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Cancer and Male Sexual Dysfunction

Cancer and Male Sexual Dysfunction

Erectile dysfunction is a common occurrence as men age. Approximately 20% of men over the age of 50 years report difficulty in achieving or maintaining an erection, and as many as 60% of men age 70 and older suffer from erectile dysfunction.[1]

The risk factors for erectile dysfunction include hyperlipidemia, diabetes, cigarette smoking, some treatments for heart disease and hypertension, hypoglycemic agents, depression, pelvic surgery, and psychological factors. Erectile dysfunction may also be a marker for cardiovascular disease,[1] although this is currently unproven.

Erectile dysfunction following cancer therapy represents a major concern for potent men. Dr. Costabile provides a comprehensive review of this subject. He describes the major breakthroughs in our understanding of erectile dysfunction, as well as different forms of therapy.

Erectile Dysfunction in Patients With Prostate Cancer

The major urologic cancer associated with the development of erectile dysfunction is prostate cancer. In 1999, it was estimated that 179,000 men were diagnosed with prostate cancer.[2] Approximately two-thirds of these patients were treated with local therapies, primarily radical prostatectomy or radiation therapy, and were at risk of developing erectile dysfunction.

The risk of erectile dysfunction following radical retropubic prostatectomy has decreased markedly since the utilization of nerve-sparing procedures. In my experience, impotence following radical prostatectomy is related to age, as well as the extent of the local tumor.

The incidence of erectile dysfunction following radiation therapy has been grossly underestimated. The author reports that 90% of men will have erectile dysfunction at 5 years following external-beam radiation therapy.[author’s reference 6]

There has been renewed interest in seed implantation for the treatment of prostate cancer, and selection of patients for this treatment modality is frequently predicated on its ability to preserve sexual function. Nevetheless, 30% of patients so treated complain of erectile dysfunction by 3 years following the implant.[3]

The Advent of Sildenafil

The introduction of effective oral treatments, such as sildenafil (Viagra), has had a revolutionary impact on erectile dysfunction. Initially developed for the treatment of angina, sildenafil is a selective inhibitor of phosphodiesterase type 5 (POE5). Phosphodiesterases comprise a diverse family of enzymes found not only cardiac tissue but also in the penis and other parts of the body. Sildenafil enhances the relaxant effects of nitrous oxide on the corpora cavernosa, thereby enabling the natural erectile response to sexual stimulation to occur.

The initial study of sildenafil in men with erectile dysfunction, an 8-week randomized, placebo-controlled trial, showed a dose-dependent effect of the drug, with improvement in 73% of patients receiving 50 mg and 78% receiving 100 mg. In the placebo group, only 28% of patients reported improvement in their erections.[4]

Nearly 18 double-blind, placebo-controlled studies have substantiated the efficacy of sildenafil in treating erectile dysfunction.[5-7] The drug appears to be effective in the treatment of erectile dysfunction caused by a broad spectrum of etiologies. The onset of effect of sildenafil appears to be 1 to 4 hours after taking the oral dose.

Unfortunately, the activity of sildenafil is reduced in men with coexisting diabetes, spinal cord injuries, or following radical prostatectomy. Nevertheless, some of these men respond. It has been my experience that few people respond in the first 3 months following radical prostatectomy, but the response rate gradually increases, and it appears that 50% of patients will respond at 1 year.

While sildenafil is not totally effective in relieving erectile dysfunction following radical prostatectomy, it appears to be efficacious in at least 75% of men who have undergone radiation therapy for prostate cancer.[8]

Sildenafil’s side effect profile is acceptable. Since phosphodiesterase 5 is found in vascular smooth muscle, men taking sildenafil often experience headache and flushing. The enzyme is also located in the gastroesophageal junction and nasopharyngeal mucosa, leading to side effects of dyspepsia and nasal congestion, as well as headache.

