related to the diabetic neuropathy, this can lead to a prolonged ejaculation and decreased pleasure for the male. Another complaint is that the penis is cold and rigidity is not as significant as with other treatments. Certainly, VEDs have a role in the early management of erectile dysfunction and remain a viable alternative for a small proportion of patients.

Intraurethral medication such as Muse® has been useful in the treatment of erectile dysfunction in men with diabetes although it has not been studied specifically. We use intraurethral medication for men who cannot tolerate oral medications. This medication is a small pellet placed within the urethra and massaged into the urethra. There are several drawbacks. It can cause dysuria and burning and it is not as effective as direct intracorporeal injections. Patients often need higher dosages and this medication is not nearly as cost effective as the other methods for the treatment for erectile dysfunction.

Penile injections are an extremely useful, successful and popular method for the treatment of erectile dysfunction in men with diabetes. The most common side effect of this medication is burning. The burning is well controlled with combination mixtures of medications as opposed to just prostaglandin and PGE-1. Men with diabetes frequently need higher doses with adjustments. The learning curve for teaching a man with diabetes to do penile injections is much quicker because many of these men are comfortable with a subcutaneous injection and insulin and the techniques are similar. The biggest risk for this method in the man with diabetes is infections. As long as patients use proper techniques and maintain tight glycemic control, the infections are close to zero percent. The only other major concern is that of a prolonged erection. A prolonged erection, also known as priapism, is defined as an erection that lasts more than 4 hours and is painful. This side effect is somewhat common in men who use injections at much higher than recommended doses. We counsel these patients very carefully and use various medications such as Sudafed®, or pseudoephedrine, to prevent this. We recommend that the patient use only one injection per day. Ejaculation sensations are preserved and many times the patient's partner will not even be aware that the man has used a penile injection.

Penile implant surgery is frequently used with great success in men with diabetes and end stage erectile dysfunction. The satisfaction rate for the couple is surprisingly high, greater than 93%. The biggest risk for surgery is infection. However, with tight glycemic control, which is defined as an A1C of less than 7, the risk for infection decreases dramatically. Experienced implanting surgeons will use strict measures to avoid infection, such as preoperative washes with antibiotic solutions, intraoperative irrigations with antibiotic solutions and maintenance of sterile environment where as the device never touches the skin. All of these techniques in concert have dramatically decreased the risk of penile implant infection. The procedure is performed on an outpatient basis and the recovery period is short. Patients are typically able to use their device within 6 to 8 weeks.

Successful management of cardiovascular disease and erectile or sexual dysfunction for the patient with diabetes is control of the diabetes disease process. Maintaining tight glycemic control is the primary key to success. There has never been more information, medications and treatments available at any time in history. A decade ago, patients did not regularly have access to glucose meters. Now, patients commonly are able to check their sugar three and four times a day, carefully monitor their intake of carbohydrates and measure their three-month average of blood sugars. We now know that hyperlipidemia and hypertension are directly associated with diabetes and these can be managed as well. The most important key here is education for the patient.

The other important lesson is that the loss of maintenance of the erection in a man with diabetes is a harbinger of silent cardiovascular disease and should not be ignored.

References: See Bibliography

August 2006
Posted August 2008
Updated August 2009

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