The disease is associated with erectile dysfunction and recurrent trauma, and, in time, may result in penile curvature, preventing sexual intercourse. It is suggested that weak erections predispose to penile trauma during sexual intercourse, resulting in subtunical bleeding and local inflammation. Peyronie's disease can be considered a hyperactive wound-healing response to recurrent microvascular injury of the tunica albuginea with overexpression of cytokines and growth factors such as tumour growth factor-ß [1].

In a recent survey, the disease's prevalence was found to be 3.2% and appeared to increase with age [2].

The natural history of Peyronie's disease varies from spontaneous resolution to a progressive status with severe penile deformation. In a follow-up study of 97 men, 40% reported a worsening of their signs and symptoms over time. However, in 47%, the disease had stabilized after resolution of the inflammatory process, and, in 13%, symptoms had even disappeared spontaneously [3].

In the early phase of the disease, the inflammatory process often is accompanied by pain during erections that gradually disappears within 12 to 18 months. Different drugs have been used for pain relief, prevention of plaque formation and penile curvature. In their review of the non-surgical treatments of Peyronie's disease, Hauck et al. [4] conclude that currently no conservative treatment is available that will result in complete relief of all these symptoms. Furthermore, most drugs taken orally, applied topically or injected intralesionally either have not been tested in randomized controlled studies or have been shown ineffective in placebo-controlled trials. In fact, most studies on medical treatment of Peyronie's disease are characterized by the absence of a control group, a low number of patients, no detailed description of criteria for measuring improvement objectively and short periods of follow-up. Indeed, medical treatment can only be recommended if sufficient data are available from randomized controlled trials, proving efficacy over placebo administration. In a recent prospective randomized trial Weidner et al. [5] investigated the widely used drug para-aminobenzoate for the treatment of Peyronie's disease: response rates were 74.3% in the treated group versus 50.0% in the placebo group. The authors concluded that the drug was not effective in improving pre-existing curvatures but was able to prevent disease progression in one third of cases. Associated pain was not relieved by the medication. The treatment regime was quite demanding with four tablets taken per day for 12 months.

Other drugs used for conservative treatment, like vitamin E, colchicines and tamoxifen did not show any positive effect, compared with placebo. Intralesional therapy has been advocated in many studies as initial treatment for pain relief and prevention of curvature: corticosteroids and verapamil are still use frequently but did not show any benefit over placebo in recent prospective studies [6,7]. Only interferon alpha-2b appeared effective as intralesional therapy, but repeated dosing had to be performed of this expensive drug, making it less attractive for general use [8]. Both oral and intralesional therapy require a high degree of patient compliance.

A relatively new concept of administrating drugs directly into the plaque is by iontophoresis: ionic molecules are transported transdermally by electromotive transport. Tissue penetration of the applied drugs is enhanced, and significant levels of the applied drug could be detected in the tunica albuginea. Preliminary results of multi-drug administration showed encouraging first results on both pain relief and prevention of curvature that deserve further exploration in randomized prospective trials [9].

Conservative measurements should be applied primarily in symptomatic patients with Peyronie's disease. In fact, most men need only reassurance and a watchful waiting approach, since pain will resolve spontaneously and plaque formation usually stabilizes with time. Treatment of erectile dysfunction, if present, also is very helpful. Only a limited amount of men with Peyronie's disease need surgical treatment because of severe curvature and associated sexual problems.

The key question in the treatment of Peyronie's disease probably is can we prevent disease progression resulting in penile shortening and curvature by early non-surgical intervention? None of the currently available treatment modalities so far has so demonstrated this effect conclusively, although disease stabilization was reported in some studies. Most studies were not designed to address this important question. Future randomized controlled studies are needed to investigate if early conservative intervention can reduce penile deformity and preserve sexual function in men suffering from Peyronie's disease.

References

1. Gholami SS, Gonzalez-Cadavid NF, Lin CS, Rajfer J, Lue TF. Peyronie's disease: a review. J Urol. 2003;169:1234–1241.

2. Schwarzer U, Sommer F, Klotz T, Braun M, Reifenrath B, Engelmann U. The prevalence of Peyronie's disease: results of a large survey. BJU Int. 2001;88:727–730.

3. Gelbard MK, Dorey F, James K. The natural history of Peyronie's disease. J Urol. 1990;144:1376–1379.

4. Hauck EW, Diemer T, Schwelz HU, Weidner W. A critical analysis of non-surgical treatment of Peyronie's disease. Eur Urol. 2006;49:987–997.

5. Weidner W, Hauck EW, Schnitker JPeyronie's Disease Study Group of Andrological Group of German Urologists. Potassium paraaminobenzoate (POTABA) in the treatment of Peyronie's disease: a prospective, placebo-controlled, randomized study. Eur Urol. 2005;47:530–535.

6. Cipollone G, Nicolai M, Mastroprimiano G, Iantorno R, Longeri D, Tenaglia R. Betametasone versus placebo nella malattia di la Peyronie. Arch Ital Urol Androl. 1998;70:165–168.

7. Levine LA, Goldman KE, Greenfield JM. Experience with intraplaque injection of verapamil for Peyronie's disease. J Urol. 2002;168:621–626.

8. Ahuja SK, Bivalacqua TJ, Case J, Vincent M, Sikka SC, Hellstrom WJG. A pilot study demonstrating clinical benefit from intralesional interferon alpha 2b in the treatment of Peyronie's disease. J Androl. 1999;20:444–448.

9. Montorsi F, Salonia A, Guazzoni G, et al.. Transdermal electromotive multi-drug administration for Peyronie's disease: preliminary results. J Androl. 2000;21:85–90.

Gert Dohle

Erasmus University Medical Centre, Rotterdam, The Netherlands

published online 7 March 2006.

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