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Keywords:

  • conservative management;
  • Peyronie's disease;
  • vitamin E

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. References

Background:  We retrospectively analysed the outcomes of conservative management of Peyronie's disease and determined the factors predicting successful outcome.

Methods:  The study involved 31 patients with Peyronie's disease who were treated at our institute between 1985 and 2003. We assessed the efficacy of vitamin E for the improvement of the symptoms, and the factors which contributed to successful outcome with conservative management using multivariate analysis.

Results:  There was no statistically significant difference in the relief rate between the vitamin E and no-medication groups. The overall estimated relief rate was 67.5% at 2 years from presentation. The multivariate analysis revealed plaque size to be the only significant factor predicting the relief from all symptoms in patients with conservative management. The rate was 100% in patients having a plaque size of 20 mm or smaller and 20.0% in those having a size of larger than 20 mm (P = 0.005).

Conclusions:  We could not confirm the benefit of vitamin E for Peyronie's disease. Plaque size was the only significant factor predicting the relief from all symptoms. Patients with larger plaque might fail to respond to the conservative management.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. References

Peyronie's disease is a localized connective tissue disorder between the tunica albuginea and the erectile tissue. It is characterized by the development of palpable penile plaques, painful erection, penile curvature, and erectile dysfunction (ED).1

The natural history of the disease remains unclear. To the best of our knowledge, there is no established conservative management effective for the early stage symptoms. Spontaneous resolution or progression can occur in the symptoms of Peyronie's disease. Thus, it is widely accepted that surgical treatment is reserved for patients with severe deformity that does not allow coitus, once the disease has stabilized. However, we have not known who would need a future surgical correction at the patients’ presentation. Therefore, it might be helpful to know the predictive factors for successful outcome which would not require surgery only with conservative treatment.1,2

Most subjects of the previous studies were Caucasians from Europe or the United States. There have been very few studies concerning the disease in Asian patients. We previously reported the time-dependent changes of the symptoms in Japanese patients with Peyronie's disease.3 We could not draw a conclusion on the use of vitamin E or identify factors contributing to the efficacy under the conservative management in that study.

The goal of this study was to clarify the outcome of conservative management and factors predicting successful outcome.

Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. References

We reviewed medical charts of 34 patients with Peyronie's disease who were fully evaluated at our institution between 1985 and 2003. Three patients were lost to follow up. Thus, 31 patients were finally evaluable in this study. Information on patients was obtained from an interview and physical examination concerning penile plaque, painful erection, penile curvature, and ED. The data concerning the angle and degree of the penile curvature were available for 29 patients (93.6%). These data were obtained via artificial erection induced by intracavernous injection of alprostadil in twenty-six patients, by pictures of the erect penis taken by two patients themselves, and by a drawing of the erect penis by one patient himself. Penile deformity was classified into three categories as follows: curvature 30 degrees or less; between 31 and 60 degrees; and greater than 60 degrees. The major axis of the palpable plaque was measured in 28 patients (90.3%). Three patients, who had definitely acquired penile curvature, were not proved to have obvious palpable plaques on the penis. We considered that these patients did not have congenital penile curvature or chordee without hypospadias, but diagnosed Peyronie's disease due to decreased elasticity of the tunica albuginea.

As for our management strategy at presentation, we recommended either that the patients take vitamin E, or watchful waiting for stabilization of the disease. We also told patients that surgery would be required at least 1 year after onset if the conservative management failed to improve the symptoms and they hoped to have an alternative treatment. We did not recommend any other option such as verapamil injection. The choice and period of the treatment with vitamin E depended on the patient's preference therefore they varied in this study.

