Treating Erectile Dysfunction in Diabetic Men

Abstracts & commentary

Sources: Rendell MS, et al. Sildenafil for treatment of erectile dysfunction in men with diabetes: A randomized controlled trial. JAMA 1999;281(5):421-426; Lipshultz LI, Kim ED. Treatment of erectile dysfunction in men with diabetes. Commentary. JAMA 1999;281(5):465-466.

Erectile dysfunction (ed) affects approximate-ly half of American men (52%) between 40-70 years of age. Diabetics suffer from it at a significantly greater rate. At least one study indicates that 28% of diabetic males suffer complete erectile incapacity, a rate almost three times greater than in the general population. The immediate mechanisms of ED consist largely of impaired penile hemodynamic functions secondary to the damage of microvascular and microneural structures in the region. Normally, nitric oxide (NO) generated in the region triggers and sustains the erectile activities of these tissues.

Sildenafil (Viagra) taken orally in 50 or 100 mg tablets acts to increase NO activity in the corpus cavernosum, thereby enhancing erectile activity. Rendell and colleagues evaluated the drug’s improvement in a double-blind study of 268 biologically matched diabetics with ED, ranging from 33-76 years of age. Following a four-week no-treatment phase, 132 randomized diabetic men were assigned to placebo and 136 were demographically matched to receive sildenafil. Approximately 80% of both the placebo and treated groups had type 2 diabetes.

The following averaged numbers emphasize the similar functional conditions of both the treated and nontreated numbers: age, 57 years (mostly 45-64); length of ED, 5.5 years; duration of diabetes, 12.1 years; type 2 diabetes, 81%; hypertension, 52%; ischemic heart disease, 26%; medications for hypertension, 54%; for cardiac, 12%; and antidepressants, 5%. Required were: stable, controlled diabetes for at least three months; plasma glucose level less than 300 mg/dL; and a stable female partner. Excluded were: patients with anatomic genital deformities; sexual disorders; severe psychiatric problems; serious systemic disease; severe hypertension; active diabetic retinopathy; severe autonomic neuropathy; diabetic ketoacidosis within 36 months; and regular use of nitrates.

Median length of treatment was 85 days for both groups. Median numbers of agent doses were 31 (range, 3-81) sildenafil and 25 (range, 2-83) placebo. Most treatment men (93%) took 100 mg sildenafil tablets, whereas 96% of the placebo patients took the largest available blank.

Outcomes at the 12-week termination of the study included the following: S = sildenafil receivers, P = placebo receivers. All quoted differences between S and P were significant at the P < 0.001 level.

1. Measurably improved erections: S = 56%.

2. Percent of successful erections during the last four weeks of treatment: S = 48%; P = 12%.

3. Numbers achieving at least one successful attempt at intercourse: S = 61%; P = 22%.

4. Ability to achieve erections at end of study compared with outset: S = 78%; P = 25%.

5. Functional improvement in maintaining erection at end of study compared to the start: S = 93%; P = 14%.

Adverse reactions occurred mainly among the sildenafil recipients as follows: transient headache 11%; dyspepsia 9%; mild respiratory symptoms 6%. Cardiac events occurred in 3% with sildenafil and 5% with placebo, but none were severe. Only 4% of the S group discontinued the drug vs. 8% in the P group.

Comment by Fred Plum, MD

Erectile dysfunction and related sexual impairments are bringing misery to more than half the American males older than age 40. Although many of the difficulties relate to psychiatric origins, neurological impairment with or without associated neuro-arteriolar disease contributes measurably to such patients’ despair. Urologists have an important position in treating urinary tract and kidney diseases, but only a few have a strong knowledge of autonomic function/dysfunction and how to identify or approach the nervous system’s visceral regulations. Other physicians of various disciplines may make a difference in these men’s lives by investigating the patient’s sexual function and to evaluating their need for treatment. Rendell et al indicate that sildenafil can bring at least a measure of erectile effectiveness to males with diabetes, but this is pharmacologically just a start. Greater understanding of the pathophysiology of normal and abnormal erectile function along with the development of new treatments can derive from greater attention, ingenuity, and treatment by neurologists. (Dr. Plum is Professor and Chairman of the Department of Neurology and Neuroscience at the Weill Medical College of Cornell University, New York.)