Other side effects can be divided into several areas, including visual effects, cardiovascular effects, and effects on blood pressure. Visual side effects include a transient change in color vision. Fortunately, there is no evidence of any long-term damage to the eye.

Sildenafil also can have transient effects on blood pressure. These effects, which are usually more prominent in the elderly, consist of an average 5-mm decrease in systolic and diastolic blood pressure.

In controlled studies, serious cardiovascular events, including myocardial infarction and death, were comparable in both the sildenafil- and placebo-treated groups.[9] As is well known, the drug is contraindicated in patients who are using organic nitrates or other nitric oxide donors, either regularly or intermittently. Concomitant use of these drugs with sildenafil can lead to severe, potentially fatal hypotensive episodes.

Other Treatments

While the major attention in erectile dysfunction over the past 3 years has focused on sildenafil, there are other effective means to treat erectile dysfunction. Intracavernosal alprostadil (Caverject, Edex) is efficacious in the majority of patients who have erectile dysfunction following radical prostatectomy. Unfortunately, I have found that pain is associated with the injection in half of my patients, and they refuse further injections. Intraurethral alprostadil (Muse) is not very effective following radical prostatectomy or radiation and is also associated with urethral pain.[4]

Combinations of two and three drugs, such as phentolamine (Regitine) and papaverine and phentolamine, papaverine, and alprostadil, are available, effective, and do not cause as much pain as single-agent alprostadil. None of these combinations has been approved by the Food and Drug Administration (FDA), however.

Prior to the advent of oral therapy and injection therapy, vacuum devices and penile prostheses were the mainstays of treatment for erectile dysfunction. The vacuum device described by the author is simple, noninvasive, and does result in erections in a majority of men who attempt its use. However, patients find it uncomfortable and unnatural, and many report a mild pain from the constricting device. Significant improvements have been made in the design of penile prostheses, and excellent results are reported.

Conclusions

The last 5 years have witnessed a significant renewal of interest in erectile dysfunction. Sildenafil has had promising results in men with mild to moderate erectile dysfunction. The future is bright, with a number of new agents under evaluation, including apomorphine, which acts centrally. Ongoing research into the etiology of erectile dysfunction will undoubtedly lead to the discovery of new agents and treatment modalities.

References

1. NIH Consensus Development Panel on Impotence: Impotence. JAMA 270:83-90, 1993.

2. Landis SH, Murray T, Bolden S, et al: Cancer statistics, 1999. CA Cancer J Clin 49:8-31, 1999.

3. Ragda H, Elgamal AA, Snow PB, et al: Ten-year disease free survival after transperineal sonography-guided iodine-125 brachytherapy with or without 45-gray external beam irradiation in the treatment of patients with clinically localized, low to high Gleason grade prostate carcinoma. Cancer 83:989-1001, 1998.

4. Goldstein I, Lue T, Padma-Nathan H, et al: Oral sildenafil in the treatment of erectile dysfunction. N Engl J Med 338:1397-1404, 1998.

5. Price D, Gingell C, Gepi-Attee S, et al: Sildenafil, a novel oral therapy for penile erectile dysfunction in patients with diabetes. Diabetic Med 14:A6, 1997.

6. Rendell MS: Sildenafil improves intercourse in patients with erectile dysfunction and diabetes. EASD (Barcelona) A300:1193, 1998.

7. Holmgren E, Giuliano F, Hultling C, et al: Sildenafil in the treatment of erectile dysfunction caused by spinal cord injury: A double-blind placebo controlled flexible dose 2-way crossover study. Neurology 50:A127, 1998.

8. Steers WD, the Sildenafil Study Group: Meta-analysis of the efficacy of sildenafil in the treatment of severe erectile dysfunction. J Urol 159(suppl 5):238A, 1998.

9. Muller JE, Mittleman MA, Maclure M, et al: Triggering myocardial infarction by sexual activity. JAMA 275:1405-1409, 1996.

 
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