To determine the predictive factors for relief from all of the symptoms of patients who were conservatively managed, data were analysed by multivariate analysis with the Cox proportional hazards model. The success of management was defined as when all of following criteria were satisfied: (i) disappearance of penile pain; (ii) decrease or stabilization of penile curvature; and (iii) decrease in size or stabilization of the fibrous plaque. The definition also required that patients did not need further treatments such as surgery. The variables for this multivariate analysis included ‘age at presentation (continuous)’, ‘vitamin E usage for at least 1 month (yes vs no)’, ‘period between onset and presentation (3 months or shorter vs longer than 3 months)’, ‘plaque size at presentation (20 mm or less vs greater than 20 mm)’, ‘pain on erection (no vs yes)’, ‘degree of the curvature (30 degrees or less vs more than 30 degrees)’.

We used the computer program JMP 5.0.1a (SAS Institute, Cary, NC, USA) for statistical analyses. The relief rate for all symptoms of Peyronie's disease was determined by the Kaplan–Meier method and the log–rank test was used for statistical analysis. The Fisher exact test was used for comparison of the relief rate of each symptom between vitamin E and no-medication groups. A P-value lower than 0.05 was considered to be statistically significant.

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. References

The patients’ characteristics are shown in Table 1. Painful erection was identified in 18 (58.1%). Only one of the 18 patients had pain in the flaccid penis. Hourglass deformity was found in one patient (3.2%). The mean dosage of vitamin E was 144.7 ± 55.0 mg per day and the mean prescription period was 6.1 ± 6.2 months. Although the proportion of pain relief was relatively high in patients with vitamin E (66.7%), there was no significant difference in improvement of symptoms between the group administered vitamin E and the one without medication (Table 2).

Table 1.  Patients’ characteristics
  1. ED, erectile dysfunction.

Number of patients31
Mean age (years)50.3 ± 14.4
Median follow up months12.6 ± 15.5
Time from onset months18.6 ± 37.4
Symptom (%)
 Pain on erection18 (58.1)
 Penile curvature
  Number27 (87.1)
  Degree
   ≤3011
   31–6015
   >60 1
  Direction
   Dorsal11
   Ventral 7
   Lateral 4
   Dorso-lateral 4
   Ventro-lateral 1
 Plaque
  Number28 (90.3)
  Mean size (mm)23.8 ± 11.6
 ED 3 (10.7)
Table 2.  Results of conservative therapy for patients with Peyronie's disease
 Vitamin E group (n = 21)No-medication group (n = 10)P-value*
  • *

    Fisher exact test. ED, erectile dysfunction.

Pain relief8/12(66.7%)1/6(16.7%)0.131
Curvature improvement4/18(22.2%)0/9(0.0%)0.267
Plaque size reduction6/20(30.0%)1/8(12.5%)0.633
ED improvement0/1(0.0%)0/2(0.0%)>0.999

Multivariate analysis showed that the only factor contributing to the overall symptom relief was ‘plaque size’ (Table 3).

Table 3.  Factors involved in the improvement under conservative management
VariablesOdds95% CIP-value
  1. Multivariate analysis with Cox Hazard's model.

Age (continuous)0.9890.8971.0770.799
Vitamin E (yes vs no)1.4000.4655.2860.538
Period from onset (≤3 months vs >3 months)0.5130.0752.8500.443
Plaque size (≤20 mm vs >20 mm)4.3631.20824.6320.025
Pain (no vs yes)0.3690.0561.0810.072
Degree (≤30 degrees vs >30 degrees)1.7870.4079.4670.421

The estimated relief rate for all presented symptoms was analysed by the Kaplan–Meier method (Fig. 1). The overall estimated relief rates of the symptoms were 67.5% at 2 years from presentation. When we divided the relief rate by the size of the plaque, the patients with plaques ‘20 mm or smaller’ showed a significantly higher rate reaching 100% at 18 months, compared with that of the ‘larger than 20 mm’ group (P = 0.005). Of 16 patients in whom conservative management failed and disease was stabilized, 12 patients underwent surgical correction.

image

Figure 1. The recovery from Peyronie's disease. The recovery rate for all symptoms of Peyronie's disease patients with time from presentation and patients at risk estimated by the Kaplan–Meier method. Log–rank test between ‘20 mm or smaller’ and ‘larger than 20 mm’; P = 0.005. mos., months.

