Erectile dysfunction both disease, symptom

Patients with diabetes who suffer from erectile dysfunction may benefit from phosphodiesterase type inhibitors.

Issue: November 2002

HOUSTON — Erectile dysfunction (ED) is a disease, but it is also a manifestation of other underlying problems, said Glenn R. Cunningham, MD, moderator of “Controversies in Erectile Dysfunction – New Medical Solutions” at ENDO 2002.

“When one is confronted with a patient that has erectile dysfunction, one needs to look for other problems as well,” said Cunningham, professor and vice chairman for research in the department of medicine at Baylor College of Medicine, here.

“Many men have very severe erectile dysfunction, others will have moderate and some will have very mild. All three categories, particularly the severe and moderate, increase with age,” Cunningham said. “Also, we recognize that aging affects the frequency of sexual events so that for individuals who are sexually active, the number of sexual events for any time then decreases with age.”

Organic and psychogenic

Traditionally, ED was simply classified as either organic or psychogenic, with different causes of each. Tom F. Lue, MD, professor of urology at the University of California at San Francisco, now believes most patients have a mixed classification: organic and psychogenic.

The incidence of ED increases with age due to decreased desire and penile sensitivity, Lue said. Men become more dependent on genital stimulation, there is reduced duration and intensity of orgasm, and the refractory period is increased. Diabetes complicates the situation, according to Lue. The patient loses sensory- and some autonomic- nerve function, and there is small vessel disease, muscle myopathy and psychological factors as well. He added that hypertension is one of the most common associated factors with erectile dysfunction. “As blood pressure goes up, so does the incidence of ED,” he said.

To diagnose ED, Lue obtains the patient’s history, conducts a physical exam, some laboratory tests to rule out curable causes and then asks the patient what he wants. “Sometimes the patient actually doesn’t want to have any treatment,” Lue said. “They are so relieved when they become impotent that the wife will not bother them anymore.” If the patient does want treatment, Lue starts with an oral medication such as sildenafil (Viagra, Pfizer). “About 65% of the patients will be satisfied with a good erection, and that’s the end of the story,” he said.

For patients who are taking nitrates, for which sildenafil is contraindicated, or for patients in which sildenafil fails, Lue will conduct further diagnostic testing. Either combined penile injection of a vasodilator and sexual stimulation or ultrasonography can be used to assess penile-vascular function. Cavernosography can be used to diagnose congenital or traumatic venous leakage in young men. Arteriography can be used to diagnose young men with traumatic arterial insufficiency.

Lue typically orders these tests for cases in which the cause of impotence is traumatic or associated with a congenital disease, and the solution is usually surgical, either arterial or venous. “Surgery would not work for the older man with diabetes with atrophy of the penis, and we do not do this kind of testing,” Lue said.

Nocturnal penile monitoring, which monitors the patient’s erections while sleeping helps the diagnostician differentiate between organic and psychogenic cause of ED. If the patient has minimal erections with minimal rigidity, the cause of ED is organic.

If sildenafil fails to provide the patient with a satisfactory erection, Lue recommends intracavernous injection, which has a success rate of about 90%. “The only problem is we have to use a needle, and sometimes you may get priapism, which is a prolonged erection,” he said. “It’s okay to have an erection for an hour or two, but it’s not okay to have an erection for a week.”

Lue said he treats priapism with phenylephrine diluted with normal saline. “Usually we give about 500 µg every three to five minutes, right into the penis,” and if used within 24 hours, “it’s very, very effective,” Lue said.

He reserves penile prosthesis implantation for patients who fail all the other less invasive treatments. Although the success rate is about 90%, Lue said, “any device is going to break, and we may have to re-do it every five to 10 years.”

Endothelial dysfunction

“Endothelial dysfunction as part of the metabolic syndrome has become increasingly a centerpiece for those of us who are concerned about the prevention or modification of cardiovascular risk in patients with diabetes and in the cause of insulin-resistant pre-diabetic states,” said Alan J. Garber, MD, PhD, professor of medicine, molecular and cellular biology and biochemistry at Baylor College of Medicine.

“Endothelial dysfunction is causally linked to the conditions associated with cardiovascular mortality, and it is a mechanism for coronary and atherosclerotic events,” he said. “One of the central underlying etiologies of endothelial dysfunction clearly is excess oxidative stress, which is a major element in patients with diabetes.”

