Current issues of ACP Journal Club are published in Annals of Internal Medicine


Therapeutics

Transurethral alprostadil restored potency in impotent men

ACP J Club. 1997 Jul-Aug;127:7. doi:10.7326/ACPJC-1997-127-1-007


Source Citation

Padma-Nathan H, Hellstrom WJ, Kaiser FE, et al., for the Medicated Urethral System for Erection (MUSE) Study Group. Treatment of men with erectile dysfunction with transurethral alprostadil. N Engl J Med. 1997 Jan 2;336:1-7.


Abstract

Objective

To evaluate the effectiveness of transurethral alprostadil (prostaglandin E1) in men with chronic organic erectile dysfunction.

Design

3-month randomized, double-blind, placebo-controlled trial.

Setting

58 centers in the United States.

Patients

1511 men (mean age 61 y) who were in a stable, monogamous, heterosexual relationship and were unable to achieve a spontaneous erection sufficient for intercourse within the past 3 months. Causes of dysfunction included vascular disease, diabetes, surgery, trauma, and other organic causes. Exclusion criteria were history of urethral stricture or obstruction, indwelling urethral catheter, anuria, penile implant or previous penile surgery, sickle cell disease, paraplegia or quadriplegia, congestive heart failure, unstable angina, recent myocardial infarction, poorly controlled diabetes mellitus, inadequately treated hypogonadism, abnormal blood test results, or receipt of investigational treatment in the past 30 days. Follow-up was 88%.

Intervention

All men meeting entry criteria self-administered transurethral alprostadil during as many as 4 clinic visits to determine an optimal dose in the clinic. 996 men (66%) had erections that were sufficient for intercourse and were allocated to home treatment with alprostadil (n = 485) at a titrated dose of 125 µg, 250 µg, 500 µg, or 1000 µg or placebo (n = 511).

Main outcome measures

Sexual intercourse, orgasm, comfort level, and adverse effects.

Main results

During the 3-month home-treatment period, more patients who received alprostadil than patients who received placebo reported having ≥ 1 occurrence of sexual intercourse (P < 0.001) (Table). Alprostadil also led to more patients having ≥ 1 orgasm (P < 0.001) (Table). Alprostadil administration was rated as comfortable or very comfortable by > 60% of recipients. More patients who received alprostadil reported penile pain than those who received placebo (33% vs 3%, {P < 0.001}*).

Conclusion

Transurethral alprostadil increased erections, sexual intercourse, and orgasms in men with chronic erectile dysfunction.

Source of funding: In part, Vivus, Inc.

For article reprint: Dr. N. Gesundheit, Vivus, Inc., 545 Middlefield Road, Suite 200, Menlo Park, CA 94025, USA. FAX 415-325-2173.

*Numbers calculated from data in article.


Table. Alprostadil vs placebo†

Outcomes at 3 mo Alprostadil EER Placebo CER RBI (95% CI) ABI |EER - CER| NNT (CI)
Sexual intercourse 65% 19% 249% (188 to 325) 46% 3 (2 to 3)
≥ 1 orgasm 64% 24% 169% (127 to 221) 40% 3 (2 to 3)

†Abbreviations defined in Glossary; RBI, ABI, NNT, and CI calculated from data in article.


Commentary

The study by Padma-Nathan and colleagues shows that transurethral alprostadil seems to work for many men with erectile dysfunction and has an acceptable level of side effects. Transurethral alprostadil joins revascularization procedures, penile prostheses, vacuum erection devices, and intracavernosal injections of vasoactive substances as a therapeutic option.

This and other trials have generally compared an active treatment of erectile dysfunction with placebo; for example, intracavernosal injections of alprostadil have also been shown to be efficacious and relatively safe (although patients can develop priapism or fibrosis) (1). What is needed now are trials that compare active strategies of treatment with a focus on patient-centered outcomes, including ease of use and satisfaction with the results.

Most treatments for erectile dysfunction tend to be invasive or require considerable education and motivation to use properly. An effective oral or topical therapy with acceptable side effects would be welcome. Yohimbine, a presynaptic α2-adrenergic receptor blocker, has shown only limited efficacy (2). 1 small study has suggested a modest benefit of a topical mixture of 3 vasodilators (3). Randomized trials of other oral agents, including the phosphodiesterase type 5 inhibitor sildenafil (4), are currently under way. At least until the final results of these studies are reported, transurethral alprostadil is an attractive therapeutic option.

Michael J. Barry, MD
Massachusetts General Hospital
Michael P. O'Leary, MD, MPH
Brigham and Women's HospitalBoston, Massachusetts, USA

Michael J. Barry, MD
Massachusetts General Hospital
Boston, Massachusetts, USA

Michael P. O'Leary, MD, MPH
Brigham and Women's Hospital
Boston, Massachusetts, USA


References

1. Linet OI, Ogrinc FG. N Engl J Med. 1996;334:873-7.

2. Yohimbine for male sexual dysfunction [Letter]. Med Lett Drugs Ther. 1994;36:115-6.

3. Gomaa A, Shalaby M, Osman M, et al. BMJ. 1996;312:1512-5.

4. Boolell M, Gepi-Attee S, Gingell JC, Allen MJ. Br J Urol. 1996;78:257-61.