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Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. References

Epidemiologically, it is revealed that the average age of the Peyronie's disease patients was 57.4 years with the prevalence of 3.2%.4 It was also reported the presenting symptom was palpable penile plaques (100%), painful erection (46.5%), and penile curvature (83.8%). The present study showed the similar result in the mean age of patients and the distribution of symptoms. Peyronie's disease can be classified into two phases, acute and chronic. In the acute inflammatory phase, a patient usually presents with painful erection, which lasts approximately 12–18 months. In a cross-sectional study of 97 patients with Peyronie's disease at 3 months to 8 years from onset, 13% showed gradual resolution.5 On the other hand, 87% of patients showed no improvement; 40% noted progression and the remaining 47% were unchanged. In our study, although 24 of 31 patients (77%) showed no improvement during the study period similar to the previous report, the estimated symptom relief rate by the Kaplan–Meier method was 67.5% at 2 years from presentation. To tie the response rate to the conservative management, prospective study might be crucial.

The recent strategy for Peyronie's disease is stepwise; a conservative management for at least 1 years and then surgery if the disease persists. Some agents have been suggested to be effective for the disease during the early inflammatory phase. These include oral medication with vitamin E, potassium aminobenzzoate (Potaba), tamoxifen, or colchicines, and intralesional injection therapy with steroids, collagenase, verapamil, or interferon-alpha-2b.6 Vitamin E, which is widely accepted, can generate a free radical oxygen scavenging effect.6 A randomized single-blind study showed that the combination of colchicines and vitamin E was more beneficial than ibuprofen alone for the early stages of Peyronie's disease.7 The administration of vitamin E was also reported to reduce pain successfully in the Japanese population.8 Although the efficacy of vitamin E for patients with Peyronie's disease is not definitely established, vitamin E might contribute to some extent to pain relief. Therefore, we cannot neglect vitamin E as a primary treatment considering its low cost and the absence of serious adverse effects.

By multivariate analysis, our study indicated that the plaque size was a predictive factor for successful management of Peyronie's disease conservatively. Moreover, in patients with smaller plaques (20 mm or smaller), the estimated overall symptom relief rate was 100% at 18 months. In previous studies, good indications for conservative management were suggested to be the following: absence of a concomitant risk for vascular disease, early disease, normal erectile function, and mild disease status (non-calcified plaque or curvature of less than 30 degrees).9,10 Thus, conservative management might be beneficial for patients with mild disease status, which was also suggested by our results. By contrast, the information might be helpful for the patients with plaques larger than 20 mm at presentation to predict the failure of conservative management in future.

Although it is not known exactly why patients with large plaques failed to respond to conservative management, we believe that it may be associated with some factors. One is the issue of disease severity itself, as an established plaque in late stage is more likely to fail to respond conservative management.11 The other factor is the contribution of calcification into the plaque. In previous studies, it was suggested the degree of calcification could be associated with the response to conservative treatment.12,13 However, no studies could be found to support the idea that larger plaques could have more calcium deposits. We could not evaluate calcium deposit into plaque because ultrasonography was not performed. To confirm these findings, a further study may be needed to assess not only size but also the properties of plaques in Peyronie's disease.

From the nature of this retrospective study, there are some limitations such as biased patients’ background, biased decision for management, possible inaccuracy in some assessments of penile deformity and plaque, varying dosage and periods of vitamin E, and the varying follow-up periods. Unfortunately, the variables for multivariate analysis in the current study did not include the presence of disease-related factors such as smoking, diabetes mellitus, and vascular diseases (including hypertension, ischemic heart disease and cerebral infarction), because the number of patients was not large enough for such analysis. In spite of these limitations, we believe that this study reconfirms the current treatment strategy for Peyronie's disease, and provides a perspective on an Asian population similar to that of previous reports from Western countries.

Conclusion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. References

The current study suggested that plaque size at presentation was the single predicting factor for successful conservative management of Peyronie's disease. Patients with larger plaques might fail to respond to conservative management.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. References