Hypertension is a clear concomitant of erectile dysfunction, and hypertension is an insulin-resistant state, said Garber. “It is true that not every hypertensive patient is insulin resistant, but most studies would agree that most patients with essential hypertension have insulin resistance whether treated or untreated and newly diagnosed compared with normal individuals,” he said.

Nitric oxide

The production of nitric oxide by endothelial cells produces cyclic guanosine monophosphate (GMP), which in turn mediates smooth-muscle relaxation. Animal studies show that it is not possible to produce the same degree of vasorelaxation in the absence of the endothelium, Garber reported.

“The maintenance and initiation of erection requires generation of nitric oxide, but there’s more than one way to produce that nitric oxide,” Garber said. “There is clearly a neuronal component of nitric oxide synthesis and release that participates in the generation of cyclic GMP required ultimately of penile vasorelaxation and the hemodynamic processes. But there is also an important contribution from endothelial generation of nitric oxide. That nitric oxide is equally important in generating the cyclic GMP that initiates the final common pathway of steps producing the altered bloodflow of a normal erectile function.”

Patients with ED also have impaired platelet aggregation and arterial vasorelaxation, which suggest underlying endothelial dysfunction, Garber said. ED patients with underlying endothelial dysfunction could then be susceptible to accelerated atherosclerosis. Although not measured routinely, Garber said that plasminogen activator inhibitor is a mark of endothelial dysfunction and accelerated atherogenic risk in insulin-resistant and diabetic patients.

Role of endocrinologists

“ED is not a disorder of aging,” is the motto of Stanley G. Korenman, MD, professor of medicine in the department of endocrinology at the University of California, Los Angeles School of Medicine. “I tell all my patients this is a physiological change that’s due to a variety of risk factors and that it is treatable,” he said. “I’m glad that patients are beginning to demand treatment from their doctors, but I wish that doctors would ask their older patients about their sex life, not just the younger patients.”

In particular, Korenman said he would like to see endocrinologists become more involved in treating ED. “Endocrinologists are responsible for only about 3% of the prescriptions written for the treatment of ED. Since endocrinologists take care of a lot of diabetes and this problem is enormous in diabetics, it’s hard for me to understand,” Korenman said.

The aging man is faced with numerous factors including disorders of sexual function, hypogonadism and emotional changes, any of which can contribute to ED. The so-called “andropause” is “unlike menopause because there’s not a single hormonal defect responsible for the syndrome, yet a syndrome occurs,” Korenman said. “Men aren’t the same when they’re 70 as when they’re 30, and maybe there’s something we can do about it.”

In addition to ED, sexual dysfunction includes ejaculatory dysfunction and defective penile sensation. Ejaculatory dysfunction is most commonly associated with drug therapy such as selective serotonin reuptake inhibitors. “Disordered penile sensation or diminished penile sensation is much more common than people are aware of, and it occurs a lot in diabetics,” Korenman said. “No one ever asks, and nobody ever finds out, but it takes more direct stimulation to get an erection when you’re older. If you have defective penile sensation, it takes yet more.”

Role of testosterone in ED

With age, many men become androgen deficient as well. Although some older men have experienced improved erectile function with androgen-replacement therapy, treatment with testosterone only helps about one third of men with ED, Korenman said.

He distinguished between testosterone that is bound to sex hormone binding globulin (SHBG), of which 90% is not available to the body’s tissues, and bioavailable testosterone, which is available to the body’s tissues. While SHBG increases with age, both types of testosterone decline with age. Between ages 30 and 65, total testosterone falls by about 50%, and bioavailable testosterone falls by about 70%. When it falls too low, the result is hypogonadism.

Hypogonadism is associated with decreased sexual interest, decreased libido, a decreased feeling of well being and a more depressed mood. “Although you can have each of these separately, they actually overlap into each other,” he said. – by Kathleen Ogle

For more information:
Cunningham GR, Lue T, Garber AJ, Korenman SG. Controversies in erectile dysfunction – new medical solutions. Symposium was presented at Endo 2002. June 19-22, 2002. San Francisco.
Lue TF. Erectile dysfunction. N Engl J Med. 2000; 342:1802-1813.